A personal literature overview argues that the psychedelic experience induced by psilocybin and similar drugs is often treated as a necessary part of therapy, echoing past attitudes toward side effects of older antidepressants and antipsychotics. The author contends that this neglect of side effects remains unresolved in clinical psychopharmacology. Recent animal studies show antidepressant-like effects through opioid and glutamatergic pathways, not solely serotonergic activation. The author concludes that developing non-hallucinogenic antidepressants would be safer and therapeutically beneficial for depressed patients.
Modern electroconvulsive therapy (ECT) and ketamine are the most effective treatments for depressed patients who do not respond to two or more antidepressants. Recent large head-to-head comparisons of intravenous ketamine versus ECT for treatment-resistant depression have produced conflicting findings, largely because of major differences in patients' baseline characteristics and treatment procedures across studies. This commentary argues that treatment decisions between ECT and ketamine should rely on predictive clinical response markers and patient preferences, not on direct comparisons that are methodologically limited. It also emphasizes that since ketamine is usually given before ECT, future studies should examine ECT's effectiveness specifically in patients who did not respond to ketamine.