Does therapy work as well as antidepressants?

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1. 1

   Psychotherapy, Antidepressants, and Combined Treatment for Depression: A Network Meta-Analysis on Social Functioning Outcomes.

   Psychotherapy and psychosomatics (Miguel et al.)Published Jun 24, 2026Checked Oct 3, 2026

   “Random effects models were used. We assessed risk of bias and conducted sensitivity analyses. Certainty of evidence was evaluated using CINeMA.ResultsOf 490 identified trials, 94 (19%; 23,874 participants) reported social functioning and were included. All active treatments outperformed control conditions. Effects varied substantially by control condition type, with waitlist comparisons yielding the largest estimates and comparisons against placebo or care as usual yielding more conservative effects. Combined psychotherapy and pharmacotherapy showed the largest effects versus placebo at posttreatment (SMD 0.75, 95% CI: 0.57-0.94) and follow-up (1.08, 0.62-1.54). Psychotherapy and pharmacotherapy did not differ at posttreatment (SMD 0.10, 95% CI: -0.05 to 0.25) or follow-up (0.27, 95% CI: 0.00-0.54). Certainty of the evidence ranged from moderate to low.ConclusionFirst-line depression treatments support not only symptom reduction but also meaningful participation in daily life. However, only one-fifth of trials assessed this outcome, highlighting the need to better integrate patient-valued outcomes into future trials.”

2. 2

   Efficacy of antidepressants in addition to psychotherapy in major depressive disorder: a systematic review and meta-analysis of randomized clinical trials.

   Psychiatry research (Gougeon et al.)Published Jul 6, 2026Checked Oct 3, 2026

   “Studies were included if they compared AD in addition to psychotherapy versus psychotherapy plus a placebo, with depression severity assessed using standardized scales. Meta-analyses were performed on depression severity outcomes, using change-from-baseline scores and endpoint scores.OutcomesEleven trials were included, involving various AD and psychotherapies. The pooled effect size for change-from-baseline scores across trials showed a nonsignificant result SMD = 0.31; CI 95% (-0.07; 0.70) (p-value = 0.1). Meta-analyses based on endpoint depression scores were non-significant, and the observed effect sizes may fall below the threshold for clinical significance. The quality of evidence was rated as very low according to the GRADE assessment.ConclusionCurrent evidence does not indicate the benefit of adding antidepressants to psychotherapy for MDD. Evidence quality is very low, with few trials, methodological limitations, intervention heterogeneity, and selected populations limiting interpretability and generalizability. Larger, high-quality RCTs in broader populations are needed and should systematically include psychotherapy alongside antidepressants.”

3. 3

   Rethinking Serotonin in Depression: Toward a Modern Clinical Framework.

   Cureus (Sheppert)Published Jun 19, 2026Checked Oct 3, 2026

   “Emerging mechanistic models suggest that SSRIs act less by correcting a chemical imbalance and more by reducing negative affective bias and modestly enhancing neuroplasticity, creating a window in which psychosocial and behavioral interventions can take hold. Because SSRIs are linked to common adverse effects, including sexual dysfunction, weight gain, and sleep disturbance, their routine use as a universal first-line treatment warrants re-examination. Recent international guidelines from the World Health Organization (WHO), the National Institute for Health and Care Excellence (NICE), and the American Psychiatric Association (APA) now prioritize psychological therapies, structured exercise, and combination approaches over antidepressant monotherapy for non-severe depression. This editorial proposes a pragmatic, patient-centered framework for general internists that accounts for real-world access barriers, screens for reversible contributors, offers evidence-based non-pharmacological options where feasible, and repositions SSRIs as adjuncts or facilitators rather than default interventions.”

4. 4

   Psychotherapy initiation is associated with discontinuation of psychotropic medications without dose escalation: a ten-year real-world cohort study (2014-2024).

   Frontiers in psychiatry (Pomares et al.)Published Jun 22, 2026Checked Oct 4, 2026

   “A retrospective cohort study was conducted using anonymized pharmacy dispensing data from the Mental Health Service of Hospital Marina Baixa (Alicante, Spain) between 2014 and 2024. Patients with at least one active prescription for a benzodiazepine or antidepressant within 90 days before psychotherapy initiation were included. Psychotropic exposure was compared in symmetric 90-day pre- and post-therapy windows using number of active agents, total Defined Daily Doses, and prevalence of benzodiazepine and antidepressant use, with stratified analyses by sex, age group, and diagnosis.ResultsThe cohort comprised 86,502 patients and 20.76 million dispensations. The median number of psychotropic medications decreased from 5 to 2 (p ConclusionsIn routine public mental health care, psychotherapy initiation is associated with substantial simplification of psychotropic treatment regimens without increasing overall medication dose, supporting a potential role in facilitating rational medication simplification.”

5. 5

   Sex-based Differences in the Efficacy and Tolerability of Selective Serotonin Reuptake Inhibitors in Adults with Major Depressive Disorder: A Systematic Review and Meta-analysis.

   Indian journal of psychological medicine (Pandey et al.)Published Sep 28, 2026Checked Oct 4, 2026

   “Eligible studies included at least one SSRI arm with extractable sex-stratified outcome data specific to SSRIs. Risk of bias was assessed using RoB 2, the Newcastle-Ottawa Scale, and design-appropriate appraisal tools. Certainty of evidence was evaluated using GRADE. Pooled estimates were generated using random-effects meta-analysis.ResultsTen studies (2005-2025) were included. Remission (six studies, 3,865 participants) showed OR: 1.18 (95% CI: 0.96-1.44; I² = 0%); response (two studies, 3,006 participants) OR: 1.39 (95% CI: 0.87-2.22; I² = 51.8%); and continuous symptom improvement (three studies, 3,050 participants) standardized mean difference 0.40 (95% CI: 0.04-0.75; I² = 74.9%), each favoring female. Certainty ranged from moderate (remission) to low (response, continuous improvement).ConclusionsSSRI efficacy outcomes showed a consistent female-favoring direction, clearest for continuous symptom improvement, but estimates were limited by heterogeneity, imprecision, and incomplete sex-stratified reporting. The evidence does not support sex-based prescribing; adequately powered, prospectively sex-stratified studies are needed.”

6. 6

   Effectiveness of fluoxetine and mindfulness therapy in improving depression in people with Type 2 Diabetes Mellitus in Primary Care Settings (DIAMAND)-A single-blind, parallel-group, randomized controlled trial from Bengaluru.

   Indian journal of psychiatry (Raveendranathan et al.)Published Aug 17, 2026Checked Oct 3, 2026

   “Depression severity, medication adherence, diabetes self-management, quality of life, HbA1c, and random blood sugar (RBS) were tested over 4 months. Repeated Measures ANOVA (RMANOVA) and effect size estimates were used for analysis.ResultsDepressive symptoms improved significantly over time across all study arms; and no significant between-group differences were observed in depression outcomes. No significant differences were found between groups for glycemic control, medication adherence, diabetes self-management, or quality of life. Effect sizes for reduction in depressive symptoms compared with TAU were 0.48 for Mindfulness, 0.45 for fluoxetine, and 0.31 for combination treatment.ConclusionsIn this RCT, depressive symptoms and medication adherence improved across all study arms; however, none demonstrated superiority over TAU. Mindfulness-based interventions may represent feasible, scalable, low-intensity approaches for mild depression in primary care settings. Future adequately powered studies with longer follow-up are needed to evaluate long-term effectiveness of psychological and pharmacological interventions.”

7. 7

   Major depressive disorder (Wikipedia)

   WikipediaPublished Oct 1, 2026Checked Oct 3, 2026

   “Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Introduced by a group of US clinicians in the mid-1970s, the term was adopted by the American Psychiatric Association for this symptom cluster under mood disorders in the 1980 version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III), and has become widely used since. The disorder causes the second-most years lived with disability, after lower back pain. The diagnosis of major depressive disorder is based on the person's experiences, and behavior reported by family or friends, and a mental status examination. There is no laboratory test for the disorder, but blood testing and similar may be done to rule out physical conditions that can cause similar symptoms. The most common time of onset is in a person's 20s. Men are much less likely to report than women, with approximately 33.2% of men and 43.0% of women with depressive symptoms reporting seeking help, possibly due to pressures of masking for men.”