For severely depressed inpatients aged 18–85, electroconvulsive therapy (ECT) led to remission in 63% of patients, while ketamine infusions led to remission in 46%, a statistically significant difference. Both treatments required a median of six sessions to achieve remission. ECT caused more serious and long-lasting side effects, including persisting amnesia, whereas ketamine caused more treatment-emergent adverse events leading to dropouts. Among those who remitted, about two-thirds in each group relapsed within 12 months, with no significant difference between treatments. Ketamine, though less effective than ECT, appears to be a safe and useful option for treating unipolar depression.
The dissociative effects of ketamine and psychedelics may be linked to their rapid antidepressant properties, but it is unclear whether these effects are necessary for therapeutic action. Because patients can often tell whether they received an active drug or placebo based on the dissociative experience, clinical trial results may be biased. The authors propose a novel approach: administering these drugs to patients during sleep to separate the subjective dissociative experience from the drug's biological effects, potentially allowing for better-controlled studies.