Henssler, Jonathan ORCID: 0000-0001-8123-5853, Bschor, Tom and Baethge, Christopher (2016). Combining Antidepressants in Acute Treatment of Depression: A Meta-Analysis of 38 Studies Including 4511 Patients. Can. J. Psychiat.-Rev. Can. Psychiat., 61 (1). S. 29 - 44. THOUSAND OAKS: SAGE PUBLICATIONS INC. ISSN 1497-0015

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Abstract

Objective: Combining antidepressants (ADs) for therapy of acute depression is frequently employed, but randomized studies have yielded conflicting results. We conducted a systematic review and meta-analysis aimed at determining efficacy and tolerability of combination therapy. Methods: MEDLINE, Embase, PsycINFO, and CENTRAL databases were systematically searched through March 2014 for controlled studies comparing combinations of ADs with AD monotherapy in adult patients suffering from acute depression. The prespecified primary outcome was standardized mean difference (SMD), secondary outcomes were response, remission, and dropouts. Results: Among 8688 articles screened, 38 studies were eligible, including 4511 patients. Combination treatment was statistically, significantly superior to monotherapy (SMD 0.29; 95% CI 0.16 to 0.42). During monotherapy, slightly fewer patients dropped out due to adverse events (OR 0.90; 95% CI 0.53 to 1.53). Studies were heterogeneous (I-2 = 63%), and there was indication of moderate publication bias (fail-safe N for an effect of 0.1:44), but results remained robust across prespecified secondary outcomes and subgroups, including analyses restricted to randomized controlled trials and low risk of bias studies. Meta-regression revealed an association of SMD with difference in imipramine-equivalent dose. Combining a reuptake inhibitor with an antagonist of presynaptic 2-autoreceptors was superior to other combinations. Conclusion: Combining ADs seems to be superior to monotherapy with only slightly more patients dropping out. Combining a reuptake inhibitor with an antagonist of presynaptic 2-autoreceptors seems to be significantly more effective than other combinations. Overall, our search revealed a dearth of well-designed studies. Objectif: Combiner les antidepresseurs pour traiter la depression aigue est une methode frequemment utilisee, mais les etudes randomisees ont offert des resultats conflictuels. Nous avons mene une revue systematique et une meta-analyse visant a determiner l'efficacite et la tolerabilite du traitement combine ou polytherapie. Methodes: Une recherche des bases de donnees MEDLINE, Embase, PsycINFO, et CENTRAL a ete systematiquement menee jusqu'en mars 2014 pour reperer les etudes controlees comparant les polytherapies d'antidepresseurs avec la monotherapie d'antidepresseur chez des patients adultes souffrant de depression aigue. Le resultat principal predetermine etait la difference des moyennes standardisees (DMS), et les resultats secondaires etaient la reponse, la remission, et les abandons. Resultats: Sur 8688 articles examines, 38 etudes etaient admissibles, portant sur 4511 patients. La polytherapie etait statistiquement significativement superieure a la monotherapie (DMS 0,29; IC a 95% 0,16 a 0,42). Durant la monotherapie, un nombre legerement moindre de patients ont abandonne en raison d'effets indesirables (RC 0,90; 0,53 a 1,53). Les etudes etaient heterogenes (I-2 = 63%), et il y avait une indication d'un biais de publication modere (N a securite integree pour un effet de 0,1: 44), mais les resultats demeuraient solides dans les resultats secondaires predetermines et les sous-groupes, y compris les analyses restreintes aux essais randomises et aux etudes a faible risque de biais. La meta-regression a revele une association de la DMS avec une difference d'imipramine pour une dose equivalente. Combiner un inhibiteur du recaptage avec un antagoniste des autorecepteurs 2 presynaptiques etait superieur aux autres combinaisons. Conclusion: Combiner des antidepresseurs semble etre superieur a la monotherapie, et un nombre legerement plus eleve de patients seulement abandonnent le traitement. Combiner un inhibiteur du recaptage avec un antagoniste des autorecepteurs 2 presynaptiques semble etre significativement plus efficace que les autres combinaisons. En general, notre recherche a revele une penurie d'etudes bien concues.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Henssler, JonathanUNSPECIFIEDorcid.org/0000-0001-8123-5853UNSPECIFIED
Bschor, TomUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baethge, ChristopherUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-291443
DOI: 10.1177/0706743715620411
Journal or Publication Title: Can. J. Psychiat.-Rev. Can. Psychiat.
Volume: 61
Number: 1
Page Range: S. 29 - 44
Date: 2016
Publisher: SAGE PUBLICATIONS INC
Place of Publication: THOUSAND OAKS
ISSN: 1497-0015
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
TREATMENT-RESISTANT DEPRESSION; DOUBLE-BLIND; MAJOR DEPRESSION; TERM OUTCOMES; AUGMENTATION; EFFICACY; COMBINATION; DISORDER; TRIALS; FLUOXETINEMultiple languages
PsychiatryMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/29144

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