Relative effectiveness of antidepressant treatments in treatment-resistant depression: a systematic review and network meta-analysis of randomized controlled trials.
Johan Saelens, Anna Gramser, Victoria Watzal, Carlos A Zarate, Rupert Lanzenberger, Christoph Kraus
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology May 1, 2025 DOI: 10.1038/s41386-024-02044-5 via PubMed
Summary
AI-generated from the abstractA systematic review and network meta-analysis of 69 randomized controlled trials with 10,285 adults who had not responded to at least two antidepressant trials compared 25 treatments for treatment-resistant depression. Six treatments showed higher response rates than placebo or sham: electroconvulsive therapy (ECT) had the strongest effect, followed by minocycline, theta-burst stimulation, repetitive transcranial magnetic stimulation, ketamine, and aripiprazole. Odds ratios ranged from 1.9 for aripiprazole to 12.86 for ECT. Moderate heterogeneity was observed. These findings may help guide evidence-based treatment choices for treatment-resistant depression.
Study at a glance
| Characteristics | Systematic review and network meta-analysis Randomized Peer reviewed |
|---|---|
| Sample size | 10,285 |
| Population | Adults with depression who had not responded to at least two antidepressant trials, excluding those with bipolar or psychotic depression |
| Interventions | electroconvulsive therapy minocycline theta-burst stimulation repetitive transcranial magnetic stimulation ketamine aripiprazole |
| Topics | Depression |
| Keywords | Depression treatment Electroconvulsive therapy Mental health interventions Brain stimulation |
| Citations | 47 |
| Key finding | Six treatments—ECT, minocycline, theta-burst stimulation, rTMS, ketamine, and aripiprazole—showed higher response rates than placebo or sham for treatment-resistant depression. |
Abstract
This systematic review and network meta-analysis (NMA) sought to compare different antidepressant treatments for treatment-resistant depression (TRD) in order to facilitate evidence-based choices. A literature search of PubMed, Cochrane Library, and Embase from inception until April 13th, 2023 identified randomized, controlled trials (RCTs) of adults with depression who had not responded to at least two antidepressant trials; all RCTs had ≥10 participants per study arm, and participants with bipolar or psychotic depression were excluded. The Cochrane Risk of Bias Tool-2 was used to assess study quality. Response rate was the primary outcome measure. Odds ratios (ORs) using a random effects NMA are reported. From 8234 records, 69 RCTs were included in this analysis, encompassing 10,285 participants (5662 F/4623 M) and 25 separate treatments. Six of the 25 treatments demonstrated a higher response rate versus placebo or sham treatment: electroconvulsive therapy (ECT), minocycline, theta-burst stimulation (TBS), repetitive transcranial magnetic stimulation (rTMS), ketamine, and aripiprazole. ORs ranged from 1.9 (95%CI = [1.25; 2.91]) for aripiprazole to 12.86 (95%CI = [4.07; 40.63]) for ECT. Moderate heterogeneity of the model was observed (I2 = 47.3% (95%CI [26.8-62%]). Of the included studies, 12.5% were rated as having high risk of bias, 28.13% as having low risk, and 59.38% as showing some concerns. Several effective treatments for TRD showed robust treatment effects across outcomes (ECT, TBS, rTMS, and ketamine), and others showed promising results for some, but not all, outcomes (minocycline, aripiprazole). These findings may help guide evidence-based treatment choices for TRD. Study Registration: PROSPERO (#CRD42023420584).