Psychiatry

IPD shows fluoxetine superior in selected pediatric MDD subgroups

An IPD meta-analysis of ten RCTs (2,584 participants) found fluoxetine showed greater symptomatic improvement versus placebo in children and several subgroups (MDs -3.90 to -2.60). Paroxetine had modest efficacy in adolescents but worse tolerability in some subgroups. Fluoxetine was associated with less deterioration in female participants (OR=0.55). Most trials had ‘some concerns’ for risk of bias, so subgroup findings require external validation before routine subgroup-based prescribing. 1

CNS stimulants linked to better outcomes than non-stimulants in ADHD with MDD

In a retrospective cohort (TriNetX, n=1,026,253; ADHD+MDD n=223,665), comorbid MDD drove higher ADHD prescribing, especially non-stimulants like bupropion. Within ADHD+MDD (matched cohorts n=159,259), CNS stimulants were associated with more favorable clinical outcomes than non-stimulants (adjusted hazards roughly 0.49–0.68). Bupropion had outcome profiles similar to stimulants for suicidality and mood-stabilizer initiation, suggesting it may be a reasonable non-stimulant alternative. Findings are observational and require prospective or randomized confirmation before changing prescribing standards. 2

Psychiatric exclusions frequent in neuropathic pain RCTs

Secondary analysis of 312 neuropathic pain RCTs found psychiatric-related exclusions in 80% of trials (60% definite, 55% probable). Depression (22%) and substance-related disorders (38%) were commonly excluded, yet reporting methods for eligibility were sparse. These exclusions likely reduce generalizability to patients with comorbid psychiatric conditions and should temper application of trial results to such patients. 3