Clinical trials with psychedelics like psilocybin face unique methodological challenges, particularly the difficulty of maintaining blinding due to the substances' pronounced subjective effects, which raises risks of expectation bias and nocebo effects. A phase II randomized, double-blind, active placebo-controlled parallel group trial with 144 patients is underway to evaluate psilocybin's efficacy and safety in treatment-resistant major depression. The trial, called EPIsoDE, is funded by the German Federal Ministry of Education and Research and addresses these challenges in its design.
Higher baseline absolute monocyte count (AMC) predicts greater symptom improvement during intravenous ketamine therapy for treatment-resistant depression. In 27 participants receiving six ketamine infusions over three weeks, baseline AMC showed a strong negative correlation with depression severity change after the first infusion and before the last infusion, meaning higher monocyte levels were associated with more symptom reduction. Baseline AMC distinguished responders and partial responders from non-responders but not between partial and full responders. Absolute neutrophil count correlated weakly with early improvement, while C-reactive protein showed no correlation. AMC may serve as a simple clinical marker for predicting ketamine treatment response.
In adults with treatment-resistant depression receiving six intravenous ketamine infusions over three weeks, higher baseline levels of the neuroprotective metabolite kynurenic acid (KYNA) in the kynurenine pathway were associated with greater symptom improvement by day 18. KYNA remained stable over time and did not track with symptom changes, suggesting it acts as a trait-like marker rather than a state-dependent one. Early shifts toward the neurotoxic branch of the pathway (kynurenine and 3-hydroxykynurenine) were linked to reductions in hopelessness and suicidality scores after the first infusion. These exploratory findings indicate that a kynurenine pathway profile biased toward neuroprotective metabolites may inform future biomarker studies of ketamine response, but require validation in larger samples.
A 42-year-old patient with severe treatment-resistant depression and psychiatric comorbidities attempted suicide five weeks after hospital admission. After starting dextromethorphan/bupropion, her mood improved and suicide risk decreased, allowing discharge.
Pregnant women in their last trimester report nightmares more often than a representative sample of women aged 14 to 93. Nightmare frequency is closely related to subjectively experienced stress during daytime. Baby-related dreams were correlated with nightmare frequency but not with daytime stress. The findings suggest that stress plays a key role in nightmares during pregnancy, and future research should examine nightmare disorders in pregnancy and whether brief interventions like Imagery Rehearsal Therapy could help.