A single intravenous infusion of ketamine reduces depression significantly more than placebo in people with major depressive disorder or bipolar depression, with effects beginning within 40 minutes, peaking at one day, and lasting up to one week. Non-ketamine NMDAR antagonists were superior to placebo only on days 5–8. Ketamine also led to greater response and remission rates at multiple time points. Adverse effects were transient and clinically insignificant, and discontinuation rates did not differ from placebo. The review analyzed 14 randomized controlled trials involving 588 participants.
Negative symptoms of schizophrenia, such as social withdrawal and lack of motivation, contribute heavily to the economic burden of the disease and have no FDA-approved treatments. This review argues that MDMA, a schedule I substance known to enhance social interaction and empathy, may offer a novel therapeutic approach. The authors examine literature on negative symptoms, existing treatments, and MDMA-assisted therapy, concluding that recent evidence suggests MDMA can be safe and potentially effective for treating negative symptoms. The review also discusses safety considerations and possible mechanisms of action, including MDMA's ability to induce metaplasticity in the brain.