Safety Reporting and Adverse-Event Profile of Mirtazapine Described in Randomized Controlled Trials in Comparison with Other Classes of Antidepressants in the Acute-Phase Treatment of Adults with Depression: Systematic Review and Meta-Analysis

• Published in: CNS drugs 2010, Vol.24 (1), p.35-53
• Main Authors: Watanabe, Norio, Omori, Ichiro M., Nakagawa, Atsuo, Cipriani, Andrea, Barbui, Corrado, McGuire, Hugh, Churchill, Rachel, Furukawa, Toshi A.
• Format: Article
• Language: English
• Subjects: Adult; Adult and adolescent clinical studies; Adverse Drug Reaction Reporting Systems; Antidepressive Agents, Tricyclic - adverse effects; Antidepressive Agents, Tricyclic - therapeutic use; Biological and medical sciences; Clinical trial. Drug monitoring; Depression; Depression, Mental; Depressive Disorder, Major - drug therapy; Drug therapy; General pharmacology; Humans; Medical sciences; Medicine; Medicine & Public Health; Meta-analysis; Mianserin - adverse effects; Mianserin - analogs & derivatives; Mianserin - therapeutic use; Mood disorders; Neurology; Neuropharmacology; Neurosciences; Original Research Article; Pharmacokinetics; Pharmacology. Drug treatments; Pharmacotherapy; Psychiatry; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Randomized Controlled Trials as Topic; Regression Analysis; Systematic review
• ISSN: 1172-7047; 1179-1934
• DOI: 10.2165/11319480-000000000-00000

Background : Mirtazapine has a unique mechanism of antidepressant action, and thus is thought to have a different profile of adverse events from that of other antidepressants. Objective : To present a methodologically rigorous systematic review of the adverse event profile of mirtazapine and point to possible problems with safety reporting in randomized controlled trials (RCTs) of the acute-phase treatment of major depression in adults with mirtazapine in comparison with other types of antidepressant. Methods : The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register was electronically searched using the following search terms: ‘depress*rs’, ‘dysthymi*’, ‘adjustment disorder*’, ‘mood disorder*’, ‘affective disorder’, ‘affective symptoms’ and ‘mirtazapine’. Pharmaceutical companies and experts in this field were contacted, and the reference lists of the relevant RCTs were checked, for additional data. No language restriction was imposed. Two authors independently assessed the quality of trials for inclusion in the review. Disagreements were resolved by consensus. Two authors independently extracted data on adverse events. Disagreements were resolved by consensus. The adequacy of safety reporting was assessed by one author. Regarding the adequacy of safety reporting, the qualitative and quantitative parameters of safety reporting were determined. Regression analyses were conducted to assess characteristics of trials influencing safety reporting. The primary and secondary outcomes in the systematic review of the adverse events associated with mirtazapine were defined as the proportion of patients having each of 43 adverse events listed in the modified version of the WHO Adverse Reaction Terminology, and the proportion of patients experiencing at least one adverse event, respectively. Meta-analyses were conducted for these outcomes. Results : Twenty-five RCTs involving 4842 patients were identified as meeting our inclusion criteria. With regard to safety reporting, only two trials and no trials were rated as ‘adequate’ in terms of the reporting of clinical adverse events and laboratory-determined toxicity, respectively. The proportion of text in the results sections of the study reports devoted to safety reporting was a mean of 22%. No associations were observed between the adequacy of safety reporting and any characteristics of the trials; however, sample size over 100 participants in total and over 50 subjects in a study arm, do