Remission in major depressive disorder (MDD) is conventionally defined as a 17-item Hamilton Depression Rating Scale (HAMD-17) score ≤7, but patients within this range may retain residual symptoms. We explored whether complete remission (HAMD-17 <4) and partial remission (HAMD-17 4–7) differ in baseline clinical features, symptom trajectories and endpoint functioning.Three cohorts were analysed separately: GSRD (N=2583, cross-sectional, tertiary centres), PANDORA (N=215, week 12) and STAR*D level 1 (N=1565). We estimated effect sizes with 95% confidence intervals, false discovery rate (FDR) correction, adjusted and imputed models, alternative cut-offs, individual symptom trajectories and cross-validated discrimination.Baseline differences between complete and partial remitters were small (median absolute standardized difference 0.08–0.15). No baseline variable survived FDR correction; only a concurrent severe-episode rating in GSRD did (odds ratio 2.10, 95% CI 1.43–3.07). In STAR*D, partial remitters had slightly higher baseline HAMD-17 (g=0.15, 95% CI 0.00–0.31), and most item-level associations were explained by overall severity. Baseline features did not discriminate the groups in individual patients (cross-validated AUC 0.42–0.55). Symptom scores of the two groups separated within 4–6 weeks and did not converge during follow-up. In STAR*D, the estimated rate of improvement did not differ detectably, and the model-estimated asymptote was higher in partial remitters. At STAR*D exit, partial remitters had worse work and social adjustment (g=0.45) and quality of life (g=−0.63) despite similar baseline values.Complete and partial remission identify different endpoint states, but baseline clinical features predict this distinction poorly. These exploratory findings require prospective confirmation.
Weight gain and impaired glucose metabolism are common complications of antipsychotic treatment in schizophrenia spectrum disorders (SSD). While beneficial in other populations, the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in SSD remain unclear. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating GLP-1 RAs versus placebo in SSD patients treated with antipsychotics. PubMed, Scopus, and Web of Science were searched until January 2026. Random-effects models were used to pool mean differences (MDs), standardized mean differences (SMDs), and risk ratios (RRs), as appropriate. Seven RCTs including 481 participants were included. Compared with placebo, GLP-1 RAs significantly reduced body weight (MD −6.98 kg; 95% CI −10.53 to −3.43), BMI (MD −2.51 kg/m²; 95% CI −3.51 to −1.51), waist circumference (MD −5.05 cm; 95% CI −6.66 to −3.44), HbA1c (MD −0.32 percentage points; 95% CI −0.38 to −0.26), and fasting blood glucose (MD −0.54 mmol/L; 95% CI −0.83 to −0.25). Heterogeneity was substantial for body weight (I²=93%) and BMI (I²=80%). No significant effects emerged for blood pressure or lipid parameters. Psychiatric symptom severity did not differ between GLP-1 RAs and placebo (SMD −0.05; 95% CI −0.36 to 0.25). Gastrointestinal adverse events were more frequent with GLP-1 RAs than with placebo, while overall study drop-out did not differ between groups. GLP-1 RAs improve short-term anthropometric and glycemic outcomes in SSD patients treated with antipsychotics. However, the limited number of trials, substantial heterogeneity in weight-related outcomes, and relatively short follow-up warrant cautious interpretation and further large-scale RCTs.
Postpartum depression (PPD) affects approximately 17% of women globally and is predicted by prior mental illness and socioeconomic disadvantage. Emerging evidence suggests that negative bias in the cognitive processing of infant cues and heightened reactivity to infant distress during pregnancy contribute to PPD risk and may thus represent a treatment target. This randomized controlled trial examined whether prenatal affective cognitive training (PACT) reduces PPD risk by modulating negative biases in pregnant women at heightened risk. Of 280 women assessed, 147 at heightened risk were randomized to PACT or care as usual (CAU). PACT comprised five individualized 90-minute sessions over five weeks, combining computerized and virtual-reality tasks targeting negative cognitive bias, attentional bias, emotion regulation, and working memory in response to infant stimuli. Affective cognition was assessed at baseline and post-intervention; mood was rated at baseline, post-intervention, and weekly for six weeks after birth. Diagnostic interviews (Present State Examination) were conducted six months postpartum. The primary outcome was PPD incidence within six months postpartum; secondary outcomes included depressive symptoms over the first six weeks and changes in affective cognition. Follow-up data were available for 121 (83%) participants (PACT n = 54; CAU n = 67). PACT did not significantly reduce PPD overall (p = 0.18) or depressive symptoms (p = 0.31) but increased positive interpretation of infant emotions (p = 0.003). Exploratory analyses indicated lower PPD incidence among multiparous participants receiving PACT than CAU (5% vs. 35%; OR=0.10, 95% CI [0.01–0.92], p = 0.04) and additional parity-specific changes in affective cognition. These exploratory findings require replication in larger trials. Trial registration The trial was registered at ClinicalTrials.gov with Trial number NCT06046456 on 21 September 2023 https://clinicaltrials.gov/study/NCT06046456.
