Psychiatry

Adjunctive options with clinically meaningful effects on negative symptoms

This PRISMA meta-analysis pooled 451 RCTs (n=42,566) targeting negative symptoms in schizophrenia-spectrum disorders. A clinically meaningful effect threshold was defined as SMD ≥0.457, derived from linkage with one-point CGI-S improvement. Adjunctive antibiotics, antidepressants, immunomodulators, integrated psychosocial interventions, physical activity, and transcranial current stimulation exceeded this threshold in high-quality studies. Immunomodulators had high-GRADE support; several other categories showed moderate to very-low GRADE ratings and substantial heterogeneity. Clinicians may consider these adjuncts individually, while recognizing uncertain generalizability and the need for more rigorous, scalable trial designs. 1

Rapid cardiometabolic deterioration after first-episode psychosis

This meta-analysis of 82 FEP cohorts followed patients from minimal antipsychotic exposure through up to 10 years of routine care. Obesity rose from 5.4% at baseline to 26.6% at 1–3 years, and metabolic syndrome from 8.5% to 18.2%. Weight increased by 2.5 kg within 4–8 weeks and by 13.4 kg beyond 5 years, with parallel BMI and waist gains. Type 2 diabetes rose from 0.5% at baseline to 5.0% after more than 5 years, while blood pressure changes remained modest. Results support immediate lifestyle counseling, structured metabolic monitoring, and aggressive management of dyslipidemia and weight from FEP onset onward. 2

Sustained methylphenidate not linked to higher psychosis risk

This Finnish registry cohort included 3956 youths diagnosed with ADHD before age 18, followed for nonaffective psychosis. Instrumental-variable analyses used hospital-district methylphenidate prescribing propensity to approximate randomized exposure to sustained 30 mg/day treatment. Across 1–4 year windows, methylphenidate showed no association with higher psychosis risk; risk differences clustered near zero with wide CIs. Among children diagnosed before age 13, sustained treatment was associated with reduced psychosis risk in secondary analyses. These findings support continuing methylphenidate when clinically indicated, with standard psychosis monitoring rather than reflexive avoidance. 3

Antidepressant-dominant, polypharmacy-heavy pharmacotherapy in BPD

This retrospective EHR study analyzed 1461 patients with BPD receiving psychotropics within 14 days of diagnosis and followed for 12 months. At baseline, 80.4% were prescribed antidepressants, often with SGAs, mood stabilizers, or anxiolytics. Polypharmacy, defined as use of more than one psychotropic, affected 83.1% at baseline and increased with age and time. The most common trajectory was switching between antidepressants, with frequent sertraline, fluoxetine, and citalopram use. Patterns indicate considerable divergence from guideline emphasis on psychotherapy and highlight substantial pharmacologic treatment burden. 4