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The time course of psychotic symptom side effects of ketamine in the treatment of depressive disorders: a systematic review and meta-analysis

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Objective: Ketamine is a potential rapid-acting treatment for depression. Studies have suggested that the side effects are minimal and temporary, but the psychotic symptom side effects have yet to be fully examined. This study investigated whether ketamine infusion in the treatment of mood disorders is associated with increases in positive symptoms and whether these symptom effects endure over time.

Methods: A systematic review and meta-analysis of studies of ketamine in the treatment of depression. Embase and Medline databases were searched for studies including (a) participants with major affective disorders, (b) 0.4 or 0.5 mg intravenously administered ketamine, (c) measurement of positive symptoms using BPRS+, and (d) a within-subject repeated-measures design with participants serving as their own baseline.

Results: Seventeen studies met the inclusion criteria, comprising 458 participants. The meta-analyses examined symptom change occurring within the first 4 h, after 1 day, and after 3 days. Results showed significant BPRS+ increases within the first 30-60 min in 72% of studies, followed by a return to baseline levels.

Conclusion: Peak symptom change occurred within the first hour post infusion. There are limited data to determine if ketamine is safe in the longer term, but there were no indications that psychotic symptoms re-occurred after the first hour and in the days following administration.

Tashakkori, M., Ford, A., Dragovic, M., Gabriel, L., & Waters, F. (2021). The time course of psychotic symptom side effects of ketamine in the treatment of depressive disorders: a systematic review and meta-analysis. Australasian psychiatry : bulletin of Royal Australian and New Zealand College of Psychiatrists, 29(1), 80–87.

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