30-Second Takeaway
- ADHD medication, including stimulants, was associated with markedly better outcomes even when SUD was present.
- Antipsychotics, especially lurasidone and ziprasidone, have the best current evidence for depressive episodes with mixed features.
- Psilocybin therapy shows large symptom reductions in difficult-to-treat mood and anxiety conditions but remains early-phase.
- Long-term cognition after first-episode psychosis appears largely stable, supporting neurodevelopmental rather than neurodegenerative models.
- Daily step count and intensity show graded protection against a range of incident mental disorders in older adults.
Week ending December 27, 2025
New data on ADHD/SUD pharmacotherapy, mixed-feature depression, psychedelics, psychosis trajectories, neuromodulation for BPD, and movement for mental health
ADHD medication in youth with SUD is linked to better clinical and mortality outcomes
Among 1.23 million individuals aged 15–25 with ADHD, about 23% had co-occurring SUD. Clinicians prescribed stimulants less often when SUD was present, while bupropion was slightly more common. In youth with ADHD and SUD, any ADHD pharmacotherapy was associated with fewer hospitalizations, emergency visits, and suicidal ideation or attempts. ADHD treatment was also associated with a 30% lower risk of mortality compared with no ADHD medication. Within the SUD subgroup, stimulant treatment outperformed non-stimulants for hospitalizations, accidental overdose, and suicidal outcomes. Findings suggest current reluctance to use stimulants in SUD may deny patients therapies linked to substantially better outcomes.
Antipsychotics, especially lurasidone and ziprasidone, stand out for mixed-feature bipolar depression
This systematic review and meta-analysis included 22 studies (n=3525) of bipolar depressive episodes with mixed features. Across randomized trials, antipsychotics showed substantial benefit over placebo for depressive symptoms (pooled SMD about -0.70). Single RCTs indicated robust effects for lurasidone and ziprasidone, with lumateperone showing a moderate effect size. Celecoxib and theta-burst stimulation were not superior to placebo in this population. Non-randomized antipsychotic studies showed smaller, more heterogeneous effects, limiting certainty. Overall, current evidence supports antipsychotics, particularly lurasidone and ziprasidone, as first-line pharmacologic options for mixed-feature depression.
Psilocybin therapy shows large effects in mood and anxiety disorders but remains experimental
This pre-registered meta-analysis synthesized psilocybin trials across anxiety, major depression, and other mood disorders. Psilocybin therapy produced very large symptom reductions in anxiety/MDD and mood disorders (SMDs around -1.4). Sustained clinical improvements were often observed after a single psilocybin-assisted session. Proposed mechanisms include 5-HT2A receptor modulation, enhanced neuroplasticity, and disruption of maladaptive cognitive patterns. Evidence extends to conditions such as addiction and end-of-life anxiety, but data are still limited for several indications. Despite large effect sizes and apparent robustness to publication bias, regulatory and implementation barriers currently restrict routine clinical use.
References
Numbered in order of appearance. Click any reference to view details.
Additional Reads
Optional additional studies from this edition.