Tricyclic antidepressants versus ‘active placebo’, placebo or no intervention for adults with major depressive disorder: a protocol for a systematic review with meta-analysis and Trial Sequential Analysis

Systematic Reviews

Klaus Munkholm¹  Caroline Kamp Jørgensen²  Christian Gluud²  Marija Barbateskovic²  Faiza Siddiqui²  Janus Christian Jakobsen³  Sophie Juul⁴  Michael Pascal Hengartner⁵  Irving Kirsch⁶ 

[1] Cochrane Denmark, Centre for Evidence-Based Medicine Odense, Department of Clinical Research, University of Southern Denmark, JB Winsløwsvej 9b, 5000, Odense, Denmark;Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital – Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen Ø, Denmark;Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital – Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen Ø, Denmark;Department of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, J.B. Winsløws Vej 19, 5000, Odense C, Denmark;Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital – Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen Ø, Denmark;Stolpegaard Psychotherapy Centre, Mental Health Services in the Capital Region of Denmark, Stolpegaardsvej 28, 2820, Gentofte, Denmark;Department of Psychology, University of Copenhagen, Østre Farimagsgade 2A, 1353, Copenhagen K, Denmark;Department of Applied Psychology, Zurich University of Applied Sciences, Pfingstweidstrasse 96, 8005, Zurich, Switzerland;Program in Placebo Studies, Harvard Medical School, 330 Brookline Avenue, 02215, Boston, MA, USA;

关键词: Antidepressants;    Tricyclic antidepressants;    Major depressive disorder;    Beneficial effects;    Adverse effects;   

DOI  :  10.1186/s13643-021-01789-0

来源: Springer

【 摘 要 】

BackgroundMajor depressive disorder is a common psychiatric disorder causing great burden on patients and societies. Tricyclic antidepressants are frequently used worldwide to treat patients with major depressive disorder. It has repeatedly been shown that tricyclic antidepressants reduce depressive symptoms with a statistically significant effect, but the effect is small and of questionable clinical importance. Moreover, the beneficial and harmful effects of all types of tricyclic antidepressants have not previously been systematically assessed. Therefore, we aim to investigate the beneficial and harmful effects of tricyclic antidepressants versus ‘active placebo’, placebo or no intervention for adults with major depressive disorder.MethodsThis is a protocol for a systematic review with meta-analysis that will be reported as recommended by Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols, bias will be assessed with the Cochrane Risk of Bias tool—version 2, our eight-step procedure will be used to assess if the thresholds for clinical significance are crossed, Trial Sequential Analysis will be conducted to control random errors and the certainty of the evidence will be assessed with the Grading of Recommendations Assessment, Development and Evaluation approach. To identify relevant trials, we will search both for published and unpublished trials in major medical databases and trial registers, such as CENTRAL, MEDLINE, EMBASE and ClinicalTrials.gov from their inception to 12 May 2021. Clinical study reports will be applied for from regulatory authorities and pharmaceutical companies. Two review authors will independently screen the results from the literature searches, extract data and perform risk of bias assessment. We will include any published or unpublished randomised clinical trial comparing tricyclic antidepressants with ‘active placebo’, placebo or no intervention for adults with major depressive disorder. The following interventions will be assessed: amineptine, amitriptyline, amoxapine, butriptyline, cianopramine, clomipramine, desipramine, demexiptiline, dibenzepin, dosulepin, dothiepin, doxepin, imipramine, iprindole, lofepramine, maprotiline, melitracen, metapramine, nortriptyline, noxiptiline, opipramol, protriptyline, tianeptine, trimipramine and quinupramine. Primary outcomes will be depressive symptoms, serious adverse events and quality of life. Secondary outcomes will be suicide or suicide-attempts and non-serious adverse events. If feasible, we will assess the intervention effects using random-effects and fixed-effect meta-analyses.DiscussionTricyclic antidepressants are recommended by clinical guidelines and frequently used worldwide in the treatment of major depressive disorder. There is a need for a thorough systematic review to provide the necessary background for weighing the benefits against the harms. This review will ultimately inform best practice in the treatment of major depressive disorder.Systematic review registrationPROSPERO CRD42021226161.

【 授权许可】

CC BY