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Navia-Pelaez JM, Silva Dias MT, Ariza Orellano LA, Campos GP, Alvarez-Leite J, Campos PP, Aggum Capettini LS. Dual effect of amitriptyline in the control of vascular tone: Direct blockade of calcium channel in smooth muscle cells and reduction of TLR4-dependent NO production in endothelial cells. Eur J Pharmacol 2022; 934:175255. [PMID: 36088982 DOI: 10.1016/j.ejphar.2022.175255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Revised: 08/01/2022] [Accepted: 09/05/2022] [Indexed: 11/03/2022]
Abstract
BACKGROUND AND PURPOSE Amitriptyline (AM) is a classical and typical tricyclic antidepressant drug. Despite its well-known effects on the nervous system, it has been described to work as a TLR4 antagonist and several clinical works suggested some unexpected cardiovascular effects. The role of amitriptyline on vascular tone is not clear, thus we hypothesized that amitriptyline has a double effect on vascular tone by both endothelial TLR4-dependent nitric oxide down-regulation and calcium channel blockade in smooth muscle cells. EXPERIMENTAL APPROACH Changes in isometric tension were recorded on a wire myograph. NO production was evaluated by fluorescence microscopy and flow cytometry in the mouse aorta and EAhy926 cells using DAF fluorescence intensity. Calcium influx was evaluated in A7r5 cells by flow cytometry. Western blot was used to analyze eNOS and nNOS phosphorylation. KEY RESULTS AM reduced PE-induced contraction by calcium influx diminution in smooth muscle cells (F/F0 = 225.6 ± 15.9 and 118.6 ± 17.6 to CT and AM, respectively). AM impaired Ach-dependent vasodilation (Emax = 95.8 ± 1.4; 78.1 ± 1.8; 60.4 ± 2.9 and -7.4 ± 1.0 for CT, 0.01, 0,1 and 1 μmol/L AM, respectively) through reduction of calcium influx and NO availability and TLR4 antagonism in a concentration-dependent manner. AM or TLR4 gene deletion significantly reduced NO production (Fluorescence = 9503 ± 871.7, 2561 ± 282, 4771 ± 728 and 1029 ± 103 to CT, AM, TLR4-/- and AM + TLR4-/-, respectively) by an increase in nNOSser852 and reduction in eNOSser1177 phosphorylation in endothelial cells. CONCLUSIONS AND IMPLICATIONS Our data show that amitriptyline impaired vascular function through two different mechanisms: blockade of TLR4 in endothelial cells and consequent decrease in NO production and calcium influx reduction in smooth muscle and endothelial cells. We also suggest, for the first time, nNOS activity reduction by AM in non-neuronal cells.
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Affiliation(s)
- Juliana Maria Navia-Pelaez
- Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Av. Antônio Carlos 6627 - Campus Pampulha, Cx Post 468, CEP 31270-901, Belo Horizonte, MG, Brazil; Department of Medicine. University of California San Diego, Biomedical Sciences Building, Room 1081 9500 Gilman Drive, La Jolla, CA, 92093-0682, USA.
| | - Melissa Tainan Silva Dias
- Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Av. Antônio Carlos 6627 - Campus Pampulha, Cx Post 468, CEP 31270-901, Belo Horizonte, MG, Brazil.
| | - Laura Alejandra Ariza Orellano
- Department of General Pathology, Faculty of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. Av. Antônio Carlos, 6627, Pampulha, 31270-901, Belo Horizonte, MG, Brazil.
| | - Gianne Paul Campos
- Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Av. Antônio Carlos 6627 - Campus Pampulha, Cx Post 468, CEP 31270-901, Belo Horizonte, MG, Brazil.
| | - Jacqueline Alvarez-Leite
- Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Av. Antônio Carlos 6627 - Campus Pampulha, Cx Post 468, CEP 31270-901, Belo Horizonte, MG, Brazil.
| | - Paula Peixoto Campos
- Department of General Pathology, Faculty of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. Av. Antônio Carlos, 6627, Pampulha, 31270-901, Belo Horizonte, MG, Brazil.
| | - Luciano Santos Aggum Capettini
- Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Av. Antônio Carlos 6627 - Campus Pampulha, Cx Post 468, CEP 31270-901, Belo Horizonte, MG, Brazil.
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Brueckle MS, Thomas ET, Seide SE, Pilz M, Gonzalez-Gonzalez AI, Nguyen TS, Harder S, Glasziou PP, Gerlach FM, Muth C. Adverse drug reactions associated with amitriptyline - protocol for a systematic multiple-indication review and meta-analysis. Syst Rev 2020; 9:59. [PMID: 32183872 PMCID: PMC7079360 DOI: 10.1186/s13643-020-01296-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Accepted: 02/16/2020] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Unwanted anticholinergic effects are both underestimated and frequently overlooked. Failure to identify adverse drug reactions (ADRs) can lead to prescribing cascades and the unnecessary use of over-the-counter products. The objective of this systematic review and meta-analysis is to explore and quantify the frequency and severity of ADRs associated with amitriptyline vs. placebo in randomized controlled trials (RCTs) involving adults with any indication, as well as healthy individuals. METHODS A systematic search in six electronic databases, forward/backward searches, manual searches, and searches for Food and Drug Administration (FDA) and European Medicines Agency (EMA) approval studies, will be performed. Placebo-controlled RCTs evaluating amitriptyline in any dosage, regardless of indication and without restrictions on the time and language of publication, will be included, as will healthy individuals. Studies of topical amitriptyline, combination therapies, or including < 100 participants, will be excluded. Two investigators will screen the studies independently, assess methodological quality, and extract data on design, population, intervention, and outcomes ((non-)anticholinergic ADRs, e.g., symptoms, test results, and adverse drug events (ADEs) such as falls). The primary outcome will be the frequency of anticholinergic ADRs as a binary outcome (absolute number of patients with/without anticholinergic ADRs) in amitriptyline vs. placebo groups. Anticholinergic ADRs will be defined by an experienced clinical pharmacologist, based on literature and data from Martindale: The Complete Drug Reference. Secondary outcomes will be frequency and severity of (non-)anticholinergic ADRs and ADEs. The information will be synthesized in meta-analyses and narratives. We intend to assess heterogeneity using meta-regression (for indication, outcome, and time points) and I2 statistics. Binary outcomes will be expressed as odds ratios, and continuous outcomes as standardized mean differences. Effect measures will be provided using 95% confidence intervals. We plan sensitivity analyses to assess methodological quality, outcome reporting etc., and subgroup analyses on age, dosage, and duration of treatment. DISCUSSION We will quantify the frequency of anticholinergic and other ADRs/ADEs in adults taking amitriptyline for any indication by comparing rates for amitriptyline vs. placebo, hence, preventing bias from disease symptoms and nocebo effects. As no standardized instrument exists to measure it, our overall estimate of anticholinergic ADRs may have limitations. SYSTEMATIC REVIEW REGISTRATION Submitted to PROSPERO; assignment is in progress.
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Affiliation(s)
- Maria-Sophie Brueckle
- Institute of General Practice, |Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany
| | - Elizabeth T. Thomas
- Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Australia
| | - Svenja E. Seide
- Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany
| | - Maximilian Pilz
- Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany
| | - Ana Isabel Gonzalez-Gonzalez
- Institute of General Practice, |Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany
| | - Truc Sophia Nguyen
- Institute of General Practice, |Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany
| | - Sebastian Harder
- Goethe University, Institute of Clinical Pharmacology, Frankfurt, Germany
| | - Paul P. Glasziou
- Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Australia
| | - Ferdinand M. Gerlach
- Institute of General Practice, |Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany
| | - Christiane Muth
- Institute of General Practice, |Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany
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Abstract
Depression and other mood disorders occur in approximately 25 percent of terminal patients. Untreated, depression and mood disorders can have a significantly negative impact on patients andfamilies. Screeningfor depression can be done as easily as asking one question: “Areyou depressed?” A positive response to this question can be followed with one of the more extensive screening tools. Anxiety disorders can also have a negative effect on patients and their families. These can be identified by also using one of the validated screening tools. Use of the antidepressant medications for treating depression and, in some cases, anxiety disorders has not been well studied in hospice and palliative care. Some of the antidepressants can also serve as adjuvant therapy in pain management.
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Affiliation(s)
- Karl E Miller
- Department of Family Medicine, Chattanooga Unit, University of Tennessee COM, Chattanooga, Tennessee, USA
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Cleare A, Pariante CM, Young AH, Anderson IM, Christmas D, Cowen PJ, Dickens C, Ferrier IN, Geddes J, Gilbody S, Haddad PM, Katona C, Lewis G, Malizia A, McAllister-Williams RH, Ramchandani P, Scott J, Taylor D, Uher R. Evidence-based guidelines for treating depressive disorders with antidepressants: A revision of the 2008 British Association for Psychopharmacology guidelines. J Psychopharmacol 2015; 29:459-525. [PMID: 25969470 DOI: 10.1177/0269881115581093] [Citation(s) in RCA: 429] [Impact Index Per Article: 42.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
A revision of the 2008 British Association for Psychopharmacology evidence-based guidelines for treating depressive disorders with antidepressants was undertaken in order to incorporate new evidence and to update the recommendations where appropriate. A consensus meeting involving experts in depressive disorders and their management was held in September 2012. Key areas in treating depression were reviewed and the strength of evidence and clinical implications were considered. The guidelines were then revised after extensive feedback from participants and interested parties. A literature review is provided which identifies the quality of evidence upon which the recommendations are made. These guidelines cover the nature and detection of depressive disorders, acute treatment with antidepressant drugs, choice of drug versus alternative treatment, practical issues in prescribing and management, next-step treatment, relapse prevention, treatment of relapse and stopping treatment. Significant changes since the last guidelines were published in 2008 include the availability of new antidepressant treatment options, improved evidence supporting certain augmentation strategies (drug and non-drug), management of potential long-term side effects, updated guidance for prescribing in elderly and adolescent populations and updated guidance for optimal prescribing. Suggestions for future research priorities are also made.
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Affiliation(s)
- Anthony Cleare
- Professor of Psychopharmacology & Affective Disorders, King's College London, Institute of Psychiatry, Psychology and Neuroscience, Centre for Affective Disorders, London, UK
| | - C M Pariante
- Professor of Biological Psychiatry, King's College London, Institute of Psychiatry, Psychology and Neuroscience, Centre for Affective Disorders, London, UK
| | - A H Young
- Professor of Psychiatry and Chair of Mood Disorders, King's College London, Institute of Psychiatry, Psychology and Neuroscience, Centre for Affective Disorders, London, UK
| | - I M Anderson
- Professor and Honorary Consultant Psychiatrist, University of Manchester Department of Psychiatry, University of Manchester, Manchester, UK
| | - D Christmas
- Consultant Psychiatrist, Advanced Interventions Service, Ninewells Hospital & Medical School, Dundee, UK
| | - P J Cowen
- Professor of Psychopharmacology, Psychopharmacology Research Unit, Neurosciences Building, University Department of Psychiatry, Warneford Hospital, Oxford, UK
| | - C Dickens
- Professor of Psychological Medicine, University of Exeter Medical School and Devon Partnership Trust, Exeter, UK
| | - I N Ferrier
- Professor of Psychiatry, Honorary Consultant Psychiatrist, School of Neurology, Neurobiology & Psychiatry, Royal Victoria Infirmary, Newcastle upon Tyne, UK
| | - J Geddes
- Head, Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK
| | - S Gilbody
- Director of the Mental Health and Addictions Research Group (MHARG), The Hull York Medical School, Department of Health Sciences, University of York, York, UK
| | - P M Haddad
- Consultant Psychiatrist, Cromwell House, Greater Manchester West Mental Health NHS Foundation Trust, Salford, UK
| | - C Katona
- Division of Psychiatry, University College London, London, UK
| | - G Lewis
- Division of Psychiatry, University College London, London, UK
| | - A Malizia
- Consultant in Neuropsychopharmacology and Neuromodulation, North Bristol NHS Trust, Rosa Burden Centre, Southmead Hospital, Bristol, UK
| | - R H McAllister-Williams
- Reader in Clinical Psychopharmacology, Institute of Neuroscience, Newcastle University, Royal Victoria Infirmary, Newcastle upon Tyne, UK
| | - P Ramchandani
- Reader in Child and Adolescent Psychiatry, Centre for Mental Health, Imperial College London, London, UK
| | - J Scott
- Professor of Psychological Medicine, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK
| | - D Taylor
- Professor of Psychopharmacology, King's College London, London, UK
| | - R Uher
- Associate Professor, Canada Research Chair in Early Interventions, Dalhousie University, Department of Psychiatry, Halifax, NS, Canada
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Filipovic BR, Filipovic BF. Psychiatric comorbidity in the treatment of patients with inflammatory bowel disease. World J Gastroenterol 2014; 20:3552-3563. [PMID: 24707138 PMCID: PMC3974522 DOI: 10.3748/wjg.v20.i13.3552] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2013] [Revised: 12/20/2013] [Accepted: 01/20/2014] [Indexed: 02/06/2023] Open
Abstract
Ulcerative colitis and Crohn’s disease, commonly known as inflammatory bowel disease (IBD), draw attention from specialists of various disorders, including gastroenterology, psychiatry, and radiology. The involvement of a cortical influence in the brain-gut axis as well as the interaction of the hypothalamic-pituitary-adrenal axis and the peripheral nervous system provide an initial explanation of the psychological symptoms associated with IBD. The involvement of structures the limbic system, such as the anterior cingulate cortex, the prefrontal cortex, and the amygdala, paves the way for the discovery of the mechanisms underlying depression depression, anxiety, alexithymia, personality traits, and other psychological impairments following the onset of IBD. Psychiatric therapy in IBD patients is almost as important as the gastroenterological approach and consists of pharmacological treatment and psychotherapy. Neither of the available psychiatric treatment methods is considered the golden standard because both methods have side effects, and psychotropic medication can provoke the worsening of IBD symptoms. Thus, both approaches must be applied with awareness of the possibility of side effects. We suggest that psychiatrists and gastroenterologists work together to reach a consensus on IBD therapy to ensure success and to reduce side effects and relapse to the lowest possible rates.
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Won E, Park SC, Han KM, Sung SH, Lee HY, Paik JW, Jeon HJ, Lee MS, Shim SH, Ko YH, Lee KJ, Han C, Ham BJ, Choi J, Hwang TY, Oh KS, Hahn SW, Park YC, Lee MS. Evidence-based, pharmacological treatment guideline for depression in Korea, revised edition. J Korean Med Sci 2014; 29:468-484. [PMID: 24753693 PMCID: PMC3991789 DOI: 10.3346/jkms.2014.29.4.468] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2013] [Accepted: 02/07/2014] [Indexed: 12/12/2022] Open
Abstract
This paper aims to introduce, summarize, and emphasize the importance of the 'Evidence-Based, Pharmacological Treatment Guideline for Depression in Korea, Revised Edition'. The guideline broadly covers most aspects of the pharmacological treatment of patients in Korea diagnosed with moderate to severe major depression according to the DSM-IV TR. The guideline establishment process involved determining and answering a number of key questions, searching and selecting publications, evaluating recommendations, preparing guideline drafts, undergoing external expert reviews, and obtaining approval. A guideline adaptation process was conducted for the revised edition. The guideline strongly recommends pharmacological treatment considered appropriate to the current clinical situation in Korea, and should be considered helpful when selecting the appropriate pharmacological treatment of patients diagnosed with major depressive disorder. Therefore, the wide distribution of this guideline is recommended.
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Affiliation(s)
- Eunsoo Won
- Department of Psychiatry, College of Medicine, Korea University, Seoul, Korea
| | - Seon-Cheol Park
- Department of Psychiatry, Yong-In Mental Hospital, Yongin, Korea
| | - Kyu-Man Han
- Department of Psychiatry, College of Medicine, Korea University, Seoul, Korea
| | - Seung-Hwan Sung
- Department of Psychiatry, College of Medicine, Soonchunhyang University, Asan, Korea
| | - Hwa-Young Lee
- Department of Psychiatry, College of Medicine, Soonchunhyang University, Asan, Korea
| | - Jong-Woo Paik
- Department of Psychiatry, School of Medicine, KyungHee University, Seoul, Korea
| | - Hong Jin Jeon
- Department of Psychiatry, School of Medicine, Sungkyunkwan University, Seoul, Korea
| | - Moon-Soo Lee
- Department of Psychiatry, College of Medicine, Korea University, Seoul, Korea
| | - Se-Hoon Shim
- Department of Psychiatry, College of Medicine, Soonchunhyang University, Asan, Korea
| | - Young-Hoon Ko
- Department of Psychiatry, College of Medicine, Korea University, Seoul, Korea
| | - Kang-Joon Lee
- Department of Psychiatry, College of Medicine, Inje Universtiy, Busan, Korea
| | - Changsu Han
- Department of Psychiatry, College of Medicine, Korea University, Seoul, Korea
| | - Byung-Joo Ham
- Department of Psychiatry, College of Medicine, Korea University, Seoul, Korea
| | - Joonho Choi
- Department of Psychiatry, College of Medicine, Hanyang University, Seoul, Korea
| | - Tae-Yeon Hwang
- Department of Psychiatry, Yong-In Mental Hospital, Yongin, Korea
| | - Kang-Seob Oh
- Department of Psychiatry, School of Medicine, Sungkyunkwan University, Seoul, Korea
| | - Sang-Woo Hahn
- Department of Psychiatry, College of Medicine, Soonchunhyang University, Asan, Korea
| | - Yong-Chon Park
- Department of Psychiatry, College of Medicine, Hanyang University, Seoul, Korea
| | - Min-Soo Lee
- Department of Psychiatry, College of Medicine, Korea University, Seoul, Korea
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Watanabe N, Omori IM, Nakagawa A, Cipriani A, Barbui C, Churchill R, Furukawa TA. Mirtazapine versus other antidepressive agents for depression. Cochrane Database Syst Rev 2011:CD006528. [PMID: 22161405 PMCID: PMC4158430 DOI: 10.1002/14651858.cd006528.pub2] [Citation(s) in RCA: 81] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
BACKGROUND Mirtazapine has a unique mechanism of antidepressive action and is one of the commonly used antidepressants in clinical practice. OBJECTIVES The aim of the present review was to assess the evidence on the efficacy and acceptability of mirtazapine compared with other antidepressive agents in the acute-phase treatment of major depression in adults. SEARCH METHODS We searched the Cochrane Collaboration Depression, Anxiety and Neurosis review group's specialised register (CCDANCTR), which includes relevant randomised controlled trials from the following bibliographic databases: The Cochrane Library (all years to April 2011), EMBASE, (1980 to July 2011) MEDLINE (1950 to July 2011) and PsycINFO (1974 to July 2011). Reference lists of the reports of relevant studies were checked and experts in the field contacted. The review was not limited to English-language articles. SELECTION CRITERIA Randomised controlled trials (RCTs) allocating participants with major depression to mirtazapine versus any other antidepressive agent. DATA COLLECTION AND ANALYSIS Two authors independently checked eligibility and extracted data on an intention-to-treat basis. The primary outcome was response to treatment. The secondary outcomes included dropouts and individual adverse events.Meta-analyses were conducted using the random-effects model. MAIN RESULTS A total of 29 RCTs (n = 4974), mostly following up the participants for six weeks in outpatient clinics and inadequately reporting the risk of bias, were included. In comparison with tricyclic antidepressants (10 trials, n = 1553) there was no robust evidence to detect a difference between mirtazapine and tricyclics in terms of response at two weeks (odds ratio (OR) 0.85, 95% confidence interval (CI) 0.64 to 1.13) or at the end of acute-phase treatment (at 6 to 12 weeks) (OR 0.89, 95% CI 0.72 to 1.10). In comparison with selective serotonin reuptake inhibitors (SSRIs) (12 trials, n = 2626) mirtazapine was significantly more effective at two weeks (OR 1.57, 95% CI 1.30 to 1.88) and at the end of acute-phase treatment (OR 1.19, 95% CI 1.01 to 1.39). Mirtazapine was significantly more effective than a serotonin-noradrenaline reuptake inhibitor (venlafaxine only, two trials, n = 415) at two weeks (OR 2.29, 95% CI 1.45 to 3.59) and at the end of acute-phase treatment (OR 1.53, 95% CI 1.03 to 2.25).In terms of dropouts, there was no robust evidence to detect a difference between mirtazapine and other antidepressants. Mirtazapine was more likely to cause weight gain or increased appetite and somnolence than SSRIs but less likely to cause nausea or vomiting and sexual dysfunction. AUTHORS' CONCLUSIONS Some statistically significant and possibly clinically meaningful differences between mirtazapine and other antidepressive agents were found for the acute-phase treatment of major depression. Mirtazapine is likely to have a faster onset of action than SSRIs during the acute-phase treatment. Dropouts occur similarly in participants treated with mirtazapine and those treated with other antidepressants, although the adverse event profile of mirtazapine is unique.
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Affiliation(s)
- Norio Watanabe
- Department of Psychiatry & Cognitive-Behavioral Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Ichiro M Omori
- Department of Psychiatry, Toyokawa City Hospital, Aichi, Japan
| | - Atsuo Nakagawa
- Department of Psychiatry, Keio University School of Medicine, Tokyo, Japan
| | - Andrea Cipriani
- Department of Public Health and Community Medicine, Section of Psychiatry and Clinical Psychology, University of Verona, Verona, Italy
| | - Corrado Barbui
- Department of Public Health and Community Medicine, Section of Psychiatry and Clinical Psychology, University of Verona, Verona, Italy
| | - Rachel Churchill
- Academic Unit of Psychiatry, School of Social and Community Medicine, University of Bristol, Bristol, UK
| | - Toshi A Furukawa
- Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine / School of Public Health, Kyoto, Japan
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General and comparative efficacy and effectiveness of antidepressants in the acute treatment of depressive disorders: a report by the WPA section of pharmacopsychiatry. Eur Arch Psychiatry Clin Neurosci 2011; 261 Suppl 3:207-45. [PMID: 22033583 DOI: 10.1007/s00406-011-0259-6] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Current gold standard approaches to the treatment of depression include pharmacotherapeutic and psychotherapeutic interventions with social support. Due to current controversies concerning the efficacy of antidepressants in randomized controlled trials, the generalizability of study findings to wider clinical practice and the increasing importance of socioeconomic considerations, it seems timely to address the uncertainty of concerned patients and relatives, and their treating psychiatrists and general practitioners. We therefore discuss both the efficacy and clinical effectiveness of antidepressants in the treatment of depressive disorders. We explain and clarify useful measures for assessing clinically meaningful antidepressant treatment effects and the types of studies that are useful for addressing uncertainties. This includes considerations of methodological issues in randomized controlled studies, meta-analyses, and effectiveness studies. Furthermore, we summarize the differential efficacy and effectiveness of antidepressants with distinct pharmacodynamic properties, and differences between studies using antidepressants and/or psychotherapy. We also address the differential effectiveness of antidepressant drugs with differing modes of action and in varying subtypes of depressive disorder. After highlighting the clinical usefulness of treatment algorithms and the divergent biological, psychological, and clinical efforts to predict the effectiveness of antidepressant treatments, we conclude that the spectrum of different antidepressant treatments has broadened over the last few decades. The efficacy and clinical effectiveness of antidepressants is statistically significant, clinically relevant, and proven repeatedly. Further optimization of treatment can be helped by clearly structured treatment algorithms and the implementation of psychotherapeutic interventions. Modern individualized antidepressant treatment is in most cases a well-tolerated and efficacious approach to minimize the negative impact of otherwise potentially devastating and life-threatening outcomes in depressive disorders.
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9
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Singh SP, Singh V, Kar N, Chan K. Efficacy of antidepressants in treating the negative symptoms of chronic schizophrenia: meta-analysis. Br J Psychiatry 2010; 197:174-9. [PMID: 20807960 DOI: 10.1192/bjp.bp.109.067710] [Citation(s) in RCA: 140] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND Treatment of negative symptoms in chronic schizophrenia continues to be a major clinical issue. AIMS To analyse the efficacy of add-on antidepressants for the treatment of negative symptoms of chronic schizophrenia. METHOD Systematic review and meta-analysis of randomised controlled trials comparing the effect of antidepressants and placebo on the negative symptoms of chronic schizophrenia, measured through standardised rating scales. Outcome was measured as standardised mean difference between end-of-trial and baseline scores of negative symptoms. RESULTS There were 23 trials from 22 publications (n = 819). The antidepressants involved were selective serotonin reuptake inhibitors, mirtazapine, reboxetine, mianserin, trazodone and ritanserin; trials on other antidepressants were not available. The overall standardised mean difference was moderate (-0.48) in favour of antidepressants and subgroup analysis revealed significant responses for fluoxetine, trazodone and ritanserin. CONCLUSIONS Antidepressants along with antipsychotics are more effective in treating the negative symptoms of schizophrenia than antipsychotics alone.
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Affiliation(s)
- Surendra P Singh
- University of Wolverhampton and Step to Health, Wolverhampton City Primary Care Trust, UK.
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10
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Nakagawa A, Watanabe N, Omori IM, Barbui C, Cipriani A, McGuire H, Churchill R, Furukawa TA. Milnacipran versus other antidepressive agents for depression. Cochrane Database Syst Rev 2009:CD006529. [PMID: 19588396 PMCID: PMC4164845 DOI: 10.1002/14651858.cd006529.pub2] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
BACKGROUND Although pharmacological and psychological interventions are both effective for major depression, antidepressant drugs are frequently used as first-line treatment in primary and secondary care settings. Milnacipran, a dual serotonin-norepinephrine reuptake inhibitor (SNRI), is one of the antidepressant drugs that clinicians use for routine depression care. OBJECTIVES To assess the evidence for the efficacy, acceptability and tolerability of milnacipran in comparison with tricyclic antidepressants (TCAs), heterocyclics, SSRIs and other newer antidepressive agents in the acute-phase treatment of major depression. SEARCH STRATEGY The Cochrane Collaboration Depression, Anxiety & Neurosis review group Controlled Trials Register (CCDANCTR-Studies and CCDANCTR-References) were electronically searched in August 2008. References of relevant trials and other reviews were also checked. Trial databases of the drug-approving agencies and ongoing clinical trial registers for all published and unpublished trials were hand-searched in 2007. All relevant authors were contacted for supplemental data. No language restriction was applied. SELECTION CRITERIA Randomised controlled trials comparing milnacipran with any other active antidepressive agents (including non-conventional agents such as herbal products like hypericum) as monotherapy in the acute phase of major depression were selected. DATA COLLECTION AND ANALYSIS Two reviewers independently checked eligibility, assessed methodological quality and extracted data from the eligible trials using a standardised data extraction form. The number of participants who responded to treatment or those who achieved remission were calculated on an intention-to-treat basis. Random-effects meta-analyses were conducted, combining data from the included trials. MAIN RESULTS A total of 16 randomised controlled trials (n=2277) were included in the meta-analysis.Despite the size of this sample, the pooled 95% confidence intervals were rather wide and there were no statistically significant differences in efficacy, acceptability and tolerability when comparing milnacipran with other antidepressive agents. However, compared with TCAs, patients taking milnacipran were associated with fewer dropouts due to adverse events (OR 0.55; 95%CI 0.35 to 0.85). There was also some weak evidence to suggest that patients taking milnacipran experienced fewer adverse events of sleepiness/ drowsiness, dry mouth or constipation compared with TCAs. AUTHORS' CONCLUSIONS Currently, there is inadequate evidence to conclude whether milnacipran is superior, inferior or the same as other antidepressive agents in terms of efficacy, acceptability and tolerability in the acute phase treatment of major depression. However, there is some evidence in favour of milnacipran over TCAs in terms of dropouts due to adverse events (acceptability) and the rates of experiencing adverse events (tolerability). Information about other clinically meaningful outcomes such as cost-effectiveness and social functioning, including the ability to return to work, is lacking. Further study is needed to answer whether milnacipran would be the better choice of antidepressant for acute major depression.
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Affiliation(s)
- Atsuo Nakagawa
- Department of Psychiatry, Keio University School of Medicine, Tokyo, Japan
| | - Norio Watanabe
- Department of Psychiatry & Cognitive-Behavioral Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Ichiro M Omori
- Cochrane Schizophrenia Group, University of Nottingham, Nottingham, UK
| | - Corrado Barbui
- Department of Medicine and Public Health, Section of Psychiatry and Clinical Psychology, University of Verona, Verona, Italy
| | - Andrea Cipriani
- Department of Medicine and Public Health, Section of Psychiatry and Clinical Psychology, University of Verona, Verona, Italy
| | - Hugh McGuire
- National Coordinating Centre for Women and Child Health, London, UK
| | - Rachel Churchill
- Academic Unit of Psychiatry, Community Based Medicine, University of Bristol, Bristol, UK
| | - Toshi A Furukawa
- Department of Psychiatry & Cognitive-Behavioral Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
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11
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Cipriani A, Santilli C, Furukawa TA, Signoretti A, Nakagawa A, McGuire H, Churchill R, Barbui C. Escitalopram versus other antidepressive agents for depression. Cochrane Database Syst Rev 2009; 2016:CD006532. [PMID: 19370639 PMCID: PMC4164382 DOI: 10.1002/14651858.cd006532.pub2] [Citation(s) in RCA: 87] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
BACKGROUND Although pharmacological and psychological interventions are both effective for major depression, antidepressant drugs remain the mainstay of treatment in primary and secondary care settings. During the last 20 years, antidepressant prescribing has risen dramatically in western countries, mainly because of the increasing consumption of selective serotonin reuptake inhibitors (SSRIs) and newer antidepressants, which have progressively become the most commonly prescribed antidepressants. Escitalopram is the pure S-enantiomer of the racemic citalopram. OBJECTIVES To assess the evidence for the efficacy, acceptability and tolerability of escitalopram in comparison with tricyclics, other SSRIs, heterocyclics and newer agents in the acute-phase treatment of major depression. SEARCH STRATEGY Electronic databases were searched up to July 2008. Trial databases of drug-approving agencies were hand-searched for published, unpublished and ongoing controlled trials. SELECTION CRITERIA All randomised controlled trials comparing escitalopram against any other antidepressant (including non-conventional agents such as hypericum) for patients with major depressive disorder (regardless of the diagnostic criteria used). DATA COLLECTION AND ANALYSIS Data were entered by two review authors (double data entry). Responders and remitters to treatment were calculated on an intention-to-treat basis. For dichotomous data, odds ratios (ORs) were calculated with 95% confidence intervals (CI). Continuous data were analysed using standardised mean differences (with 95% CI) using the random effects model. MAIN RESULTS Fourteen trials compared escitalopram with another SSRI and eight compared escitalopram with a newer antidepressive agent (venlafaxine, bupropion and duloxetine). Escitalopram was shown to be significantly more effective than citalopram in achieving acute response (OR 0.67, 95% CI 0.50 to 0.87). Escitalopram was also more effective than citalopram in terms of remission (OR 0.53, 95% CI 0.30 to 0.93). Significantly fewer patients allocated to escitalopram withdrew from trials compared with patients allocated to duloxetine, for discontinuation due to any cause (OR 0.62, 95% CI 0.38 to 0.99). AUTHORS' CONCLUSIONS Some statistically significant differences favouring escitalopram over other antidepressive agents for the acute phase treatment of major depression were found, in terms of efficacy (citalopram and fluoxetine) and acceptability (duloxetine). There is insufficient evidence to detect a difference between escitalopram and other antidepressants in early response to treatment (after two weeks of treatment). Cost-effectiveness information is also needed in the field of antidepressant trials. Furthermore, as with most standard systematic reviews, the findings rely on evidence from direct comparisons. The potential for overestimation of treatment effect due to sponsorship bias should also be borne in mind.
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Affiliation(s)
- Andrea Cipriani
- Department of Medicine and Public Health, Section of Psychiatry and Clinical Psychology, University of Verona, Policlinico "G.B.Rossi", Piazzale L.A. Scuro, 10, Verona, Italy, 37134.
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12
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Anderson IM, Ferrier IN, Baldwin RC, Cowen PJ, Howard L, Lewis G, Matthews K, McAllister-Williams RH, Peveler RC, Scott J, Tylee A. Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2000 British Association for Psychopharmacology guidelines. J Psychopharmacol 2008; 22:343-96. [PMID: 18413657 DOI: 10.1177/0269881107088441] [Citation(s) in RCA: 335] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
A revision of the 2000 British Association for Psychopharmacology evidence-based guidelines for treating depressive disorders with antidepressants was undertaken to incorporate new evidence and to update the recommendations where appropriate. A consensus meeting involving experts in depressive disorders and their management was held in May 2006. Key areas in treating depression were reviewed, and the strength of evidence and clinical implications were considered. The guidelines were drawn up after extensive feedback from participants and interested parties. A literature review is provided, which identifies the quality of evidence to inform the recommendations, the strength of which are based on the level of evidence. These guidelines cover the nature and detection of depressive disorders, acute treatment with antidepressant drugs, choice of drug versus alternative treatment, practical issues in prescribing and management, next-step treatment, relapse prevention, treatment of relapse, and stopping treatment.
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Affiliation(s)
- I M Anderson
- Senior Lecturer and Honorary Consultant Psychiatrist, Neuroscience and Psychiatry Unit, University of Manchester, UK.
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13
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Peles E, Schreiber S, Adelson M. Tricyclic antidepressants abuse, with or without benzodiazepines abuse, in former heroin addicts currently in methadone maintenance treatment (MMT). Eur Neuropsychopharmacol 2008; 18:188-93. [PMID: 17997285 DOI: 10.1016/j.euroneuro.2007.10.001] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2007] [Revised: 09/25/2007] [Accepted: 10/01/2007] [Indexed: 10/22/2022]
Abstract
BACKGROUND To measure suspected abuse of the tricyclic antidepressant amitriptyline among methadone maintenance treatment (MMT) patients in Israel, we studied cross-sectionally, all our 303 patients (February, 2007). METHODS Tricyclics presence was screened in one of the random urine samples routinely taken for tests of other drugs. ASI questionnaire, variables from patients' records. FINDINGS 48 (15.8%) patients were positive for amitriptyline. Logistic regression (multivariate analyses) found that the extent of being amitriptyline-positive was higher in benzodiazepine (BDZ) abusers (OR=11.6 95% CI 4.4-30.7), in subjects with positive antibody to hepatitis C (OR=2.2, 95% CI 1.02-4.9) and in patients treated with high-dose methadone (>150 mg/day) (OR=2.4, 95% CI 1.2-4.9). Amitriptyline was found in 12 (7.5%) of the "privileged" group of patients (stabilized patients who, based on their long-standing cessation of any type of street-drugs abuse and prolonged normative behavior in treatment are granted "take home" methadone doses) who, by definition, should not be abusing anything. CONCLUSION The high prevalence of amitriptyline abuse found in our patients, and its potential cardiac hazards when combined with BDZ abuse, emphasizes the importance of amitriptyline routine monitoring in order to decrease the potential risk associated with amitriptyline combined with methadone and BDZ, and to implement appropriate interventions.
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Affiliation(s)
- Einat Peles
- Dr. Miriam and Sheldon G. Adelson Clinic for Drug Abuse, Treatment and Research, Israel
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14
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Schrag A, Barone P, Brown RG, Leentjens AFG, McDonald WM, Starkstein S, Weintraub D, Poewe W, Rascol O, Sampaio C, Stebbins GT, Goetz CG. Depression rating scales in Parkinson's disease: critique and recommendations. Mov Disord 2007; 22:1077-92. [PMID: 17394234 PMCID: PMC2040268 DOI: 10.1002/mds.21333] [Citation(s) in RCA: 465] [Impact Index Per Article: 25.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Depression is a common comorbid condition in Parkinson's disease (PD) and a major contributor to poor quality of life and disability. However, depression can be difficult to assess in patients with PD due to overlapping symptoms and difficulties in the assessment of depression in cognitively impaired patients. As several rating scales have been used to assess depression in PD (dPD), the Movement Disorder Society commissioned a task force to assess their clinimetric properties and make clinical recommendations regarding their use. A systematic literature review was conducted to explore the use of depression scales in PD and determine which scales should be selected for this review. The scales reviewed were the Beck Depression Inventory (BDI), Hamilton Depression Scale (Ham-D), Hospital Anxiety and Depression Scale (HADS), Zung Self-Rating Depression Scale (SDS), Geriatric Depression Scale (GDS), Montgomery-Asberg Depression Rating Scale (MADRS), Unified Parkinson's Disease Rating Scale (UPDRS) Part I, Cornell Scale for the Assessment of Depression in Dementia (CSDD), and the Center for Epidemiologic Studies Depression Scale (CES-D). Seven clinical researchers with clinical and research experience in the assessment of dPD were assigned to review the scales using a structured format. The most appropriate scale is dependent on the clinical or research goal. However, observer-rated scales are preferred if the study or clinical situation permits. For screening purposes, the HAM-D, BDI, HADS, MADRS, and GDS are valid in dPD. The CES-D and CSDD are alternative instruments that need validation in dPD. For measurement of severity of depressive symptoms, the Ham-D, MADRS, BDI, and SDS scales are recommended. Further studies are needed to validate the CSDD, which could be particularly useful for the assessment of severity of dPD in patients with comorbid dementia. To account for overlapping motor and nonmotor symptoms of depression, adjusted instrument cutoff scores may be needed for dPD, and scales to assess severity of motor symptoms (e.g., UPDRS) should also be included to help adjust for confounding factors. The HADS and the GDS include limited motor symptom assessment and may, therefore, be most useful in rating depression severity across a range of PD severity; however, these scales appear insensitive in severe depression. The complex and time-consuming task of developing a new scale to measure depression specifically for patients with PD is currently not warranted.
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Affiliation(s)
- Anette Schrag
- University Department of Clinical Neurosciences, Royal Free and University College Medical School, London, UK.
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Cipriani A, Signoretti A, Furukawa TA, Churchill R, Tomelleri S, Omori IM, McGuire H, Barbui C. Venlafaxine versus other anti-depressive agents for depression. Cochrane Database Syst Rev 2007:CD006530. [PMID: 25267891 PMCID: PMC4176661 DOI: 10.1002/14651858.cd006530] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
This is the protocol for a review and there is no abstract. The objectives are as follows: To determine the efficacy of venlafaxine in comparison with other anti-depressive agents in alleviating the acute symptoms of major depressive disorder.To review acceptability of treatment with venlafaxine in comparison with other anti-depressive agents.To investigate the adverse effects of venlafaxine in comparison with other anti-depressive agents.
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Affiliation(s)
- Andrea Cipriani
- Department of Medicine and Public Health, Section of Psychiatry and Clinical Psychology, University of Verona, Verona, Italy
| | - Alessandra Signoretti
- Department of Medicine and Public Health, Section of Psychiatry and Clinical Psychology, University of Verona, Verona, Italy
| | - Toshi A Furukawa
- Department of Psychiatry & Cognitive-Behavioral Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Rachel Churchill
- Academic Unit of Psychiatry, Community Based Medicine, University of Bristol, Bristol, UK
| | - Silva Tomelleri
- Department of Medicine and Public Health, Section of Psychiatry, University of Verona, Verona, Italy
| | - Ichiro M Omori
- Cochrane Schizophrenia Group, University of Nottingham, Nottingham, UK
| | - Hugh McGuire
- National Coordinating Centre for Women and Child Health, London, UK
| | - Corrado Barbui
- Department of Medicine and Public Health, Section of Psychiatry and Clinical Psychology, University of Verona, Verona, Italy
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16
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Cipriani A, Furukawa TA, Veronese A, Watanabe N, Churchill R, McGuire H, Barbui C. Paroxetine versus other anti-depressive agents for depression. Cochrane Database Syst Rev 2007:CD006531. [PMID: 25267892 PMCID: PMC4176672 DOI: 10.1002/14651858.cd006531] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
This is the protocol for a review and there is no abstract. The objectives are as follows: To determine the efficacy of paroxetine in comparison with other anti-depressive agents in alleviating the acute symptoms of major depressive disorder.To review acceptability of treatment with paroxetine in comparison with other anti-depressive agents.To investigate the adverse effects of paroxetine in comparison with other anti-depressive agents.
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Affiliation(s)
- Andrea Cipriani
- Department of Medicine and Public Health, Section of Psychiatry and Clinical Psychology, University of Verona, Verona, Italy
| | - Toshi A Furukawa
- Department of Psychiatry & Cognitive-Behavioral Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Antonio Veronese
- Section of Evidence Based Mental Health, Health Service & Population Research Department, Institute of Psychiatry, King’s College London, London, UK
| | - Norio Watanabe
- Department of Psychiatry & Cognitive-Behavioral Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Rachel Churchill
- Academic Unit of Psychiatry, Community Based Medicine, University of Bristol, Bristol, UK
| | - Hugh McGuire
- National Coordinating Centre for Women and Child Health, London, UK
| | - Corrado Barbui
- Department of Medicine and Public Health, Section of Psychiatry and Clinical Psychology, University of Verona, Verona, Italy
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17
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Lotrakul M, Saipanish R. Psychiatric services in primary care settings: a survey of general practitioners in Thailand. BMC FAMILY PRACTICE 2006; 7:48. [PMID: 16867187 PMCID: PMC1550240 DOI: 10.1186/1471-2296-7-48] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/03/2006] [Accepted: 07/24/2006] [Indexed: 01/30/2023]
Abstract
Background General Practitioners (GPs) in Thailand play an important role in treating psychiatric disorders since there is a shortage of psychiatrists in the country. Our aim was to examine GP's perception of psychiatric problems, drug treatment and service problems encountered in primary care settings. Methods We distributed 1,193 postal questionnaires inquiring about psychiatric practices and service problems to doctors in primary care settings throughout Thailand. Results Four hundred and thirty-four questionnaires (36.4%) were returned. Sixty-seven of the respondents (15.4%) who had taken further special training in various fields were excluded from the analysis, giving a total of 367 GPs in this study. Fifty-six per cent of respondents were males and they had worked for 4.6 years on average (median = 3 years). 65.6% (SD = 19.3) of the total patients examined had physical problems, 10.7% (SD = 7.9) had psychiatric problems and 23.9% (SD = 16.0) had both problems. The most common psychiatric diagnoses were anxiety disorders (37.5%), alcohol and drugs abuse (28.1%), and depressive disorders (29.2%). Commonly prescribed psychotropic drugs were anxiolytics and antidepressants. The psychotropic drugs most frequently prescribed were diazepam among anti-anxiety drugs, amitriptyline among antidepressant drugs, and haloperidol among antipsychotic drugs. Conclusion Most drugs available through primary care were the same as what existed 3 decades ago. There should be adequate supply of new and appropriate psychotropic drugs in primary care. Case-finding instruments for common mental disorders might be helpful for GPs whose quality of practice was limited by large numbers of patients. However, the service delivery system should be modified in order to maintain successful care for a large number of psychiatric patients.
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Affiliation(s)
- Manote Lotrakul
- Department of Psychiatry, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
| | - Ratana Saipanish
- Department of Psychiatry, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
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18
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Ausejo Segura M, Sáenz Calvo A, Jiménez Arriero MA. Efectividad de los nuevos antidepresivos frente a los clásicos inhibidores de la recaptación de la serotonina. Aten Primaria 2006; 38:5-7. [PMID: 16790211 PMCID: PMC7676053 DOI: 10.1157/13090019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
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Lavoie KL, Barone S. Prescription privileges for psychologists: a comprehensive review and critical analysis of current issues and controversies. CNS Drugs 2006; 20:51-66. [PMID: 16396524 DOI: 10.2165/00023210-200620010-00005] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
Abstract
The debate over whether clinical psychologists should be granted the right to prescribe psychoactive medications has received considerable attention over the past 2 decades in North America and, more recently, in the UK. Proponents of granting prescription privileges to clinical psychologists argue that mental healthcare services are in crisis and that the mental health needs of society are not being met. They attribute this crisis primarily to the inappropriate prescribing practices of general practitioners and a persistent shortage of psychiatrists. It is believed that, as they would increase the scope of the practice of psychology, prescription privileges for psychologists would enhance mental health services by increasing public access to qualified professionals who are able to prescribe. The profession of psychology remains divided on the issue, and opponents have been equally outspoken in their arguments. The purpose of the present article is to place the pursuit of prescription privileges for psychologists in context by discussing the historical antecedents and major forces driving the debate. The major arguments put forth for and against prescription privileges for psychologists are presented, followed by a critical analysis of the validity and coherence of those arguments. Through this analysis, the following question is addressed. Is there currently sufficient empirical support for the desirability, feasibility, safety and cost effectiveness of granting prescription privileges to psychologists? Although proponents of granting prescription privileges to psychologists present several compelling arguments in favour of this practice, there remains a consistent lack of empirical evidence for the desirability, feasibility, safety and cost effectiveness of this proposal. More research is needed before we can conclude that prescription privileges for psychologists are a safe and logical solution to the problems facing the mental healthcare system.
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Affiliation(s)
- Kim L Lavoie
- Division of Chest Medicine, Research Center, Hôpital du Sacré-Coeur de Montreal, Quebec, Canada
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20
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Moja PL, Cusi C, Sterzi RR, Canepari C. Selective serotonin re-uptake inhibitors (SSRIs) for preventing migraine and tension-type headaches. Cochrane Database Syst Rev 2005:CD002919. [PMID: 16034880 DOI: 10.1002/14651858.cd002919.pub2] [Citation(s) in RCA: 68] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
BACKGROUND Headache is a common medical problem. In view of recent discoveries about the role of serotonin in pain mechanisms, selective serotonin re-uptake inhibitors (SSRIs) have been evaluated for the prevention of migraine and tension-type headaches (TTH). OBJECTIVES To evaluate the efficacy and tolerability of SSRIs for preventing migraine and TTH. SEARCH STRATEGY We searched MEDLINE (1966-2004), EMBASE (1994-2003), the Cochrane Central Register of Controlled Trials (Issue 4, 2003), and reference lists of retrieved articles. Headache Quarterly was hand searched from 1990 to 2003. SELECTION CRITERIA We included randomised controlled trials comparing SSRIs with any type of control intervention in patients of either sex, over 18 years of age, with migraine or TTH. DATA COLLECTION AND ANALYSIS Two authors independently extracted data (headache frequency, index, severity, and duration; use of symptomatic/analgesic medication; days off work; quality of life; mood improvement; cost-effectiveness; and adverse events) and assessed the methodological quality of trials. MAIN RESULTS Thirteen studies utilizing five SSRIs met the inclusion criteria (636 participants). Most of the included studies had methodological and/or reporting shortcomings; follow up rarely extended beyond 3 months. After 2 months SSRIs did not significantly lower headache index scores in patients with migraine when compared to placebo (SMD -0.14; 95% CI -0.57 to 0.30). Patients with chronic TTH treated with an SSRI had a significantly higher analgesic intake of 5 more doses per month when compared to patients treated with a tricyclic antidepressant (WMD 4.98; 95% CI 1.12 to 8.84). Tricyclics also significantly reduced headache duration by 1.26 hours per day (WMD 1.26; 95% CI 0.06 to 2.45) and marginally reduced headache indexes (SMD 0.42; 95% CI 0.00 to 0.85) when compared to SSRIs in patients with chronic TTH. When the data on adverse events were considered without regard to headache diagnostic subgroups, there were no significant differences between SSRIs and placebo for withdrawals due to adverse events (Peto OR 1.02; 95% CI 0.31 to 3.34). For minor adverse events, SSRIs were generally more tolerable than tricyclics (OR 0.34; 95% CI 0.13 to 0.92). However, there were no differences in the number of patients withdrawing due to any reason in the SSRI and tricyclic groups (OR 1.01; 95% CI 0.56 to 1.80). AUTHORS' CONCLUSIONS Over 2 months of treatment, SSRIs are no more efficacious than placebo in patients with migraine. In patients with chronic TTH, SSRIs are less efficacious than tricyclic antidepressants. In comparison with SSRIs, the burden of adverse events in patients receiving tricyclics was greater. These results are based on short-term trials and may not generalise to longer-term treatment.
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Affiliation(s)
- P L Moja
- Centro Cochrane Italiano, Istituto Mario Negri, Via Eritrea, 62, Milano, Italy, 20157.
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Steimer W, Zöpf K, von Amelunxen S, Pfeiffer H, Bachofer J, Popp J, Messner B, Kissling W, Leucht S. Amitriptyline or Not, That Is the Question: Pharmacogenetic Testing of CYP2D6 and CYP2C19 Identifies Patients with Low or High Risk for Side Effects in Amitriptyline Therapy. Clin Chem 2005; 51:376-85. [PMID: 15590749 DOI: 10.1373/clinchem.2004.041327] [Citation(s) in RCA: 115] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
AbstractBackground: Amitriptyline has been replaced in many countries by alternative and more expensive drugs based on claims of improved tolerability and toxicity and despite slightly reduced efficacy. Preliminary studies indicate that adverse effects could be linked to polymorphisms of drug-metabolizing enzymes, but information on their clinical impact remains scanty and includes mainly case reports. We conducted a prospective blinded two-center study seeking correlations between CYP2C19 and CYP2D6 genotypes, drug concentrations, adverse events, and therapy response.Methods: Fifty Caucasian inpatients with at least medium-grade depressive disorder received amitriptyline at a fixed dose of 75 mg twice a day. Blood samples for concentration monitoring of amitriptyline and nortriptyline were taken weekly until discharge along with evaluations of depression (Hamilton Depression Scale and Clinical Global Impression Scale) and side effect (Dosage Record and Treatment Emergent Symptoms Scale; DOTES) scores.Results: In a ROC analysis, nortriptyline but not amitriptyline concentrations correlated with side effects (DOTES sum score ≥5; area under the curve, 0.733; P = 0.008). Carriers of two functional CYP2D6 alleles had a significantly lower risk of side effects than carriers of only one functional allele (12.1% vs 76.5%; P = 0.00001). The lowest risk was observed for carriers of two functional CYP2D6 alleles combined with only one functional CYP2C19 allele [0 of 13 (0%) vs 9 of 11 (81.8%) for the high-risk group; P = 0.00004]. We found no correlations between drug concentrations or genotypes and therapeutic response.Conclusions: Combined pharmacogenetic testing for CYP2D6 and CYP2C19 identifies patients with low risk for side effects in amitriptyline therapy and could possibly be used to individualize antidepressive regimens and reduce treatment cost. Identification of genotypes associated with slightly reduced intermediate metabolism may be more important than currently anticipated. It could also be the key to demonstrating cost-effectiveness for CYP2D6 genotyping in critical dose drugs.
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Affiliation(s)
- Werner Steimer
- Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
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