SynthesisCanadian journal of psychiatry. Revue canadienne de psychiatrie2016
Combining Antidepressants in Acute Treatment of Depression: A Meta-Analysis of 38 Studies Including 4511 Patients.
Synthesis in Canadian journal of psychiatry. Revue canadienne de psychiatrie, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 4 syntheses or guidelines pooled it, 61 citations in OpenAlex.
- [Second-step strategies in antidepressant pharmacotherapy : Results of current meta-analyses].Der Nervenarzt · 2025Pooled it
- Treatment Effects in Randomized and Nonrandomized Studies of Pharmacological Interventions: A Meta-Analysis.JAMA network open · 2024Pooled it
- Combining Antidepressants vs Antidepressant Monotherapy for Treatment of Patients With Acute Depression: A Systematic Review and Meta-analysis.JAMA psychiatry · 2022Pooled it
- Pharmacological Augmentation in Unipolar Depression: A Guide to the Guidelines.The international journal of neuropsychopharmacology · 2020Pooled it
- Efficacy and safety of venlafaxine hydrochloride combined with tandospirone citrate for patients with vascular depression accompanied by somatic symptoms: An open-labeled randomized control trial.CNS neuroscience & therapeutics · 2024Trial
- Pretreatment Reward Sensitivity and Frontostriatal Resting-State Functional Connectivity Are Associated With Response to Bupropion After Sertraline Nonresponse.Biological psychiatry · 2020Trial
- Trial
- Mechanism-guided identification of antidepressant G protein-coupled receptor drug targets.Cell · 2026Article
- Reinitiation of antidepressant pharmacotherapy among patients discharged from the hospital: A population-based cohort study.PLOS mental health · 2026Article
- Co-Administration Treatment in Drug-Naïve Major Depression: Exploratory Real-World Patterns and Predictors in China.Neuropsychiatric disease and treatment · 2026Article
- Two-stage Bayesian network meta-analysis of individualized treatment rules for multiple treatments with siloed data.Statistical methods in medical research · 2026Article
- Socioeconomic status, antidepressant use, and return to work after disability due to common mental disorders.European psychiatry : the journal of the Association of European Psychiatrists · 2025Article
- RE: A case of treatment-resistant depression in an older adult and a discussion of treatment options.BJPsych bulletin · 2023Article
- The prevalence of off-label use and supratherapeutic blood levels of outpatient psychotropic medication in suicidal adolescents.Frontiers in psychiatry · 2023Article
- Commentary: Meta-analysis overstates benefit of antidepressant combination therapy with α2-antagonists and reuptake inhibitors in major depression.Frontiers in psychiatry · 2023Article
- A case of treatment-resistant depression in an older adult and a discussion of treatment options.BJPsych bulletin · 2022Article
- Concordance of the treatment patterns for major depressive disorders between the Canadian Network for Mood and Anxiety Treatments (CANMAT) algorithm and real-world practice in China.Frontiers in pharmacology · 2022Article
- Antidepressant Use and Suicide Rates in Adults Aged 75 and Above: A Swedish Nationwide Cohort Study.Frontiers in public health · 2021Article
- Pharmacotherapy, drug-drug interactions and potentially inappropriate medication in depressive disorders.PloS one · 2021Article
- Visualizing Patterns of Medication Switching Among Major Depressive Patients with Various Stability and Difficulty to Treatments.Neuropsychiatric disease and treatment · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveCombining 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.
methodsMEDLINE, 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.
resultsAmong 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 α2-autoreceptors was superior to other combinations.
conclusionCombining ADs seems to be superior to monotherapy with only slightly more patients dropping out. Combining a reuptake inhibitor with an antagonist of presynaptic α2-autoreceptors seems to be significantly more effective than other combinations. Overall, our search revealed a dearth of well-designed studies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.