Fine-tuning of dopamine receptor signaling with aripiprazole counteracts ketamine's dissociative action, but not its antidepressant effect.
Translational psychiatry March 8, 2025 Daiki Nakatsuka, Taro Suwa, Yuichi Deguchi et al. 1 citation
Aripiprazole, a partial dopamine receptor agonist, can suppress the dissociative side effects of the rapid-acting antidepressant ketamine without diminishing its antidepressant effects. Experiments in mice showed that aripiprazole blocked ketamine-induced psychotomimetic behaviors while preserving or enhancing antidepressant-like effects in the forced swim test, whereas the antagonist raclopride suppressed both. Brain mapping identified the ventral tegmental area as a key region. In a small clinical study of nine depressed patients, co-administering 12 mg of aripiprazole with ketamine reduced dissociative symptoms while maintaining antidepressant benefits. These findings suggest that combining aripiprazole with ketamine may offer a preferred therapy for treatment-resistant depression.