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Citrome L, Álvarez-Barón E, Gabarda-Inat I, Thangavelu K, Tocco M. The specific anti-hostility effect of lurasidone in patients with an acute exacerbation of schizophrenia: results of pooled post hoc analyses in adolescents and adults. Int Clin Psychopharmacol 2025; 40:214-223. [PMID: 39052354 PMCID: PMC12122092 DOI: 10.1097/yic.0000000000000563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2024] [Accepted: 06/27/2024] [Indexed: 07/27/2024]
Abstract
Symptoms of hostility in patients during acute exacerbations of schizophrenia have been associated with aggressive behavior. Data suggest that some second-generation antipsychotics have specific anti-hostility effects, independent of sedation and positive symptom improvement. Two post hoc analyses were performed to examine the efficacy of lurasidone for reducing hostility in patients with schizophrenia. One analysis pooled adults ( N = 1168) from 5 placebo-controlled, 6-week trials of lurasidone (40-160 mg). Another analysis pooled younger patients (up to age 25 years, N = 427) from the adult studies and a similarly designed trial of lurasidone (40 or 80 mg) in adolescent patients (13-17 years old). The outcome measure was mean change in the hostility item (P7) of the Positive and Negative Syndrome Scale (PANSS). To address pseudospecificity, results were adjusted for positive symptom change and sedation. In adults with a baseline PANSS hostility score ≥2, significant improvement in hostility was observed for all doses with a dose-related increase in effect size (Cohen's d): lurasidone 40 mg = 0.18, 80 mg = 0.24, 120 mg = 0.36, and 160 mg = 0.53. The same dose-response pattern was observed for the more severe hostility subgroups (P7: ≥3, ≥4), and in the early-onset population. Results suggest that lurasidone has specific, dose-related anti-hostility effects.
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Affiliation(s)
- Leslie Citrome
- Department of Psychiatry and Behavioral Sciences, New York Medical College, Valhalla, New York, USA
| | | | | | | | - Michael Tocco
- Medical Department, Sumitomo Pharma America, Inc., Marlborough, Massachusetts, USA
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Bernardo M, Marsá MD, González-Pinto A, Carrasco MM, Sola VP, Sáiz PA, Vieta E, Torrens M, Arango C, Crespo-Facorro B. Efficacy of Lurasidone in First-Episode Psychosis: Patient Phenotypes, Dosage, and Recommendations from an Expert Panel. Neurol Ther 2025; 14:85-98. [PMID: 39760831 PMCID: PMC11762036 DOI: 10.1007/s40120-024-00700-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Accepted: 12/16/2024] [Indexed: 01/07/2025] Open
Abstract
INTRODUCTION For patients with psychosis, early, intensive therapeutic intervention is thought to improve long-term outcomes. Furthermore, patients with a first-episode psychosis (FEP) who experience a good early response to antipsychotic medication show a clinical and functional benefit over the longer term if they continue low-dose antipsychotic treatment. Lurasidone is an atypical antipsychotic agent which is approved in Europe for the treatment of schizophrenia in adults and adolescents (13-17 years). The efficacy and tolerability of lurasidone have been demonstrated in both antipsychotic-naïve and previously treated patients. AREAS COVERED This paper provides a review and commentary regarding the use of lurasidone in patients with FEP. Case studies based on the authors' clinical experiences with lurasidone in real-world practice are provided. EXPERT OPINION In our experience, lurasidone has shown efficacy in FEP in different patient profiles, including those with psychoses associated with substance use disorders. Lurasidone provides clinically relevant benefits, especially in patients with affective symptomatology, and has a good tolerability profile.
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Affiliation(s)
- Miquel Bernardo
- Department of Psychiatry and Psychology, Clínic Barcelona, Institute of Neuroscience, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain.
| | - Marina Díaz Marsá
- Hospital Clínico San Carlos, Universidad Complutense, CIBERSAM, Madrid, Spain
| | - Ana González-Pinto
- Hospital Universitario de Álava, BIOARABA. UPV/EHU, CIBERSAM, Vitoria, Spain
| | - Manuel Martín Carrasco
- Clínica Psiquiátrica Padre Menni, Pamplona, FIDMAG Research Foundation, Barcelona, Spain
| | - Víctor Pérez Sola
- Mental Health Institute Hospital del Mar, Barcelona, Hospital del Mar Research Institute, University Pompeu Fabra, University of Vic-Central Catalunya, RIAPAD, Barcelona, Spain
| | - Pilar Alejandra Sáiz
- Department of Psychiatry, Universidad de Oviedo, CIBERSAM, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Instituto Universitario de Neurociencias del Principado de Asturias (INEUROPA), Servicio de Salud del Principado de Asturias (SESPA), Oviedo, Spain
| | - Eduard Vieta
- Department of Psychiatry and Psychology, Clínic Barcelona, Institute of Neuroscience, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain
| | - Marta Torrens
- Mental Health Institute Hospital del Mar, Barcelona, Hospital del Mar Research Institute, University Pompeu Fabra, University of Vic-Central Catalunya, RIAPAD, Barcelona, Spain
| | - Celso Arango
- Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón School of Medicine, Universidad Complutense, IiSGM, CIBERSAM, Madrid, Spain
| | - Benedicto Crespo-Facorro
- Department of Psychiatry, Faculty of Medicine, Mental Health Unit, Virgen del Rocio University Hospital, Translational Psychiatry Group, IBiS-CSIC, CIBERSAM, University of Seville, Seville, Spain
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Mostafa YE, Metwally MES, Elsebaei F. Prominently selective fluorescence approach with distinctive biopharmaceutical utility for analysis of lurasidone in human plasma and urine: Application to in vitro dissolution and content uniformity testing. LUMINESCENCE 2024; 39:e4887. [PMID: 39238324 DOI: 10.1002/bio.4887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 07/17/2024] [Accepted: 08/13/2024] [Indexed: 09/07/2024]
Abstract
A relevant approach based on the attractive inherited merits of fluorescence spectroscopy has been established for quantitative estimation of a newly approved second-generation atypical antipsychotic lurasidone (LUR) in its raw materials and pharmaceutical dosage forms. This study brings to light the strong native fluorescence of LUR at 400 nm in water after excitation at 316 nm. Different experimental parameters that may compromise the fluorescence of the drug were carefully investigated and optimized. A linear response was established between the relative fluorescence intensity and concentration over the concentration range of 50-650 ng/mL with excellent correlation (r = 0.9998). The validity of the method was evidenced in accordance with International Council for Harmonization guidelines, with minimal detection and quantification limits of 2.88 and 8.73 ng/mL, respectively. The method was effectively applied for the estimation of LUR in spiked human plasma and urine samples with acceptable recoveries. The biopharmaceutical significance of the method was heightened by its successful applications for both content uniformity and in vitro dissolution testing. Three different tools accredited the greenness character of the presented study. Eco-friendliness, effortlessness, and cost effectiveness are crucial hallmarks of our study. The presented study demonstrates potential applicability in quality control laboratories with limited resources.
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Affiliation(s)
- Yasmeen E Mostafa
- Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
| | - Mohammed El-Sayed Metwally
- Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
| | - Fawzi Elsebaei
- Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
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Maruyama H, Sano F, Sakaguchi R, Okamoto K, Miura I. Effect of Lurasidone on Life Engagement in Schizophrenia: Post-Hoc Analysis of the JEWEL Study. Neuropsychiatr Dis Treat 2024; 20:1453-1463. [PMID: 39072313 PMCID: PMC11283796 DOI: 10.2147/ndt.s466479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Accepted: 07/03/2024] [Indexed: 07/30/2024] Open
Abstract
Purpose To evaluate the effect of lurasidone on a new, patient Life Engagement scale in schizophrenia. Patients and Methods This post-hoc analysis included participants (ages 18 to 74) diagnosed with schizophrenia who were randomized to lurasidone (40 mg/day) or placebo in a 6-week double-blind efficacy study and those who continued in a subsequent 12-week open-label extension study during which patients received either 40 or 80/mg day lurasidone (flexibly dosed). Change in life engagement was measured using the Positive and Negative Syndrome Scale (PANSS) 11-item Life Engagement subscale score, and individual subscale items, at week 6 during the double-blind phase and extension phase week 12 during the open-label extension phase. Results Analysis focused on 478 subjects randomized to lurasidone or placebo during the 6-week trial, and 146 who received lurasidone during the extension phase. During the 6-week trial, there was a significantly greater change on the PANSS11 Life Engagement subscale score from baseline to week 6 in the lurasidone group compared to the placebo group (mean changes of -6.4 and -4.8, respectively, p = 0.006; effect size = 0.27). Further improvement was evident during the extension phase for patients who received lurasidone in both phases, with a mean change from double-blind baseline to week 12 of the open-label treatment phase of -10.1 on in PANSS11 Life Engagement subscale. Conclusion This post-hoc analysis suggests that lurasidone may improve life engagement in patients with schizophrenia, a meaningful outcome from patients' perspective. Further studies are needed to confirm this effect. Eudract Number Trial registration: EudraCT Numbers: 2016-000060-42; 2016-000061-23.
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Affiliation(s)
| | - Fumiya Sano
- Department of Data Science, Drug Development Division, Sumitomo Pharma Co., Ltd, Tokyo, Japan
| | - Reiko Sakaguchi
- Department of Clinical Research, Drug Development Division, Sumitomo Pharma Co., Ltd, Tokyo, Japan
| | - Keisuke Okamoto
- Department of Clinical Operation, Drug Development Division, Sumitomo Pharma Co., Ltd, Tokyo, Japan
| | - Itaru Miura
- Department of Neuropsychiatry, Fukushima Medical University, Fukushima, Japan
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Calisti F, Tocco M, Mao Y, Goldman R. Long-term safety and effectiveness of lurasidone in adolescents and young adults with schizophrenia: pooled post hoc analyses of two 12-month extension studies. Ann Gen Psychiatry 2024; 23:26. [PMID: 39020362 PMCID: PMC11256627 DOI: 10.1186/s12991-024-00502-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Accepted: 05/01/2024] [Indexed: 07/19/2024] Open
Abstract
BACKGROUND AND OBJECTIVES The aim of this analysis was to evaluate the long-term safety and effectiveness of lurasidone in the treatment of schizophrenia in adolescents and young adults (13-25). METHODS The 2 pooled studies used similar designs and outcome measures. Patients (13-25) with schizophrenia completed an initial double-blind 6-week trial of lurasidone (40 and 80 mg/day) in the adolescent trial and (80 and 160 mg/day) in the young adult trial. In open-label long-term trials, adolescent patients were treated with 20-80 mg/day lurasidone, and adults were treated with 40-160 mg/day lurasidone. Efficacy was evaluated based on the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity Scale (CGI-S). RESULTS The safety population consisted of 306 patients (mean age, 16.2 years; 208 patients (68.0%) who completed 12 months of treatment; 8.2% who discontinued treatment by 12 months due to an adverse event). The mean (SD) changes in the PANSS total score from the extension baseline to months 6 and 12 were - 11.8 (13.9) and - 15.3 (15.0), respectively (OC), and the mean (SD) changes in the CGI-S score were - 0.8 (1.0) and - 1.0 (1.1), respectively (OC). The most frequent adverse events were headache (17.6%), anxiety (11.4%), schizophrenia (9.8%), and nausea (9.8%). No clinically meaningful changes were observed in weight, metabolic parameters, or prolactin. CONCLUSIONS In adolescents and young adults with schizophrenia, treatment with lurasidone was generally well tolerated and effective. Long-term treatment was associated with a continued reduction in symptoms of schizophrenia. Long-term treatment was associated with minimal effects on weight, metabolic parameters, and prolactin. CLINICALTRIALS gov identifiers D1050234, D1050302.
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Affiliation(s)
| | - Michael Tocco
- Former Employee of Sumitomo Pharma America, Inc, 84 Waterford Drive, Marlborough, MA 01752, USA.
| | - Yongcai Mao
- Sumitomo Pharma America, Inc, 84 Waterford Drive, Marlborough, MA, 01752, USA
| | - Robert Goldman
- Former Employee of Sumitomo Pharma America, Inc, 84 Waterford Drive, Marlborough, MA 01752, USA
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Cavallotto C, Chiappini S, Mosca A, d’Andrea G, Di Carlo F, Piro T, Susini O, Stefanelli G, Di Cesare A, Ricci V, Pepe M, Dattoli L, Di Nicola M, Pettorruso M, Martinotti G. Examining Lurasidone Efficacy in Patients with Schizophrenia Spectrum Illness and Concurrent Alcohol and Substance Use Disorder: A Prospective, Multicentric, Real-World Investigation. J Clin Med 2024; 13:2206. [PMID: 38673478 PMCID: PMC11051375 DOI: 10.3390/jcm13082206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Revised: 03/18/2024] [Accepted: 04/09/2024] [Indexed: 04/28/2024] Open
Abstract
Background: Dual disorders (DD) entail the coexistence of a substance use disorder (SUD) and another mental health condition, often within psychotic and affective disorders. This study aims to evaluate lurasidone, an innovative atypical antipsychotic, in individuals diagnosed with schizophrenia spectrum disorder and concurrent comorbidities of alcohol use disorder/substance use disorder (AUD/SUD). Methods: A cohort of 23 subjects diagnosed with schizophrenia spectrum disorder and comorbid AUD/SUD underwent psychometric assessments at baseline (T0) and one-month (T1) post-lurasidone initiation. Results: Lurasidone exhibited significant reductions in psychopathological burden, evidenced by decreased total PANSS scores (Z = 2.574, p = 0.011). Positive symptoms, substance craving (VAS Craving; Z = 3.202, p = 0.001), and aggressivity (MOAS scale; Z = 2.000, p = 0.050) were notably reduced. Clinical Global Impression (CGI) scores significantly improved (Z = 2.934, p = 0.003). Quality of life enhancements were observed in SF-36 subscales (energy, emotional well-being, and social functioning) (p < 0.05) and Q-LES-Q-SF scale (Z = -2.341, p = 0.021). A safety analysis indicated lurasidone's good tolerability, with only 8.7% reporting discontinuation due to side effects. Conclusions: This study offers initial evidence supporting lurasidone's efficacy and safety in dual diagnoses, highlighting positive effects on psychopathology, substance craving, and quality of life. These findings emphasize the need for tailored, comprehensive treatment strategies in managing the complexities of this patient population.
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Affiliation(s)
- Clara Cavallotto
- Department of Neurosciences, Imaging and Clinical Sciences, “G. D’Annunzio” University, 66100 Chieti, Italy; (C.C.); (G.d.); (F.D.C.); (T.P.); (G.S.); (L.D.); (M.P.)
| | - Stefania Chiappini
- School of Medicine, UniCamillus International Medical School University, 00131 Rome, Italy;
| | - Alessio Mosca
- Department of Neurosciences, Imaging and Clinical Sciences, “G. D’Annunzio” University, 66100 Chieti, Italy; (C.C.); (G.d.); (F.D.C.); (T.P.); (G.S.); (L.D.); (M.P.)
| | - Giacomo d’Andrea
- Department of Neurosciences, Imaging and Clinical Sciences, “G. D’Annunzio” University, 66100 Chieti, Italy; (C.C.); (G.d.); (F.D.C.); (T.P.); (G.S.); (L.D.); (M.P.)
| | - Francesco Di Carlo
- Department of Neurosciences, Imaging and Clinical Sciences, “G. D’Annunzio” University, 66100 Chieti, Italy; (C.C.); (G.d.); (F.D.C.); (T.P.); (G.S.); (L.D.); (M.P.)
| | - Tommaso Piro
- Department of Neurosciences, Imaging and Clinical Sciences, “G. D’Annunzio” University, 66100 Chieti, Italy; (C.C.); (G.d.); (F.D.C.); (T.P.); (G.S.); (L.D.); (M.P.)
| | - Ottavia Susini
- Department of Neurosciences, Imaging and Clinical Sciences, “G. D’Annunzio” University, 66100 Chieti, Italy; (C.C.); (G.d.); (F.D.C.); (T.P.); (G.S.); (L.D.); (M.P.)
| | - Giulia Stefanelli
- Department of Neurosciences, Imaging and Clinical Sciences, “G. D’Annunzio” University, 66100 Chieti, Italy; (C.C.); (G.d.); (F.D.C.); (T.P.); (G.S.); (L.D.); (M.P.)
| | - Andrea Di Cesare
- Department of Mental Health, ASL 02 Lanciano-Vasto-Chieti, 66100 Chieti, Italy;
| | - Valerio Ricci
- Department of Psychiatry, “San Luigi Gonzaga” Hospital, University of Turin, 10124 Turin, Italy
| | - Maria Pepe
- University Policlinic Foundation “A. Gemelli” IRCSS-Catholic University of the Sacred Heart, Largo Agostino Gemelli, 8, 00136 Rome, Italy (M.D.N.)
| | - Luigi Dattoli
- Department of Neurosciences, Imaging and Clinical Sciences, “G. D’Annunzio” University, 66100 Chieti, Italy; (C.C.); (G.d.); (F.D.C.); (T.P.); (G.S.); (L.D.); (M.P.)
| | - Marco Di Nicola
- University Policlinic Foundation “A. Gemelli” IRCSS-Catholic University of the Sacred Heart, Largo Agostino Gemelli, 8, 00136 Rome, Italy (M.D.N.)
| | - Mauro Pettorruso
- Department of Neurosciences, Imaging and Clinical Sciences, “G. D’Annunzio” University, 66100 Chieti, Italy; (C.C.); (G.d.); (F.D.C.); (T.P.); (G.S.); (L.D.); (M.P.)
| | - Giovanni Martinotti
- Department of Neurosciences, Imaging and Clinical Sciences, “G. D’Annunzio” University, 66100 Chieti, Italy; (C.C.); (G.d.); (F.D.C.); (T.P.); (G.S.); (L.D.); (M.P.)
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Ricci V, De Berardis D, Maina G. Third-Generation Antipsychotics and Lurasidone in the Treatment of Substance-Induced Psychoses: A Narrative Review. Healthcare (Basel) 2024; 12:339. [PMID: 38338224 PMCID: PMC10855531 DOI: 10.3390/healthcare12030339] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 01/09/2024] [Accepted: 01/25/2024] [Indexed: 02/12/2024] Open
Abstract
This narrative review explores the efficacy and tolerability of third-generation antipsychotics (TGAs)-aripiprazole, cariprazine, brexpiprazole, and lurasidone-for the management of substance-induced psychosis (SIP). SIP is a psychiatric condition triggered by substance misuse or withdrawal, characterized by unique features distinct from those of primary psychotic disorders. These distinctive features include a heightened prevalence of positive symptoms, such as hallucinations and delusions, in addition to a spectrum of mood and cognitive disturbances. This review comprehensively investigates various substances, such as cannabinoids, cocaine, amphetamines, and LSD, which exhibit a greater propensity for inducing psychosis. TGAs exhibit substantial promise in addressing both psychotic symptoms and issues related to substance misuse. This review elucidates the distinctive pharmacological properties of each TGA, their intricate interactions with neurotransmitters, and their potential utility in the treatment of SIP. We advocate for further research to delineate the long-term effects of TGAs in this context and underscore the necessity for adopting an integrated approach that combines pharmacological and psychological interventions. Our findings underscore the intricate and multifaceted nature of treating SIP, highlighting the potential role of TGAs within therapeutic strategies.
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Affiliation(s)
- Valerio Ricci
- San Luigi Gonzaga Hospital, University of Turin, Regione Gonzole 10, 10043 Orbassano, Italy;
| | - Domenico De Berardis
- NHS, Department of Mental Health, Psychiatric Service for Diagnosis and Treatment, Hospital “G. Mazzini”, ASL 4, 64100 Teramo, Italy;
| | - Giuseppe Maina
- San Luigi Gonzaga Hospital, University of Turin, Regione Gonzole 10, 10043 Orbassano, Italy;
- Department of Neurosciences “Rita Levi Montalcini”, University of Turin, 10124 Torino, Italy
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Tocco M, Newcomer JW, Mao Y, Pikalov A. Lurasidone and risk of metabolic syndrome: results from short and long-term studies in patients with bipolar depression. CNS Spectr 2023; 28:680-687. [PMID: 36961124 DOI: 10.1017/s1092852923001190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/25/2023]
Abstract
OBJECTIVE The elevated prevalence of metabolic syndrome (MetS) in patients with depression has been associated with increased mortality. This post hoc analysis assessed the effect of treatment with lurasidone on risk of MetS in patients with bipolar depression. METHODS Data used in the current analyses consisted of 3 double-blind (DB), placebo-controlled, 6-week studies in adults with bipolar I depression (N = 1192), consisting of 1 monotherapy, and 2 adjunctive trials (lithium or valproate). Also analyzed was a 6-month open-label (OL) extension study (monotherapy, N = 316; adjunctive therapy, N = 497); and a 5-month, OL, stabilization phase followed by randomization to a 28-week DB, placebo-controlled, adjunctive therapy study with lurasidone (N = 490). MetS was defined based on NCEP ATP III criteria (2005 revision). RESULTS The proportion of patients with new-onset MetS was similar for lurasidone vs placebo in the short-term studies (monotherapy, 13.9% vs 15.3%; adjunctive therapy, 13.6% vs 11.0%); and remained stable during both the 6-month extension phase study (monotherapy, 15.2%; adjunctive therapy, 16.9%), and the 5-month stabilization study (adjunctive therapy, 12.2%). After 28 weeks of DB treatment (following 5-month treatment in the stabilization study), new onset MetS was observed at endpoint (OC) in 26.2% of the lurasidone group, and 30.8% of the placebo group. CONCLUSIONS This post hoc analysis found that both short and long-term treatment with lurasidone was associated with a relatively low risk for the development of MetS in patients with bipolar I disorder. These findings are consistent with similar analyses in patients with schizophrenia.
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Affiliation(s)
- Michael Tocco
- Sunovion Pharmaceuticals Inc., Fort Lee, NJ, USA
- Sunovion Pharmaceuticals Inc., Marlborough, MA, USA
| | - John W Newcomer
- Thriving Mind South Florida, Miami, FL, USA
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
| | - Yongcai Mao
- Sunovion Pharmaceuticals Inc., Fort Lee, NJ, USA
- Sunovion Pharmaceuticals Inc., Marlborough, MA, USA
| | - Andrei Pikalov
- Sunovion Pharmaceuticals Inc., Fort Lee, NJ, USA
- Sunovion Pharmaceuticals Inc., Marlborough, MA, USA
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Wei YM, Wang XJ, Yang XD, Wang CS, Wang LL, Xu XY, Zhao GJ, Li B, Zhu DM, Wu Q, Shen YF. Safety and effectiveness of lurasidone in the treatment of Chinese schizophrenia patients: An interim analysis of post-marketing surveillance. World J Psychiatry 2023; 13:937-948. [DOI: 10.5498/wjp.v13.i11.937] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 10/11/2023] [Accepted: 10/27/2023] [Indexed: 11/17/2023] Open
Abstract
BACKGROUND Schizophrenia is a psychiatric disorder characterized by chronic or recurrent symptoms. Lurasidone was licensed in China in 2019 for the treatment of adult schizophrenia in adults with a maximum dose of 80 mg/d. However, post-market surveillance (PMS) with an adequate sample size is required for further validation of the drug’s safety profile and effectiveness.
AIM To conduct PMS in real-world clinical settings and evaluate the safety and effectiveness of lurasidone in the Chinese population.
METHODS A prospective, multicenter, open-label, 12-wk surveillance was conducted in mainland China. All patients with schizophrenia from 10 sites who had begun medication with lurasidone between September 2019 and August 2022 were eligible for enrollment. Safety assessments included adverse events (AEs), adverse drug reactions (ADRs), extrapyramidal symptoms (EPS), akathisia, use of EPS drugs, weight gain, and laboratory values as metabolic parameters and the QTc interval. The effectiveness was assessed using the brief psychiatric rating scale (BPRS) from baseline to the end of treatment.
RESULTS A total of 965 patients were enrolled in the full analysis set and 894 in the safety set in this interim analysis. The average daily dose was 61.7 ± 19.08 mg (mean ± SD) during the treatment. AEs and ADRs were experienced by 101 patients (11.3%) and 78 patients (8.7%), respectively, which were mostly mild. EPS occurred in 25 individuals with a 2.8% incidence, including akathisia in 20 individuals (2.2%). Moreover, 59 patients received drugs for treating EPS during the treatment, with an incidence of 6.6% which dropped to 5.4% at the end of the treatment. The average weight change was 0.20 ± 2.36 kg (P = 0.01687) with 0.8% of patients showing a weight gain of ≥ 7% at week 12 compared with that at the baseline. The mean values of metabolic parameters and the QTc interval at baseline and week 12 were within normal ranges. The mean changes in total BPRS scores were -8.9 ± 9.76 (n = 959), -13.5 ± 12.29 (n = 959), and -16.8 ± 13.97 (n = 959) after 2/4, 6/8, and 12 wk, respectively (P < 0.001 for each visit compared with the baseline) using the last-observation-carried-forward method.
CONCLUSION The interim analysis of the PMS of adult patients with schizophrenia demonstrate the safety and effectiveness of lurasidone in the Chinese population. No new safety or efficacy concerns were identified.
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Affiliation(s)
- Yu-Mei Wei
- Shanghai Clinical Research Center for Mental Health, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
| | - Xi-Jin Wang
- Department of Psychiatry, The First Psychiatric Hospital of Harbin, Harbin 150056, Heilongjiang Province, China
| | - Xiao-Dong Yang
- Department of Psychiatry, Shandong Provincial Mental Health Center, Jinan 250014, Shandong Province, China
| | - Chuan-Sheng Wang
- Department of Psychiatry, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang 453002, Henan Province, China
| | - Li-Li Wang
- Department of Psychiatry, Tianjin Mental Health Center, Tianjin Anding Hospital, Tianjin 300222, China
| | - Xiao-Ying Xu
- Department of Psychiatry, The Fifth People’s Hospital of Zigong, Zigong 643020, Sichuan Province, China
| | - Gui-Jun Zhao
- Department of Psychiatry, Guangyuan Mental Health Center, Guangyuan 628001, Guizhou Province, China
| | - Bin Li
- Department of Psychology, Fujian Energy General Hospital, Fuzhou 350001, Fujian Province, China
| | - Dao-Min Zhu
- Department of Sleep Disorders, Affiliated Psychological Hospital of Anhui Medical University, Hefei Fourth People’s Hospital, Anhui Mental Health Center, Hefei 230022, Anhui Province, China
| | - Qi Wu
- Sumitomo Pharma (China), Co., Ltd., Shanghai 200025, China
| | - Yi-Feng Shen
- Shanghai Key Laboratory of Psychotic Disorders, Shanghai Clinical Research Center for Mental Health, Shanghai Jiao Tong University, Shanghai 200030, China
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Miura I, Horikoshi S, Ichinose M, Suzuki Y, Watanabe K. Lurasidone for the Treatment of Schizophrenia: Design, Development, and Place in Therapy. Drug Des Devel Ther 2023; 17:3023-3031. [PMID: 37789971 PMCID: PMC10544203 DOI: 10.2147/dddt.s366769] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Accepted: 09/15/2023] [Indexed: 10/05/2023] Open
Abstract
This review aims to provide a comprehensive overview of the current literature on the drug design, development, and therapy of lurasidone for the treatment of schizophrenia. Lurasidone has antagonistic effects on the dopamine D2, 5-hydroxytryptamine (5-HT)2A, and 5-HT7 receptors and a partial agonistic effect on the 5-HT1A receptor with low affinities for muscarinic M1, histamine H1, and a1 adrenergic receptors. The receptor-binding profile of lurasidone is thought to be associated with fewer side effects such as anticholinergic effects, lipid abnormalities, hyperglycemia, and weight gain. Behavioral pharmacological studies have demonstrated that lurasidone exerts anxiolytic and antidepressive effects and improves cognitive function, which are associated with the modulation of 5-HT7 and 5-HT1A receptors. Literature search using PubMed was performed to find published studies of randomized controlled trials and recent meta-analyses regarding efficacy and safety, particularly metabolic side effects of lurasidone in schizophrenia. In short-term studies, the results of randomized placebo-controlled trials and meta-analyses have suggested that lurasidone was superior to placebo in improving total psychopathology, positive symptoms, negative symptoms, and general psychopathology in patients with acute schizophrenia. Regarding safety, lurasidone had minimal metabolic side effects, and was identified as one of the drugs with the most benign profiles for metabolic side effects. Long-term trials revealed that lurasidone had the preventive effects on relapse, with minimal effects on weight gain and other metabolic side effects. Furthermore, lurasidone improves cognitive and functional performance of patients with schizophrenia, especially in long-term treatment. Patients with schizophrenia require long-term treatment with antipsychotics for relapse prevention; thus, minimizing weight gain and other side effects is crucial. Lurasidone is suitable as one of the first-line antipsychotic drugs in the acute phase, and a switching strategy should be considered during the maintenance phase, to balance efficacy and adverse effects and achieve favorable outcomes in the long-term course of schizophrenia.
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Affiliation(s)
- Itaru Miura
- Department of Neuropsychiatry, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Sho Horikoshi
- Department of Neuropsychiatry, Fukushima Medical University School of Medicine, Fukushima, Japan
- Department of Neuropsychiatry, Horikoshi Psychosomatic Clinic, Fukushima, Japan
| | - Mizue Ichinose
- Department of Neuropsychiatry, Fukushima Medical University School of Medicine, Fukushima, Japan
- Department of Neuropsychiatry, Hoshigaoka Hospital, Koriyama, Japan
| | - Yuhei Suzuki
- Department of Neuropsychiatry, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Kenya Watanabe
- Department of Pharmacy, Fukushima Medical University Hospital, Fukushima, Japan
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11
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Yu H, Qi X, Fang Y, Wang K, Zhang D, Chen Q, Liu D, Ren X. Factors associated with increased risk of lurasidone-induced somnolence: Two case-control studies based on one bioequivalence trial in healthy volunteers. Heliyon 2023; 9:e17905. [PMID: 37539152 PMCID: PMC10395280 DOI: 10.1016/j.heliyon.2023.e17905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 06/28/2023] [Accepted: 06/30/2023] [Indexed: 08/05/2023] Open
Abstract
Somnolence is a common adverse effect of antipsychotic drugs used to treat psychotic disorders. It causes problems in many areas of life, such as gainful employment, driving, childcare, and social interactions. Somnolence is a major problem for a relatively new antipsychotic drug, lurasidone, whose dose-effect relationship remains unclear. Based on data from a bioequivalence study of two 40 mg lurasidone hydrochloride tablets, we designed two case-control studies to explore the correlation between somnolence and exposure to lurasidone and determine the factors associated with lurasidone-induced somnolence. In the first case-control study, lurasidone was administered to healthy volunteers; 30 experienced somnolence (as pre-defined) but 29 did not. Moreover, plasma concentration at 1 h was significantly associated with somnolence (OR = 1.124; p = 0.001). In the second case-control study, 48 volunteers administered lurasidone were classified into somnolence and no-somnolence groups based on different time-related criteria. We observed a positive association between plasma concentration at 0.75 h and somnolence (OR = 1.024; p = 0.002). Receiver operating characteristic analysis revealed that a plasma lurasidone concentration >21.65 ng/mL 1 h after administration strongly predicted somnolence. Our findings in healthy volunteers need to be further validated in patients in clinical settings to determine the optimal dose and duration of lurasidone administration.
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12
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Tarzian M, Soudan M, Alhajji M, Ndrio M, Fakoya AO. Lurasidone for Treating Schizophrenia and Bipolar Depression: A Review of Its Efficacy. Cureus 2023; 15:e38071. [PMID: 37228542 PMCID: PMC10208134 DOI: 10.7759/cureus.38071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/24/2023] [Indexed: 05/27/2023] Open
Abstract
Lurasidone is an antipsychotic medication that blocks dopamine D2 and serotonin 5-hydroxy-tryptamine (5-HT)2A receptors and affects other serotoninergic and noradrenergic receptors. It has rapid absorption and linear pharmacokinetics. The rates of metabolic syndrome for patients taking lurasidone are comparable to placebo groups. Lurasidone is a safe and effective treatment for patients with acute schizophrenia and bipolar depression. It has been found to improve the brief psychiatric rating scale and other secondary measures in schizophrenic patients and reduce depressive symptoms in bipolar I depression. The once-daily administration of lurasidone is generally well-tolerated and does not cause clinically significant differences in extrapyramidal symptoms, adverse effects, or weight gain compared to a placebo. However, lurasidone's effectiveness in combination with lithium or valproate has been mixed. Further research is needed to determine optimal dosing, treatment duration, and combination with other mood stabilizers. Long-term safety and effectiveness and its use in different subpopulations should also be evaluated.
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Affiliation(s)
- Martin Tarzian
- Psychiatry, University of Medicine and Health Sciences, Basseterre, KNA
| | - Majd Soudan
- Psychiatry, Nuvance Health Medical Practice - Primary Care Carmel, New York, USA
| | - Muhammed Alhajji
- Internal Medicine, Augusta University/University of Georgia Medical Partnership, Athens, USA
| | - Mariana Ndrio
- Psychiatry, University of Medicine and Health Sciences, Basseterre, KNA
| | - Adegbenro O Fakoya
- Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport, USA
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13
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Abstract
PURPOSE Clozapine represents the criterion standard therapy for patients with treatment-resistant schizophrenia. Unfortunately, a significant percentage of such patients are also partial responders to clozapine. Consequently, several augmentation strategies have been proposed with various and sometimes controversial efficacy. Among these add-on treatments, lurasidone has been recently introduced and could represent a potential option, especially for the additional positive effect on cognitive symptoms. METHODS This case series aims to determine possible advantages of lurasidone augmentation in four patients treated with clozapine, who were diagnosed with treatment-resistant schizophrenia. Positive and Negative Syndrome Scales were used to evaluate psychopathology, the Udvalg for Kliniske Undersøgelser scale for tolerability and safety. FINDING All patients achieved a significant reduction of both positive and negative symptoms, with no significant adverse effects to be reported. IMPLICATIONS Our observation suggests that lurasidone can lead to clinically significant improvements in psychopathology with a good tolerability profile when added to clozapine.
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14
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Guilera T, Chart Pascual JP, Blasco MDC, Calvo Estopiñán P, Piernas González RA, Ramírez Martínez I, Rodríguez Moyano C, Prieto Pérez R, Gabarda-Inat I, Prados-Ojeda JL, Diaz-Marsà M, Martín-Carrasco M. Lurasidone for the treatment of schizophrenia in adult and paediatric populations. Drugs Context 2023; 12:dic-2022-10-1. [PMID: 36793449 PMCID: PMC9914098 DOI: 10.7573/dic.2022-10-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Accepted: 12/13/2022] [Indexed: 02/05/2023] Open
Abstract
Schizophrenia is a common debilitating disorder characterized by significant impairments in how reality is perceived, combined with behavioural changes. In this review, we describe the lurasidone development programme for adult and paediatric patients. Both the pharmacokinetic and pharmacodynamic characteristics of lurasidone are revisited. In addition, pivotal clinical studies conducted on both adults and children are summarized. Several clinical cases, which demonstrate the role of lurasidone in real-world practice, are also presented. Current clinical guidelines recommend lurasidone as the first-line treatment in the acute and long-term management of schizophrenia in both adult and paediatric populations.
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Affiliation(s)
- Teresa Guilera
- Psychiatry Service, Santa Maria University Hospital, Lleida, Spain,Institute for Biomedical Research in Lleida Dr Pifarré Foundation (IRBLleida), Lleida, Spain
| | | | | | | | | | | | | | | | | | - Juan L Prados-Ojeda
- Servicio de Salud Mental, Hospital Universitario Reina Sofía, Córdoba, Spain,Departamento de Ciencias Morfológicas y Sociosanitarias, Universidad de Córdoba, Córdoba, Spain,Instituto Maimónides de Investigación Biomédica de Córdoba, Córdoba, Spain
| | - Marina Diaz-Marsà
- Instituto de Psiquiatría y Salud Mental, Hospital Clínico San Carlos, IdISSC, CIBERSAM, Facultad de Medicina, Universidad Complutense, Madrid, Spain
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15
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Fagiolini A, Olivola M, Lavatelli L, Bellomo A, Lobaccaro C, Falsetto N, Micillo M, Cuomo A. Treatment persistence in patients with schizophrenia treated with lurasidone in Italian clinical practice. Ann Gen Psychiatry 2022; 21:49. [PMID: 36527022 PMCID: PMC9756598 DOI: 10.1186/s12991-022-00425-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Accepted: 11/15/2022] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND AND RATIONALE Treatment persistence combines clinician and patient judgment of efficacy, tolerability and safety into a comprehensive measure of effectiveness and is defined as the act of continuing a treatment over time. Studies have reported poor treatment persistence to antipsychotic medications in patients with schizophrenia. This study evaluated treatment persistence to lurasidone (LUR) in patients with schizophrenia in a real-world Italian setting. METHODS This was a retrospective observational study of patients with schizophrenia who started treatment with LUR ≥ 6 months before inclusion. Following informed consent, data were collected starting from the index date (start of LUR treatment) at all visits occurring as per clinical practice. The primary endpoint was treatment persistence during the first 6 months, defined as the time between index date and all-cause discontinuation. Patients treated with LUR > 180 days were considered persistent. As secondary endpoint, treatment persistence was evaluated for a period of ≥ 18 months. RESULTS Forty-five patients were enrolled and 41 (91.11%) completed the study. Forty-one patients (91.11%) were included in the eligible population as they initiated LUR treatment ≥ 6 months before data collection. Patients were 43.0 ± 15.89 years old and 61% were female. Twenty-two patients (53.66%) started LUR treatment in a hospital setting and 19 (46.34%) in an outpatient setting. Based on Clinical Global Impression-Severity scale (CGI-S) at LUR initiation, 12 patients (29.27%) were severely ill, 17.07% markedly ill, 19.51% moderately ill, 2.44% mildly ill and 4.88% borderline mentally ill. Thirty-two patients (78.05%) were treatment persistent for ≥ 180 days. Among the 19 patients observed for ≥ 18 months, 11 (57.89%) were persistent for ≥ 18 months. Among the 22 study patients observed for < 18 months, 12 (54.54%) were persistent. An improvement in schizophrenia severity according to CGI-S was observed at inclusion (following LUR therapy) compared to the index date. Six patients (14.63%) experienced at least one adverse drug reaction: akathisia (7.32%), extrapyramidal disorder (4.88%), hyperprolactinemia (2.44%), restlessness (2.44%), and galactorrhea (2.44%). None were serious. CONCLUSIONS Persistence to LUR in patients with schizophrenia was relatively high: 78% and 58% of patients were still on LUR after 6 and 18 months of treatment, respectively. This may reflect LUR's relatively favorable balance between efficacy and tolerability, as well as favorable patient satisfaction and acceptance.
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Affiliation(s)
- Andrea Fagiolini
- Università Di Siena, V.Le Mario Bracci, 16, 53100, Siena (SI), Italy.
| | - Miriam Olivola
- Department of Brain and Behavioral Sciences, University of Pavia and Servizio Psichiatrico Di Diagnosi E Cura ASST Pavia, IRCCS Policlinico San Matteo, Viale Repubblica 34, 27100, Pavia, Italy
| | - Lisa Lavatelli
- Psichiatria 1 ASST Grande Ospedale Metropolitano Niguarda, Piazza Dell'Ospedale Maggiore, 3, 20162, Milan, MI, Italy
| | - Antonello Bellomo
- University of Foggia, Viale Luigi Pinto, 1, 71122, Foggia, MI, Italy
| | | | | | - Marco Micillo
- Angelini Pharma S.P.A, Viale Amelia70, 00181, Rome, Italy
| | - Alessandro Cuomo
- University of Siena, V.Le Mario Bracci, 16, 53100, Siena, SI, Italy
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16
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Ricci V, Martinotti G, De Berardis D, Maina G. Lurasidone use in Cannabis-Induced Psychosis: A Novel Therapeutic Strategy and Clinical Considerations in Four Cases Report. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:16057. [PMID: 36498129 PMCID: PMC9737174 DOI: 10.3390/ijerph192316057] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 11/29/2022] [Accepted: 11/30/2022] [Indexed: 06/17/2023]
Abstract
BACKGROUND Lurasidone is an atypical antipsychotic approved for the acute and maintenance treatment of schizophrenia. Recently, lurasidone was also extended FDA approval for adults with major depressive episodes associated with bipolar I disorder (bipolar depression), as either a monotherapy or as adjunctive therapy with lithium or valproate. The use of low doses of atypical antipsychotics is an essential component of early intervention in psychosis, but little has yet been studied on first episode cannabis-induced psychosis. For its particular performance and tolerability, lurasidone is becoming an important option for the treatment of first-episode psychosis in youth. Case presentation four patients experiencing first cannabis-induced psychotic episode were treated with lurasidone. In all patients, there was an improvement in the clinical picture of psychosis. The recovery was positive, not only with the remission of positive and negative symptoms, but also regarding disruptive behaviour, with the return of functioning. All the patients were treated with lurasidone, with a target dose of 74-128 mg/day. No significant side effects were reported. CONCLUSION There are non-controlled studies for the use of lurasidone in first episode psychosis cannabis induced. These findings suggest that lurasidone is an atypical antipsychotic beneficial in this clinical picture. Treatment with medium-high doses of lurasidone could be effective and tolerable in this phase of the disorder. Randomized control trials with longer follow-up are recommended to confirm these positive results.
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Affiliation(s)
- Valerio Ricci
- San Luigi Gonzaga Hospital, University of Turin, 10043 Orbassano, Italy
| | - Giovanni Martinotti
- Department of Neurosciences, Imaging and Clinical Sciences, Università Degli Studi G. D’Annunzio Chieti-Pescara, 66100 Chieti, Italy
| | - Domenico De Berardis
- National Health Service, Department of Mental Health, Psychiatric Service for Diagnosis and Treatment, Hospital “G. Mazzini”, 64100 Teramo, Italy
| | - Giuseppe Maina
- San Luigi Gonzaga Hospital, University of Turin, 10043 Orbassano, Italy
- Department of Neurosciences “Rita Levi Montalcini”, University of Turin, 10043 Orbassano, Italy
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17
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Calisti F, Cattaneo A, Calabrese M, Mao Y, Tocco M, Pikalov A, Goldman R. Efficacy and safety of lurasidone in schizophrenia: pooled analysis of European results from double-blind, placebo-controlled 6-week studies. Int Clin Psychopharmacol 2022; 37:215-222. [PMID: 35276716 DOI: 10.1097/yic.0000000000000398] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
The objective of this study is to confirm the efficacy and safety of lurasidone in the acute treatment of schizophrenia in European patients. Data were pooled from three studies of patients randomized to 6 weeks of double-blind, placebo-controlled, fixed-dose (40/80 mg and 120/160 mg) lurasidone. The primary efficacy endpoint was a week 6 change in the Positive and Negative Syndrome Scale (PANSS) total score and secondary endpoints included the Clinical Global Impression, Severity scale (CGI-S). In total 328 safety patients were enrolled; 72.6% were completers. Endpoint change was significantly greater in patients treated with 40-80 mg/d and 120-160 mg/d compared to placebo on the PANSS total score ( P < 0.001) and the CGI-Severity score ( P < 0.001) for all comparisons. For PANSS total scores, endpoint effect sizes for lurasidone 40-80 mg/d and 120-160 mg/d were 0.68 to 0.77, respectively. Adverse events with a frequency ≥5% (and were greater than for combined lurasidone) were insomnia (11.7%), akathisia (11.3%), headache (7.4%), Parkinsonism (6.5%) and nausea (5.7%). Median changes (in mg/dL) at endpoint were minimal for total cholesterol (-8.0); triglycerides (-8.5) and glucose (-2.0) and in mean weight (-0.2 kg). In European patients with schizophrenia, short-term treatment with lurasidone in doses of 40-160 mg/d was generally safe, well-tolerated and effective with minimal effects on weight and metabolic parameters.
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Affiliation(s)
- Fabrizio Calisti
- Angelini RR&D (Regulatory, Research, & Development), Angelini Pharma S.p.A., Viale Amelia, Rome, Italy
| | - Agnese Cattaneo
- Angelini RR&D (Regulatory, Research, & Development), Angelini Pharma S.p.A., Viale Amelia, Rome, Italy
| | - Mariangela Calabrese
- Angelini RR&D (Regulatory, Research, & Development), Angelini Pharma S.p.A., Viale Amelia, Rome, Italy
| | - Yongcai Mao
- Sunovion Pharmaceuticals Inc, Fort Lee, NJ, and Marlborough, Massachusetts, USA
| | - Michael Tocco
- Sunovion Pharmaceuticals Inc, Fort Lee, NJ, and Marlborough, Massachusetts, USA
| | - Andrei Pikalov
- Sunovion Pharmaceuticals Inc, Fort Lee, NJ, and Marlborough, Massachusetts, USA
| | - Robert Goldman
- Sunovion Pharmaceuticals Inc, Fort Lee, NJ, and Marlborough, Massachusetts, USA
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18
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Risk of Drug-induced Movement Disorders with Newer Antipsychotic Agents. Tremor Other Hyperkinet Mov (N Y) 2022; 12:19. [PMID: 35836971 PMCID: PMC9187243 DOI: 10.5334/tohm.695] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Accepted: 05/27/2022] [Indexed: 01/19/2023] Open
Abstract
Background: The last decade has seen development of numerous novel antipsychotic drugs with unique mechanisms including long-acting formulations for clinical use. A comparative assessment of these new drugs with each other and previous antipsychotics have not been performed with regards to risk for drug-induced movement disorders (DIMD). Methods: Medline was searched from January 2010 to February 2022 for primary research articles and review articles in English using the search terms “extrapyramidal” and “tardive” with individual drug names of novel antipsychotics. Results: We identified articles describing the risk of DIMD with 6 novel antipsychotics, 4 novel formulations, and 3 experimental antipsychotics. Both short- and long-term data generally showed comparable to lower risk of DIMD with novel antipsychotics and recent long-acting formulations compared to previously marketed antipsychotics. Discussion: Several novel antipsychotics, particularly lumateperone and pimavanserin, show promise in being able to treat psychosis while reducing the risk of DIMD. Long-acting paliperidone may reduce risk of DIMD while other long-acting injectable formulations of SGA have similar risk of DIMD compared to oral formulations. New drug targets for treating psychosis without dopamine blockade also show promise.
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19
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Ostuzzi G, Bertolini F, Tedeschi F, Vita G, Brambilla P, del Fabro L, Gastaldon C, Papola D, Purgato M, Nosari G, Del Giovane C, Correll C, Barbui C. Oral and long-acting antipsychotics for relapse prevention in schizophrenia-spectrum disorders: a network meta-analysis of 92 randomized trials including 22,645 participants. World Psychiatry 2022; 21:295-307. [PMID: 35524620 PMCID: PMC9077618 DOI: 10.1002/wps.20972] [Citation(s) in RCA: 50] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
According to current evidence and guidelines, continued antipsychotic treatment is key for preventing relapse in people with schizophrenia-spectrum disorders, but evidence-based recommendations for the choice of the individual antipsychotic for maintenance treatment are lacking. Although oral antipsychotics are often prescribed first line for practical reasons, long-acting injectable antipsychotics (LAIs) are a valuable resource to tackle adherence issues since the earliest phase of disease. Medline, EMBASE, PsycINFO, CENTRAL and CINAHL databases and online registers were searched to identify randomized controlled trials comparing LAIs or oral antipsychotics head-to-head or against placebo, published until June 2021. Relative risks and standardized mean differences were pooled using random-effects pairwise and network meta-analysis. The primary outcomes were relapse and dropout due to adverse events. We used the Cochrane Risk of Bias tool to assess study quality, and the CINeMA approach to assess the confidence of pooled estimates. Of 100 eligible trials, 92 (N=22,645) provided usable data for meta-analyses. Regarding relapse prevention, the vast majority of the 31 included treatments outperformed placebo. Compared to placebo, "high" confidence in the results was found for (in descending order of effect magnitude) amisulpride-oral (OS), olanzapine-OS, aripiprazole-LAI, olanzapine-LAI, aripiprazole-OS, paliperidone-OS, and ziprasidone-OS. "Moderate" confidence in the results was found for paliperidone-LAI 1-monthly, iloperidone-OS, fluphenazine-OS, brexpiprazole-OS, paliperidone-LAI 1-monthly, asenapine-OS, haloperidol-OS, quetiapine-OS, cariprazine-OS, and lurasidone-OS. Regarding tolerability, none of the antipsychotics was significantly worse than placebo, but confidence was poor, with only aripiprazole (both LAI and OS) showing "moderate" confidence levels. Based on these findings, olanzapine, aripiprazole and paliperidone are the best choices for the maintenance treatment of schizophrenia-spectrum disorders, considering that both LAI and oral formulations of these antipsychotics are among the best-performing treatments and have the highest confidence of evidence for relapse prevention. This finding is of particular relevance for low- and middle-income countries and constrained-resource settings, where few medications may be selected. Results from this network meta-analysis can inform clinical guidelines and national and international drug regulation policies.
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Affiliation(s)
- Giovanni Ostuzzi
- WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neuroscience, Biomedicine and Movement Sciences, Section of PsychiatryUniversity of VeronaVeronaItaly
| | - Federico Bertolini
- WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neuroscience, Biomedicine and Movement Sciences, Section of PsychiatryUniversity of VeronaVeronaItaly
| | - Federico Tedeschi
- WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neuroscience, Biomedicine and Movement Sciences, Section of PsychiatryUniversity of VeronaVeronaItaly
| | - Giovanni Vita
- WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neuroscience, Biomedicine and Movement Sciences, Section of PsychiatryUniversity of VeronaVeronaItaly
| | - Paolo Brambilla
- Department of Pathophysiology and TransplantationUniversity of MilanMilanItaly,Department of Neurosciences and Mental HealthFondazione IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoMilanItaly
| | - Lorenzo del Fabro
- Department of Pathophysiology and TransplantationUniversity of MilanMilanItaly,Department of Neurosciences and Mental HealthFondazione IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoMilanItaly
| | - Chiara Gastaldon
- WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neuroscience, Biomedicine and Movement Sciences, Section of PsychiatryUniversity of VeronaVeronaItaly
| | - Davide Papola
- WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neuroscience, Biomedicine and Movement Sciences, Section of PsychiatryUniversity of VeronaVeronaItaly
| | - Marianna Purgato
- WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neuroscience, Biomedicine and Movement Sciences, Section of PsychiatryUniversity of VeronaVeronaItaly
| | - Guido Nosari
- Department of Pathophysiology and TransplantationUniversity of MilanMilanItaly,Department of Neurosciences and Mental HealthFondazione IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoMilanItaly
| | - Cinzia Del Giovane
- Institute of Primary Health CareUniversity of BernBernSwitzerland,Population Health LaboratoryUniversity of FribourgFribourgSwitzerland
| | - Christoph U. Correll
- Department of PsychiatryZucker Hillside HospitalGlen OaksNYUSA,Department of Psychiatry and Molecular MedicineZucker School of Medicine at Hofstra/NorthwellHempsteadNYUSA,Department of Child and Adolescent PsychiatryCharité Universitätsmedizin BerlinBerlinGermany
| | - Corrado Barbui
- WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neuroscience, Biomedicine and Movement Sciences, Section of PsychiatryUniversity of VeronaVeronaItaly
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20
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Correll CU, Tocco M, Hsu J, Goldman R, Pikalov A. Short-term Efficacy and Safety of Lurasidone Versus Placebo in Antipsychotic-Naïve vs. Previously Treated Adolescents with an Acute Exacerbation of Schizophrenia. Eur Psychiatry 2022; 65:1-35. [PMID: 35322769 PMCID: PMC9058440 DOI: 10.1192/j.eurpsy.2022.11] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 02/07/2022] [Accepted: 02/17/2022] [Indexed: 11/23/2022] Open
Abstract
Background To evaluate the efficacy of short-term lurasidone in antipsychotic treatment-naïve (TN) adolescents with schizophrenia versus those treated previously (TP) with antipsychotics. Methods Patients aged 13–17 with schizophrenia, and a Positive and Negative Symptom Scale (PANSS) score ≥ 70 and < 120, were randomized to 6 weeks of double-blind treatment with lurasidone (40 or 80 mg/day) or placebo. In a post-hoc, pooled-dose analysis, efficacy was evaluated for TN (criteria: never received antipsychotic treatment) versus TP at the time of the study. Treatment response criteria: ≥20% reduction in PANSS total score. Results Altogether, 57 TN and 269 TP patients enrolled in the 6-week DB study. Mean endpoint change in PANSS total score was significantly greater for lurasidone versus placebo in both the TN group (−25.0 vs. -14.4; p < 0.02; effect size = 0.75), and in the TP group (−17.3 vs. -10.0; p < 0.001; effect size = 0.45); and responder rates were higher for lurasidone versus placebo in both the TN group 84.6% versus 38.9%; number needed to treat [NNT] = 3 and in the TP group (60% vs. 42%; NNT = 6). Rates of treatment-emergent adverse events, and mean changes in body weight and metabolic parameters were similar for the TN and TP groups. Conclusions In a 6-week, placebo-controlled trial, lurasidone demonstrated significant efficacy in adolescents with schizophrenia regardless of previous antipsychotic therapy status; however, the effect size was notably larger in the TN patient group. In both the TN and TP groups, minimal effects were noted on weight, metabolic parameters, or prolactin.
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Affiliation(s)
- Christoph U. Correll
- Department of Psychiatry, Northwell Health, The Zucker Hillside Hospital, Glen Oaks, New York, USA
- Department of Psychiatry and Molecular Medicine, Hofstra Northwell School of Medicine, Hempstead, New York, USA
- Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany
| | - Michael Tocco
- Global Medical Affairs, Sunovion Pharmaceuticals Inc., Fort Lee, New Jersey, USA
- Sunovion Pharmaceuticals Inc., Marlborough, Massachusetts, USA
| | - Jay Hsu
- Global Medical Affairs, Sunovion Pharmaceuticals Inc., Fort Lee, New Jersey, USA
- Sunovion Pharmaceuticals Inc., Marlborough, Massachusetts, USA
| | - Robert Goldman
- Global Medical Affairs, Sunovion Pharmaceuticals Inc., Fort Lee, New Jersey, USA
- Sunovion Pharmaceuticals Inc., Marlborough, Massachusetts, USA
| | - Andrei Pikalov
- Global Medical Affairs, Sunovion Pharmaceuticals Inc., Fort Lee, New Jersey, USA
- Sunovion Pharmaceuticals Inc., Marlborough, Massachusetts, USA
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21
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Safety and effectiveness of lurasidone in adolescents with schizophrenia: results of a 2-year, open-label extension study. CNS Spectr 2022; 27:118-128. [PMID: 33077012 DOI: 10.1017/s1092852920001893] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
BACKGROUND Minimal long-term benefit: Risk data are available regarding antipsychotic treatments for schizophrenia in pediatric populations. This study evaluated the long-term safety, tolerability, and effectiveness of lurasidone in adolescents with schizophrenia. METHODS Patients aged from 13 to 17 who completed 6 weeks of double-blind (DB), placebo-controlled treatment with lurasidone were enrolled in a 2-year, open-label (OL), flexible dose (20-80 mg/day) lurasidone treatment study. Safety was assessed via spontaneous reporting, rating scales, body weight measurement, metabolic, and prolactin testing. Effectiveness measures included the Positive and Negative Syndrome Scale (PANSS) total score. RESULTS About 271 patients completed 6 weeks of DB treatment and entered the 2-year OL extension study. Altogether, 42.4% discontinued prematurely, 10.7% due to adverse events. During OL treatment, the most common adverse events were headache (24.0%); anxiety (12.9%), schizophrenia, and nausea (12.5%); sedation/somnolence (12.2%); and nasopharyngitis (8.9%). Minimal changes were observed on metabolic parameters and prolactin. Mean change from DB baseline in weight at week 52 and week 104 was +3.3 kg and + 4.9 kg, respectively, compared to an expected weight gain of +3.4 kg and + 5.7 kg, respectively, based on the sex- and age-matched US Center for Disease Control normative data. Continued improvement was observed in PANSS total score, with mean change from OL baseline of -15.6 at week 52 and -18.4 at week 104. CONCLUSION In adolescents with schizophrenia, long-term lurasidone treatment was associated with minimal effects on body weight, lipids, glycemic indices, and prolactin. Continued improvement in symptoms of schizophrenia was observed over 2 years of lurasidone treatment.
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Long-term safety and effectiveness of open-label lurasidone in antipsychotic-Naïve versus previously treated adolescents with Schizophrenia: A post-hoc analysis. Schizophr Res 2022; 240:205-213. [PMID: 35032906 DOI: 10.1016/j.schres.2021.12.046] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Revised: 08/16/2021] [Accepted: 12/27/2021] [Indexed: 11/20/2022]
Abstract
BACKGROUND There is a relative lack of long-term, prospective data evaluating the safety and effectiveness of treatment in early-onset adolescent patients with schizophrenia who are treatment-naïve. The aim of this post-hoc analysis was to examine the long-term safety and effectiveness of lurasidone in adolescents with schizophrenia who were antipsychotic treatment-naïve (TN; at the time of enrolment in the initial study) compared to adolescents treated previously (TP) with an antipsychotic. METHODS Patients aged 13-17 who completed 6 weeks of double-blind (DB), placebo-controlled treatment with lurasidone were enrolled in a 2-year, open-label (OL), flexible-dose (20-80 mg/day) lurasidone study. RESULTS The long-term analysis sample consisted of 50 TN and 221 TP patients, of whom 40% and 43%, respectively, discontinued prematurely. The three most common adverse events for TN and TP patients, respectively, were headache (26.0%, 23.5%); schizophrenia (14.0%, 12.2%), dizziness (16.0%, 4.1%), and nausea (16.0%, 11.8%). At endpoint, mean increase in weight was similar to expected weight gain based on growth charts for both TN (+4.5 kg vs. + 5.7 kg) and TP (+4.6 kg vs. + 6.6 kg) patients. Minimal changes were observed for each group in metabolic parameters and prolactin. Mean improvement was consistently greater in the TN vs. TP group (-19.2 vs. -15.9; effect size of 0.33) for between-group change in PANSS total score at Week 104. CONCLUSIONS In both TN and TP adolescents with schizophrenia, long-term treatment with lurasidone was associated with minimal effects on body weight, lipids, glycemic indices, and prolactin, with generally small differences noted in rates of reported AEs. Continued improvement in symptoms of schizophrenia was evident for both the TN and TP groups. These data indicate that lurasidone is a safe and efficacious treatment option for treatment-naïve youth with schizophrenia, who are generally most sensitive to antipsychotic adverse effects.
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Filts Y, Litman RE, Martínez J, Anta L, Naber D, Correll CU. Long-term efficacy and safety of once-monthly Risperidone ISM® in the treatment of schizophrenia: Results from a 12-month open-label extension study. Schizophr Res 2022; 239:83-91. [PMID: 34847501 DOI: 10.1016/j.schres.2021.11.030] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 10/04/2021] [Accepted: 11/17/2021] [Indexed: 10/19/2022]
Abstract
OBJECTIVE To evaluate long-term efficacy, safety and tolerability of Risperidone ISM® in patients with schizophrenia, a multicenter, open-label extension of the PRISMA-3 study was conducted. METHODS Eligible placebo (unstable) and Risperidone ISM® (stabilized) rollover patients from a previous 12-week double-blind phase and de novo stable patients received once-monthly intramuscular injections of Risperidone ISM® 75 or 100 mg for 12 months. The long term-efficacy assessment included the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Severity (CGI-S) and Clinical Global Impression-Improvement (CGI-I) scales. Safety evaluation included treatment-emergent adverse events (TEAEs), injection site reactions (ISR), laboratory tests and several safety scales. RESULTS Altogether, 215 patients entered the study (55 unstable, 119 stabilized and 41 stable patients). Most patients (74.9%) completed, and discontinuation rates were broadly similar across the study subgroups, mainly due to withdrawal of consent (12.1%). PANSS total and subscales scores decreased from baseline to endpoint in all groups, with the largest decrease for unstable patients. Improvement from baseline to 12 months was also shown for CGI-S and CGI-I scores for both unstable and stabilized patients; the CGI-S and CGI-I scores remained almost unchanged for the stable group. At least one treatment-related TEAE was reported in 39.1% of patients; the most common were headache (12.1%), hyperprolactinemia (9.8%) and asthenia (5.1%). ISR were reported in 8 (0.3%) patients; injection site pain score was low across the 2355 doses assessed. CONCLUSION Risperidone ISM® is an effective, safe, and well-tolerated long-term treatment of schizophrenia in adults, regardless of the initial disease severity or whether patients were previously treated with Risperidone ISM® during an acute exacerbation or switched from stable doses of oral risperidone.
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Affiliation(s)
- Yuriy Filts
- Communal Noncommercial Enterprise of Lviv Regional Council, Lviv Regional Clinical Psychiatric Hospital, Lviv, Ukraine
| | - Robert E Litman
- CBH Health LLC, Gaithersburg, MD, USA; Department of Psychiatry, Georgetown University Medical School, Washington, DC, USA
| | - Javier Martínez
- Medical Department, Laboratorios Farmacéuticos ROVI, S.A., Calle Alfonso Gómez, 45-A, 28037 Madrid, Spain
| | - Lourdes Anta
- Medical Department, Laboratorios Farmacéuticos ROVI, S.A., Calle Alfonso Gómez, 45-A, 28037 Madrid, Spain.
| | - Dieter Naber
- Department of Psychiatry and Psychotherapy, Hamburg-Eppendorf University, Hamburg, Germany
| | - Christoph U Correll
- Department of Psychiatry Research, The Zucker Hillside Hospital, Glen Oaks, NY, USA; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Department of Psychiatry and Molecular Medicine, Hempstead, NY, USA; Charité Universitätsmedizin Berlin, Department of Child and Adolescent Psychiatry, Berlin, Germany
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DelBello MP, Tocco M, Pikalov A, Deng L, Goldman R. Tolerability, Safety, and Effectiveness of Two Years of Treatment with Lurasidone in Children and Adolescents with Bipolar Depression. J Child Adolesc Psychopharmacol 2021; 31:494-503. [PMID: 34324397 PMCID: PMC8568779 DOI: 10.1089/cap.2021.0040] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Objectives: To evaluate long-term safety and effectiveness of lurasidone in children and adolescents with bipolar depression. Methods: Participants, ages 10-17 years, with bipolar depression, who completed 6 weeks of double-blind (DB) treatment with lurasidone or placebo were enrolled in a 2-year, open-label (OL) extension study of lurasidone (20-80 mg/d). The primary effectiveness measure was the Children's Depression Rating Scale, Revised (CDRS-R). Results: A total of 306 participants entered the 2-year extension study; 195 (63.7%) completed 52 weeks, and 168 (54.9%) completed 104 weeks of treatment. For all participants entering the extension study, mean change in CDRS from OL baseline was -13.4 at week 52, and -16.4 at week 104 (-11.3 at last observation carried forward [LOCF]-endpoint). Overall, 31 participants (10.1%) discontinued due to an adverse event (AE); the three most common AEs were headache (23.9%), nausea (16.4%), and somnolence (9.8%). OL treatment with lurasidone was associated with few effects on metabolic parameters or prolactin. Mean change from DB baseline in weight was +4.25 kg at week 52 (vs. an expected weight gain of +3.76 kg), and +6.75 kg at week 104 (vs. an expected weight gain of +6.67 kg), based on the sex- and age-matched United States Center for Disease Control normative data. Conclusions: For youth with bipolar depression, up to 2 years of treatment with lurasidone was generally well tolerated, safe, and effective with relatively low rates of discontinuation due to AEs, minimal effects on weight, metabolic parameters or prolactin, and continued improvement in depressive symptoms. Clinical Trial Registration number: NCT01914393.
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Affiliation(s)
- Melissa P. DelBello
- Division of Bipolar Disorders Research, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.,Address correspondence to: Melissa P. DelBello, MD, MS, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, 234 Goodman Street, Cincinnati, OH 45219, USA
| | - Michael Tocco
- Sunovion Pharmaceuticals, Inc., Marlborough, Massachusetts, USA
| | - Andrei Pikalov
- Sunovion Pharmaceuticals, Inc., Fort Lee, New Jersey, USA
| | - Ling Deng
- Sunovion Pharmaceuticals, Inc., Fort Lee, New Jersey, USA
| | - Robert Goldman
- Sunovion Pharmaceuticals, Inc., Marlborough, Massachusetts, USA
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Iyo M, Ishigooka J, Nakamura M, Sakaguchi R, Okamoto K, Mao Y, Tsai J, Fitzgerald A, Takai K, Higuchi T. Safety and Effectiveness of Lurasidone in Patients with Schizophrenia: A 12-Week, Open-Label Extension Study. Neuropsychiatr Dis Treat 2021; 17:2683-2695. [PMID: 34429604 PMCID: PMC8379682 DOI: 10.2147/ndt.s320021] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Accepted: 07/24/2021] [Indexed: 12/02/2022] Open
Abstract
PURPOSE The goal of this study was to evaluate the safety and effectiveness of lurasidone among patients with schizophrenia in a 12-week open-label extension study. PATIENTS AND METHODS Patients who completed a 6-week, double-blind, placebo-controlled study were enrolled in a 12-week open-label extension study with flexible dosing of lurasidone at 40 or 80 mg/day. Safety assessments included adverse events, vital signs, laboratory tests, and electrocardiogram (ECG) parameters. Effectiveness measures included the Positive and Negative Syndrome Scale (PANSS) total score, Clinical Global Impression-Severity Scale (CGI-S), Calgary Depression Scale for Schizophrenia (CDSS) and quality of life measure. RESULTS A total of 289 patients were enrolled in the open-label extension study. Rates of treatment-emergent adverse events (TEAEs) were low; akathisia was the most common TEAE with an incidence of 6.6%. There were 54 patients (18.7%) who discontinued the extension study, with 17 (5.9%) discontinuing due to adverse events. Minimal or no effects of lurasidone on weight, body mass index, metabolic parameters, prolactin, and ECG parameters were evident. There was continued improvement to week 12 in PANSS and CGI-S scores beyond the initial gains made during the prior 6-week double-blind study. Non-responders to lurasidone 40 mg/day in the prior 6-week study showed a mean (standard deviation) improvement from open-label baseline of 10.7 (13.8) points on the PANSS total score after lurasidone dose was increased to a modal dose of 80 mg/day during the extension study. Changes from double-blind baseline in CDSS and quality of life were maintained in the extension study. CONCLUSION Treatment with lurasidone 40 or 80 mg once daily (flexibly dosed) continued to be well tolerated with patients demonstrating further improvement in symptoms over the course of a 12-week open-label extension study in patients with schizophrenia.
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Affiliation(s)
- Masaomi Iyo
- Department of Psychiatry, Graduate School of Medicine, Chiba University, Chiba, Japan
| | | | - Masatoshi Nakamura
- Department of Data Science, Drug Development Division, Sumitomo Dainippon Pharma Co., Ltd., Tokyo, Japan
| | - Reiko Sakaguchi
- Department of Clinical Research, Drug Development Division, Sumitomo Dainippon Pharma Co., Ltd., Tokyo, Japan
| | - Keisuke Okamoto
- Department of Clinical Operation, Drug Development Division, Sumitomo Dainippon Pharma Co., Ltd., Tokyo, Japan
| | - Yongcai Mao
- Division of Data Science, Sunovion Pharmaceuticals Inc., Fort Lee, NJ, USA
| | - Joyce Tsai
- Division of Clinical Research, Sunovion Pharmaceuticals Inc., Fort Lee, NJ, USA
| | - Alison Fitzgerald
- Division of Clinical Operations, Sunovion Pharmaceuticals Inc., Fort Lee, NJ, USA
| | - Kentaro Takai
- Medical Affairs, Sumitomo Dainippon Pharma Co., Ltd., Tokyo, Japan
| | - Teruhiko Higuchi
- Japan Depression Center, Tokyo, Japan
- National Center of Neurology and Psychiatry, Tokyo, Japan
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Costamagna I, Calisti F, Cattaneo A, Hsu J, Tocco M, Pikalov A, Goldman R. Efficacy and safety of lurasidone in adolescents and young adults with schizophrenia: A pooled post hoc analysis of double-blind, placebo-controlled 6-week studies. Eur Psychiatry 2021; 64:e35. [PMID: 33966678 PMCID: PMC8204589 DOI: 10.1192/j.eurpsy.2021.30] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 03/22/2021] [Accepted: 03/25/2021] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND The aim of this pooled analysis was to evaluate the efficacy and safety of lurasidone in the treatment of an acute exacerbation of schizophrenia in adolescents and young adults. METHODS The six pooled studies in this analysis used similar study designs and outcome measures. Patients (aged 13-25 years) were randomized to 6 weeks of double-blind, placebo-controlled treatment with lurasidone in fixed doses of 40, 80, 120, or 160 mg. The primary efficacy endpoint was Week 6 change in the Positive and Negative Syndrome Scale (PANSS) total score; secondary efficacy endpoints included Week 6 change in the Clinical Global Impression-Severity scale. RESULTS The safety population consisted of 537 patients (mean age: 18.1 years); 82.6% of patients completed the studies. Treatment with lurasidone was significantly better than placebo at all doses (p < 0.001) for change in the PANSS total score at Week 6. Placebo-adjusted PANSS scores ranged from -9.4 to -16.1 (effect sizes: 0.53-0.90), with effect sizes increasing at higher doses. For lurasidone (combined doses), three adverse events occurred with a frequency of ≥5% (nausea: 13.5%; somnolence: 12.1%; akathisia: 10.1%). At last observation carried forward (LOCF)-endpoint weight gain of ≥7% was similar for lurasidone versus placebo (3.6 vs. 4.7%). Minimal median changes were observed at endpoint in cholesterol, -2.0 mg/dL; triglycerides, 0.0 mg/dL; and glucose, 0.0 mg/dL. CONCLUSIONS In adolescents and young adults with schizophrenia, treatment with lurasidone in doses of 40-160 mg/d was a safe, well-tolerated, and effective treatment. Short-term treatment with lurasidone was associated with minimal effects on weight and metabolic parameters.
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Affiliation(s)
- Isabella Costamagna
- Angelini RR&D (Regulatory, Research, & Development), Angelini Pharma S.p.A., Viale Amelia, 70, 00181 Rome, Italy
| | - Fabrizio Calisti
- Angelini RR&D (Regulatory, Research, & Development), Angelini Pharma S.p.A., Viale Amelia, 70, 00181 Rome, Italy
| | - Agnese Cattaneo
- Angelini RR&D (Regulatory, Research, & Development), Angelini Pharma S.p.A., Viale Amelia, 70, 00181 Rome, Italy
| | - Jay Hsu
- Sunovion Pharmaceuticals Inc., Fort Lee, New Jersey, USA
| | - Michael Tocco
- Sunovion Pharmaceuticals Inc., Marlborough, Massachusetts, USA
| | - Andrei Pikalov
- Sunovion Pharmaceuticals Inc., Fort Lee, New Jersey, USA
| | - Robert Goldman
- Sunovion Pharmaceuticals Inc., Marlborough, Massachusetts, USA
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27
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Iyo M, Ishigooka J, Nakamura M, Sakaguchi R, Okamoto K, Mao Y, Tsai J, Fitzgerald A, Nosaka T, Higuchi T. Efficacy and safety of lurasidone in acutely psychotic patients with schizophrenia: A 6-week, randomized, double-blind, placebo-controlled study. Psychiatry Clin Neurosci 2021; 75:227-235. [PMID: 33890388 PMCID: PMC8361730 DOI: 10.1111/pcn.13221] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 03/29/2021] [Accepted: 04/13/2021] [Indexed: 12/23/2022]
Abstract
AIM The aim of this study was to evaluate the efficacy of lurasidone in acute schizophrenia in Japan and other countries. METHODS Subjects (aged 18-74 years) diagnosed with schizophrenia were randomized to lurasidone 40 mg/day or placebo. The primary efficacy endpoint was change from baseline on the Positive and Negative Syndrome Scale (PANSS) total score at Week 6. Secondary efficacy assessments included the Clinical Global Impression-Severity Scale (CGI-S). Safety endpoints included adverse events, and laboratory and electrocardiogram parameters. RESULTS A total of 483 subjects were randomized to lurasidone or placebo; 107 subjects were from Japan. Mean changes from baseline at Week 6 endpoint in PANSS total scores were -19.3 in the lurasidone group and -12.7 in the placebo group (treatment difference: P < 0.001, effect size = 0.41). Changes from baseline for Week 6 CGI-S scores were -1.0 for lurasidone and -0.7 for placebo (treatment difference: P < 0.001, effect size = 0.41). All-cause discontinuation during the 6-week, double-blind period was 19.4% for lurasidone and 25.4% for placebo, and discontinuation rates due to adverse event were 5.7% for lurasidone and 6.4% for placebo. The following common treatment-emergent adverse events occurred in more than 2% on lurasidone and at a rate at least twice that of the placebo group: akathisia (4.0%), dizziness (2.8%), somnolence (2.8%), abdominal discomfort (2.0%) and asthenia (2.0%). No significant changes in bodyweight or metabolic parameters were observed. CONCLUSION Lurasidone 40 mg once daily dosing demonstrated efficacy in a patient population with acute schizophrenia, including subjects from Japan, and was generally safe and well-tolerated.
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Affiliation(s)
- Masaomi Iyo
- Department of PsychiatryGraduate School of Medicine, Chiba UniversityChibaJapan
| | | | - Masatoshi Nakamura
- Department of Data Science, Drug Development DivisionSumitomo Dainippon Pharma Co., Ltd.TokyoJapan
| | - Reiko Sakaguchi
- Department of Clinical ResearchDrug Development Division, Sumitomo Dainippon Pharma Co., Ltd.TokyoJapan
| | - Keisuke Okamoto
- Department of Clinical OperationDrug Development Division, Sumitomo Dainippon Pharma Co., Ltd.TokyoJapan
| | - Yongcai Mao
- Division of Data ScienceSunovion Pharmaceuticals Inc.New JerseyUSA
| | - Joyce Tsai
- Division of Clinical ResearchSunovion Pharmaceuticals Inc.New JerseyUSA
| | - Alison Fitzgerald
- Division of Clinical OperationsSunovion Pharmaceuticals Inc.New JerseyUSA
| | - Tadashi Nosaka
- Medical AffairsSumitomo Dainippon Pharma Co., Ltd.TokyoJapan
| | - Teruhiko Higuchi
- Japan Depression CenterTokyoJapan
- National Center of Neurology and PsychiatryTokyoJapan
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Khan N, Nasar A, Bajwa S, Jawad Butt A, Azher A, Mushtaq T, Rashid A, Haq MMU, Rasul G, Dogar FA. TULIP study: Trail of Lurasidone in bipolar disorder in Pakistan. Saudi J Biol Sci 2021; 28:1128-1132. [PMID: 33424407 PMCID: PMC7783817 DOI: 10.1016/j.sjbs.2020.11.044] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Revised: 11/08/2020] [Accepted: 11/10/2020] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND This study examined usefulness and efficiency of Lurasidone in appraisal with the placebo as for the treatment of Bipolar Disorders. METHODS Seven treatment centers in Pakistan were selected for the purpose of starting a six week-long control trial (randomized and double-blind placebo). 76 subjects, already diagnosed with Bipolar I or II based on DSM 5 diagnosis, were selected after randomization. Patients were allocated in one of the two groups. Primary efficacy of the drug was measured using Young Mania Rating Scale. Positive response of the drug was defined as 50% reduction in symptoms from the baseline/13 point less than the baseline score on Young Mania Rating Scale. Efficacy and safety of the drug was assessed using variety of markers such as administering extra-pyramidal symptoms rating scale, adverse side effects reported, electrocardiograms, body weight, vital signs changes, and laboratory investigations. RESULTS Patients treated with Lurasidone showed enhanced improvement in their overall health and symptoms manifestation in comparison to patients who were given placebo. Lurasidone treated patients showed a better response to the drug (66%), in comparison with the placebo treated patients (42%). LIMITATIONS Study was conducted on small scale due to complexity. CONCLUSION Patients treated with Lurasidone showed reduction in bipolar symptoms and tolerate the drug well.
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Affiliation(s)
- Nasar Khan
- Division of Developmental Disabilities, Queens University, Kingston, ON, Canada
| | - Amina Nasar
- Department of Psychiatry, Queens University, Kingston, ON, Canada
| | - Saqib Bajwa
- Gujranwala Medical and Dental College, Gujranwala, Pakistan
| | | | - Afia Azher
- Allama Medical College, Lahore, Pakistan
| | | | - Alina Rashid
- Shaukat Khanum Cancer Research Center, Lahore, Pakistan
| | | | - Ghulam Rasul
- Chair Bolan Institute of Psychiatry and Behavioral Sciences Quetta, Pakistan
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Riva MA, Albert U, de Filippis S, Vita A, De Berardis D. Identification of clinical phenotypes in schizophrenia: the role of lurasidone. Ther Adv Psychopharmacol 2021; 11:20451253211012250. [PMID: 34025981 PMCID: PMC8120523 DOI: 10.1177/20451253211012250] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Accepted: 04/01/2021] [Indexed: 12/16/2022] Open
Abstract
The treatment of schizophrenia includes the control of symptoms, the prevention of relapses, and amelioration of adaptive skills for patient re-integration into society. Antipsychotic drugs are the agents of choice for the treatment of schizophrenia, as they reduce the positive symptoms of psychosis. Lurasidone is a second-generation antipsychotic drug representing a novel and useful clinical tool for the management of schizophrenia. A board consisting of a panel of Italian expert psychiatrists was organized with the following aims: (a) defining the current modalities of use of lurasidone, highlighted through 17 specific questions; (b) defining and agreeing the main features of the drug and the principal reasons to suggest its administration. We established that lurasidone is suggested at any age, with no gender difference, at all stages of the disease. The switch from previous treatments is done primarily because of lack of efficacy as well as poor adherence/tolerability. Lurasidone is among the best-tolerated antipsychotics, and its use is indicated in the presence of different comorbidities. A wide range of dosages is available, allowing safe titration in particular cases, with the highest dose (148 mg) generally used for the treatment of the acute phase. The discontinuation rate due to poor tolerability, low compliance, and interactions with other drugs is very low. Akathisia is the most reported adverse event, but it may be controlled by dose reduction. Lurasidone does not possess a marked sedative action but, in agitated patients, can be associated with sedative drugs, such as benzodiazepines. The most frequent reason for switching to other therapies is the need for long-acting formulations, as in patients at risk of very low adherence or suicide. Lurasidone does not strongly impact metabolism or the cardiovascular system (QT interval), and does not influence the metabolism of other drugs, showing good efficacy and tolerability.
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Affiliation(s)
- Marco Andrea Riva
- Department of Pharmacological and Biomolecular Sciences, University of Milan, Milano, Italy
| | - Umberto Albert
- Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Friuli-Venezia Giulia, Italy
| | | | - Antonio Vita
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Domenico De Berardis
- NHS, Department of Mental Health, Hospital "G. Mazzini", ASL 4, Teramo, 64100, Italy
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Okubo R, Hasegawa T, Fukuyama K, Shiroyama T, Okada M. Current Limitations and Candidate Potential of 5-HT7 Receptor Antagonism in Psychiatric Pharmacotherapy. Front Psychiatry 2021; 12:623684. [PMID: 33679481 PMCID: PMC7930824 DOI: 10.3389/fpsyt.2021.623684] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Accepted: 01/29/2021] [Indexed: 12/13/2022] Open
Abstract
Several mood-stabilizing atypical antipsychotics and antidepressants weakly block serotonin (5-HT) receptor type-7 (5-HT7R); however, the contributions of 5-HT7R antagonism to clinical efficacy and pathophysiology are yet to be clarified. A novel mood-stabilizing antipsychotic agent, lurasidone exhibits predominant binding affinity to 5-HT7R when compared with other monoamine receptors. To date, we have failed to discover the superior clinical efficacy of lurasidone on schizophrenia, mood, or anxiety disorders when compared with conventional mood-stabilizing atypical antipsychotics; however, numerous preclinical findings have indicated the possible potential of 5-HT7R antagonism against several neuropsychiatric disorders, as well as the generation of novel therapeutic options that could not be expected with conventional atypical antipsychotics. Traditional experimental techniques, electrophysiology, and microdialysis have demonstrated that the effects of 5-HT receptor type-1A (5-HT1AR) and 5-HT7R on neurotransmission are in contrast, but the effect of 5-HT1AR is more predominant than that of 5-HT7R, resulting in an insufficient understanding of the 5-HT7R function in the field of psychopharmacology. Accumulating knowledge regarding the pharmacodynamic profiles of 5-HT7R suggests that 5-HT7R is one of the key players in the establishment and remodeling of neural development and cytoarchitecture during the early developmental stage to the mature brain, and dysfunction or modulation of 5-HT7R is linked to the pathogenesis/pathophysiology of neuropsychiatric and neurodevelopmental disorders. In this review, to explore candidate novel applications for the treatment of several neuropsychiatric disorders, including mood disorders, schizophrenia, and other cognitive disturbance disorders, we discuss perspectives of psychopharmacology regarding the effects of 5-HT7R antagonism on transmission and intracellular signaling systems, based on preclinical findings.
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Affiliation(s)
- Ruri Okubo
- Division of Neuroscience, Laboratory Department of Neuropsychiatry, Graduate School of Medicine, Mie University, Tsu, Japan
| | - Toshiki Hasegawa
- Division of Neuroscience, Laboratory Department of Neuropsychiatry, Graduate School of Medicine, Mie University, Tsu, Japan
| | - Kouji Fukuyama
- Division of Neuroscience, Laboratory Department of Neuropsychiatry, Graduate School of Medicine, Mie University, Tsu, Japan
| | - Takashi Shiroyama
- Division of Neuroscience, Laboratory Department of Neuropsychiatry, Graduate School of Medicine, Mie University, Tsu, Japan
| | - Motohiro Okada
- Division of Neuroscience, Laboratory Department of Neuropsychiatry, Graduate School of Medicine, Mie University, Tsu, Japan
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Hopkins SC, Ogirala A, Loebel A, Koblan KS. Characterization of specific and distinct patient types in clinical trials of acute schizophrenia using an uncorrelated PANSS score matrix transform (UPSM). Psychiatry Res 2020; 294:113569. [PMID: 33223272 DOI: 10.1016/j.psychres.2020.113569] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Accepted: 11/07/2020] [Indexed: 10/23/2022]
Abstract
Understanding the specificity of symptom change in schizophrenia can facilitate the evaluation antipsychotic efficacy for different symptom domains. Previous work identified a transform of PANSS using an uncorrelated PANSS score matrix (UPSM) to reduce pseudospecificity among symptom domains during clinical trials of schizophrenia. Here we used UPSM-transformed factor scores to identify 5 distinct patient types, each having elevated and specific severity among each of 5 symptom domains. Subjects from placebo-controlled clinical trials of acute schizophrenia were clustered (baseline) and classified (post-baseline) by a machine-learning algorithm. At baseline, all 5 patient types were similar in PANSS total score. Post-baseline, subjects' memberships among the 5 UPSM patient types were relatively stable over treatment duration and were relatively insensitive to overall improvements in symptoms, in contrast to other methods based on untransformed PANSS items. Using UPSM-transformed PANSS, drug treatment effect sizes versus placebo were doubly-dissociated for specificity across symptom domains and within specific patient types. This approach illustrates how broader clinical trial populations can nevertheless be utilized to characterize the specificity of new mechanisms across the dimensions of schizophrenia psychopathology.
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Long-Term Assessment of Lurasidone in Schizophrenia: Post Hoc Analysis of a 12-Month, Double Blind, Active-Controlled Trial and 6-Month Open-Label Extension Study. Neurol Ther 2020; 10:121-147. [PMID: 33098548 PMCID: PMC8140059 DOI: 10.1007/s40120-020-00221-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Accepted: 10/14/2020] [Indexed: 11/05/2022] Open
Abstract
Introduction A post hoc analysis of a double-blind (DB) active control trial and an open-label extension (OLE) study was conducted to evaluate the long-term effects of lurasidone in patients with schizophrenia. Methods In the DB trial, patients were randomised to receive lurasidone or risperidone for 12 months. In OLE, all patients received lurasidone for an additional 6 months. Treatment-emergent adverse events (TEAEs) were evaluated. Efficacy assessments included relapse rate (DB trial only), and Positive and Negative Syndrome Scale, Clinical Global Impression–Severity scale, and Montgomery–Åsberg Depression Rating Scale. Results In the DB trial, patients with schizophrenia were randomised to lurasidone (n = 399) and risperidone (n = 190), of whom 129 and 84 continued into OLE, respectively. During the DB trial, incidence of TEAEs was similar for lurasidone (84.1%) and risperidone (84.2%). Lurasidone was associated with minimal changes in metabolic variables and prolactin levels, whereas risperidone was associated with clinically significant increases in prolactin and fasting glucose levels. The proportion of patients with metabolic syndrome was significantly lower in patients treated with lurasidone versus risperidone at the end of the DB trial (25.5% vs 40.4%; p = 0.0177). During OLE, patients switching from risperidone to lurasidone experienced a reduction in weight and prolactin levels; those continuing treatment with lurasidone experienced minimal changes in metabolic variables and prolactin. At the end of OLE, the proportion of patients with metabolic syndrome was no longer significantly different between groups (23.5% vs 31.5%; p = not significant). Efficacy outcomes were generally similar between groups during the DB trial, and were maintained during OLE. Conclusion Lurasidone was generally well tolerated and effective in clinically stable schizophrenia patients over the long term. Lurasidone was also generally well tolerated and maintained effectiveness over 6 months in patients switching from risperidone. Patients switching from risperidone experienced improvements in metabolic parameters and prolactin levels. These findings confirm lurasidone’s long-term effectiveness and favourable metabolic profile in patients with schizophrenia. Trial Registration ClinicalTrials.gov identifier NCT00641745.
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Tocco M, Newcomer JW, Mao Y, Pikalov A, Loebel A. Lurasidone and risk for metabolic syndrome: results from short- and long-term clinical studies in patients with schizophrenia. CNS Spectr 2020; 26:1-11. [PMID: 32921337 DOI: 10.1017/s1092852920001698] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
OBJECTIVE To assess the effects of treatment with lurasidone on risk for metabolic syndrome (MetS) in patients with schizophrenia. METHODS Rates of metabolic syndrome during treatment with lurasidone (40-160 mg/d) were analyzed using pooled, short-term data from three randomized, double-blind, placebo-controlled studies (vs olanzapine and quetiapine XR); long-term data from two active-comparator-controlled studies (vs risperidone and quetiapine XR); and data from two open-label studies in which patients were switched from olanzapine or risperidone to lurasidone. RESULTS MetS was defined based on the National Cholesterol Education Program criteria. In short-term studies, the odds of meeting criteria for MetS at week 6 LOCF (adjusted for baseline metabolic syndrome status) was similar for the lurasidone and placebo groups (OR = 1.18; [95% CI, 0.81-1.71]; P = .39), but the odds (vs placebo) were significantly greater for olanzapine (OR = 2.81; [95% CI, 1.53-5.15]; P < .001) and quetiapine (OR = 3.49; [95% CI, 1.93-6.29]; P < .0001). No dose effect was observed for lurasidone across the dose range of 40-160 mg/d. In long-term studies, the odds of MetS after 12 months of treatment was significantly higher for risperidone compared with lurasidone (OR = 2.12; 95% CI, 1.15-3.90; P = .016) and for quetiapine XR compared with lurasidone (OR = 3.92; 95% CI, 1.15-13.40; P = .029). In open-label extension studies, the rate of MetS decreased in patients switched to lurasidone after 6 weeks of treatment with olanzapine or 12 months of treatment with risperidone. CONCLUSION In this analysis of lurasidone clinical trials, the odds of developing metabolic syndrome were minimal during short- and long-term treatment with lurasidone (40-160 mg/d).
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Affiliation(s)
| | - John W Newcomer
- Thriving Mind, Miami, FL, USA
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
| | - Yongcai Mao
- Sunovion Pharmaceuticals Inc., Fort Lee, NJ, USA
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Cassioli E, Sensi C, Mannucci E, Ricca V, Rotella F. Pharmacological treatment of acute-phase anorexia nervosa: Evidence from randomized controlled trials. J Psychopharmacol 2020; 34:864-873. [PMID: 32448045 DOI: 10.1177/0269881120920453] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
BACKGROUND Anorexia nervosa (AN) is the psychiatric disorder with the highest mortality rate, with a standard mortality ratio of 5.86. Despite the large use of psychotropic drugs in the clinical setting, Food and Drug Administration has not approved any psychoactive treatment for AN. AIMS The aim of this study was to perform an updated systematic review and meta-analysis of published randomized controlled trials (RCTs) investigating psychopharmacological treatment in acute-phase AN. METHODS The present paper follows the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. An extensive literature search was performed. All RCTs enrolling patients with acute-phase AN, comparing at least one psychotropic drug with another drug, placebo, treatment-as-usual or no treatment were included. The main outcome was the effect of psychoactive drugs on body mass index (BMI); data on psychopathological outcomes were also collected when available. RESULTS A total of 19 RCTs met all specified criteria. Of these, 11 were excluded from quantitative analyses. Of the eight studies included in the meta-analyses, five reported data on BMI, showing no significant difference between olanzapine and placebo for weight recovery. No significant result was found for AN psychopathology, depressive and anxious symptoms for any of the molecules studied. CONCLUSIONS RCTs published in this field display methodological biases, low sample sizes and short follow-up periods. Further research efforts are needed in this field as no evidence has been demonstrated for the use of any psychotropic drug in acute-phase AN neither for weight recovery, nor for comorbid psychiatric symptoms.
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Affiliation(s)
- Emanuele Cassioli
- Department of Health Sciences, University of Florence, Florence, Italy
| | - Carolina Sensi
- Department of Health Sciences, University of Florence, Florence, Italy
| | | | - Valdo Ricca
- Department of Health Sciences, University of Florence, Florence, Italy
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Feng Y, Shi J, Wang L, Zhang X, Tan Y, Zhao J, Ning Y, Xie S, Liu X, Liu Q, Li K, Wang X, Li L, Xu X, Deng W, Luo X, Wang G. Randomized, double-blind, 6-week non-inferiority study of lurasidone and risperidone for the treatment of schizophrenia. Psychiatry Clin Neurosci 2020; 74:336-343. [PMID: 31823444 PMCID: PMC7317929 DOI: 10.1111/pcn.12965] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Revised: 11/18/2019] [Accepted: 12/09/2019] [Indexed: 02/05/2023]
Abstract
AIM The aim of the present study was to evaluate the efficacy and safety of lurasidone for the treatment of Chinese schizophrenic patients. METHODS Hospitalized schizophrenia patients aged 18-65 were randomized to 6 weeks of double-blind, double-dummy, flexible-dose treatment with lurasidone (40 or 80 mg/day) or risperidone (2, 4 or 6 mg/day). Efficacy was evaluated using a non-inferiority comparison of lurasidone relative to risperidone based on week 6 change in the Positive and Negative Syndrome Scale (PANSS) total score. Safety assessments included adverse events, clinical laboratory measures, and electrocardiograms. RESULTS Four hundred and forty-four patients were screened to obtain an intent-to-treat sample of 384 patients, of whom 54 patients discontinued treatment prior to 6 weeks. Lurasidone met the criteria for non-inferiority versus risperidone on the PANSS total score. Adjusted mean (SE) change at week 6 on the PANSS total score was -31.2 (1.0) and -34.9 (1.0) in the lurasidone and risperidone group, respectively. The mean difference score was 3.7, and the upper boundary of the 95%-confidence interval (1.0-6.3) was less than the prespecified margin of 7.0. No clinically meaningful between-treatment group differences were evident on secondary efficacy measures, including PANSS positive, PANSS negative, Clinical Global Impression scale - Severity, and Calgary Depression Scale for Schizophrenia scales. The incidence of adverse events was lower for lurasidone vs risperidone for extrapyramidal symptoms (17.0% vs 38.2%), akathisia (7.2% vs 13.6%), prolactin increase (3.1% vs 14.1%), and weight increase (0.5% vs 5.2%). CONCLUSION Lurasidone was found to be non-inferior to risperidone on the primary endpoint with minimal effects on weight, metabolic parameters, or prolactin levels.
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Affiliation(s)
- Yuan Feng
- Department of Psychiatry, Beijing Anding Hospital, National Clinical Research Center for Mental Disorders, Capital Medical University, Beijing, China
| | - Jianguo Shi
- Department of Psychiatry, Xi'an Mental Health Center, Xi'an, China
| | - Lili Wang
- Department of Psychiatry, Tianjin Anding Hospital, Tianjin, China
| | - Xia Zhang
- Department of Psychiatry, Wuxi Mental Health Center, Wuxi, China
| | - Yunlong Tan
- Department of Psychiatry, Beijing Huilongguan Hospital, Beijing, China
| | - Jingyuan Zhao
- Department of Psychiatry, Henan Provincial Mental Hospital, Xinxiang, China
| | - Yuping Ning
- Department of Psychiatry, Guangzhou Brain Hospital, Guangzhou, China
| | - Shiping Xie
- Department of Psychiatry, Nanjing Brain Hospital, Nanjing, China
| | - Xuejun Liu
- Department of Psychiatry, Brain Hospital of Hunan Province, Changsha, China
| | - Qi Liu
- Department of Psychiatry, Sixth Hospital of Peking University, Beijing, China
| | - Keqing Li
- Department of Psychiatry, Hebei Mental Health Center, Baoding, China
| | - Xiaoliang Wang
- Mental Health Institute, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lehua Li
- Department of Psychiatry, Second Xiangya Hospital of Central South University, Changsha, China
| | - Xiufeng Xu
- Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Wei Deng
- Department of Psychiatry, West China Hospital of Sichuan University, Chengdu, China
| | - Xiaoyan Luo
- Medical Division, Sumitomo Pharma(Suzhou)Co., Ltd, Beijing, China
| | - Gang Wang
- Department of Psychiatry, Beijing Anding Hospital, National Clinical Research Center for Mental Disorders, Capital Medical University, Beijing, China
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Chow CL, Kadouh NK, Bostwick JR, VandenBerg AM. Akathisia and Newer Second‐Generation Antipsychotic Drugs: A Review of Current Evidence. Pharmacotherapy 2020; 40:565-574. [DOI: 10.1002/phar.2404] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Affiliation(s)
| | - Nour K. Kadouh
- College of Pharmacy University of Michigan Ann Arbor Michigan
| | | | - Amy M. VandenBerg
- Department of Pharmacy Services Michigan Medicine Ann Arbor Michigan
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Mattingly GW, Haddad PM, Tocco M, Xu J, Phillips D, Pikalov A, Loebel A. Switching to Lurasidone following 12 months of treatment with Risperidone: results of a 6-month, open-label study. BMC Psychiatry 2020; 20:199. [PMID: 32370778 PMCID: PMC7201608 DOI: 10.1186/s12888-020-02523-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Accepted: 02/28/2020] [Indexed: 01/15/2023] Open
Abstract
BACKGROUND Patients with a diagnosis of schizophrenia are at an increased risk for developing metabolic syndrome, which is associated with greater cardiovascular morbidity and mortality. Treatment with some commonly used antipsychotic medications may increase the risk of developing metabolic syndrome. The aim of the study was to evaluate the safety of lurasidone in patients who continued lurasidone or switched from risperidone to lurasidone. A secondary aim was assessment of the effect of long-term lurasidone on the Positive and Negative Syndrome Scale (PANSS). METHODS The treatment sample in the current study consisted of clinically stable patients with schizophrenia (N = 223) who had completed a 12-month, double-blind study of lurasidone vs. risperidone. In the current extension study, all patients received 6 months of open-label treatment with lurasidone, either continuing lurasidone assigned during the preceding double-blind trial, or switching from double-blind risperidone to lurasidone. Safety and tolerability parameters included body weight, prolactin, and metabolic laboratory tests. RESULTS Six months of OL treatment with lurasidone was generally well-tolerated, with a low incidence of parkinsonism (4.5%) and akathisia (3.1%). Overall, few adverse events were rated as severe (4.9%), and discontinuation due to an adverse event was low in the lurasidone continuation vs. risperidone switch groups (3.7% vs. 6.9%). In the lurasidone continuation versus risperidone switch groups, change from OL baseline to 6-month endpoint (observed case) was observed in mean body weight (- 0.6 vs. -2.6 kg), median total cholesterol (- 4.0 vs. + 4.5 mg/dL), triglycerides (- 4.5 vs. -5.5 mg/dL), glucose (0.0 vs. -3.0 mg/dL) and prolactin (males, + 0.15 vs. -11.2 ng/mL; females, + 1.3 vs. -30.8 ng/mL). Improvement in PANSS total score was maintained, from OL baseline to endpoint in the continuation vs. switch groups (+ 1.0 vs. -1.0; OC). CONCLUSIONS In this 6-month extension study, lurasidone treatment was generally well-tolerated and associated with minimal effects on weight, metabolic parameters, and prolactin levels. Patients who switched from risperidone to lurasidone experienced reductions in weight, metabolic parameters and prolactin levels commensurate with increases in these safety parameters experienced during the previous 12 months of treatment with risperidone. TRIAL REGISTRATION ClinicalTrials.gov NCT00641745 (Date of Registration: March 24, 2008).
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Affiliation(s)
- Greg W. Mattingly
- grid.4367.60000 0001 2355 7002Washington University School of Medicine, St. Louis, MO USA
| | - Peter M. Haddad
- grid.413548.f0000 0004 0571 546XHamad Medical Corporation, Doha, Qatar ,grid.412603.20000 0004 0634 1084Clinical Professor of Psychiatry, Qatar University, Doha, Qatar ,grid.5379.80000000121662407Honorary Professor of Psychiatry, University of Manchester, Manchester, UK ,grid.451052.70000 0004 0581 2008Honorary Consultant Psychiatrist, GMMH NHS Foundation Trust, Manchester, UK
| | - Michael Tocco
- Sunovion Pharmaceuticals Inc., Fort Lee, NJ, 84 Waterford Dr, Marlborough, MA, 01752, USA.
| | - Jane Xu
- grid.419756.8Sunovion Pharmaceuticals Inc., Fort Lee, NJ, 84 Waterford Dr, Marlborough, MA 01752 USA
| | - Debra Phillips
- grid.419756.8Sunovion Pharmaceuticals Inc., Fort Lee, NJ, 84 Waterford Dr, Marlborough, MA 01752 USA
| | - Andrei Pikalov
- grid.419756.8Sunovion Pharmaceuticals Inc., Fort Lee, NJ, 84 Waterford Dr, Marlborough, MA 01752 USA
| | - Antony Loebel
- grid.419756.8Sunovion Pharmaceuticals Inc., Fort Lee, NJ, 84 Waterford Dr, Marlborough, MA 01752 USA
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Higuchi T, Ishigooka J, Iyo M, Hagi K. Safety and effectiveness of lurasidone for the treatment of schizophrenia in Asian patients: Results of a 26-week open-label extension study. Asia Pac Psychiatry 2020; 12:e12377. [PMID: 31837113 DOI: 10.1111/appy.12377] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2018] [Accepted: 11/15/2019] [Indexed: 01/26/2023]
Abstract
INTRODUCTION This study was designed to evaluate the long-term safety and effectiveness of lurasidone in the treatment of schizophrenia among Asian patients. METHODS Patients (N = 281) with schizophrenia who had completed a randomized, double-blind (DB), 6-week comparison of lurasidone (40 and 80 mg/day) and placebo were enrolled in a 26-week extension study in which all patients received open-label (OL), flexible doses of lurasidone (40 or 80 mg/day). Effectiveness was measured using the Positive and Negative Syndrome Scale (PANSS) scale. RESULTS Fifty-seven percent of patients completed the OL extension study; 16.7% discontinued early due to lack of effectiveness; and 10.3% due to adverse events. The most common adverse events were insomnia (11.3%), akathisia (11.0%), and nasopharyngitis (10.6%). Adverse events related to weight gain, metabolic parameters, prolactin, and ECG measures were uncommon. Mean change in the PANSS total score from the DB baseline to OL endpoint was -28.4, with mean improvement of -7.5 observed from baseline to OL endpoint, and with a PANSS responder rate of 73.7%. DISCUSSION The results of the current 26-week extension study found lurasidone to be a generally safe, well-tolerated, and effective long-term treatment for schizophrenia in Asian patients.
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Affiliation(s)
| | | | - Masaomi Iyo
- Department of Psychiatry, National University Corporation Chiba University, Graduate School of Medicine, Chiba, Japan
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Abstract
PURPOSE/BACKGROUND In addition to clozapine, other atypical antipsychotic drugs pharmacologically similar to clozapine, for example, olanzapine, risperidone, and melperone, are also effective in a similar proportion of treatment-resistant schizophrenia (TRS) patients, ~40%. The major goal of this study was to compare 2 doses of lurasidone, another atypical antipsychotic drug, and time to improvement in psychopathology and cognition during a 6-month trial in TRS patients. METHODS/PROCEDURES The diagnosis of TRS was based on clinical history and lack of improvement in psychopathology during a 6-week open trial of lurasidone 80 mg/d (phase 1). This was followed by a randomized, double-blind, 24-week trial of lurasidone, comparing 80- and 240-mg/d doses (phase 2). FINDINGS/RESULTS Significant non-dose-related improvement in the Positive and Negative Syndrome Scale-Total and subscales and in 2 of 7 cognitive domains, speed of processing and executive function, were noted. Twenty-eight (41.8%) of 67 patients in the combined sample improved ≥20% in the Positive and Negative Syndrome Scale-Total. Of the 28 responders, 19 (67.9%) first reached ≥20% improvement between weeks 6 and 24 during phase 2, including some who had previously failed to respond to clozapine. IMPLICATIONS/CONCLUSIONS Improvement with lurasidone is comparable with those previously reported for clozapine, melperone, olanzapine, and risperidone in TRS patients. In addition, this study demonstrated that 80 mg/d lurasidone, an effective and tolerable dose for non-TRS patients, was also effective in TRS patients but required longer duration of treatment. Direct comparison of lurasidone with clozapine in TRS patients is indicated.
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Novel antipsychotics specificity profile: A clinically oriented review of lurasidone, brexpiprazole, cariprazine and lumateperone. Eur Neuropsychopharmacol 2019; 29:971-985. [PMID: 31255396 DOI: 10.1016/j.euroneuro.2019.06.008] [Citation(s) in RCA: 93] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Revised: 06/05/2019] [Accepted: 06/12/2019] [Indexed: 12/19/2022]
Abstract
Second generation antipsychotics (SGAs) are effective options in the treatment of schizophrenia and mood disorders, each with characteristic efficacy and safety features. In order to optimize the balance between efficacy and side effects, it is of upmost importance to match compound specificity against patient clinical profile. As the number of SGAs increased, this review can assist physicians in the prescription of three novel SGAs already on the market, namely lurasidone, brexpiprazole, cariprazine, and lumateperone, which is in the approval phase for schizophrenia treatment at the FDA. Besides schizophrenia, EMA and/or FDA approved lurasidone for bipolar depression, brexpiprazole as augmentation in major depressive disorder and cariprazine for the acute treatment of manic or mixed episodes associated with bipolar I disorder. These new antipsychotics were developed with the aim of improving efficacy on negative and depressive symptoms and reducing metabolic and cardiovascular side effects compared to prior SGAs, while keeping the risk of extrapyramidal symptoms low. They succeeded quite well in containing these side effects, despite weight gain during acute treatment remains a possible concern for brexpiprazole, while cariprazine and lurasidone show higher risk of akathisia compared to placebo and other SGAs such as olanzapine. The available studies support the expected benefits on negative symptoms, cognitive dysfunction and depressive symptoms, while the overall effect on acute psychotic symptoms may be similar to other SGAs such as quetiapine, aripiprazole and ziprasidone. The discussed new antipsychotics represent useful therapeutic options but their efficacy and side effect profiles should be considered to personalize prescription.
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Kishimoto T, Hagi K, Nitta M, Kane JM, Correll CU. Long-term effectiveness of oral second-generation antipsychotics in patients with schizophrenia and related disorders: a systematic review and meta-analysis of direct head-to-head comparisons. World Psychiatry 2019; 18:208-224. [PMID: 31059621 PMCID: PMC6502423 DOI: 10.1002/wps.20632] [Citation(s) in RCA: 86] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Second-generation antipsychotics (SGAs) are recommended for maintenance treatment in schizophrenia. However, comparative long-term effectiveness among SGAs is unclear. Here we provide a systematic review and meta-analysis of randomized trials lasting ≥⃒6 months comparing SGAs head-to-head in schizophrenia and related disorders. The primary outcome was all-cause discontinuation. Secondary outcomes included efficacy and tolerability, i.e., psychopathology, inefficacy-related and intolerability-related discontinuation, relapse, hospitalization, remission, functioning, quality of life, and adverse events. Pooled risk ratio and standardized mean difference were calculated using random-effects models. Across 59 studies (N=45,787), lasting 47.4±32.1 weeks (range 24-186), no consistent superiority of any SGA emerged across efficacy and tolerability outcomes. Regarding all-cause discontinuation, clozapine, olanzapine and risperidone were significantly (p<0.05) superior to several other SGAs, while quetiapine was inferior to several other SGAs. As to psychopathology, clozapine and olanzapine were superior to several other SGAs, while quetiapine and ziprasidone were inferior to several other SGAs. Data for other efficacy outcomes were sparse. Regarding intolerability-related discontinuation, risperidone was superior and clozapine was inferior to several other SGAs. Concerning weight gain, olanzapine was worse than all other compared non-clozapine SGAs, and risperidone was significantly worse than several other SGAs. As to prolactin increase, risperidone and amisulpride were significantly worse than several other SGAs. Regarding parkinsonism, olanzapine was superior to risperidone, without significant differences pertaining to akathisia. Concerning sedation and somnolence, clozapine and quetiapine were significantly worse than some other SGAs. In summary, different long-term SGA efficacy and tolerability patterns emerged. The long-term risk-benefit profiles of specific SGAs need to be tailored to individual patients to optimize maintenance treatment outcomes.
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Affiliation(s)
- Taishiro Kishimoto
- Keio University School of MedicineTokyoJapan,Zucker Hillside Hospital, Psychiatry Research, Northwell Health, Glen OaksNew YorkNYUSA,Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, HempsteadNew YorkNYUSA,Feinstein Institute for Medical Research, ManhassetNew YorkNYUSA
| | - Katsuhiko Hagi
- Zucker Hillside Hospital, Psychiatry Research, Northwell Health, Glen OaksNew YorkNYUSA,Sumitomo Dainippon Pharma Co., Ltd.TokyoJapan
| | | | - John M. Kane
- Zucker Hillside Hospital, Psychiatry Research, Northwell Health, Glen OaksNew YorkNYUSA,Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, HempsteadNew YorkNYUSA,Feinstein Institute for Medical Research, ManhassetNew YorkNYUSA
| | - Christoph U. Correll
- Zucker Hillside Hospital, Psychiatry Research, Northwell Health, Glen OaksNew YorkNYUSA,Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, HempsteadNew YorkNYUSA,Feinstein Institute for Medical Research, ManhassetNew YorkNYUSA,Department of Child and Adolescent PsychiatryCharité UniversitätsmedizinBerlinGermany
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Demyttenaere K, Detraux J, Racagni G, Vansteelandt K. Medication-Induced Akathisia with Newly Approved Antipsychotics in Patients with a Severe Mental Illness: A Systematic Review and Meta-Analysis. CNS Drugs 2019; 33:549-566. [PMID: 31065941 DOI: 10.1007/s40263-019-00625-3] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Akathisia is a common and distressing movement disorder that can be associated with the use of antipsychotics. It is characterized by a subjective (inner restlessness) and an objective (excessive movements) component. Akathisia can have a negative impact on clinical outcome and even lead to treatment discontinuation. Although medication-induced akathisia is more commonly associated with the use of first-generation antipsychotics (FGAs), it also occurs with second-generation antipsychotics (SGAs), including the newly approved antipsychotics (NAPs) asenapine, lurasidone, iloperidone, cariprazine, and brexpiprazole. Until now, no meta-analysis has been published on the risk of akathisia for all NAPs, as monotherapy or adjunctive treatment, in patients with a severe mental illness. OBJECTIVE The primary objectives of this systematic review and meta-analysis were to (i) compare akathisia incidence rates of the NAPs, as monotherapy or adjunctive treatment, in adult patients with a severe mental illness (i.e., schizophrenia, bipolar disorder, or major depressive disorder), using data from published and unpublished randomized controlled trials; and (ii) examine the role of several study characteristics explaining differences in akathisia incidence rates between studies. METHODS A systematic literature search, using the PubMed, EMBASE, and Cochrane Library databases (until October 2018), was conducted for English-language placebo- as well as active-controlled clinical trials, including subjective (percentage of patients reporting akathisia) and/or scale-defined medication-induced akathisia incidence rates with NAPs (as monotherapy or as adjunctive treatment) in adult patients with schizophrenia, bipolar disorder, or major depressive disorder. Additional unpublished clinical trials were identified through the ClinicalTrials.gov electronic database. Two meta-analyses (incidence rates and odds ratio [OR] [placebo vs. active] of medication-induced akathisia with NAPs) were performed to obtain an optimal estimation of akathisia risks of adult patients with a severe mental illness under these treatment conditions and to assess the role of study characteristics. RESULTS Two hundred and thirteen reports were selected as potentially eligible for our meta-analysis. Of these, 48 met the inclusion criteria. Eight records, identified through the ClinicalTrials.gov database and cross-referencing, and which fulfilled the inclusion criteria, were added, resulting in a total of 56 records (iloperidone = 5, asenapine = 11, lurasidone = 15, brexpiprazole = 13, cariprazine = 12). The estimated weighted mean incidence rate of akathisia was 7.7% (95% confidence interval [CI] 6.5-9.1), with estimates being 3.9% (95% CI 2.4-6.3) for iloperidone, 6.8% (95% CI 5.1-9.0) for asenapine, 10.0% (95% CI 7.4-13.5) for brexpiprazole, 12.7% (95% CI 10.1-16.1) for lurasidone, and 17.2% (95% CI 13.4-22.1) for cariprazine. After Tukey-adjustment for multiple testing, the incidence rate of akathisia was significantly (p < 0.05) lower for iloperidone than for brexpiprazole, lurasidone, and cariprazine. In addition, the incidence rate of akathisia was significantly (p < 0.05) lower for asenapine than for lurasidone and cariprazine. Finally, the incidence rate of akathisia was significantly (p < 0.05) lower for brexpiprazole than for cariprazine. Type of medication (p < 0.0001), diagnosis (p = 0.02), and race (p = 0.0003) significantly explained part of the heterogeneity of the incidence estimates of akathisia between studies. The estimated weighted OR of akathisia under medication, compared with placebo, was 2.43 (95% CI 1.91-3.10). The OR was smallest for iloperidone (OR 1.20; 95% CI 0.42-3.45) and increased for brexpiprazole (OR 2.04; 95% CI 1.09-3.83), asenapine (OR 2.37; 95% CI 1.32-4.27), lurasidone (OR 3.74; 95% CI 2.32-6.02), and cariprazine (OR 4.35; 95% CI 2.80-6.75). Only type of medication (p = 0.03) explained systematic differences in the OR for akathisia between placebo versus active treatment across studies. After Tukey-adjustment for multiple testing, no significant differences between these ORs were found. The severity of akathisia with NAPs generally is mild to moderate, only leading to treatment discontinuation in a minority of cases (< 5%). CONCLUSIONS The use of a NAP raises the akathisia risk more than two-fold when compared with patients receiving placebo. Although distinctions between the different NAPs were not clear in placebo-controlled trials, the results of our meta-analyses and systematic review generally indicate that these differences more than likely reflect real differences, with iloperidone showing the most and cariprazine showing the least benign akathisia profile. Moreover, due to patient characteristics and methodological issues, incidence rates of akathisia with NAPs found in this meta-analysis may even be an underestimation of true incidence rates.
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Affiliation(s)
- Koen Demyttenaere
- Department of Neurosciences, Research Group Psychiatry, Department of Psychiatry, Faculty of Medicine, University Psychiatric Center KU Leuven and University of Leuven, Campus Gasthuisberg, Herestraat 49, 3000, Louvain, Belgium.
| | - Johan Detraux
- Department of Neurosciences, Research Group Psychiatry, KU Leuven, University Psychiatric Centre, 3070, Kortenberg, Belgium
| | - Giorgio Racagni
- Department of Pharmacological Sciences, Università degli Studi di Milano, Milan, Italy
| | - Kristof Vansteelandt
- Department of Neurosciences, Research Group Psychiatry, KU Leuven, University Psychiatric Centre, 3070, Kortenberg, Belgium
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Abstract
Introduction Lurasidone is an atypical antipsychotic that was approved in Europe in 2014 for the treatment of schizophrenia in adults aged ≥ 18 years. Clinical experience with lurasidone in Europe is currently limited, and there is therefore a need to provide practical guidance on using lurasidone for the treatment of adults with schizophrenia. Methods A panel of European psychiatrists with extensive experience of prescribing lurasidone was convened to provide recommendations on using lurasidone to treat adults with schizophrenia. Results Extensive evidence from clinical trials and the panel’s clinical experience suggest that lurasidone is as effective as other atypical agents, with the possible exception of clozapine. Lurasidone is associated with a lower propensity for metabolic side effects (in particular, weight gain) and hyperprolactinaemia than most other atypical antipsychotics and has a relatively benign neurocognitive side effect profile. Patients switching to lurasidone from another antipsychotic may experience weight reduction and/or improvements in the ability to focus/concentrate. Most side effects with lurasidone (such as somnolence) are transitory, easily managed and/or ameliorated by dose adjustment. Akathisia and extrapyramidal symptoms may occur in a minority of patients, but these can be managed effectively with dose adjustment, adjunctive therapy and/or psychosocial intervention. Conclusions Given the crucial importance of addressing the physical as well as mental healthcare needs of patients, lurasidone is a rational therapeutic choice for adults with schizophrenia, both in the acute setting and over the long term. Funding Sunovion Pharmaceuticals Europe Ltd. Electronic supplementary material The online version of this article (10.1007/s40120-019-0138-z) contains supplementary material, which is available to authorized users.
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Carbon M, Kane JM, Leucht S, Correll CU. Tardive dyskinesia risk with first- and second-generation antipsychotics in comparative randomized controlled trials: a meta-analysis. World Psychiatry 2018; 17:330-340. [PMID: 30192088 PMCID: PMC6127753 DOI: 10.1002/wps.20579] [Citation(s) in RCA: 119] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Tardive dyskinesia (TD) risk with D2/serotonin receptor antagonists or D2 receptor partial agonists (second-generation antipsychotics, SGAs) is considered significantly lower than with D2 antagonists (first-generation antipsychotics, FGAs). As some reports questioned this notion, we meta-analyzed randomized controlled studies (RCTs) to estimate the risk ratio (RR) and annualized rate ratio (RaR) of TD comparing SGAs vs. FGAs and SGAs vs. SGAs. Additionally, we calculated raw and annualized pooled TD rates for each antipsychotic. Data from 57 head-to-head RCTs, including 32 FGA and 86 SGA arms, were meta-analyzed, yielding 32 FGA-SGA pairs and 35 SGA-SGA pairs. The annualized TD incidence across FGA arms was 6.5% (95% CI: 5.3-7.8%) vs. 2.6% (95% CI: 2.0-3.1%) across SGA arms. TD risk and annualized rates were lower with SGAs vs. FGAs (RR=0.47, 95% CI: 0.39-0.57, p<0.0001, k=28; RaR=0.35, 95% CI: 0.28-0.45, p<0.0001, number-needed-to-treat, NNT=20). Meta-regression showed no FGA dose effect on FGA-SGA comparisons (Z=-1.03, p=0.30). FGA-SGA TD RaRs differed by SGA comparator (Q=21.8, df=7, p=0.003), with a significant advantage of olanzapine and aripiprazole over other non-clozapine SGAs in exploratory pairwise comparisons. SGA-SGA comparisons confirmed the olanzapine advantage vs. non-clozapine SGAs (RaR=0.66, 95% CI: 0.49-0.88, p=0.006, k=17, NNT=100). This meta-analysis confirms a clinically meaningfully lower TD risk with SGAs vs. FGAs, which is not driven by high dose FGA comparators, and documents significant differences with respect to this risk between individual SGAs.
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Affiliation(s)
- Maren Carbon
- Department of PsychiatryZucker Hillside HospitalGlen OaksNYUSA
| | - John M. Kane
- Department of PsychiatryZucker Hillside HospitalGlen OaksNYUSA,Department of Psychiatry and Molecular MedicineHofstra Northwell School of MedicineHempsteadNYUSA,Center for Psychiatric NeuroscienceFeinstein Institute for Medical ResearchManhassetNYUSA,Department of Psychiatry and PsychotherapyKlinikum rechts der Isar der Technischen Universität MünchenMunichGermany
| | - Stefan Leucht
- Department of Psychiatry and PsychotherapyKlinikum rechts der Isar der Technischen Universität MünchenMunichGermany
| | - Christoph U. Correll
- Department of PsychiatryZucker Hillside HospitalGlen OaksNYUSA,Department of Psychiatry and Molecular MedicineHofstra Northwell School of MedicineHempsteadNYUSA,Center for Psychiatric NeuroscienceFeinstein Institute for Medical ResearchManhassetNYUSA,Campus Virchow‐Klinikum, Charité‐Universitätsmedizin Berlin, and Department of Child and Adolescent PsychiatryBerlin Institute of HealthBerlinGermany
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Ng-Mak D, Tongbram V, Ndirangu K, Rajagopalan K, Loebel A. Efficacy and metabolic effects of lurasidone versus brexpiprazole in schizophrenia: a network meta-analysis. J Comp Eff Res 2018; 7:737-748. [PMID: 29697278 DOI: 10.2217/cer-2018-0016] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Aim: To assess the relative efficacy and metabolic effects of lurasidone and brexpiprazole in the acute treatment of schizophrenia. Methods: Five lurasidone and three brexpiprazole trials were identified. In the absence of head-to-head trials, a Bayesian network meta-analysis comparing lurasidone and brexpiprazole was performed. Results: Nonstatistically significant differences in efficacy measures were observed between lurasidone and brexpiprazole. Significant differences favoring lurasidone for weight change (-0.69 kg; 95% CrI: -1.22 to -0.15), total cholesterol (-7.60 mg/dl; 95% CrI: -13.94 to -1.22), and low-density lipoprotein (-6.58 mg/dl; 95% CrI: -12.11 to -1.04) were observed, with a trend indicating half the risk of experiencing ≥7% weight gain. Conclusion: This network meta-analysis suggested that lurasidone had similar efficacy and fewer metabolic effects than brexpiprazole in patients with acute schizophrenia.
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Affiliation(s)
- Daisy Ng-Mak
- Sunovion Pharmaceuticals, Inc., Marlborough, MA 01752, USA
| | | | | | | | - Antony Loebel
- Sunovion Pharmaceuticals, Inc., Fort Lee, NJ 07024, USA
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Osborne IJ, Mace S, Taylor D. A prospective year-long follow-up of lurasidone use in clinical practice: factors predicting treatment persistence. Ther Adv Psychopharmacol 2018; 8:117-125. [PMID: 29607004 PMCID: PMC5846921 DOI: 10.1177/2045125317749740] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2017] [Accepted: 10/10/2017] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Our aim was to follow up patients prescribed lurasidone over 1 year to determine factors predicting treatment persistence. METHODS We used noninterventional, observational, prospective follow up of patients consecutively prescribed lurasidone in a large inner-city NHS mental health trust. We also performed retrospective analysis of outcomes from patient case notes. RESULTS Data were available for 69 patients consecutively prescribed lurasidone, of whom three (4%) were lost to follow up. Out of the 66 patients not lost to follow-up, 21 (32%) remained on lurasidone at 1 year. The main reasons for discontinuation were perceived ineffectiveness (49% of discontinuers) and adverse effects (36% of discontinuers), whilst a further seven refused all treatment. Median treatment time on lurasidone was 154 days (95% confidence interval (CI), 33-275). Patients who were not treatment-resistant had a substantially reduced risk of discontinuation, relative risk (RR) 0.18 [95% CI 0.08, 0.41, p < 0.001]. Medium doses (>37-74 mg) of lurasidone reduced the risk of discontinuation by 75% [RR 0.25 (95% CI 0.11, 0.58, p = 0.001)]; high doses (>74-148 mg) reduced the risk of discontinuation by 86% [RR 0.14 (95% CI 0.06, 0.35, p < 0.001)]. Risk of discontinuation was approximately doubled when the reason for prescribing lurasidone was poor tolerability of prior treatment [RR 2.01 (95% CI 1.05, 3.85, p = 0.035)]. CONCLUSION The likelihood of treatment continuation with lurasidone can be vastly improved by targeting individuals most likely to benefit and by using optimal doses.
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Affiliation(s)
- Ian J Osborne
- Pharmacy Department, Maudsley Hospital, Denmark Hill, London, SE5 8AZ, UK
| | - Shubhra Mace
- Pharmacy Department, Maudsley Hospital, London, UK Institute of Pharmaceutical Science, King's College, London, UK
| | - David Taylor
- Maudsley Hospital, Pharmacy Department, Denmark Hill, London SE5 8AZ, UK Institute of Pharmaceutical Science, King's College, London, 5th Floor, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK
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Evaluation of the long-term safety and tolerability of cariprazine in patients with schizophrenia: results from a 1-year open-label study. CNS Spectr 2018; 23:39-50. [PMID: 28478771 DOI: 10.1017/s1092852917000220] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
OBJECTIVE Cariprazine, a dopamine D3/D2 partial agonist atypical antipsychotic with preferential binding to D3 receptors, is approved for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder. The efficacy and safety of cariprazine was established in three randomized, double-blind, placebo-controlled, 6-week trials in patients with acute exacerbation of schizophrenia. This 53-week study evaluated the long-term safety and tolerability of cariprazine in patients with schizophrenia. METHODS This was a multicenter, open-label, flexible-dose study of cariprazine 3-9 mg/d in adults with schizophrenia. Participants included new patients and patients who had completed one of two phase III lead-in studies (NCT01104766, NCT01104779). Eligible patients entered a no-drug screening period of up to 1 week followed by 48 weeks of flexibly dosed, open-label cariprazine treatment (3-9 mg/d) and 4 weeks of safety follow-up. RESULTS A total of 586 patients received open-label cariprazine treatment, ~39% of whom completed the study. No unexpected safety issues or deaths were reported. The most common (≥10%) adverse events (AEs) observed were akathisia (16%), headache (13%), insomnia (13%), and weight gain (10%). Serious AEs occurred in 59 (10.1%) patients, and 73 (12.5%) patients discontinued the study due to AEs during open-label treatment. Mean changes in metabolic, hepatic, and cardiovascular parameters were not considered clinically relevant. Mean body weight increased by 1.5 kg during the study, prolactin levels decreased slightly, and measures of efficacy remained stable. CONCLUSIONS Long-term cariprazine treatment at doses up to 9 mg/d appeared to be generally safe and well tolerated in patients with schizophrenia.
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Zhang Y, Liu Y, Su Y, You Y, Ma Y, Yang G, Song Y, Liu X, Wang M, Zhang L, Kou C. The metabolic side effects of 12 antipsychotic drugs used for the treatment of schizophrenia on glucose: a network meta-analysis. BMC Psychiatry 2017; 17:373. [PMID: 29162032 PMCID: PMC5698995 DOI: 10.1186/s12888-017-1539-0] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2017] [Accepted: 11/13/2017] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Antipsychotics have serious metabolic side effects on blood glucose. However, the comparative influence of these drugs on blood glucose levels has not been comprehensively evaluated. We conducted a network meta-analysis to create a hierarchy of the side effects of 12 antipsychotic drugs on changes in blood glucose levels. METHODS A systematic search of the PubMed, EMBASE and Cochrane databases (last search June 2016) was conducted to identify studies that reported randomized controlled trials (RCTs) comparing changes in blood glucose levels between patients receiving one of 12 antipsychotic drugs or a placebo for the treatment of schizophrenia or related disorders. The studies we searched were limited to those published in English. Two reviewers independently extracted data. The primary outcome of interest was changes in fasting glucose levels. RESULTS We included 47 studies with 114 relevant arms. Of the antipsychotic drugs, only olanzapine was associated with significantly increased glucose levels compared to a placebo (mean difference (MD) = 3.95, 95% confidence interval (CI) = 0.14 to 7.76). Moreover, olanzapine was associated with a significantly greater change in the glucose levels than ziprasidone (MD = 5.51, 95% CI = 1.62 to 9.39), lurasidone (MD = 5.58, 95% CI = 0.53 to 10.64) or risperidone (MD = 3.05, 95% CI = 0.87 to 5.22). Ziprasidone and lurasidone were associated with minimal glucose changes compared to the other antipsychotics. CONCLUSIONS Olanzapine was associated with a significantly greater change in blood glucose levels than ziprasidone, lurasidone, risperidone or placebo treatment. The application of a hierarchy of glucose metabolism-related side effects may help clinicians tailor the choice of antipsychotic drug to meet the needs of individual patients.
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Affiliation(s)
- Yangyu Zhang
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, Jilin Province 130021 China
| | - Yingyu Liu
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, Jilin Province 130021 China
| | - Yingying Su
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, Jilin Province 130021 China
| | - Yueyue You
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, Jilin Province 130021 China
| | - Yue Ma
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, Jilin Province 130021 China
| | - Guang Yang
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, Jilin Province 130021 China
| | - Yan Song
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, Jilin Province 130021 China
| | - Xinyu Liu
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, Jilin Province 130021 China
| | - Mohan Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, Jilin Province 130021 China
| | - Lili Zhang
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, Jilin Province 130021 China
| | - Changgui Kou
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, Jilin Province 130021 China
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Calabrese JR, Pikalov A, Streicher C, Cucchiaro J, Mao Y, Loebel A. Lurasidone in combination with lithium or valproate for the maintenance treatment of bipolar I disorder. Eur Neuropsychopharmacol 2017; 27:865-876. [PMID: 28689688 DOI: 10.1016/j.euroneuro.2017.06.013] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2016] [Revised: 06/07/2017] [Accepted: 06/20/2017] [Indexed: 10/19/2022]
Abstract
Lurasidone (DS-RAn) has demonstrated efficacy in the acute treatment of bipolar depression, both as monotherapy, and as combination therapy with lithium or valproate. To evaluate the recurrence prevention efficacy of lurasidone for the maintenance treatment of bipolar I disorder, patients received up to 20 weeks of open-label lurasidone (20-80mg/d) combined with lithium or valproate during an initial stabilization phase. A total of 496 patients met stabilization criteria and were randomized to 28 weeks of double-blind treatment with lurasidone (20-80mg/d) or placebo, in combination with lithium or valproate. Based on a Cox proportional hazard model, treatment with lurasidone reduced the probability of recurrence of any mood episode by 29% (primary endpoint), however, the reduction did not achieve statistical significance. Probability of recurrence on lurasidone was significantly lower in patients with an index episode of depression (HR, 0.57; P=0.039), in patients with any index episode who were not rapid-cycling (HR, 0.69; P=0.046), and when recurrence was based on MADRS, YMRS, or CGI-BP-S severity criteria (HR, 0.53; P=0.025; sensitivity analysis). Long-term treatment with lurasidone combined with lithium or valproate was found to be safe and well-tolerated, with minimal effects on weight or metabolic parameters.
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Affiliation(s)
- Joseph R Calabrese
- University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, United States
| | - Andrei Pikalov
- Sunovion Pharmaceuticals Inc., Marlborough, MA, United States; Sunovion Pharmaceuticals Inc., Fort Lee, NJ, United States
| | - Caroline Streicher
- Sunovion Pharmaceuticals Inc., Marlborough, MA, United States; Sunovion Pharmaceuticals Inc., Fort Lee, NJ, United States
| | - Josephine Cucchiaro
- Sunovion Pharmaceuticals Inc., Marlborough, MA, United States; Sunovion Pharmaceuticals Inc., Fort Lee, NJ, United States
| | - Yongcai Mao
- Sunovion Pharmaceuticals Inc., Marlborough, MA, United States; Sunovion Pharmaceuticals Inc., Fort Lee, NJ, United States
| | - Antony Loebel
- Sunovion Pharmaceuticals Inc., Marlborough, MA, United States; Sunovion Pharmaceuticals Inc., Fort Lee, NJ, United States
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Goldman R, Loebel A, Cucchiaro J, Deng L, Findling RL. Efficacy and Safety of Lurasidone in Adolescents with Schizophrenia: A 6-Week, Randomized Placebo-Controlled Study. J Child Adolesc Psychopharmacol 2017; 27:516-525. [PMID: 28475373 PMCID: PMC5568017 DOI: 10.1089/cap.2016.0189] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE To evaluate the efficacy and safety of lurasidone in acutely symptomatic adolescent patients with schizophrenia. METHODS Patients aged 13-17 years were randomly assigned to 6 weeks of double-blind, fixed-dose lurasidone (40 or 80 mg/day) or placebo. Primary and key secondary efficacy measures were change from baseline to week 6 in the Positive and Negative Symptom Scale (PANSS) total score and Clinical Global Impressions-Severity (CGI-S) score, respectively, using mixed model for repeated measurement (MMRM) analysis. The proportion of patients achieving treatment response at endpoint, based on ≥20% reduction in PANSS total score, was analyzed using a logistic regression model. RESULTS Least-squares (LS) mean change in PANSS total score from baseline to week 6 was -18.6 with lurasidone 40 mg/day (N = 108; p < 0.001 vs. placebo; effect size = 0.51), -18.3 with lurasidone 80 mg/day (N = 106; p < 0.001 vs. placebo; effect size = 0.48), and -10.5 with placebo (N = 112). Similarly, LS mean change in CGI-S score from baseline to week 6 was significantly greater with lurasidone 40 mg/day (-1.0; p < 0.001; effect size = 0.49) and 80 mg/day (-0.9; p = 0.0015; effect size = 0.45) compared with placebo (-0.5). A significantly higher proportion of patients met responder criteria on lurasidone 40 and 80 mg/day versus placebo (63.9% and 65.1% vs. 42.0%; p < 0.001 for both comparisons). The rate of study discontinuation was 10.3% in lurasidone-treated and 17.7% in placebo-treated patients. The most common adverse events (incidence ≥5% in either lurasidone dose group and at least twice the rate of placebo) for lurasidone 40 mg/day, 80 mg/day, and placebo, respectively, were nausea (12.7%, 14.4%, and 2.7%), somnolence (9.1%, 11.5%, and 5.4%), akathisia (9.1%, 8.7%, and 1.8%), vomiting (8.2%, 6.7%, and 1.8%), and sedation (5.5%, 1.9%, and 1.8%). Treatment with lurasidone was not associated with clinically meaningful effects on body weight, lipids, measures of glycemic control, or prolactin. CONCLUSIONS In this 6-week study, lurasidone at doses of 40 and 80 mg/day demonstrated statistically significant and clinically meaningful symptom improvement in adolescent patients with schizophrenia. Lurasidone was generally well tolerated with few effects on weight and metabolic parameters, consistent with findings in adult patients with schizophrenia.
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Affiliation(s)
- Robert Goldman
- Sunovion Pharmaceuticals, Inc., Marlborough, Massachusetts
| | - Antony Loebel
- Sunovion Pharmaceuticals, Inc., Marlborough, Massachusetts
| | | | - Ling Deng
- Sunovion Pharmaceuticals, Inc., Marlborough, Massachusetts
| | - Robert L. Findling
- Johns Hopkins University, Baltimore, Maryland
- Department of Psychiatry and Behavioral Sciences, Kennedy Krieger Institute and Johns Hopkins University, Baltimore, Maryland
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