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Chakrabarti S. Treatment Attitudes and Adherence Among Patients with Bipolar Disorder: A Systematic Review of Quantitative and Qualitative Studies. Harv Rev Psychiatry 2019; 27:290-302. [PMID: 31385812 DOI: 10.1097/hrp.0000000000000228] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Systematic reviews about treatment attitudes of patients influencing adherence in bipolar disorder (BD) are rare. METHODS A systematic review was conducted according to the PRISMA guidelines and principles of thematic synthesis. Selectively identified quantitative and qualitative studies were used to examine the attitude-adherence relationship in BD, the types and correlates of treatment attitudes, and the impact of psychosocial interventions on attitudes. RESULTS The final list of 163 articles included 114 observational reports (incorporating 21 psychosocial intervention trials), 45 qualitative/descriptive studies, and 4 patient surveys. A positive association between treatment attitudes and adherence was found in most quantitative and qualitative studies, though the strength of the relationship was unclear. Thematic analysis of qualitative studies suggested that patient attitudes influencing adherence were based on perceived advantages and disadvantages of treatment. The principal correlates of patients' attitudes were family attitudes, the clinician-patient alliance, social support, and patients' knowledge of BD. Though negative attitudes such as denial, concerns about adverse treatment consequences, and stigmatizing effects of treatment were common, many patients believed treatment to be beneficial and necessary. The limited data on the effect of psychosocial interventions indicated that treatments selectively targeting attitudes enhanced adherence. LIMITATIONS The studies were heterogeneous in design; the quality was uneven (fair to poor); and the risk of bias moderate to high. CONCLUSIONS Despite these flaws, awareness of the existing evidence on the attitude-adherence association and other aspects of treatment attitudes in BD can help in efforts to address nonadherence in BD.
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Affiliation(s)
- Subho Chakrabarti
- From the Department of Psychiatry, Postgraduate Institute of Medical Education & Research (PGIMER), Chandigarh (India)
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2
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The identification of biomarkers predicting acute and maintenance lithium treatment response in bipolar disorder: A plea for further research attention. Psychiatry Res 2018; 269:658-672. [PMID: 30216918 DOI: 10.1016/j.psychres.2018.08.034] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Revised: 06/19/2018] [Accepted: 08/13/2018] [Indexed: 12/13/2022]
Abstract
The prediction of acute and maintenance lithium treatment response carries major clinical and neurobiological implications, warranting systematic review. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) compliant review searched major electronic databases from inception until December 2017 for studies documenting a clinical diagnosis of bipolar disorder (BD) made according to the mainstream diagnostic manuals and confirmed by a structured interview. Eligible studies allowed a quantitative comparison of endpoint vs baseline mean values of a given biomarker, regardless of the mood phase of patients with BD, and the disorder was assessed for severity using validated rating tool(s). Owing to the purposely applied stringent selection criteria, 16 acute and 12 maintenance studies could be included. The anticipated publication bias limited the chances of reportable generalizable findings, hindering a side-by-side comparison of different records across varying biomarkers and subsequent meta-analyses. The PRISMA approach was nonetheless preferred; it aimed at enhancing the homogeneity of the included results and minimizing the chances of "apples and oranges" with respect to the present research theme. The present critical review confirms the need for future research to specifically assess either pretreatment and/or posttreatment putative biomarkers of patients with BD and treated with lithium.
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Wingård L, Taipale H, Reutfors J, Westerlund A, Bodén R, Tiihonen J, Tanskanen A, Andersen M. Initiation and long-term use of benzodiazepines and Z-drugs in bipolar disorder. Bipolar Disord 2018; 20:634-646. [PMID: 29450954 DOI: 10.1111/bdi.12626] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVES Increasing evidence points to the harmful effects of long-term benzodiazepine treatment. Our objective was to study the incidence of, and predictors for, long-term use of benzodiazepines and Z-drugs in bipolar disorder. METHODS We conducted a population-based cohort study, using data from Swedish national registers. Swedish residents aged 18-75 years with a recorded diagnosis of bipolar disorder or mania between July 2006 and December 2012, and no history of benzodiazepine/Z-drug use in the past year, were included. Patients were followed for 1 year with regard to prescription fills of benzodiazepines/Z-drugs. Initiators were followed for another year during which continuous use for >6 months was defined as "long-term". Patient and prescription characteristics were investigated as potential predictors for long-term use in multivariate logistic regression models. RESULTS Out of the 21 883 patients included, 29% started benzodiazepine/Z-drug treatment, of whom one in five became long-term users. Patients who were prescribed clonazepam or alprazolam had high odds for subsequent long-term use (adjusted odds ratios [aORs] 3.78 [95% confidence interval (CI) 2.24-6.38] and 2.03 [95% CI 1.30-3.18], respectively), compared to those prescribed diazepam. Polytherapy with benzodiazepines/Z-drugs also predicted long-term use (aOR 2.46, 95% CI 1.79-3.38), as did age ≥60 years (aOR 1.93, 95% CI 1.46-2.53, compared to age <30 years), and concomitant treatment with psychostimulants (aOR 1.78, 95% CI 1.33-2.39). CONCLUSIONS The incidence of subsequent long-term use among bipolar benzodiazepine initiators is high. Patients on clonazepam, alprazolam or benzodiazepine/Z-drug polytherapy have the highest risk of becoming long-term users, suggesting that these treatments should be used restrictively.
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Affiliation(s)
- Louise Wingård
- Centre for Pharmacoepidemiology (CPE), Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Heidi Taipale
- Centre for Psychiatric Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.,Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, Kuopio, Finland.,School of Pharmacy, University of Eastern Finland, Kuopio, Finland
| | - Johan Reutfors
- Centre for Pharmacoepidemiology (CPE), Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Anna Westerlund
- Centre for Pharmacoepidemiology (CPE), Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Robert Bodén
- Centre for Pharmacoepidemiology (CPE), Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.,Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden
| | - Jari Tiihonen
- Centre for Psychiatric Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.,Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, Kuopio, Finland
| | - Antti Tanskanen
- Centre for Psychiatric Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.,Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, Kuopio, Finland
| | - Morten Andersen
- Centre for Pharmacoepidemiology (CPE), Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.,Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,Research Unit of General Practice, University of Southern Denmark, Odense, Denmark
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Sportiche S, Geoffroy PA, Brichant-Petitjean C, Gard S, Khan JP, Azorin JM, Henry C, Leboyer M, Etain B, Scott J, Bellivier F. Clinical factors associated with lithium response in bipolar disorders. Aust N Z J Psychiatry 2017; 51:524-530. [PMID: 27557821 DOI: 10.1177/0004867416664794] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Bipolar disorder is a common chronic illness characterized by high levels of morbidity and all-cause mortality. Lithium is one of the gold standard mood stabilizer treatments, but the identification of good, partial and non-responders in clinical settings is inconsistent. METHODS We used an established rating scale (the Alda scale) to classify the degree of lithium response (good response, partial response, non-response) in a large, multicentre clinically representative sample of well-characterized cases of bipolar disorders I and II. Next, we examined previously reported clinical predictors of response to determine which factors significantly differentiated between the three response groups. RESULTS Of 754 cases, 300 received lithium, for at least 6 months, as a treatment for bipolar disorder (40%). Of these cases, 17% were classified as good response, 52% as partial response and 31% as non-response. Lifetime history of mixed episodes ( p = 0.017) and alcohol use disorders ( p = 0.015) both occurred in >20% of partial response and non-response groups but <10% of good response cases. Family history of bipolar disorder I was of borderline statistical significance, being more frequent in the good response group (38%) compared with the non-response group (18%). There was a trend ( p = 0.06) for bipolar disorder II to be associated with non-response. CONCLUSIONS Only three factors previously identified as predictors of lithium response significantly differentiated the response groups identified in our sample. Interestingly, these factors have all been found to co-occur more often than expected by chance, and it can be hypothesized that they may represent a shared underlying factor or dimension. Further prospective studies of predictors and the performance of the Alda scale are recommended.
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Affiliation(s)
- Sarah Sportiche
- 1 Inserm, U1144, Paris, France.,2 AP-HP, GH Saint-Louis - Lariboisière - F. Widal, Pôle de Psychiatrie et de Médecine Addictologique, Paris, France.,3 Fondation FondaMental, Créteil, France
| | - Pierre Alexis Geoffroy
- 1 Inserm, U1144, Paris, France.,2 AP-HP, GH Saint-Louis - Lariboisière - F. Widal, Pôle de Psychiatrie et de Médecine Addictologique, Paris, France.,3 Fondation FondaMental, Créteil, France.,4 Université Paris Diderot and Sorbonne Paris Cité, UMR-S 1144, Paris, France.,5 Université Paris Descartes, UMR-S 1144, Paris, France
| | - Clara Brichant-Petitjean
- 1 Inserm, U1144, Paris, France.,2 AP-HP, GH Saint-Louis - Lariboisière - F. Widal, Pôle de Psychiatrie et de Médecine Addictologique, Paris, France.,3 Fondation FondaMental, Créteil, France
| | - Sebastien Gard
- 3 Fondation FondaMental, Créteil, France.,6 Hôpital Charles Perrens, Centre Expert Bipolaire, Pôle de Psychiatrie Générale Universitaire, Bordeaux, France
| | - Jean-Pierre Khan
- 3 Fondation FondaMental, Créteil, France.,7 Service de Psychiatrie et Psychologie Clinique, CHU de Nancy, Centre Psychothérapique de Nancy-Laxou, Nancy, France.,8 Université de Lorraine, Nancy, France
| | - Jean-Michel Azorin
- 3 Fondation FondaMental, Créteil, France.,9 Pôle de psychiatrie, Hôpital Sainte Marguerite, Assistance Publique Hôpitaux de Marseille, Marseille, France.,10 EA 3279-Self-perceived Health Assessment Research Unit, School of Medicine, Timone University, Marseille, France
| | - Chantal Henry
- 3 Fondation FondaMental, Créteil, France.,11 Inserm, U955, Equipe de psychiatrie génétique et Université Paris Est, Faculté de médecine et AP-HP, Pôle de psychiatrie, Hôpitaux Universitaires Henri Mondor, Créteil, France.,12 Institut Pasteur, Unité Perception et Mémoire, Paris, France
| | - Marion Leboyer
- 3 Fondation FondaMental, Créteil, France.,11 Inserm, U955, Equipe de psychiatrie génétique et Université Paris Est, Faculté de médecine et AP-HP, Pôle de psychiatrie, Hôpitaux Universitaires Henri Mondor, Créteil, France
| | - Bruno Etain
- 1 Inserm, U1144, Paris, France.,2 AP-HP, GH Saint-Louis - Lariboisière - F. Widal, Pôle de Psychiatrie et de Médecine Addictologique, Paris, France.,3 Fondation FondaMental, Créteil, France.,4 Université Paris Diderot and Sorbonne Paris Cité, UMR-S 1144, Paris, France
| | - Jan Scott
- 13 Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.,14 Centre for Affective Disorders, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), London, UK
| | - Frank Bellivier
- 1 Inserm, U1144, Paris, France.,2 AP-HP, GH Saint-Louis - Lariboisière - F. Widal, Pôle de Psychiatrie et de Médecine Addictologique, Paris, France.,3 Fondation FondaMental, Créteil, France.,4 Université Paris Diderot and Sorbonne Paris Cité, UMR-S 1144, Paris, France
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Aagaard J, Foldager L, Makki A, Hansen V, Müller-Nielsen K. The efficacy of psychoeducation on recurrent depression: a randomized trial with a 2-year follow-up. Nord J Psychiatry 2017; 71:223-229. [PMID: 27997274 DOI: 10.1080/08039488.2016.1266385] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
BACKGROUND The efficacy of psychoeducation is well documented in the treatment of relapse prevention of schizophrenia, and recently also in bipolar disorder; however, for recurrent depression only few controlled studies focusing on the efficacy of psychoeducation have been conducted. AIMS This randomized study tests the efficacy of treatment-as-usual supplemented with a psychoeducative programme for patients with recurrent depression, treated at Community Mental Health Centres (CMHC) in Denmark. The primary outcome measurements concern was decline in consumption of psychiatric inpatient services and decline in Beck's Depression Inventory (BDI). METHODS Eighty patients were randomized, either to the psychoeducative programme (consisting of eight sessions, each of 2 hours duration) and 2-year outpatient follow-up (42 cases), or only to 2-year outpatient follow-up (38 controls). The patients were monitored during 2 years after randomization. Data were collected from interviews including BDI, drug treatment and social measurements, and register data concerning use of psychiatric services. RESULTS At 2-year follow-up, a significant reduction in the consumption of psychiatric inpatient services and in BDI was found; however, it was uniform for case and control patients. Drop-out/non-compliance was significantly more frequent among patients randomized to the control group. Furthermore, during follow-up the case group got a significant stronger attachment to the Labour market than the control group. CONCLUSIONS The primary hypothesis could not be confirmed. Secondary outcome measurements concerning drop-out/non-compliance and attachment to the Labour market were significantly in favour of cases.
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Affiliation(s)
- Jørgen Aagaard
- a Unit for Psychiatric Research and Department M, Aarhus University Hospital , Risskov , Denmark.,b Aalborg University Hospital, Psychiatric Hospital , Unit for Psychiatric Research and Clinic South , Aalborg , Denmark
| | - Leslie Foldager
- c Department of Animal Science , Aarhus University , Aarhus , Denmark.,d Bioinformatics Research Centre, Aarhus University , Aarhus , Denmark
| | - Ahmad Makki
- b Aalborg University Hospital, Psychiatric Hospital , Unit for Psychiatric Research and Clinic South , Aalborg , Denmark
| | - Vibeke Hansen
- a Unit for Psychiatric Research and Department M, Aarhus University Hospital , Risskov , Denmark
| | - Klaus Müller-Nielsen
- e Department for Child and Youth Psychiatry , Kolding Hospital , Kolding , Denmark
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Scott J, Geoffroy PA, Sportiche S, Brichant-Petit-Jean C, Gard S, Kahn JP, Azorin JM, Henry C, Etain B, Bellivier F. Cross-validation of clinical characteristics and treatment patterns associated with phenotypes for lithium response defined by the Alda scale. J Affect Disord 2017; 208:62-67. [PMID: 27750061 DOI: 10.1016/j.jad.2016.08.069] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2016] [Revised: 07/31/2016] [Accepted: 08/28/2016] [Indexed: 11/26/2022]
Abstract
BACKGROUND It is increasingly recognised that reliable and valid assessments of lithium response are needed in order to target more efficiently the use of this medication in bipolar disorders (BD) and to identify genotypes, endophenotypes and biomarkers of response. METHODS In a large, multi-centre, clinically representative sample of 300 cases of BD, we assess external clinical validators of lithium response phenotypes as defined using three different recommended approaches to scoring the Alda lithium response scale. The scale comprises an A scale (rating lithium response) and a B scale (assessing confounders). RESULTS Analysis of the two continuous scoring methods (A scale score minus the B scale score, or A scale score in those with a low B scale score) demonstrated that 21-23% of the explained variance in lithium response was accounted for by a positive family history of BD I and the early introduction of lithium. Categorical definitions of response suggest poor response is also associated with a positive history of alcohol and/or substance use comorbidities. High B scale scores were significantly associated with longer duration of illness prior to receiving lithium and the presence of psychotic symptoms. LIMITATIONS The original sample was not recruited specifically to study lithium response. The Alda scale is designed to assess response retrospectively. CONCLUSIONS This cross-validation study identifies different clinical phenotypes of lithium response when defined by continuous or categorical measures. Future clinical, genetic and biomarker studies should report both the findings and the method employed to assess lithium response according to the Alda scale.
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Affiliation(s)
- Jan Scott
- Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom; Centre for Affective Disorders, Institute of Psychiatry, London, United Kingdom.
| | - Pierre Alexis Geoffroy
- Inserm, U1144, Paris F-75006, France; AP-HP, GH Saint-Louis - Lariboisière - F. Widal, Pôle de Psychiatrie et de Médecine Addictologique, 75475 Paris, France; Fondation FondaMental, Créteil 94000, France; Université Paris Diderot, Sorbonne Paris Cité, UMR-S 1144, Paris F-75013, France
| | - Sarah Sportiche
- Inserm, U1144, Paris F-75006, France; AP-HP, GH Saint-Louis - Lariboisière - F. Widal, Pôle de Psychiatrie et de Médecine Addictologique, 75475 Paris, France; Fondation FondaMental, Créteil 94000, France
| | - Clara Brichant-Petit-Jean
- Inserm, U1144, Paris F-75006, France; AP-HP, GH Saint-Louis - Lariboisière - F. Widal, Pôle de Psychiatrie et de Médecine Addictologique, 75475 Paris, France; Fondation FondaMental, Créteil 94000, France
| | - Sebastien Gard
- Fondation FondaMental, Créteil 94000, France; Hôpital Charles Perrens, Centre Expert Trouble Bipolaire, Service de Psychiatrie Adulte, Pôle 3-4-7, Bordeaux, France
| | - Jean-Pierre Kahn
- Fondation FondaMental, Créteil 94000, France; Service de Psychiatrie et Psychologie Clinique, CHU de Nancy, Hôpitaux de Brabois, Vandoeuvre Les Nancy, France; Université de Lorraine, France
| | - Jean-Michel Azorin
- Fondation FondaMental, Créteil 94000, France; Pôle de psychiatrie, Hôpital Sainte Marguerite, Assistance Publique Hôpitaux de Marseille, France; EA 3279-Self-perceived Health Assessment Research Unit, School of Medicine, Timone University, Marseille, France
| | - Chantal Henry
- Institut Pasteur, Unit of Perception and Memory, F-75015 Paris, France; Pôle de Psychiatrie, Hôpital Albert Chenevier, 40 rue de Mesly, 94000 Créteil, France
| | - Bruno Etain
- Centre for Affective Disorders, Institute of Psychiatry, London, United Kingdom; Inserm, U1144, Paris F-75006, France; AP-HP, GH Saint-Louis - Lariboisière - F. Widal, Pôle de Psychiatrie et de Médecine Addictologique, 75475 Paris, France; Fondation FondaMental, Créteil 94000, France; Université Paris Diderot, Sorbonne Paris Cité, UMR-S 1144, Paris F-75013, France
| | - Frank Bellivier
- Inserm, U1144, Paris F-75006, France; AP-HP, GH Saint-Louis - Lariboisière - F. Widal, Pôle de Psychiatrie et de Médecine Addictologique, 75475 Paris, France; Fondation FondaMental, Créteil 94000, France; Université Paris Diderot, Sorbonne Paris Cité, UMR-S 1144, Paris F-75013, France
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Chakrabarti S. Medication non-adherence in bipolar disorder: Review of rates, demographic and clinical predictors. World J Meta-Anal 2017; 5:103. [DOI: 10.13105/wjma.v5.i4.103] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2017] [Revised: 04/24/2017] [Accepted: 06/13/2017] [Indexed: 02/06/2023] Open
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Chakrabarti S. Treatment-adherence in bipolar disorder: A patient-centred approach. World J Psychiatry 2016; 6:399-409. [PMID: 28078204 PMCID: PMC5183992 DOI: 10.5498/wjp.v6.i4.399] [Citation(s) in RCA: 74] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2016] [Revised: 10/31/2016] [Accepted: 11/22/2016] [Indexed: 02/05/2023] Open
Abstract
About half of the patients diagnosed with bipolar disorder (BD) become non-adherent during long-term treatment, a rate largely similar to other chronic illnesses and one that has remained unchanged over the years. Non-adherence in BD is a complex phenomenon determined by a multitude of influences. However, there is considerable uncertainty about the key determinants of non-adherence in BD. Initial research on non-adherence in BD mostly limited itself to examining demographic, clinical and medication-related factors impacting adherence. However, because of inconsistent results and failure of these studies to address the complexities of adherence behaviour, demographic and illness-related factors were alone unable to explain or predict non-adherence in BD. This prompted a shift to a more patient-centred approach of viewing non-adherence. The central element of this approach includes an emphasis on patients’ decisions regarding their own treatment based on their personal beliefs, life circumstances and their perceptions of benefits and disadvantages of treatment. Patients’ decision-making processes are influenced by the nature of their relationship with clinicians and the health-care system and by people in their immediate environment. The primacy of the patient’s perspective on non-adherence is in keeping with the current theoretical models and concordance-based approaches to adherence behaviour in BD. Research over the past two decades has further endorsed the critical role of patients’ attitudes and beliefs regarding medications, the importance of a collaborative treatment-alliance, the influence of the family, and the significance of other patient-related factors such as knowledge, stigma, patient satisfaction and access to treatment in determining non-adherence in BD. Though simply moving from an illness-centred to a patient-centred approach is unlikely to solve the problem of non-adherence in BD, such an approach is more likely to lead to a better understanding of non-adherence and more likely to yield effective solutions to tackle this common and distressing problem afflicting patients with BD.
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Kessing LV. Treatment Options in Bipolar Disorder: Lessons from Population-Based Registers with Focus on Lithium. ACTA ACUST UNITED AC 2015. [DOI: 10.1007/s40501-015-0047-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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Smith EG, Austin KL, Kim HM, Eisen SV, Kilbourne AM, Miller DR, Zivin K, Hannemann C, Sauer BC, Valenstein M. Mortality associated with lithium and valproate treatment of US Veterans Health Administration patients with mental disorders. Br J Psychiatry 2015; 207:55-63. [PMID: 25953891 DOI: 10.1192/bjp.bp.113.138685] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2013] [Accepted: 09/26/2014] [Indexed: 11/23/2022]
Abstract
BackgroundThe mood stabilisers lithium and valproate might plausibly have differing associations with mortality because of differing effects on mental health and various physiological indicators.AimsTo assess associations between lithium, valproate and non-suicide mortality.MethodIntention-to-treat, propensity score-matched cohort study.ResultsLithium was associated with significantly reduced non-suicide mortality in the intent-to-treat cohort over 0-90 days (hazard ratio (HR) = 0.67, 95% CI 0.51-0.87) but not longer. In secondary analyses, a sizeable reduction in mortality was observed during active treatment with lithium across all time periods studied (for example 365-day HR = 0.62, 95% CI 0.45-0.84), but significantly increased risks were observed among patients discontinuing lithium by 180 days (HR = 1.54, 95% CI 1.01-2.37).ConclusionsPatients initiating lithium had lower non-suicide mortality over 0-90 days than patients initiating valproate and consistently lower non-suicide mortality among patients maintaining treatment, but elevated risk among patients discontinuing treatment by 180 days. Although residual confounding or selection effects cannot be excluded, this study suggests potential benefits to enhancing lithium treatment persistence and the monitoring of patients discontinuing lithium. There is a need for further research.
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Affiliation(s)
- Eric G Smith
- Eric G. Smith, MD, PhD, MPH, VA Center for Healthcare Organization and Implementation Research, Department of Veterans Affairs VA Medical Center, Bedford, Massachusetts, and Departments of Psychiatry and Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, Massachusetts; Karen L. Austin, MPH, Serious Mental Illness Treatment Resource and Evaluation Center, Department of Veterans Affairs, Ann Arbor, Michigan; Hyungjin Myra Kim, ScD, VA Center for Clinical Management Research, Department of Veterans Affairs VA Medical Center, Ann Arbor, Michigan, and Center for Statistical Consultation and Research, University of Michigan, Ann Arbor, Michigan; Susan V. Eisen, PhD, VA Center for Healthcare Organization and Implementation Research, Department of Veterans Affairs VA Medical Center, Bedford, Massachusetts, and Department of Health Policy and Management, Boston University School of Public Health, Boston, Massachusetts; Amy M. Kilbourne, PhD, MPH, Quality Enhancement Research Initiative (QUERI), Department of Veterans Affairs, Washington DC, and Department of Psychiatry, University of Michigan Medical School, Ann Arbor, Michigan; Donald R. Miller, ScD, VA Center for Healthcare Organization and Implementation Research, Department of Veterans Affairs VA Medical Center, Bedford, Massachusetts; Kara Zivin, PhD, VA Center for Clinical Management Research, Department of Veterans Affairs VA Medical Center, Ann Arbor, Michigan, and Department of Psychiatry, University of Michigan Medical School, Ann Arbor, Michigan; Claire Hannemann, MPH, Serious Mental Illness Treatment Resource and Evaluation Center, Department of Veterans Affairs, Ann Arbor, Michigan; Brian C. Sauer, PhD, VA IDEAS2.0 Center and Health Services Research and Development Researcher Enhancement Award Program, Department of Veterans Affairs, Salt Lake City, Utah, and Department of Internal Medicine, University of Utah, Salt Lake City, Utah; Marcia Valenstein, MD, MS, VA Center for Clin
| | - Karen L Austin
- Eric G. Smith, MD, PhD, MPH, VA Center for Healthcare Organization and Implementation Research, Department of Veterans Affairs VA Medical Center, Bedford, Massachusetts, and Departments of Psychiatry and Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, Massachusetts; Karen L. Austin, MPH, Serious Mental Illness Treatment Resource and Evaluation Center, Department of Veterans Affairs, Ann Arbor, Michigan; Hyungjin Myra Kim, ScD, VA Center for Clinical Management Research, Department of Veterans Affairs VA Medical Center, Ann Arbor, Michigan, and Center for Statistical Consultation and Research, University of Michigan, Ann Arbor, Michigan; Susan V. Eisen, PhD, VA Center for Healthcare Organization and Implementation Research, Department of Veterans Affairs VA Medical Center, Bedford, Massachusetts, and Department of Health Policy and Management, Boston University School of Public Health, Boston, Massachusetts; Amy M. Kilbourne, PhD, MPH, Quality Enhancement Research Initiative (QUERI), Department of Veterans Affairs, Washington DC, and Department of Psychiatry, University of Michigan Medical School, Ann Arbor, Michigan; Donald R. Miller, ScD, VA Center for Healthcare Organization and Implementation Research, Department of Veterans Affairs VA Medical Center, Bedford, Massachusetts; Kara Zivin, PhD, VA Center for Clinical Management Research, Department of Veterans Affairs VA Medical Center, Ann Arbor, Michigan, and Department of Psychiatry, University of Michigan Medical School, Ann Arbor, Michigan; Claire Hannemann, MPH, Serious Mental Illness Treatment Resource and Evaluation Center, Department of Veterans Affairs, Ann Arbor, Michigan; Brian C. Sauer, PhD, VA IDEAS2.0 Center and Health Services Research and Development Researcher Enhancement Award Program, Department of Veterans Affairs, Salt Lake City, Utah, and Department of Internal Medicine, University of Utah, Salt Lake City, Utah; Marcia Valenstein, MD, MS, VA Center for Clin
| | - Hyungjin Myra Kim
- Eric G. Smith, MD, PhD, MPH, VA Center for Healthcare Organization and Implementation Research, Department of Veterans Affairs VA Medical Center, Bedford, Massachusetts, and Departments of Psychiatry and Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, Massachusetts; Karen L. Austin, MPH, Serious Mental Illness Treatment Resource and Evaluation Center, Department of Veterans Affairs, Ann Arbor, Michigan; Hyungjin Myra Kim, ScD, VA Center for Clinical Management Research, Department of Veterans Affairs VA Medical Center, Ann Arbor, Michigan, and Center for Statistical Consultation and Research, University of Michigan, Ann Arbor, Michigan; Susan V. Eisen, PhD, VA Center for Healthcare Organization and Implementation Research, Department of Veterans Affairs VA Medical Center, Bedford, Massachusetts, and Department of Health Policy and Management, Boston University School of Public Health, Boston, Massachusetts; Amy M. Kilbourne, PhD, MPH, Quality Enhancement Research Initiative (QUERI), Department of Veterans Affairs, Washington DC, and Department of Psychiatry, University of Michigan Medical School, Ann Arbor, Michigan; Donald R. Miller, ScD, VA Center for Healthcare Organization and Implementation Research, Department of Veterans Affairs VA Medical Center, Bedford, Massachusetts; Kara Zivin, PhD, VA Center for Clinical Management Research, Department of Veterans Affairs VA Medical Center, Ann Arbor, Michigan, and Department of Psychiatry, University of Michigan Medical School, Ann Arbor, Michigan; Claire Hannemann, MPH, Serious Mental Illness Treatment Resource and Evaluation Center, Department of Veterans Affairs, Ann Arbor, Michigan; Brian C. Sauer, PhD, VA IDEAS2.0 Center and Health Services Research and Development Researcher Enhancement Award Program, Department of Veterans Affairs, Salt Lake City, Utah, and Department of Internal Medicine, University of Utah, Salt Lake City, Utah; Marcia Valenstein, MD, MS, VA Center for Clin
| | - Susan V Eisen
- Eric G. Smith, MD, PhD, MPH, VA Center for Healthcare Organization and Implementation Research, Department of Veterans Affairs VA Medical Center, Bedford, Massachusetts, and Departments of Psychiatry and Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, Massachusetts; Karen L. Austin, MPH, Serious Mental Illness Treatment Resource and Evaluation Center, Department of Veterans Affairs, Ann Arbor, Michigan; Hyungjin Myra Kim, ScD, VA Center for Clinical Management Research, Department of Veterans Affairs VA Medical Center, Ann Arbor, Michigan, and Center for Statistical Consultation and Research, University of Michigan, Ann Arbor, Michigan; Susan V. Eisen, PhD, VA Center for Healthcare Organization and Implementation Research, Department of Veterans Affairs VA Medical Center, Bedford, Massachusetts, and Department of Health Policy and Management, Boston University School of Public Health, Boston, Massachusetts; Amy M. Kilbourne, PhD, MPH, Quality Enhancement Research Initiative (QUERI), Department of Veterans Affairs, Washington DC, and Department of Psychiatry, University of Michigan Medical School, Ann Arbor, Michigan; Donald R. Miller, ScD, VA Center for Healthcare Organization and Implementation Research, Department of Veterans Affairs VA Medical Center, Bedford, Massachusetts; Kara Zivin, PhD, VA Center for Clinical Management Research, Department of Veterans Affairs VA Medical Center, Ann Arbor, Michigan, and Department of Psychiatry, University of Michigan Medical School, Ann Arbor, Michigan; Claire Hannemann, MPH, Serious Mental Illness Treatment Resource and Evaluation Center, Department of Veterans Affairs, Ann Arbor, Michigan; Brian C. Sauer, PhD, VA IDEAS2.0 Center and Health Services Research and Development Researcher Enhancement Award Program, Department of Veterans Affairs, Salt Lake City, Utah, and Department of Internal Medicine, University of Utah, Salt Lake City, Utah; Marcia Valenstein, MD, MS, VA Center for Clin
| | - Amy M Kilbourne
- Eric G. Smith, MD, PhD, MPH, VA Center for Healthcare Organization and Implementation Research, Department of Veterans Affairs VA Medical Center, Bedford, Massachusetts, and Departments of Psychiatry and Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, Massachusetts; Karen L. Austin, MPH, Serious Mental Illness Treatment Resource and Evaluation Center, Department of Veterans Affairs, Ann Arbor, Michigan; Hyungjin Myra Kim, ScD, VA Center for Clinical Management Research, Department of Veterans Affairs VA Medical Center, Ann Arbor, Michigan, and Center for Statistical Consultation and Research, University of Michigan, Ann Arbor, Michigan; Susan V. Eisen, PhD, VA Center for Healthcare Organization and Implementation Research, Department of Veterans Affairs VA Medical Center, Bedford, Massachusetts, and Department of Health Policy and Management, Boston University School of Public Health, Boston, Massachusetts; Amy M. Kilbourne, PhD, MPH, Quality Enhancement Research Initiative (QUERI), Department of Veterans Affairs, Washington DC, and Department of Psychiatry, University of Michigan Medical School, Ann Arbor, Michigan; Donald R. Miller, ScD, VA Center for Healthcare Organization and Implementation Research, Department of Veterans Affairs VA Medical Center, Bedford, Massachusetts; Kara Zivin, PhD, VA Center for Clinical Management Research, Department of Veterans Affairs VA Medical Center, Ann Arbor, Michigan, and Department of Psychiatry, University of Michigan Medical School, Ann Arbor, Michigan; Claire Hannemann, MPH, Serious Mental Illness Treatment Resource and Evaluation Center, Department of Veterans Affairs, Ann Arbor, Michigan; Brian C. Sauer, PhD, VA IDEAS2.0 Center and Health Services Research and Development Researcher Enhancement Award Program, Department of Veterans Affairs, Salt Lake City, Utah, and Department of Internal Medicine, University of Utah, Salt Lake City, Utah; Marcia Valenstein, MD, MS, VA Center for Clin
| | - Donald R Miller
- Eric G. Smith, MD, PhD, MPH, VA Center for Healthcare Organization and Implementation Research, Department of Veterans Affairs VA Medical Center, Bedford, Massachusetts, and Departments of Psychiatry and Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, Massachusetts; Karen L. Austin, MPH, Serious Mental Illness Treatment Resource and Evaluation Center, Department of Veterans Affairs, Ann Arbor, Michigan; Hyungjin Myra Kim, ScD, VA Center for Clinical Management Research, Department of Veterans Affairs VA Medical Center, Ann Arbor, Michigan, and Center for Statistical Consultation and Research, University of Michigan, Ann Arbor, Michigan; Susan V. Eisen, PhD, VA Center for Healthcare Organization and Implementation Research, Department of Veterans Affairs VA Medical Center, Bedford, Massachusetts, and Department of Health Policy and Management, Boston University School of Public Health, Boston, Massachusetts; Amy M. Kilbourne, PhD, MPH, Quality Enhancement Research Initiative (QUERI), Department of Veterans Affairs, Washington DC, and Department of Psychiatry, University of Michigan Medical School, Ann Arbor, Michigan; Donald R. Miller, ScD, VA Center for Healthcare Organization and Implementation Research, Department of Veterans Affairs VA Medical Center, Bedford, Massachusetts; Kara Zivin, PhD, VA Center for Clinical Management Research, Department of Veterans Affairs VA Medical Center, Ann Arbor, Michigan, and Department of Psychiatry, University of Michigan Medical School, Ann Arbor, Michigan; Claire Hannemann, MPH, Serious Mental Illness Treatment Resource and Evaluation Center, Department of Veterans Affairs, Ann Arbor, Michigan; Brian C. Sauer, PhD, VA IDEAS2.0 Center and Health Services Research and Development Researcher Enhancement Award Program, Department of Veterans Affairs, Salt Lake City, Utah, and Department of Internal Medicine, University of Utah, Salt Lake City, Utah; Marcia Valenstein, MD, MS, VA Center for Clin
| | - Kara Zivin
- Eric G. Smith, MD, PhD, MPH, VA Center for Healthcare Organization and Implementation Research, Department of Veterans Affairs VA Medical Center, Bedford, Massachusetts, and Departments of Psychiatry and Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, Massachusetts; Karen L. Austin, MPH, Serious Mental Illness Treatment Resource and Evaluation Center, Department of Veterans Affairs, Ann Arbor, Michigan; Hyungjin Myra Kim, ScD, VA Center for Clinical Management Research, Department of Veterans Affairs VA Medical Center, Ann Arbor, Michigan, and Center for Statistical Consultation and Research, University of Michigan, Ann Arbor, Michigan; Susan V. Eisen, PhD, VA Center for Healthcare Organization and Implementation Research, Department of Veterans Affairs VA Medical Center, Bedford, Massachusetts, and Department of Health Policy and Management, Boston University School of Public Health, Boston, Massachusetts; Amy M. Kilbourne, PhD, MPH, Quality Enhancement Research Initiative (QUERI), Department of Veterans Affairs, Washington DC, and Department of Psychiatry, University of Michigan Medical School, Ann Arbor, Michigan; Donald R. Miller, ScD, VA Center for Healthcare Organization and Implementation Research, Department of Veterans Affairs VA Medical Center, Bedford, Massachusetts; Kara Zivin, PhD, VA Center for Clinical Management Research, Department of Veterans Affairs VA Medical Center, Ann Arbor, Michigan, and Department of Psychiatry, University of Michigan Medical School, Ann Arbor, Michigan; Claire Hannemann, MPH, Serious Mental Illness Treatment Resource and Evaluation Center, Department of Veterans Affairs, Ann Arbor, Michigan; Brian C. Sauer, PhD, VA IDEAS2.0 Center and Health Services Research and Development Researcher Enhancement Award Program, Department of Veterans Affairs, Salt Lake City, Utah, and Department of Internal Medicine, University of Utah, Salt Lake City, Utah; Marcia Valenstein, MD, MS, VA Center for Clin
| | - Claire Hannemann
- Eric G. Smith, MD, PhD, MPH, VA Center for Healthcare Organization and Implementation Research, Department of Veterans Affairs VA Medical Center, Bedford, Massachusetts, and Departments of Psychiatry and Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, Massachusetts; Karen L. Austin, MPH, Serious Mental Illness Treatment Resource and Evaluation Center, Department of Veterans Affairs, Ann Arbor, Michigan; Hyungjin Myra Kim, ScD, VA Center for Clinical Management Research, Department of Veterans Affairs VA Medical Center, Ann Arbor, Michigan, and Center for Statistical Consultation and Research, University of Michigan, Ann Arbor, Michigan; Susan V. Eisen, PhD, VA Center for Healthcare Organization and Implementation Research, Department of Veterans Affairs VA Medical Center, Bedford, Massachusetts, and Department of Health Policy and Management, Boston University School of Public Health, Boston, Massachusetts; Amy M. Kilbourne, PhD, MPH, Quality Enhancement Research Initiative (QUERI), Department of Veterans Affairs, Washington DC, and Department of Psychiatry, University of Michigan Medical School, Ann Arbor, Michigan; Donald R. Miller, ScD, VA Center for Healthcare Organization and Implementation Research, Department of Veterans Affairs VA Medical Center, Bedford, Massachusetts; Kara Zivin, PhD, VA Center for Clinical Management Research, Department of Veterans Affairs VA Medical Center, Ann Arbor, Michigan, and Department of Psychiatry, University of Michigan Medical School, Ann Arbor, Michigan; Claire Hannemann, MPH, Serious Mental Illness Treatment Resource and Evaluation Center, Department of Veterans Affairs, Ann Arbor, Michigan; Brian C. Sauer, PhD, VA IDEAS2.0 Center and Health Services Research and Development Researcher Enhancement Award Program, Department of Veterans Affairs, Salt Lake City, Utah, and Department of Internal Medicine, University of Utah, Salt Lake City, Utah; Marcia Valenstein, MD, MS, VA Center for Clin
| | - Brian C Sauer
- Eric G. Smith, MD, PhD, MPH, VA Center for Healthcare Organization and Implementation Research, Department of Veterans Affairs VA Medical Center, Bedford, Massachusetts, and Departments of Psychiatry and Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, Massachusetts; Karen L. Austin, MPH, Serious Mental Illness Treatment Resource and Evaluation Center, Department of Veterans Affairs, Ann Arbor, Michigan; Hyungjin Myra Kim, ScD, VA Center for Clinical Management Research, Department of Veterans Affairs VA Medical Center, Ann Arbor, Michigan, and Center for Statistical Consultation and Research, University of Michigan, Ann Arbor, Michigan; Susan V. Eisen, PhD, VA Center for Healthcare Organization and Implementation Research, Department of Veterans Affairs VA Medical Center, Bedford, Massachusetts, and Department of Health Policy and Management, Boston University School of Public Health, Boston, Massachusetts; Amy M. Kilbourne, PhD, MPH, Quality Enhancement Research Initiative (QUERI), Department of Veterans Affairs, Washington DC, and Department of Psychiatry, University of Michigan Medical School, Ann Arbor, Michigan; Donald R. Miller, ScD, VA Center for Healthcare Organization and Implementation Research, Department of Veterans Affairs VA Medical Center, Bedford, Massachusetts; Kara Zivin, PhD, VA Center for Clinical Management Research, Department of Veterans Affairs VA Medical Center, Ann Arbor, Michigan, and Department of Psychiatry, University of Michigan Medical School, Ann Arbor, Michigan; Claire Hannemann, MPH, Serious Mental Illness Treatment Resource and Evaluation Center, Department of Veterans Affairs, Ann Arbor, Michigan; Brian C. Sauer, PhD, VA IDEAS2.0 Center and Health Services Research and Development Researcher Enhancement Award Program, Department of Veterans Affairs, Salt Lake City, Utah, and Department of Internal Medicine, University of Utah, Salt Lake City, Utah; Marcia Valenstein, MD, MS, VA Center for Clin
| | - Marcia Valenstein
- Eric G. Smith, MD, PhD, MPH, VA Center for Healthcare Organization and Implementation Research, Department of Veterans Affairs VA Medical Center, Bedford, Massachusetts, and Departments of Psychiatry and Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, Massachusetts; Karen L. Austin, MPH, Serious Mental Illness Treatment Resource and Evaluation Center, Department of Veterans Affairs, Ann Arbor, Michigan; Hyungjin Myra Kim, ScD, VA Center for Clinical Management Research, Department of Veterans Affairs VA Medical Center, Ann Arbor, Michigan, and Center for Statistical Consultation and Research, University of Michigan, Ann Arbor, Michigan; Susan V. Eisen, PhD, VA Center for Healthcare Organization and Implementation Research, Department of Veterans Affairs VA Medical Center, Bedford, Massachusetts, and Department of Health Policy and Management, Boston University School of Public Health, Boston, Massachusetts; Amy M. Kilbourne, PhD, MPH, Quality Enhancement Research Initiative (QUERI), Department of Veterans Affairs, Washington DC, and Department of Psychiatry, University of Michigan Medical School, Ann Arbor, Michigan; Donald R. Miller, ScD, VA Center for Healthcare Organization and Implementation Research, Department of Veterans Affairs VA Medical Center, Bedford, Massachusetts; Kara Zivin, PhD, VA Center for Clinical Management Research, Department of Veterans Affairs VA Medical Center, Ann Arbor, Michigan, and Department of Psychiatry, University of Michigan Medical School, Ann Arbor, Michigan; Claire Hannemann, MPH, Serious Mental Illness Treatment Resource and Evaluation Center, Department of Veterans Affairs, Ann Arbor, Michigan; Brian C. Sauer, PhD, VA IDEAS2.0 Center and Health Services Research and Development Researcher Enhancement Award Program, Department of Veterans Affairs, Salt Lake City, Utah, and Department of Internal Medicine, University of Utah, Salt Lake City, Utah; Marcia Valenstein, MD, MS, VA Center for Clin
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Scheen L, Brandt L, Bodén R, Tiihonen J, Andersen M, Kieler H, Reutfors J. Predictors for initiation of pharmacological prophylaxis in patients with newly diagnosed bipolar disorder--A nationwide cohort study. J Affect Disord 2015; 172:204-10. [PMID: 25451419 DOI: 10.1016/j.jad.2014.09.044] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2014] [Revised: 09/24/2014] [Accepted: 09/25/2014] [Indexed: 12/14/2022]
Abstract
BACKGROUND Treatment guidelines state that all patients with bipolar disorder should use pharmacological prophylaxis; however the actual use of prophylactic drugs after bipolar disorder diagnosis is unknown. Our aim was to assess the use of, and predictors for, pharmacoprophylaxis in newly diagnosed bipolar disorder patients. METHODS Data from three Swedish nationwide registers were obtained. We identified patients aged 18-75 with a first time diagnosis of bipolar disorder between 2006 and 2012 (n=31,770) and reviewed subsequent mood-stabilizer and antipsychotic prescription fills. In multivariable Cox regression models, we studied demographic and illness related factors as predictors of prescription fills after diagnosis. RESULTS In total, 72.2% (95% confidence interval [CI] 71.7-72.7%) of the patients filled a prescription of a prophylactic drug within 3 months after diagnosis. Pharmacological prophylaxis was mainly associated with a longer duration of hospitalization at bipolar disorder diagnosis (adjusted hazard ratio [AHR] 2.18; CI 2.02-2.35 for a hospitalization of ≥28 days compared to <7 days) and previous use of any mood-stabilizer or antipsychotic (inpatients: AHR 1.24; CI 1.17-1.31 and outpatients: AHR 1.78; CI 1.73-1.84). LIMITATIONS We had no information on drug prescriptions that were never filled. CONCLUSIONS The proportion of newly diagnosed bipolar disorder patients without pharmacological prophylaxis is substantial. Patients who are naïve to mood-stabilizers and antipsychotics and are hospitalized for a brief period at diagnosis are the ones least likely to initiate pharmacoprophylaxis, suggesting that this group deserves attention in order to improve the long term prognosis.
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Affiliation(s)
- Louise Scheen
- Centre for Pharmacoepidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
| | - Lena Brandt
- Centre for Pharmacoepidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - Robert Bodén
- Centre for Pharmacoepidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden
| | - Jari Tiihonen
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland
| | - Morten Andersen
- Centre for Pharmacoepidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - Helle Kieler
- Centre for Pharmacoepidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - Johan Reutfors
- Centre for Pharmacoepidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
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Brown ES, Davila D, Nakamura A, Carmody TJ, Rush AJ, Lo A, Holmes T, Adinoff B, Caetano R, Swann AC, Sunderajan P, Bret ME. A randomized, double-blind, placebo-controlled trial of quetiapine in patients with bipolar disorder, mixed or depressed phase, and alcohol dependence. Alcohol Clin Exp Res 2014; 38:2113-8. [PMID: 24976394 DOI: 10.1111/acer.12445] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2013] [Accepted: 04/02/2014] [Indexed: 12/16/2022]
Abstract
BACKGROUND Alcohol dependence is common in bipolar disorder (BPD) and associated with treatment nonadherence, violence, and hospitalization. Quetiapine is a standard treatment for BPD. We previously reported improvement in depressive symptoms, but not alcohol use, with quetiapine in BPD and alcohol dependence. However, mean alcohol use was low and a larger effect size on alcohol-related measures was observed in those with higher levels of alcohol consumption. In this study, efficacy of quetiapine in patients with BPD and alcohol dependence was examined in patients with higher mean baseline alcohol use than in the prior study. METHODS Ninety outpatients with bipolar I or II disorders, depressed or mixed mood state, and current alcohol dependence were randomized to 12 weeks of sustained release quetiapine (to 600 mg/d) add-on therapy or placebo. Drinking was quantified using the Timeline Follow Back method. Additional assessment tools included the Hamilton Rating Scale for Depression, Inventory of Depressive Symptomatology-Self-Report, Young Mania Rating Scale, Penn Alcohol Craving Scale, liver enzymes, and side effects. Alcohol use and mood were analyzed using a declining-effects random-regression model. RESULTS Baseline and demographic characteristics in the 2 groups were similar. No significant between-group differences were observed on the primary outcome measure of drinks per day or other alcohol-related or mood measures (p > 0.05). Overall side effect burden, glucose, and cholesterol were similar in the 2 groups. However, a significant weight increase was observed with quetiapine at week 6 (+2.9 lbs [SE 1.4] quetiapine vs. -2.0 lbs [SE 1.4], p = 0.03), but not at week 12. Scores on the Barnes Akathisia Scale increased significantly more (p = 0.04) with quetiapine (+0.40 [SE 0.3]) than placebo (-0.52 [SE 0.3]) at week 6 but not week 12. Retention (survival) in the study was similar in the groups. CONCLUSIONS Findings suggest that quetiapine does not reduce alcohol consumption in patients with BPD and alcohol dependence.
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Affiliation(s)
- E Sherwood Brown
- Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, Texas
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Abstract
AbstractObjective:Review of literature on non-compliance with medication in psychiatric patients.Method:Computer and manual search of English language literature on non-compliance with drugs, psychiatric disorder, and phenomena which may be related, such as readmission and discharge against medical advice.Results:The literature is discussed and a tentative checklist of risk factors for non-compliance is offered, as is advice on ways in which the problem may be minimised. It is noted that there is an emphasis on major mental disorders in the published literature.Conclusion:There is no stereotypical defaulter. A high index of suspicion is essential. As far as possible, the patient should be educated to share in the responsibility for treatment, and concerned relatives and others can often play a pivotal role. More research is required on compliance problems in the minor psychiatric disorders. Close liaison with the general practitioner is vital.
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A randomized, double-blind, placebo-controlled, trial of lamotrigine therapy in bipolar disorder, depressed or mixed phase and cocaine dependence. Neuropsychopharmacology 2012; 37:2347-54. [PMID: 22669171 PMCID: PMC3442350 DOI: 10.1038/npp.2012.90] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Bipolar disorder is associated with very high rates of substance dependence. Cocaine use is particularly common. However, limited data are available on the treatment of this population. A 10-week, randomized, double-blind, placebo-controlled trial of lamotrigine was conducted in 120 outpatients with bipolar disorder, depressed or mixed mood state, and cocaine dependence. Other substance use was not exclusionary. Cocaine use was quantified weekly by urine drug screens and participant report using the timeline follow-back method. Mood was assessed with the Hamilton rating scale for depression, quick inventory of depressive symptomatology self-report, and young mania rating scale. Cocaine craving was assessed with the cocaine-craving questionnaire. Data were analyzed using a random regression analysis that used all available data from participants with at least one postbaseline assessment (n=112). Lamotrigine and placebo groups were similar demographically (age 45.1±7.3 vs 43.5±10.0 years, 41.8% vs 38.6% women). Urine drug screens (primary outcome measure) and mood symptoms were not significantly different between groups. However, dollars spent on cocaine showed a significant initial (baseline to week 1, p=0.01) and by-week (weeks 1-10, p=0.05) decrease in dollars spent on cocaine, favoring lamotrigine. Few positive trials of medications for cocaine use, other than stimulant replacement, have been reported, and none have been reported for bipolar disorder. Reduction in amount of cocaine use by self-report with lamotrigine suggests that a standard treatment for bipolar disorder may reduce cocaine use. A study limitation was weekly assessment of urine drug screens that decreased the ability to detect between-group differences.
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Acquired lithium resistance revisited: discontinuation-induced refractoriness versus tolerance. J Affect Disord 2012; 140:6-13. [PMID: 22154708 DOI: 10.1016/j.jad.2011.09.021] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2011] [Accepted: 09/22/2011] [Indexed: 11/21/2022]
Abstract
BACKGROUND While some patients fail to respond to lithium from the outset, others are initially responsive and then develop treatment resistance. These acquired forms of lithium resistance have received relatively little clinical attention. METHODS We review the literature on the two different forms of acquired treatment resistance lithium that occur following an initial good response to lithium-discontinuation-induced refractoriness and tolerance- and discuss the possible neurobiological mechanisms involved. RESULTS Multiple investigators have reported cases of discontinuation-induced refractoriness, where following a good long-term response, patients discontinue lithium, suffer a major recurrence, and then do not again respond as well or at all to lithium once it is reinstituted at previously effective doses. The development of tolerance has similarly been multiply documented where lithium doses are consistently maintained, but after an extended period of excellent responsiveness, affective episodes of increasing severity, frequency, or duration begin to break through. These two forms of acquired treatment resistance appear to have different underlying neurobiological mechanisms and require differential treatment strategies. LIMITATIONS Recognition of acquired forms of lithium resistance depends on careful case descriptions and longitudinal monitoring of patients who are usually treated naturalistically and not in controlled clinical trials. CONCLUSION To the extent that these forms of acquired lithium resistance can be better recognized and their development slowed, prevented, or ameliorated, it could yield substantial clinical and public health benefits in avoiding the morbidity and mortality that can accompany lithium non-responsive bipolar disorder.
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Post RM, Fleming J, Kapczinski F. Neurobiological correlates of illness progression in the recurrent affective disorders. J Psychiatr Res 2012; 46:561-73. [PMID: 22444599 DOI: 10.1016/j.jpsychires.2012.02.004] [Citation(s) in RCA: 116] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2011] [Revised: 01/02/2012] [Accepted: 02/09/2012] [Indexed: 11/19/2022]
Abstract
Some clinical aspects of affective illness progression, such as episode-, stress-, and substance-induced sensitization, have been well documented in the literature, but others have received less attention. These include cognitive deficits, treatment-refractoriness, and neurobiological correlates of illness progression, which are the primary focus of this paper. We review the evidence that cognitive dysfunction, treatment resistance, medical comorbidities, and neurobiological abnormalities increase as a function of the number of prior episodes or duration of illness in the recurrent unipolar and bipolar disorders. Substantial evidence supports the view that cognitive dysfunction and vulnerability to a diagnosis of dementia in old age increases as a function of number of prior mood episodes as does non-response to many therapeutic interventions as well as naturalistic treatment. Neurobiological abnormalities that correlate with the number of mood episodes or duration of illness include: anatomical, functional, and biochemical deficits in the prefrontal cortex and hippocampus, as well as amygdala hyperactivity and cortisol hyper-secretion. Some neurotrophic factors and inflammatory markers may also change with greater illness burden. Causality cannot be inferred from these correlative relationships. Nonetheless, given the potentially grave consequences of episode recurrence and progression for morbidity and treatment non-responsiveness, it is clinically wise to assume episodes are causing some of the progressive cognitive and neurobiological abnormalities. As such, earlier and more sustained long-term prophylaxis to attempt to reduce these adverse outcomes is indicated.
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Affiliation(s)
- Robert M Post
- Bipolar Collaborative Network, 5415 W Cedar Lane, Suite 201-B, Bethesda, MD 20814, United States.
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Pfennig A, Schlattmann P, Alda M, Grof P, Glenn T, Müller-Oerlinghausen B, Suwalska A, Rybakowski J, Willich SN, Bauer M, Berghöfer A. Influence of atypical features on the quality of prophylactic effectiveness of long-term lithium treatment in bipolar disorders. Bipolar Disord 2010; 12:390-6. [PMID: 20636636 DOI: 10.1111/j.1399-5618.2010.00826.x] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
OBJECTIVES There is still debate about whether the quality of long-term efficacy of lithium in patients with bipolar disorders is influenced by atypical features. Extended Cox regression models allow for the use of all follow-up data on diseases with multiple episodes. The aim of the present analysis was to apply the best suited of these models to analyze the influence of atypical features on the widely used outcome measure of time to recurrence in a large multicenter cohort of lithium responders established by the International Group for the Study of Lithium Treated Patients. METHODS A conditional extended Cox model with a random frailty term was applied to the data of 336 bipolar I and II disorder patients, all of whom were responders to lithium with treatment for up to 30 years. RESULTS Differences were found in the long-term outcome, even in patients who have demonstrated a relatively good response to lithium treatment. The hazard for recurrence was negatively influenced by the presence of atypical features, mainly mood-incongruent psychotic symptoms, interepisodic residual symptomatology, and rapid cycling. CONCLUSIONS As a result of the findings, physicians should regularly reassess the quality of response in bipolar disorder patients with atypical features and, if necessary, modify treatment. Extended Cox regression models are well suited for evaluating long-term outcome and should be used more extensively to analyze treatment outcome in psychiatric and somatic disorders.
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Affiliation(s)
- Andrea Pfennig
- Department of Psychiatry and Psychotherapy, Carl Gustav Carus University Hospital, Technische Universität Dresden, Dresden, Germany.
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Bipolar disorder and medical adherence: A Chinese perspective. Asian J Psychiatr 2010; 3:7-11. [PMID: 23051130 DOI: 10.1016/j.ajp.2009.11.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2009] [Revised: 07/27/2009] [Accepted: 11/30/2009] [Indexed: 12/11/2022]
Abstract
BACKGROUND The aim of this study was to explore the perspectives of New Zealand Chinese with bipolar disorder in regards to medication adherence. METHOD Nine New Zealand Chinese with bipolar disorder (BD) type I or II who had reasonable performance in role functioning were interviewed and data analysis was guided by an inductive approach. RESULTS Relationships with doctors had the most impact on the participants' attitudes towards medication. The majority of the participants in this study went to see Chinese psychiatrists and were professionally linked with Chinese social workers. Meetings with health professionals have been described by the participants as forms of interpersonal interactions. With a deep feeling of trust and respect towards their doctors, the participants felt more positive towards using prescribed medication. In contrast, when the participants experienced feelings of neglect by their doctors they felt less satisfaction towards the treatment. However, when the participants saw Western health professionals, their attitudes towards medication were more related to perceived efficacy of treatment. CONCLUSIONS There is a strong need for facilitating the connection between health professionals and clients. Furthermore, it would be useful for educating Chinese clients on how medication works, their side effects, and interaction with other drugs.
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Brown ES, Carmody TJ, Schmitz JM, Caetano R, Adinoff B, Swann AC, John Rush A. A randomized, double-blind, placebo-controlled pilot study of naltrexone in outpatients with bipolar disorder and alcohol dependence. Alcohol Clin Exp Res 2009; 33:1863-9. [PMID: 19673746 PMCID: PMC3040070 DOI: 10.1111/j.1530-0277.2009.01024.x] [Citation(s) in RCA: 69] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
BACKGROUND Alcohol dependence is extremely common in patients with bipolar disorder and is associated with unfavorable outcomes including treatment nonadherence, violence, increased hospitalization, and decreased quality of life. While naltrexone is a standard treatment for alcohol dependence, no controlled trials have examined its use in patients with co-morbid bipolar disorder and alcohol dependence. In this pilot study, the efficacy of naltrexone in reducing alcohol use and on mood symptoms was assessed in bipolar disorder and alcohol dependence. METHODS Fifty adult outpatients with bipolar I or II disorders and current alcohol dependence with active alcohol use were randomized to 12 weeks of naltrexone (50 mg/d) add-on therapy or placebo. Both groups received manual-driven cognitive behavioral therapy designed for patients with bipolar disorder and substance-use disorders. Drinking days and heavy drinking days, alcohol craving, liver enzymes, and manic and depressed mood symptoms were assessed. RESULTS The 2 groups were similar in baseline and demographic characteristics. Naltrexone showed trends (p < 0.10) toward a greater decrease in drinking days (binary outcome), alcohol craving, and some liver enzyme levels than placebo. Side effects were similar in the 2 groups. Response to naltrexone was significantly related to medication adherence. CONCLUSIONS Results suggest the potential value and acceptable tolerability of naltrexone for alcohol dependence in bipolar disorder patients. A larger trial is needed to establish efficacy.
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Affiliation(s)
- E Sherwood Brown
- Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
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Pompili M, Serafini G, Del Casale A, Rigucci S, Innamorati M, Girardi P, Tatarelli R, Lester D. Improving adherence in mood disorders: the struggle against relapse, recurrence and suicide risk. Expert Rev Neurother 2009; 9:985-1004. [PMID: 19589049 DOI: 10.1586/ern.09.62] [Citation(s) in RCA: 67] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Medication nonadherence is a major obstacle to translating treatment efficacy from research settings into effectiveness in clinical practice for patients with affective disorders. Adherence to beneficial drug therapy is associated with lower mortality compared with poor adherence. Reduced adherence is associated with increased suicide risk, especially when lithium is discontinued. The aim of this paper is to review the prevalence, predictors and methods for improving medication adherence in unipolar and bipolar affective disorders. Studies were identified through Medline and PsycInfo searches of English language publications between 1976 and 2009. This was supplemented by a hand search and the inclusion of selected descriptive articles on good clinical practice. Estimates of medication nonadherence for unipolar and bipolar disorders range from 10 to 60% (median: 40%). This prevalence has not changed significantly with the introduction of new medications. There is evidence that attitudes and beliefs are at least as important as side effects in predicting adherence. The limited number of empirical studies on reducing nonadherence indicate that, if recognized, the problem may be overcome. Clinical data highlight the importance of extended courses of medication in improving the long-term prognosis of patients with affective disorders.
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Affiliation(s)
- Maurizio Pompili
- Department of Psychiatry, Sant'Andrea Hospital, Sapienza University of Rome, Via di Grottarossa 1035, 00189 Roma, Italy.
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Baca-Garcia E, Sher L, Perez-Rodriguez MM, Burke AK, Sullivan GM, Grunebaum MF, Stanley BH, Mann JJ, Oquendo MA. Treatment of depressed bipolar patients with alcohol use disorders: plenty of room for improvement. J Affect Disord 2009; 115:262-8. [PMID: 18973953 PMCID: PMC2730967 DOI: 10.1016/j.jad.2008.09.012] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2008] [Revised: 09/07/2008] [Accepted: 09/15/2008] [Indexed: 11/21/2022]
Abstract
BACKGROUND We aimed to examine the adequacy of antidepressant treatment and compliance with treatment in bipolar patients with and without alcohol use disorders (AUD). We hypothesize that the adequacy of antidepressant treatment and the compliance with treatment for those with AUD are lower than for those without AUD. METHODS Subjects were 97 patients with current bipolar major depressive episode, 39 (40.2%) with lifetime history of AUD and 58 (59.8%) without AUD. Adequacy of antidepressant medication treatment in the 3 previous months was assessed using the Antidepressant Treatment History Form. Compliance rates were estimated. RESULTS Rates of inadequate treatment were high in all patients. Bipolar patients with AUD (74.3%) showed higher rates of inadequate antidepressant treatment than those without AUD (67.3%). The proportion of intensive treatment was higher in bipolars without AUD (15.5%) than in those with AUD (2.6%). Median compliance was similar in bipolars with and without AUD. LIMITATIONS We lack serum medication levels to assess the compliance. We do not have data to address the possibility that the presence of AUD adversely affected prescribing practices. CONCLUSIONS Bipolars with AUD had lower rates of adequate treatment than those without AUD, but the two groups were not different in terms of self-reported treatment adherence. The finding that bipolar patients with or without comorbid AUD did not receive adequate treatment is of considerable clinical relevance. It raises the question as to whether inadequate treatment of depression contributes to the high rates of morbidity, and attempted and completed suicides in bipolar patient populations.
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Affiliation(s)
- Enrique Baca-Garcia
- Molecular Imaging and Neuropathology Division, NYS Psychiatric Institute and Columbia University, New York 10032, USA.
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Pompili M, Rihmer Z, Innamorati M, Lester D, Girardi P, Tatarelli R. Assessment and treatment of suicide risk in bipolar disorders. Expert Rev Neurother 2009; 9:109-136. [PMID: 19102673 DOI: 10.1586/14737175.9.1.109] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Completed suicide and suicide attempts are major issues in the management of bipolar disorders. There is evidence that suicide rates among these patients are more than 20-fold higher than the general population and, furthermore, suicidal behavior is much more lethal in bipolar disorder than in the general population. Patients with mood disorders may sometimes exhibit highly perturbed mixed states, which usually increase the risk of suicide. Such states are particularly frequent in bipolar II patients, especially if patients are treated with antidepressant monotherapy (unprotected by mood stabilizers), when depression switches into mania (or vice versa), or when depression lifts and functioning approaches normality. Researchers worldwide agree that treatment involving lithium is the best way to protect patients from suicide risk. Psychosocial activities, including psychoeducation, can protect bipolar patients either directly or, more probably, indirectly by increasing adherence to treatment and helping in daily difficulties that otherwise may lead to demoralization or hopelessness. An extensive understanding of the psychosocial circumstances and the psychopathology of bipolar patients (including temperament) may help clinicians describe the clinical picture accurately and prevent suicidal behavior in these patients.
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Rohayem J, Baylé JF, Richa S. Prédicteurs de réponse prophylactique au lithium. Encephale 2008; 34:394-9. [DOI: 10.1016/j.encep.2007.05.002] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2006] [Accepted: 05/15/2007] [Indexed: 10/21/2022]
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Kessing LV, Søndergård L, Kvist K, Andersen PK. Adherence to lithium in naturalistic settings: results from a nationwide pharmacoepidemiological study. Bipolar Disord 2007; 9:730-6. [PMID: 17988363 DOI: 10.1111/j.1399-5618.2007.00405.x] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
OBJECTIVES To estimate adherence to lithium in a nationwide sample of all patients treated with lithium and to characterize adherence according to gender and age. METHODS Adherence to lithium was estimated using data obtained by linking Medicinal Product Statistics with the Danish Medical Register on Vital Statistics, identifying all persons who received lithium among the 5.3 million persons living in Denmark during the period 1995 to 2000 inclusive. RESULTS The median time to discontinuation of lithium was 181.0 days [95% confidence interval (CI) 135.7-181.0] and 25% of patients stopped treatment with lithium within 45.2 days. Adherence to lithium was significantly poorer for women (135.7 days; 95% CI 90.5-135.7) than for men (316.7 days; 95% CI 271.4-407.1) and for younger (18-39 years) and older (>or=60 years) patients compared to middle-aged patients. CONCLUSIONS The results highlight the need for increased focus on long-term adherence to lithium with intensified psychological support, especially among younger and older female patients.
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Affiliation(s)
- Lars Vedel Kessing
- Department of Psychiatry, University Hospital of Copenhagen, Rigshospitalet, University of Copenhagen, Denmark.
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Sajatovic M, Blow FC, Kales HC, Valenstein M, Ganoczy D, Ignacio RV. Age comparison of treatment adherence with antipsychotic medications among individuals with bipolar disorder. Int J Geriatr Psychiatry 2007; 22:992-8. [PMID: 17323327 DOI: 10.1002/gps.1777] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Few studies have evaluated medication adherence among older vs younger individuals with bipolar disorder (BPD). We compared adherence with antipsychotic medication among older (age 60 and older) and younger individuals using a large case registry (n = 73,964). METHODS Adherence was evaluated using the medication possession ratio (MPR) for patients receiving antipsychotic medication. RESULTS Twenty six thousand five hundred and thirty younger individuals (mean age 46.9) and 6,461 older individuals (mean age 69.2) were prescribed antipsychotic medication. Among older individuals, 61.0% (n = 3,350) were fully adherent, while 19.0% (n = 1,043) were partially adherent and 20.0% (n = 1,098) were non-adherent. Among younger individuals, 49.5% (n = 10,644) were fully adherent, while 21.8% (n = 4,680) were partially adherent, and 28.7% (n = 6,170) were non-adherent. As with younger patients, comorbid substance abuse and homelessness predicted non-adherence among older patients with BPD. CONCLUSION Older individuals with BPD were more adherent with antipsychotic medications compared to younger individuals. However, a substantial proportion (approximately 39%) of older patients with BPD still have difficulties with adherence.
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Affiliation(s)
- Martha Sajatovic
- Psychiatry and Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
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Machado-Vieira R, Soares JC. Transtornos de humor refratários a tratamento. REVISTA BRASILEIRA DE PSIQUIATRIA 2007; 29 Suppl 2:S48-54. [PMID: 17713691 DOI: 10.1590/s1516-44462006005000058] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
OBJETIVOS E MÉTODO: Os transtornos de humor estão entre os transtornos psiquiátricos mais prevalentes. Apesar de novas descobertas e avanços no estudo das bases neurobiológicas e abordagens terapêuticas no transtorno bipolar e depressão recorrente, elevadas taxas de recorrência, sintomas subsindrômicos persistentes e refratariedade terapêutica são aspectos clínicos desafiadores e precisam ser abordados. O objetivo desta revisão da literatura é o de avaliar os conceitos e critérios de resistência e refratariedade ao tratamento, e evidenciar as principais alternativas terapêuticas para transtornos do humor resistentes aos tratamentos disponíveis. RESULTADOS: Fatores genéticos, erro diagnóstico e de tratamento, não-aderência, e estressores biológicos e psicossociais podem levar à perda de mecanismos regulatórios e ao aumento na prevalência de casos de refratariedade nos transtornos de humor. Com relação aos tratamentos disponíveis, o uso de doses apropriadas, seguido por associação com um segundo ou terceiro fármaco, e após, se indicado, a troca de medicação, são etapas necessárias na busca de melhor eficácia. Entretanto, no paradigma de refratariedade terapêutica, tratamentos atuando em sistemas já conhecidos, especialmente monoaminas, freqüentemente apresentam limitada eficácia. Assim, a busca por tratamentos mais eficazes para os transtornos de humor torna-se um aspecto chave para diminuir sua morbidade. CONCLUSÃO: Estratégias focadas na regulação de vias ativadoras de neuroplasticidade, incluindo agentes antiglutamatérgicos, antagonistas de receptor glucocorticóide e neuropeptídeos, podem representar opções terapêuticas promissoras.
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Affiliation(s)
- Rodrigo Machado-Vieira
- Programa de Transtornos do Humor e Ansiedade, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-3711, USA.
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Abstract
Classic Kraepelian observations and contemporary epidemiological studies have noted a high prevalence rate between bipolar disorder and alcoholism. The extent to which these two illnesses are comorbid (i.e., two distinct disease processes each with an independent course of illness), genetically linked, or different phenotypic expressions of bipolar illness itself continues to be investigated. It is increasingly clear that co-occurring alcohol abuse or dependence in bipolar disorder phenomenologically changes the illness presentation with higher rates of mixed or dysphoric mania, rapid cycling, increased symptom severity, and higher levels of novelty seeking, suicidality, aggressivity, and impulsivity. It is very encouraging that interest and efforts at evaluating pharmacotherapeutic compounds has substantially increased over the past few years in this difficult-to-treat patient population. This article will review the clinical studies that have evaluated the effectiveness of conventional mood stabilizers (lithium, carbamazepine, divalproex, and atypical antipsychotics) in the treatment of alcohol withdrawal and relapse prevention in patients with alcoholism and in the treatment of bipolar disorder with comorbid alcoholism. A number of add-on, adjunctive medications, such as naltrexone, acamprosate, topiramate, and the atypical antipsychotics quetiapine and clozapine, may be candidates for further testing.
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Affiliation(s)
- Mark A Frye
- Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine at UCLA, University of California-Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA, USA.
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Rosa AR, Andreazza AC, Sanchez-Moreno J, Gazalle FK, Santin A, Stein A, Barros HMT, Vieta E, Kapczinski F. Validation of the Portuguese version of the Lithium Attitudes Questionnaire (LAQ) in bipolar patients treated with lithium: cross-over study. Clin Pract Epidemiol Ment Health 2006; 2:32. [PMID: 17121674 PMCID: PMC1664563 DOI: 10.1186/1745-0179-2-32] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2006] [Accepted: 11/22/2006] [Indexed: 12/17/2022]
Abstract
BACKGROUND Poor adherence to lithium is very common in bipolar patients and it is a frequent cause of recurrence during prophylactic treatment. Several reports suggest that attitudes of bipolar patients interfere with adherence to lithium. The Lithium Attitudes Questionnaire (LAQ) is a brief questionnaire developed as a means of identifying and grouping the problems patients commonly have with taking lithium regularly. The original version is validated in patients, but a validated version in Portuguese is not yet available. METHODS One-hundred six patients with bipolar disorder (DSM-IV criteria) criteria under lithium treatment for at least one month were assessed using LAQ. LAQ is a brief questionnaire administered under interview conditions, which includes 19 items rating attitudes towards prophylactic lithium treatment. We analysed the internal consistency, concurrent validity, sensitivity and specificity of the Portuguese version of LAQ. RESULTS The internal consistency, evaluated by Cronbach's alpha was 0.78. The mean total LAQ score was 4.1. Concurrent validity was confirmed by a negative correlation between plasma lithium concentration and total LAQ score (r = -0,198; p = 0.048). We analysed the scale's discriminative capacity revealing a sensitivity of 69% and a specificity of 71% in the identification of negative attitudes of bipolar patients. CONCLUSION The psychometric assessment of the Portuguese version of LAQ showed good internal consistency, sensitivity and specificity. The results were similar to the original version in relation to attitudes of bipolar patients towards lithium therapy.
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Affiliation(s)
- Adriane R Rosa
- Bipolar Disorders Program, Centro de Pesquisas, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos, 2350, 90035-003, Porto Alegre, RS, Brazil
- Bipolar Disorders Program, Clinical Institute of Neuroscience, Hospital Clinic de Barcelona, Villarroel 170, Barcelona 08036, Barcelona, Spain
| | - Ana Cristina Andreazza
- Bipolar Disorders Program, Centro de Pesquisas, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos, 2350, 90035-003, Porto Alegre, RS, Brazil
- Department of Biochemistry, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos, 2600- Anexo, 90035-003, Porto Alegre, RS, Brazil
| | - Jose Sanchez-Moreno
- Bipolar Disorders Program, Clinical Institute of Neuroscience, Hospital Clinic de Barcelona, Villarroel 170, Barcelona 08036, Barcelona, Spain
| | - Fernando K Gazalle
- Post-Graduate Psychiatry Program, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Aida Santin
- Bipolar Disorders Program, Centro de Pesquisas, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos, 2350, 90035-003, Porto Alegre, RS, Brazil
| | - Airton Stein
- Departamento de Farmacologia, Fundação Faculdade Federal de Ciências Médicas de Porto Alegre, RS, Brazil
| | - Helena MT Barros
- Departamento de Farmacologia, Fundação Faculdade Federal de Ciências Médicas de Porto Alegre, RS, Brazil
| | - Eduard Vieta
- Bipolar Disorders Program, Clinical Institute of Neuroscience, Hospital Clinic de Barcelona, Villarroel 170, Barcelona 08036, Barcelona, Spain
| | - Flávio Kapczinski
- Bipolar Disorders Program, Centro de Pesquisas, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos, 2350, 90035-003, Porto Alegre, RS, Brazil
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Abstract
In this chapter we review research on the diagnosis, course, etiology, and pharmacological and psychosocial treatment of bipolar disorder (BD). BD is a highly recurrent and severe illness, with high rates of suicidality and functional impairment. The disorder is heritable and appears to share susceptibility genes with schizophrenia. It is characterized by dysregulation in the dopamine and serotonin systems and by pathology in the brain systems involved in regulating emotion. Psychosocial stressors, notably life events and familial expressed emotion, significantly influence the course of the illness in the context of these vulnerabilities. Findings of randomized clinical trials indicate that psychosocial interventions enhance long-term outcomes when added to pharmacotherapy. Much remains to be clarified about the interactive contributions of genetic, neurobiological, and psychosocial factors to the course of the disorder, and the moderators and mediators of treatment effects.
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Affiliation(s)
- David J. Miklowitz
- Department of Psychology, University of Colorado, Boulder, Colorado 80309-0345;
| | - Sheri L. Johnson
- Department of Psychology, University of Miami, Coral Gables, Florida 33124-0751;
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Kirov G, Tredget J. Add-on topiramate reduces weight in overweight patients with affective disorders: a clinical case series. BMC Psychiatry 2005; 5:19. [PMID: 15817130 PMCID: PMC1087494 DOI: 10.1186/1471-244x-5-19] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2004] [Accepted: 04/07/2005] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The weight-gain caused by many psychotropic drugs is a major cause for poor compliance with such medications and could also increase cardio-vascular morbidity among psychiatric patients. Recent reports have shown that the anticonvulsant topiramate causes weight loss in various patient groups. The drug has also shown effectiveness in open trials as a mood stabilizer in patients with affective disorders, but not in controlled trials in the acute treatment of mania. We used topiramate to treat 12 patients with affective disorders who had a body-mass index > 30 kg/m2. METHODS Topiramate was prescribed as part of our routine clinical practice, as an add-on medication, or as a replacement of a mood stabilizer. Patients' weight was recorded in 1 to 2 monthly intervals. Patients were followed up for between 6 and 12 months. The final dose of topiramate varied from 200 to 600 mg/day. RESULTS Topiramate was effective in reducing the weight in 10 out of the 12 patients. At six months the 12 patients had lost a mean of 7.75 kg (SD = 6.9 kg, p < 0.001) and at 12 months 9 patients had lost a mean of 9.61 kg (SD = 6.7 kg, p = 0.003). Three patients stopped the treatment: one due to side effects, one due to possible side effects, and one suffered a manic relapse and showed no sustained weight loss. There were no other clear changes in the course of illness of the patients. CONCLUSION The evidence of a strong weight-reducing potential of topiramate is indisputable and clinically significant. Topiramate could be considered in the treatment of bipolar patients who are overweight, or whose concerns about weight gain compromise their compliance with long-term prophylactic medication. So far there is no evidence that topiramate has anti-manic effect and it should not be used as monotherapy.
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Affiliation(s)
- George Kirov
- Department of Psychological Medicine, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK
| | - John Tredget
- Department of Psychological Medicine, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK
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Aagaar J, Nielsen JA. Experience from the first ACT programme in Denmark. II. Severe mental illness. A register diagnosis. Nord J Psychiatry 2004; 58:171-4. [PMID: 15204225 DOI: 10.1080/08039480410005576] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Community psychiatry in Denmark has been criticized because of drop-outs of the patients with severe mental illness. In order to deal with these problems, the first Assertive Community Treatment (ACT) project in Denmark was started in the Tønder region on 1 May 2001. Before starting the clinical study, an epidemiological analysis of severe mental illness was performed. Severe mental illness was defined from register data on the basis of psychosis and high use of psychiatric services. Data concerning drop-out (inactive during a period), death and address were obtained. The point prevalence rate of severe mental illness on 31 December 2000 in Sønderjylland (SJ) county was 1.31/1000. The rate of inactive patients was 0.28/1000. The rates were distributed inhomogeneously between regions. In a 4-year cohort, half of the patients were inactive at least once. The Tønder and Aabenraa regions had homogeneous patterns. In conclusion, the register diagnosis is a target group for ACT. The register diagnosis and the status active/inactive may be used as an unbiased effect parameter.
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Affiliation(s)
- Jørgen Aagaar
- Community Mental Health Centre Tønder, and Department of Psychiatric Demography, Psychiatric Hospital in Aarhus, Risskov, Denmark.
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32
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Gyulai L, Bowden CL, McElroy SL, Calabrese JR, Petty F, Swann AC, Chou JCY, Wassef A, Risch CS, Hirschfeld RMA, Nemeroff CB, Keck PE, Evans DL, Wozniak PJ. Maintenance efficacy of divalproex in the prevention of bipolar depression. Neuropsychopharmacology 2003; 28:1374-82. [PMID: 12784116 DOI: 10.1038/sj.npp.1300190] [Citation(s) in RCA: 102] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Breakthrough depression is a common problem in the treatment of bipolar disorder. Only one, recently published, double-blind, placebo-controlled trial has examined the efficacy of divalproex in the prevention of depressive episodes in bipolar patients. This report describes, in further detail, the findings from that trial of the effect of divalproex on multiple dimensions of depressive morbidity in bipolar disorder. A randomized, double-blind, parallel-group, multicenter study was conducted over a 52-week maintenance period. Bipolar I patients, who may have been treated with open-label lithium or divalproex and who met recovery criteria within 3 months of onset of an index manic episode, were randomized to maintenance treatment with divalproex, lithium, or placebo in a 2 : 1 : 1 ratio. Adjunctive paroxetine or sertraline for breakthrough depression was allowed in maintenance phase. Outcome measures were the rate of early discontinuation for depression, time to depressive relapse, proportion of patients with depressive relapse, mean change in Depressive Syndrome Scale score, proportion of patients receiving antidepressants, and time in the study. Among patients taking an antidepressant, a higher percentage of patients on placebo than divalproex discontinued early for depression. Patients who were previously hospitalized for affective episodes or took divalproex in the open period relapsed later on divalproex than on lithium during the maintenance period. Divalproex-treated patients had less worsening of depressive symptoms than lithium-treated patients during maintenance. Indices of severity of prestudy illness course predicted worse outcome in all treatment groups. Divalproex improved several dimensions of depressive morbidity and reduced the probability of depressive relapse in bipolar disorder, particularly in patients who had responded to divalproex when manic, and among patients with a more severe course of illness.
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Affiliation(s)
- Laszlo Gyulai
- Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA.
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Dharmendra MS, Eagles JM. Factors associated with patients' knowledge of and attitudes towards treatment with lithium. J Affect Disord 2003; 75:29-33. [PMID: 12781347 DOI: 10.1016/s0165-0327(02)00027-7] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Treatment with lithium is often compromised by poor adherence, by side-effects and by patients' having serum levels outside the therapeutic range. These factors may be affected by patients' knowledge and attitudes towards lithium, and we set out to establish factors associated with knowledge about and attitudes towards lithium among a large representative sample of patients. METHOD Patients known to be taking lithium in Grampian during 1995 were surveyed postally during 1998 with the Lithium Knowledge Test (LKT) and the Lithium Attitudes Questionnaire (LAQ). Scores on these measures were analysed against patients' sociodemographic and clinical characteristics by stepwise multiple regression. RESULTS Of 742 patients, 411 (55%) completed an LKT and 362 (49%) completed an LAQ. Stepwise multiple regression established that positive attitudes towards lithium on the LAQ were associated with higher serum lithium levels (P=0.005) and with continuing to take lithium (P<0.001). Higher knowledge on the LKT was associated with positive attitudes on the LAQ (P=0.002), with younger age (P<0.001), and with shorter duration of treatment (P=0.01) LIMITATIONS The study was retrospective and the response rate was relatively low. CONCLUSIONS Education about lithium is likely to be of particular importance in the elderly and 'refresher courses' are advisable for those who have been on lithium for lengthy periods. Interventions which modify attitudes, rather than enhancing knowledge, are likely to be helpful in promoting adherence.
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Affiliation(s)
- M S Dharmendra
- Royal Cornhill Hospital, Cornhill Road, Aberdeen, AB25 2ZH, UK
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Frye MA, Altshuler LL, McElroy SL, Suppes T, Keck PE, Denicoff K, Nolen WA, Kupka R, Leverich GS, Pollio C, Grunze H, Walden J, Post RM. Gender differences in prevalence, risk, and clinical correlates of alcoholism comorbidity in bipolar disorder. Am J Psychiatry 2003; 160:883-889. [PMID: 12727691 DOI: 10.1176/appi.ajp.160.5.883] [Citation(s) in RCA: 128] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
OBJECTIVE The prevalence of lifetime alcohol abuse and/or dependence (alcoholism) in patients with bipolar disorder has been reported to be higher than in all other axis I psychiatric diagnoses. This study examined gender-specific relationships between alcoholism and bipolar illness, which have previously received little systematic study. METHOD The prevalence of lifetime alcoholism in 267 outpatients enrolled in the Stanley Foundation Bipolar Network was evaluated by using the Structured Clinical Interview for DSM-IV. Alcoholism and its relationship to retrospectively assessed measures of the course of bipolar illness were evaluated by patient-rated and clinician-administered questionnaires. RESULTS As in the general population, more men (49%, 57 of 116) than women with bipolar disorder (29%, 44 of 151) met the criteria for lifetime alcoholism. However, the risk of having alcoholism was greater for women with bipolar disorder (odds ratio=7.35) than for men with bipolar disorder (odds ratio=2.77), compared with the general population. Alcoholism was associated with a history of polysubstance use in women with bipolar disorder and with a family history of alcoholism in men with bipolar disorder. CONCLUSIONS This study suggests that there are gender differences in the prevalence, risk, and clinical correlates of alcoholism in bipolar illness. Although this study is limited by the retrospective assessment of illness variables, the magnitude of these gender-specific differences is substantial and warrants further prospective study.
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Affiliation(s)
- Mark A Frye
- Department of Psychiatry and Biobehavioral Sciences, UCLA Bipolar Research Program, University of California-Los Angeles School of Medicine, 300 UCLA Medical Plaza, Suite 1544, Los Angeles, CA 90095, USA.
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35
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Cognitive–Behavioral Treatment of Bipolar Disorder and Substance Abuse: A Preliminary Randomized Study. ADDICTIVE DISORDERS & THEIR TREATMENT 2002. [DOI: 10.1097/00132576-200205000-00004] [Citation(s) in RCA: 55] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Abstract
The prevalence of geriatric mania is uncertain. Although there are high rates of mania in clinical and residential facilities, community based epidemiologic studies are limited. Given the difficulty in making an accurate diagnosis, geriatric mania appears to be underreported. Although the commonly held opinion is that onset and prevalence of mania decreases with age, there is contradictory evidence that, particularly in men, the incidence of new onset mania increases with age. Clinically, the diagnosis and treatment of geriatric mania is challenging, because these patients present with comorbid medical, neurologic, and dementing illnesses. This paper reviews presentations of mania in the elderly and updates the pharmacologic treatment of mania in the elderly. Although few of the studies target the elderly, the published data in younger patients on the use of the atypical antipsychotics, as well as the advent of newer anticonvulsants, have demonstrated promise in the treatment of older patients.
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Affiliation(s)
- William M McDonald
- Wesley Woods Health Center, Fuqua Center for Late-Life Depression, 1841 Clifton Road, NE, Atlanta, GA 30329-5102, USA.
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37
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Licht RW, Vestergaard P, Rasmussen NA, Jepsen K, Brodersen A, Hansen PE. A lithium clinic for bipolar patients: 2-year outcome of the first 148 patients. Acta Psychiatr Scand 2002. [PMID: 11722321 DOI: 10.1111/j.1600-0447.2001.00389.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
OBJECTIVE This paper describes the outcome for the first 148 patients referred to a lithium clinic. METHOD Two-year follow-up data from treatment charts are reported for all patients entering a lithium clinic in the study period. RESULTS Lithium was given as the only mood stabilizer in 132 (89.2%) of the cases. Thirty-two (21.6%) patients were readmitted with a new affective disorder episode. Twenty-nine (19.6%) patients discontinued treatment prematurely. Variables predicting the recurrence of new affective disorder episodes as well as premature discontinuation of treatment were identified. CONCLUSION The majority of bipolar patients received lithium for prophylaxis against recurrent affective disorder episodes. The outcome was moderate but comparable to the 30-40% improvement usually reported in follow-up studies of bipolar patients given long-term prophylactic treatment with lithium. Better long-term treatment results for bipolar patients depend on both the development of more effective mood stabilizing drugs or drug combinations and the improvement of patients' adherence to treatment.
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Affiliation(s)
- R W Licht
- Mood Disorders Research Unit, Aarhus University Psychiatric Hospital, Skovagervej 2, DK-8240 Risskov, Denmark
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38
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Coryell W, Arndt S, Turvey C, Endicott J, Solomon D, Mueller T, Leon AC, Keller M. Lithium and suicidal behavior in major affective disorder: a case-control study. Acta Psychiatr Scand 2001; 104:193-7. [PMID: 11531655 DOI: 10.1034/j.1600-0447.2001.00338.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
OBJECTIVE A number of studies have suggested that lithium may be particularly effective in reducing suicide risks among patients with major affective disorders. The design of many of these studies left them open to biases associated with treatment compliance, however. METHOD Subjects were drawn from a naturalistic, long-term follow-up of patients with major affective disorders. Fifteen who committed suicide while receiving somatotherapy where matched to non-suicidal patients who were similarly receiving somatotherapy at the same point in follow-up. The same procedure was followed for 41 patients who made a serious suicide attempt during follow-up. RESULTS Six (40.0%) of the patients who committed suicide, and eight (53.3%) of their controls, were thought to have been taking lithium in the preceding week. Among attempters and their controls, nine (22.0%) and eight (19.5%), respectively, were taking lithium. CONCLUSION These results do not support previous suggestions that lithium has uniquely antisuicidal properties. Other existing datasets should be explored with this design to establish whether lithium does, or does not, offer special protection against suicide.
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Affiliation(s)
- W Coryell
- Department of Psychiatry, University of Iowa, Iowa City, 52242-1000, USA
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39
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Abstract
BACKGROUND Prior reports suggested that bipolar patients in Taiwan had comparable long-term outcome to Western patients despite markedly lower rates of co-occurring substance use disorders. Thus, predictors of long-term outcome identified from Taiwanese bipolar samples may be less influenced by substance abuse. METHODS One hundred and one patients with bipolar disorder (DSM-III-R) having been naturalistically treated for at least 15 years were recruited. These patients were annually followed for 2 years to assess overall outcome, psychiatric symptoms, rehospitalization, work, and social adjustment. A combination of medical record reviews and direct personal interviews with patients and family members provided the clinical data. RESULTS Of these patients, 16.8% expressed a poor overall long-term outcome, even though only two (2.0%) patients exhibited alcohol dependence during the follow-up period. Multivariate regression showed that full compliance with medication was the strongest predictor of favorable overall long-term outcome, followed by younger age at onset and male sex. Younger age at onset as well as male sex, but not full compliance, also predicted a favorable psychosocial outcome. LIMITATIONS Recruiting our sample from a clinical population with uncontrollable long-term treatment limits the generalizability of the findings. CONCLUSIONS Compliance with pharmacotherapy is important to achieve a favorable overall long-term outcome of bipolar disorder. A portion of bipolar patients may have an unfavorable psychosocial outcome regardless of the psychopharmacological intervention or presence of substance abuse.
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Affiliation(s)
- S M Tsai
- Department of Psychiatry, Taipei Medical College and Hospital, 252 Wu-Hsing Street, Taipei 110, Taiwan.
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40
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Vestergaard P, Licht RW. 50 Years with lithium treatment in affective disorders: present problems and priorities. World J Biol Psychiatry 2001; 2:18-26. [PMID: 12587181 DOI: 10.3109/15622970109039980] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Lithium has been used as a treatment for various psychiatric- and somatic-illnesses for more than 50 years. Today the main use of lithium is for the prevention of episode recurrences in bipolar disorder. The main emphasis of this review will be on the efficacy and effectiveness of lithium prophylaxis in bipolar disorder but the review will also discuss other indications for lithium treatment, the historical development, pharmacokinetic and -dynamic issues, unwanted effects of lithium and the organisation of treatment services. Finally, although not the main purpose of this review, a short description of alternative mood stabilizing drugs will also be presented.
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Affiliation(s)
- P Vestergaard
- Mood Disorders Research Unit, Aarhus University Psychiatric Hospital, Skovagervej 2, 8240 Risskov, Denmark.
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41
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Abstract
Bipolar disorder is marked by frequent recurrences, a course from childhood or early adulthood until death, marked increased rates of suicide, and substantial functional morbidity. Maintenance treatment is generally recommended to reduce the ravages of the illness. This article reviews the evidence that lithium, divalproex, and carbamazepine may reduce suicidal risk. It reviews the evidence for relapse prevention for lithium, valproate, and other drugs often employed in the maintenance phase treatment of bipolar disorder. Both lithium and divalproex appear beneficial in prevention of relapse, although recent studies indicate more modest effects for lithium than did early studies from the 1970s.
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Affiliation(s)
- C L Bowden
- The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
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42
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Kusalic M, Engelsmann F. Predictors of lithium treatment responsiveness in bipolar patients. A two-year prospective study. Neuropsychobiology 2000; 37:146-9. [PMID: 9597671 DOI: 10.1159/000026497] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Twenty-nine bipolar patients were assessed before the start of lithium therapy to study the prognostic criteria of long-term response to therapy. Assessment included clinical and demographic data and laboratory tests administered before and 2-5 days after initiation of therapy. The tests included calcium and magnesium serum levels, and thyroid hormonal status. Patients were followed up for 2 years. None of the single variables predicted the response to lithium therapy, but a combination of clinical and demographic variables, used in a discriminant function analysis, correctly identified 78.9% of responders. Multiple regression analysis predicted 46.2% of the outcome. The strongest univariate predictors were mood quality, illness duration, and substance abuse.
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Affiliation(s)
- M Kusalic
- Department of Psychiatry, McGill University, Royal Victoria Hospital, Montréal, Canada
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43
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Rush AJ, Post RM, Nolen WA, Keck PE, Suppes T, Altshuler L, McElroy SL. Methodological issues in developing new acute treatments for patients with bipolar illness. Biol Psychiatry 2000; 48:615-24. [PMID: 11018232 DOI: 10.1016/s0006-3223(00)00898-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
One important aim of the recent reorganization of the National Institute of Mental Health (NIMH) is to streamline the development of new treatments for patients with severe mental illnesses, such as bipolar disorder. Researching new treatments for patients with bipolar disorder presents specific problems not readily addressed by traditional efficacy trial methodologies that aim to maximize internal validity. This article reexamines several assumptions that have guided the design of these efficacy trials but that also create obstacles for studies of bipolar disorder and suggests potential solutions. This article draws on literature from neurology and psychiatry and discussions at a MacArthur Foundation-sponsored Conference on Longitudinal Methodology in 1992 (David J. Kupfer, M.D., Chair), which brought together investigators to consider alternative designs for patients with severe and persistent mental illness. In addition, we benefited from discussions at two NIMH-sponsored conferences, one held in 1989 (Prien and Potter 1990) and the other in 1994 (Prien and Rush 1996), at which investigators and methodologists discussed issues surrounding the development and conduct of informative efficacy trials for patients with bipolar disorder. Based on these discussions and recent literature reviews, we 1) outline common problems in the development and evaluation of effective acute treatments for bipolar disorder and 2) suggest possible solutions to these impediments. We also discuss alternative designs by which to build a sequence of acute treatment studies from which efficacy, safety, and the comparative value of different treatments can be established.
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Affiliation(s)
- A J Rush
- Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas 75390-9086, USA
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Chen G, Masana MI, Manji HK. Lithium regulates PKC-mediated intracellular cross-talk and gene expression in the CNS in vivo. Bipolar Disord 2000; 2:217-36. [PMID: 11249800 DOI: 10.1034/j.1399-5618.2000.20303.x] [Citation(s) in RCA: 63] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
It has become increasingly appreciated that the long-term treatment of complex neuropsychiatric disorders like bipolar disorder (BD) involves the strategic regulation of signaling pathways and gene expression in critical neuronal circuits. Accumulating evidence from our laboratories and others has identified the family of protein kinase C (PKC) isozymes as a shared target in the brain for the long-term action of both lithium and valproate (VPA) in the treatment of BD. In rats chronically treated with lithium at therapeutic levels, there is a reduction in the levels of frontal cortical and hippocampal membrane-associated PKC alpha and PKC epsilon. Using in vivO microdialysis, we have investigated the effects of chronic lithium on the intracellular cross-talk between PKC and the cyclic AMP (cAMP) generating system in vivo. We have found that activation of PKC produces an increase in dialysate cAMP levels in both prefrontal cortex and hippocampus, effects which are attenuated by chronic lithium administration. Lithium also regulates the activity of another major signaling pathway the c-Jun N-terminal kinase pathway--in a PKC-dependent manner. Both Li and VPA, at therapeutically relevant concentrations, increase the DNA binding of activator protein 1 (AP-1) family of transcription factors in cultured cells in vitro, and in rat brain ex vivo. Furthermore, both agents increase the expression of an AP-1 driven reporter gene, as well as the expression of several endogenous genes known to be regulated by AP-1. Together, these results suggest that the PKC signaling pathway and PKC-mediated gene expression may be important mediators of lithium's long-term therapeutic effects in a disorder as complex as BD.
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Affiliation(s)
- G Chen
- Department of Psychiatry and Behavioral Neurosciences, WSU School of Medicine, Detroit, MI 48201, USA.
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45
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Brodersen A, Licht RW, Vestergaard P, Olesen AV, Mortensen PB. Sixteen-year mortality in patients with affective disorder commenced on lithium. Br J Psychiatry 2000; 176:429-33. [PMID: 10912217 DOI: 10.1192/bjp.176.5.429] [Citation(s) in RCA: 43] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
BACKGROUND Lithium treatment is claimed to reduce mortality in patients with affective disorder, but the evidence is conflicting. AIM To estimate mortality rates from a cohort of patients with affective disorder commenced on lithium with an observation period of two years and a follow-up after 16 years. METHOD The mortality rates of patients were compared with those of the general Danish population, standardised for age, gender and calendar time with respect to death from all causes, suicide and death from cardiovascular disease. RESULTS Forty of the study's 133 patients died during the 16-year observation period (11 from suicide). Mortality among patients commenced on lithium was twice that of the general population. The statistically significantly elevated mortality was due largely to an excess of suicides; mortality from all other causes was similar to the background populations. Thirty-two patients died after the first two years of observation and were included in the analysis of the association between death and treatment compliance. Suicide occurred more frequently among those patients not complying with treatment. CONCLUSION Mortality, especially suicide, was significantly increased in unselected patients with affective disorder commenced on lithium relative to the general population.
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Affiliation(s)
- A Brodersen
- Mood Disorders Research Unit, Psychiatric Hospital in Aarhus, Risskov, Denmark
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46
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Schumann C, Lenz G, Berghöfer A, Müller-Oerlinghausen B. Non-adherence with long-term prophylaxis: a 6-year naturalistic follow-up study of affectively ill patients. Psychiatry Res 1999; 89:247-57. [PMID: 10708271 DOI: 10.1016/s0165-1781(99)00108-0] [Citation(s) in RCA: 68] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
In a retrospective 6-year follow-up, we assessed the reasons for and the frequency and consequences of non-adherence in 76 affectively ill patients receiving lithium prophylaxis in two lithium clinics. Thirty-eight bipolar (50%), 21 unipolar (27.6%) and 17 schizoaffective patients (22.4%) diagnosed according to DSM-III-R, were investigated with a specialized follow-up documentation. Of the patients 53.9% discontinued prophylaxis at some time; 43.2% of the discontinuations occurred during the first 6 months. In contrast to other studies the main reason reported for non-adherence was resistance against long-term treatment. According to the Lithium Attitudes Questionnaire non-adherent patients showed significantly less acceptance of the prophylaxis in general, of the effectiveness of lithium and of the severity of their illness than adherent patients. In a multivariate analysis of various parameters, only the negative attitude to prophylaxis correlated significantly with non-adherence. Significant correlation was found between treatment outcome and duration of initial prophylaxis. During the 6-year follow-up only the adherent patients showed a significant reduction of the number and duration of admissions. Our findings confirmed non-adherence as a major problem in the effectiveness of lithium prophylaxis. The authors recommend prospective investigations of attitudes and the impact of psychoeducation on long-term adherence.
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Affiliation(s)
- C Schumann
- Department of Psychiatry, University of Vienna, Austria.
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47
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Abstract
BACKGROUND This study aimed to investigate the demographical and clinical factors and their predictive powers before and at the end of the 6th and 12th month of lithium prophylaxis. METHODS Subjects meeting the following criteria were included in the investigation: (1) bipolar patients (DSM-IV); (2) having at least a 3-year lithium prophylaxis; (3) being in either the 'definite poor' or 'definite good' response groups. Both groups were compared regarding sociodemographic and clinical variables. RESULTS At the pretreatment point of the prophylaxis, four variables that could predict poor response with 74.1% power were severe episodes, higher ratio of mania/depression, psychotic index episode and being unmarried. At the end of the 6th month, the five variables having 84.89% predictive power for poor response were again the previous three variables and additionally bipolar I diagnosis and poor response to the first 6 months of lithium. At the end of the 12th month, the three variables for poor response had 91.37% predictive power and these were again the previous first two variables and a poor response to the first 12 months of lithium. LIMITATIONS This was a retrospective study; psychosocial stress was not evaluated by standardized criteria; and the predictive value of personality disorders could not be tested thoroughly. CONCLUSIONS This study suggests that it is possible to predict, rather reliably, the response to prophylactic lithium regarding clinical variables.
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Affiliation(s)
- O Yazici
- Istanbul University, Istanbul Medical Faculty, Psychiatry Department, Capa, Turkey
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48
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Kulhara P, Basu D, Mattoo SK, Sharan P, Chopra R. Lithium prophylaxis of recurrent bipolar affective disorder: long-term outcome and its psychosocial correlates. J Affect Disord 1999; 54:87-96. [PMID: 10403151 DOI: 10.1016/s0165-0327(98)00145-1] [Citation(s) in RCA: 41] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND Discrepancy between efficacy of prophylactic lithium and its effectiveness in ordinary clinical practice necessitates long-term follow-up data from specialised lithium clinics. Also, role of psychosocial factors in influencing the outcome is unclear. METHODS One hundred and eighteen patients of bipolar affective disorder attending a lithium clinic were followed-up for approximately 11 years (range 2-27 years). Demographic and clinical data, measures of social support and psychosocial stress were obtained at the intake in 1989-1990. Study design combined retrospective chart-review (till the time of intake) with prospective follow-up till July 1995. RESULTS On lithium, the patients had a mean of 0.43 relapses per year (manic, 0.26; depressive, 0.17) which was significantly less (p < 0.01) than the pre-lithium episode frequency. The figure for entirely relapse-free patients was 24%, and 62% had relapses up to one episode per year (median = 0.3 per year). Fifty-eight (49%) patients were good responders to lithium (relapses < or = 0.30 per year). In comparison to good responders, partial/poor responders had a significantly greater number of pre-lithium depressive episodes, poor lithium compliance, more psychosocial stress and lower social support at intake. These variables correlated well with relapses and explained 32% of the variance of the data. CONCLUSIONS Lithium had a definite prophylactic effect on long-term outcome. Social support and stressful life events are significant correlates of response to lithium. CLINICAL IMPLICATIONS Lithium prophylaxis of bipolar affective disorders seems justified though psychosocial factors appear to modulate its effectiveness. LIMITATIONS Other psychotropic medications were used during relapse and the assessment of psychosocial factors was cross-sectional.
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Affiliation(s)
- P Kulhara
- Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
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49
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Turvey CL, Coryell WH, Solomon DA, Leon AC, Endicott J, Keller MB, Akiskal H. Long-term prognosis of bipolar I disorder. Acta Psychiatr Scand 1999; 99:110-9. [PMID: 10082186 DOI: 10.1111/j.1600-0447.1999.tb07208.x] [Citation(s) in RCA: 54] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
This study examined the contribution of demographic, syndromal and longitudinal course variables to the long-term prognosis of 165 bipolar patients prospectively observed over 10 years as part of the National Institute of Mental Health Collaborative Study of Depression. Although most baseline clinical and demographic variables were not strong prognostic indicators, switching polarity within episodes was. Most episodes among the poor-prognosis patients were polyphasic, while most episodes among the comparison group with a better prognosis were monophasic. There was no evidence of shortening of cycle lengths over follow-up for either the poor-prognosis group or the entire sample. The relevance of these findings to the 'kindling' model is discussed.
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Affiliation(s)
- C L Turvey
- Department of Psychiatry, University of Iowa, Iowa City 52242-1000, USA
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50
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Greil W, Kleindienst N, Erazo N, Müller-Oerlinghausen B. Differential response to lithium and carbamazepine in the prophylaxis of bipolar disorder. J Clin Psychopharmacol 1998; 18:455-60. [PMID: 9864077 DOI: 10.1097/00004714-199812000-00007] [Citation(s) in RCA: 103] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
In a randomized, prospective, multicenter study with an observation period of 2.5 years, the differential prophylactic efficacy of lithium versus carbamazepine was compared in 171 patients fulfilling DSM-IV criteria for bipolar disorder. Serum drug levels were 0.6+/-0.1 mmol/L for lithium and 6.1+/-1.3 microg/mL for carbamazepine. Patients were subdivided into a classical subgroup (bipolar I patients without mood-incongruent delusions and without comorbidity, N = 67) and a nonclassical subgroup including all other patients (N = 104). Classical bipolar patients had a lower rehospitalization rate with lithium than with carbamazepine prophylaxis (p = 0.005). For the nonclassical group, a trend in favor of carbamazepine was found. In the lithium group, there was a positive association between hospitalization rate and number of nonclassical features (bipolar II/not otherwise specified, mood-incongruent delusions, comorbidity; p = 0.035). For carbamazepine, this association was negative (p = 0.033). Analyses including mixed states as an additional nonclassical feature confirmed the results. In conclusion, lithium seems to be superior to carbamazepine in treating classical bipolar cases. Patients with nonclassical features might profit more from prophylaxis with carbamazepine, which seems to have a broader spectrum of activity.
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Affiliation(s)
- W Greil
- Psychiatric Hospital of the University of Munich, Germany.
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