Combination therapies outperform monotherapy for treatment-resistant depression, achieving an additional 6.5% reduction in depression scores over 12 weeks. The most effective combinations were olanzapine with fluoxetine and quetiapine with SSRIs/SNRIs. Injectable treatments, particularly ayahuasca, produced rapid effects, with a 77% reduction in depression scores at 15 days. Intranasal treatments reached efficacy sooner than oral ones, with 28-day efficacy similar to the 12-week efficacy of the olanzapine-fluoxetine combination. Dropout rates due to adverse events were similar across methods (4.5%-5.2%), but total dropouts were highest for oral (17.9%) and lowest for intranasal routes (10.6%). There was considerable variation in headache, dizziness, and nausea incidence across administration routes.
Esketamine, a drug used for treatment-resistant depression, is associated with a range of adverse drug events, including psychiatric, neurological, and cardiovascular effects. Analysis of reports from the US Food and Drug Administration Adverse Event Reporting System identified the most common adverse events as dissociation, sedation, and increased blood pressure. Network toxicology analysis suggested that esketamine may interact with multiple biological targets and pathways, potentially explaining its toxicological mechanisms. The findings indicate that while esketamine is effective, careful monitoring for specific adverse events is warranted.