Treatment approaches and efficacy in psychedelic-induced psychosis: A systematic review

Psychedelics are increasingly used in the general population, yet they are associated with increased risk of psychosis in a minority of users that can experience psychedelic-induced psychosis (<1 % in controlled trial settings). In contrast, the evidence regarding the treatment of psychedelics-induced psychosis remains to date scarce. We conducted a PRISMA 2020-compliant systematic review (CRD42023399591), searching electronic databases (inception-August 2024) for interventional, observational studies, case series, or case reports on the treatment of psychedelic-induced psychosis. Frequencies of population, treatment, and outcome characteristics were analyzed. We included 14 case series, 20 case reports, and one prospective study, reporting on 93 cases of psychedelic-induced psychosis, between 1955 and 2024. The primary substances implicated were LSD (47.3 %) and MDMA (38.7 %), and the average patient age of 23.7 ± 6.3 years, with a predominance of male subjects (88 %). Psychosis lasted an average of 1.8 weeks. We identified two main treatment categories: first-generation antipsychotics (n = 37) and second-generation antipsychotics (n = 57). Electroconvulsive therapy was used in a minor subset of cases (n = 9). The response rate for first-generation antipsychotics (27 %) was significantly lower than that for second-generation agents (91.3 %) and electroconvulsive therapy (91 %). Follow-up data indicated 34 % of patients later developed schizophrenia spectrum disorders, and 20.4 % were diagnosed with bipolar disorder. However, the lack of comprehensive follow-up limits the interpretation of findings In conclusion, the evidence supporting treatment options remains limited, primarily based on case reports. Our findings suggest that second-generation antipsychotics seem to be more beneficial in managing psychedelic-induced psychosis, warranting further investigation into optimized treatment protocols.