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Combination antidepressant therapy is more effective than monotherapy for acute severe depression and nonresponding depression
Clinical Question
What is the treatment efficacy and tolerability of combination therapy compared with monotherapy for acute severe depression and recurrent depression in adults?
Bottom line
This review found that combination therapy using a reuptake inhibitor (ie, a selective serotonin reuptake inhibitor, serotonin–noradrenaline reuptake inhibitor, or tricyclic antidepressant) with an antagonist of presynaptic alpha2-autoreceptors (mirtazapine or trazodone) is more effective than monotherapy for first-line treatment of acute severe depression and for those patients who are initially nonresponders to monotherapy. Dropout rates due to adverse events were similar for both combination therapy and monotherapy. 1a
Reference
Study design: Meta-analysis (randomized controlled trials)
Funding: Industry + foundation
Setting: Various (meta-analysis)
Synopsis
The optimal management of an initial episode of acute severe depression and nonresponsive depression in adults remains uncertain. These investigators thoroughly searched, without language restrictions, multiple databases including MEDLINE, PsycINFO, Embase, and the Cochrane Central Register of Controlled Trials for randomized trials that compared antidepressant monotherapy with a combination of 2 antidepressants. Eligible trials included both first-line antidepressant treatment trials and trials that included patients resistant to improvement with initial therapy. In studies that included nonresponders, monotherapy (control group) patients received either continued monotherapy with the same antidepressant at the same or higher dose, or monotherapy with a different antidepressant. Two individuals independently evaluated individual trials for study eligibility and risk of bias using the Cochrane scoring tool. Disagreements were resolved by consensus agreement. The primary outcome was treatment efficacy measured as the standardized mean difference (SMD). Of the 39 individual trials, 15 were classified as "low risk of bias." Heterogeneity was minimal when restricted to studies with low risk of bias and an analysis for publication bias found minimal risk for altering the results. Overall, combination therapy provided superior efficacy than monotherapy for both first-line treatment and among nonresponders (SMD 0.31; 95% CI 0.19 - 0.44). Results were similar when restricting the analyses to only studies with low risk of bias. The combination of a monoamine reuptake inhibitor with an antagonist of presynaptic alpha2-autoreceptors (ie, mirtazapine or trazodone) is associated with superior efficacy compared with monotherapy for both first-line treatment and for nonresponding patients. Combination therapy with bupropion was not associated with superior outcomes compared with monotherapy for first-line treatment, but was superior to monotherapy for nonresponding patients. Dropout rates due to adverse events were similar for both types of therapy.
Reviewer
David C. Slawson, MD
Professor and Vice Chair of Family Medicine for Education and Scholarship
Atrium Health
Professor of Family Medicine, UNC Chapel Hill
Charlotte, NC
Comments
Combination therapy for depression - more effective than mon
I would want to know the dose of either trazodone or mirtazapine that they were using with the SSRI or SNRI. Were the improvements mainly on anxiety and/or sleep?
Drug pushing; Act IX
Enter Big Pharma stage right.
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Combination therapy in acute and resistant depressive illnes
This study clearly emphasizes that a combination therapy of antidepressants brought out better outcome than the mono therapy.But for the minimal impact On SMD all other parameters made it clearly evident that mono therapy can not match the results of combination therapy in acute and other poorly responding depressive states.it was consoling that the adverse effects of combination therapy were almost similar to those of mono therapy
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rx of depression
combination of antidepressants more effective than single agents