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Acta Psychiatr Scand. 2017 Feb;135(2):106-116. doi: 10.1111/acps.12672. Epub 2016 Nov 23.

Manic switches induced by antidepressants: an umbrella review comparing randomized controlled trials and observational studies.

Author information

1
Academic Psychiatry Department, Centre Hospitalier Guillaume Régnier, Rennes, France.
2
EA 4712 Behavior and Basal Ganglia, CHU Rennes, Rennes 1 University, Rennes, France.
3
Laboratory of Experimental and Clinical Pharmacology, Faculty of Medicine, Rennes 1 University, Rennes, France.
4
INSERM CIC-P 1414, Clinical Investigation Center, CHU Rennes, Rennes 1 University, Rennes, France.
5
CESP, University of Paris-Sud, Université Paris-Saclay, UVSQ, INSERM U1178, Maison de Solenn, Paris Cedex, France.
6
Department of Internal Medicine, Rennes University Hospital, Rennes, France.
7
Department of Pharmacology, Pharmacovigilance, Pharmacoepidemiology and Drug Information Center, Rennes University Hospital, Rennes, France.
8
Pharmacoepidemiology Team (CTAD-PEPI), Rennes University Hospital, Rennes, France.
9
Department of Medical and Clinical Pharmacology, Midi-Pyrénées Centre for Pharmacovigilance, Pharmacoepidemiology and Drug Information, INSERM U 1027 Pharmacoepidemiology Research Unit, Toulouse, France.
10
Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Palo Alto, CA, USA.

Abstract

OBJECTIVE:

We aimed to explore whether the prevalence of manic switch was underestimated in randomized controlled trials (RCTs) compared to observational studies (OSs).

METHOD:

Meta-analyses and simple and systematic reviews were identified by two reviewers in a blinded, standardized manner. All relevant references were extracted to include RCTs and OSs that provided data about manic switch prevalence after antidepressant treatment for a major depressive episode. The primary outcome was manic switch prevalence in the different arms of each study. A meta-regression was conducted to quantify the impact of certain variables on manic switch prevalence.

RESULTS:

A total of 57 papers (35 RCTs and 22 OSs) were included in the main analysis. RCTs underestimated the rate of manic switch [0.53 (0.32-0.87)]. Overestimated prevalence was related to imipraminics [1.85 (1.22-2.79)]; to serotonin-norepinephrine reuptake inhibitors [1.74 (1.06-2.86)]; and to other classes of drugs [1.58 (1.08-2.31)], compared to placebo treatment. The prevalence of manic switch was lower among adults than among children [0.2 (0.07-0.59)]; and higher [20.58 (8.41-50.31)] in case of bipolar disorder.

CONCLUSION:

Our results highlight an underestimation of the rates of manic switch under antidepressants in RCTs compared to the rates observed in observational studies.

KEYWORDS:

affective disorders; depression; meta-analysis; randomized controlled trial

PMID:
27878807
DOI:
10.1111/acps.12672
[Indexed for MEDLINE]
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