Drug Psychosis May Pull the Schizophrenia Trigger

Feb 04, 2020

A study examining the connection between substance-induced psychosis and subsequent diagnosis of schizophrenia or schizoaffective disorder provides key implications for treatment.


Substance-induced psychotic disorders, more colloquially referred to as drug-induced psychoses, may represent up to one-quarter of first hospitalizations for psychosis.1 These persons are often excluded from early psychosis studies, which limits evidence on their prevalence, clinical course, and outcomes.2

Many people with substance-induced psychoses will later transition to a diagnosis of schizophrenia, but estimates vary widely between early psychosis services and population-based registers. A recent review found that 21% of people with first-episode substance-induced psychosis later received a diagnosis of schizophrenia or schizoaffective disorder.3

Murrie and colleagues4 synthesized the results of longitudinal observations studies of transition from substance-induced psychosis to schizophrenia, using transition from other brief and atypical psychoses as a comparison group. They also aimed to investigate potential moderators of transition risk. The authors searched PsycINFO, MEDLINE, and Embase for studies from 1980-2018 that reported follow-up diagnoses in people with substance-induced psychosis, brief psychosis, atypical psychosis, schizophreniform psychosis, and psychosis NOS.

Inclusion criteria were: 1) a baseline diagnosis of substance-induced, brief, atypical, NOS, or schizophreniform psychosis, 2) a follow-up diagnosis with a minimum follow-up period of 6 months, and 3) the number of people with schizophrenia at the follow-up assessment. Studies defining psychosis with symptom scales or self-report were excluded.

The primary outcome was the proportion of people with a follow-up diagnosis of schizophrenia. Potential moderating variables included service setting, country, urban versus rural, age, sex, diagnostic system, diagnostic method, dropout rate, symptom severity scale scores, global assessment of function, cohorts limited to first-episode psychosis, year of follow-up, and use of toxicology to establish follow-up.

The authors first performed a meta-analysis of substance-induced psychoses compared with brief and atypical psychoses. Secondly, they performed separate meta-analyses of substance type (eg, stimulants, hallucinogens, cannabis) as a separate subgroup. Subgroup analyses for study-level data were also performed to investigate potential moderators of the primary outcome.

A total of 50 studies (including 25 studies of substance-induced psychosis) met the inclusion/exclusion criteria, with 79 estimates of transition to schizophrenia among almost 41,000 people. The median follow-up period was 4 years. Mean study age was 28 and 61% of participants were male. Forty two of the studies examined first-episode psychosis cohorts.

Overall, 25% (95% CI 18-35%) of people with substance-induced psychosis had a follow-up diagnosis of schizophrenia, which was lower than the estimates for brief, atypical, and NOS psychoses (36%) and for schizophreniform disorder (65%). Transition from substance-induced psychosis to schizophrenia was not moderated by study design characteristics, sex, duration of follow-up, or publication year, but transition rates were lower in studies of older cohorts. The risk of transition to schizophrenia was highest for cannabis (34%), hallucinogens (26%), and amphetamines (22%) and lowest for alcohol (9%) and sedatives (10%).

The authors concluded that the overall proportion of transition from substance-induced psychosis to schizophrenia was 25%, and the strongest predictor was the type of substance. There was significant heterogeneity of estimates. Furthermore, substance-induced psychosis had a lower rate of transition than brief, atypical, and unspecified psychoses. The authors note variable designs of included studies and the heterogeneity of estimates as primary limitations.

The bottom line

Findings have important implications for mental health services. Substance-induce psychoses are common reasons for seeking care, and these serious conditions are associated with substantial risk of transition to schizophrenia. A key implication of study findings is that the treatment of cannabis-, amphetamine-, and hallucinogen-induced psychoses should be considered in the same framework of intervention as for other brief psychotic disorders, including engagement, assessment, and care, which may help decrease rates of transition to schizophrenia.


Dr Miller is Associate Professor, Department of Psychiatry and Health Behavior, Augusta University, Augusta, GA. He is the Schizophrenia Section Chief for Psychiatric Times.

The author reports that he receives research support from Augusta University, the National Institute of Mental Health, the Brain and Behavior Research Foundation, and the Stanley Medical Research Institute.




1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Publishing; 2013.

2. Fusar-Poli P, Cappucciati M, Bonoldi I, et al. Prognosis of brief psychotic episodes: a meta-analysis. JAMA Psychiatry. 2016;73:211–220.

3. Fusar-Poli P, Cappucciati M, Rutigliano G, et al. Diagnostic stability of ICD/DSM first episode psychosis diagnoses: meta-analysis. Schizophr Bull. 2016;42:1395–1406.

4. Murrie B, Lappin J, Large M, Sara G. Transition of Substance-Induced, Brief, and Atypical Psychoses to Schizophrenia: A Systematic Review and Meta-analysis. Schizophr Bull. 16 October 2019 [Epub ahead of print].