Ketamine produces rapid antidepressant effects within 24 hours, thought to involve mTORC1 activation. In a double-blind crossover trial, 20 depressed patients received either rapamycin (an mTORC1 inhibitor) or placebo before ketamine. Rapamycin did not block ketamine's 24-hour antidepressant effects. Over two weeks, rapamycin prolonged ketamine's benefits: response rates were 41% with rapamycin versus 13% with placebo, and remission rates were 29% versus 7%. These findings question whether systemic or local mTORC1 blockade matters and suggest rapamycin may extend ketamine's effects, potentially informing mechanisms of depression relapse.
Ketamine administration produces transient psychopathological effects in both healthy volunteers and patients with schizophrenia, with the nature and severity of these effects varying according to experimental factors such as dose, route of administration, and participant characteristics. The meta-analysis quantifies these outcomes, showing that ketamine reliably induces psychotic-like symptoms, dissociation, and cognitive impairments in healthy individuals, while its effects in patients with schizophrenia are more complex and may involve both symptom exacerbation and potential therapeutic benefits depending on the context.