May 28, 2026

Top News
AAFP: Combination Antidepressant Therapy Outperforms Monotherapy for Acute Severe and Nonresponding Depression
Diagnosis & Treatment
Psilocybin research is no longer just for hard-to-treat cases — a new trial targeted recurrent depression in people who had not failed standard treatment, and the results are promising - Space Daily

A new clinical trial demonstrates promising results for psilocybin in treating recurrent depression in patients who have not failed standard treatments, expanding the potential use case beyond refractory cases.

Diagnosis & Treatment
New depression treatment targets the immune system instead of the brain

An anti-inflammatory drug for rheumatoid arthritis showed early promise in easing symptoms of hard-to-treat depression in a small clinical trial, highlighting a potential immune-targeted treatment avenue.

Clinical Pearl
Psilocybin-assisted therapy for difficult-to-treat depression: underwhelming, but still vital?

The EPISODE trial for psilocybin-assisted therapy in treatment-resistant depression shows only modest effects and raises methodological concerns, challenging the current evidence base for this psychedelic intervention.

Diagnosis & Treatment
EEG Prediction and Clinical Efficacy of tDCS in Major Depression

A clinical trial investigating the clinical efficacy and EEG-based prediction of high-dose versus conventional home-transcranial direct current stimulation (tDCS) for major depressive disorder.

Digital Health
Efficacy and Safety of Transcranial Temporal Interference Stimulation for Depression

A clinical trial investigating the efficacy and safety of Transcranial Temporal Interference Stimulation for Major Depressive Disorder.

Clinical Pearls

Bite-sized clinical takeaways from today's literature (sources from Apr 23 – May 28)

  • Consider initiating long-acting injectable antipsychotics early in the schizophrenia treatment course to improve adherence and reduce relapse, rather than reserving them for established non-adherence.
  • Utilize combination antidepressant therapy as a key strategy for acute severe or nonresponding depression, as it demonstrates superior efficacy compared to monotherapy.
  • Monitor for reversible cerebral vasoconstriction syndrome (RCVS) in patients taking sertraline, as this rare but serious neurological adverse event requires clinical vigilance.
  • Assess cannabis delivery methods in clinical evaluations, as multi-modal use is associated with a fourfold higher risk of Cannabis Use Disorder compared to oral-only use.
  • Follow new guidance on deprescribing stimulants in adult ADHD to manage long-term pharmacotherapy and implement structured discontinuation strategies when appropriate.
  • Reassess the risk-benefit profile of stimulant prescribing in ADHD using updated evidence to support clinical decision-making for attention-deficit/hyperactivity disorder management.
  • Consider the synergistic potential of combining intermittent ketamine with neuromodulation to enhance treatment response in patients with depression.
  • Evaluate psilocybin-assisted therapy as a potential intervention for chronic suicidal ideation and residual anhedonia, noting emerging evidence for its efficacy in high-risk and treatment-resistant populations.
  • Be aware that recent trials like EPISODE suggest modest effects for psilocybin in treatment-resistant depression, indicating a need for critical appraisal of the current evidence base for psychedelic interventions.
  • Recognize that first-line guidance for adult ADHD now includes specific clinical directions for managing long-term pharmacotherapy and potential discontinuation strategies.

Diagnosis & Treatment 2

First Guidance on Deprescribing Stimulants in Adult ADHD - Medscape

First guidance on deprescribing stimulants in adult ADHD provides clinical direction for managing long-term pharmacotherapy and potential discontinuation strategies.

Psilocybin Helped Reduce Depression Symptoms Within Just Days, Recent Clinical Trial Reveals - The Debrief

A recent clinical trial demonstrates that psilocybin rapidly reduces depression symptoms within days, highlighting its potential as a fast-acting intervention for depressive disorders.

Clinical Pearl 2

Viloxazine Extended Release in Adults With Attention-Deficit/Hyperactivity Disorder and Depression and/or Anxiety Symptoms: Results From a Decentralized, Open-Label, Phase 4 Trial

A decentralized Phase 4 trial evaluates the efficacy and safety of viloxazine ER in adults with ADHD and comorbid depression or anxiety, leveraging its multimodal norepinephrine and serotonin profile.

Psychotropic-Induced Reversible Cerebral Vasoconstriction Syndrome in a Young Man Taking Sertraline - Psychiatrist.com

This case report describes reversible cerebral vasoconstriction syndrome (RCVS) in a patient taking sertraline, highlighting a rare but serious neurological adverse event associated with this SSRI that clinicians should monitor for.

Drug Development 5

The Efficacy of Psilocybin Therapy for Depression in Parkinson's Disease

A clinical trial is recruiting to evaluate the efficacy of psilocybin therapy for treating depression in patients with Parkinson's disease.

VA begins MDMA therapy trial for veterans' mental health - Audacy

The Department of Veterans Affairs has initiated a clinical trial evaluating MDMA-assisted therapy for veterans with mental health conditions, representing a significant step in the development of novel psychopharmacological treatments for PTSD and related disorders.

Psilocybin as a Novel Therapy for Residual Anhedonia

A clinical trial is recruiting to evaluate psilocybin as a treatment for residual anhedonia and emotional blunting, addressing a key symptom of depression often resistant to standard pharmacotherapy.

New Study Conducted at Sheppard Pratt Finds Psilocybin-Assisted Therapy May Reduce Chronic Suicidal Ideation - PR Newswire

A study conducted at Sheppard Pratt suggests psilocybin-assisted therapy may reduce chronic suicidal ideation, highlighting a potential psychopharmacological intervention for high-risk psychiatric patients.

Alkermes to Showcase Leadership in Psychiatry and Orexin Biology With New Data at the American Society of Clinical Psychopharmacology Annual Meeting - BioSpace

Alkermes is presenting new data on psychiatry and orexin biology at the ASCP annual meeting, indicating potential updates on its pipeline or mechanism of action relevant to psychopharmacology.

Journal Article 1

Buproprion vs SSRIs: Antidepressant-Naive, Obese Patients With Major Depressive Disorder - Psychiatric Times

This article title suggests a comparative analysis of bupropion versus SSRIs in antidepressant-naive, obese patients with major depressive disorder, though the provided text lacks specific clinical findings or outcomes.

Mechanism of Action 1

A Single Dose of Psilocybin Eased Nerve Pain in Mice for Weeks - ZME Science

Preclinical mouse data shows a single dose of psilocybin provides prolonged relief from nerve pain, suggesting potential mechanisms for pain management relevant to psychiatric pharmacology.

Substance Use 1

Associations between modes of cannabis use and cannabis use disorder: Evidence from the 2022 to 2023 United States National Survey on Drug Use and Health

Multi-modal cannabis use is associated with a fourfold higher risk of Cannabis Use Disorder compared to oral-only use, highlighting the need to assess delivery methods in clinical evaluations.