Antidepressant medication and interpersonal psychotherapy (IPT) are both recommended interventions in depression treatment guidelines based on literature reviews and meta-analyses. However, ‘conventional’ meta-analyses comparing their efficacy are limited by their reliance on reported study-level information and a narrow focus on depression outcome measures assessed at treatment completion. Individual participant data (IPD) meta-analysis, considered the gold standard in evidence synthesis, can improve the quality of the analyses when compared with conventional meta-analysis.

We describe the protocol for a systematic review and IPD meta-analysis comparing the efficacy of antidepressants and IPT for adult acute-phase depression across a range of outcome measures, including depressive symptom severity as well as functioning and well-being, at both post-treatment and follow-up (PROSPERO: CRD42020219891).

We will conduct a systematic literature search in PubMed, PsycINFO, Embase and the Cochrane Library to identify randomised clinical trials comparing antidepressants and IPT in the acute-phase treatment of adults with depression. We will invite the authors of these studies to share the participant-level data of their trials. One-stage IPD meta-analyses will be conducted using mixed-effects models to assess treatment effects at post-treatment and follow-up for all outcome measures that are assessed in at least two studies.

This will be the first IPD meta-analysis examining antidepressants versus IPT efficacy. This study has the potential to enhance our knowledge of depression treatment by comparing the short- and long-term effects of two widely used interventions across a range of outcome measures using state-of-the-art statistical techniques.

More than half of patients who present with depressive disorders also have elevated comorbid anxiety symptoms. Given the high comorbidity between these disorders, it is important to understand the extent that psychotherapies for depression additionally ameliorate symptoms of anxiety.

Systematic searches were conducted in PubMed, PSYCinfo, EMBASE, and the Cochrane Registry of Controlled Trials. Included studies were randomized controlled trials that compared psychotherapy compared with a control condition for the treatment of adults with a primary diagnosis or elevated symptoms of depression and that examined the effects of treatment on anxiety outcomes. Acute phase depression and anxiety (continuous measure) outcomes were extracted. Effect sizes were calculated by subtracting the average post-treatment scores of the psychotherapy group from the average post-treatment scores of the comparison group divided by the pooled standard deviation.

Fifty-two studies of varying quality met the inclusion criteria. Pooled effect sizes showed that anxiety outcomes were significantly lower in the psychotherapy conditions than in control conditions at post-treatment [g = 0.52; 95% confidence interval (CI) 0.44–0.60; NNT (numbers-needed-to-treat) = 3.50]. Moderate heterogeneity was observed (I2 = 55%, 95% CI 40–66). Bivariate metaregression analysis revealed a significant association between depression and anxiety effect sizes at post-treatment Longer-term follow-ups of up to 14 months post-baseline showed indications for a small lasting effect of psychotherapy on anxiety outcomes (g = 0.27).

This meta-analysis provides evidence that psychotherapy aimed at depression can also reduce anxiety symptoms in relation to control conditions.

The influence of baseline severity has been examined for antidepressant medications but has not been studied properly for cognitive–behavioural therapy (CBT) in comparison with pill placebo.

To synthesise evidence regarding the influence of initial severity on efficacy of CBT from all randomised controlled trials (RCTs) in which CBT, in face-to-face individual or group format, was compared with pill-placebo control in adults with major depression.

A systematic review and an individual-participant data meta-analysis using mixed models that included trial effects as random effects. We used multiple imputation to handle missing data.

We identified five RCTs, and we were given access to individual-level data (n = 509) for all five. The analyses revealed that the difference in changes in Hamilton Rating Scale for Depression between CBT and pill placebo was not influenced by baseline severity (interaction P = 0.43). Removing the non-significant interaction term from the model, the difference between CBT and pill placebo was a standardised mean difference of –0.22 (95% CI –0.42 to –0.02, P = 0.03, I 2 = 0%).

Patients suffering from major depression can expect as much benefit from CBT across the wide range of baseline severity. This finding can help inform individualised treatment decisions by patients and their clinicians.