Objectives: Stimulant medications are increasingly prescribed for conditions including stimulant use disorders, yet both therapeutic and nontherapeutic use have been linked to stimulant-induced psychosis. Despite extensive literature, no prior systematic review has compared psychotic outcomes across these 2 contexts of use. Methods: Following PRISMA guidelines, we systematically searched PubMed, Embase, and Scopus through April 2025 and registered the protocol in PROSPERO (CRD420251049204). Eligible studies examined stimulant-induced psychosis among therapeutic (prescribed) and nontherapeutic (illicit, recreational, or misused) users. Data were extracted on demographics, stimulant type, dosage, route, comorbidities, clinical characteristics, and outcomes. Meta-analyses were conducted for incidence and prevalence where data permitted. Risk of bias was assessed using RoB 2.0, ROBINS-I, and JBI tools. Results: Seventy-seven studies (n = 687,912) were included: 9 therapeutic and 68 nontherapeutic. Therapeutic stimulants were primarily oral methylphenidate or amphetamine at guideline doses, while nontherapeutic use commonly involved high-dose methamphetamine or mixed stimulants through intravenous or smoked routes. The pooled incidence of stimulant-induced psychosis in therapeutic use was 0.6% (95% CI: 0.3–0.9). Prevalence estimates differed markedly: 0.2% (95% CI: 0.0–0.3) in therapeutic users versus 32.8% (95% CI: 25.5–40.2) in nontherapeutic users. Nontherapeutic psychosis was characterized by higher dosages, acute onset, persecutory delusions, hallucinations, and greater recurrence risk, whereas therapeutic cases often resolved with dose reduction or discontinuation. Evidence on treatment effectiveness, neurobiology, and genetic factors was limited and heterogeneous. Conclusions: Stimulant-induced psychosis occurs in both therapeutic and nontherapeutic contexts but at vastly different prevalence rates. While prescribed stimulants pose a low but clinically relevant risk, particularly in individuals with psychiatric vulnerability, nontherapeutic use carries a substantial burden of psychosis with significant public health implications. These findings underscore the need for careful monitoring in clinical practice, risk profiling, and targeted harm-reduction strategies in nonmedical use settings.
Jangra et al. (Tue,) studied this question.