Substance abuse and mental illness are commonly comorbid, yet there is no one clear answer that explains why people with mental illness are likely to be substance abusers.1 Mounting evidence suggests that patients who first present with a drug-induced psychotic episode tend to be at substantial risk for future psychosis.1 Although a drug-induced psychosis may be difficult to distinguish from primary psychosis, it is important to accurately diagnose the disorder because it guides treatment.

Typically, substance-induced psychosis can be diagnosed when the patient’s symptoms lessen as the psychoactive drug is either excreted or metabolized.1 In the case of cannabis use, up to 50% of patients eventually develop schizophrenia.2 The conversion rates to schizophrenia for other drugs are still substantial: approximately 30% for amphetamines, 24% for hallucinogens, 21% for opioids, and 5% for alcohol.2

Such was the case with a Danish registry study, in which 6788 patients with substance abuse disorder were followed for 20 years to determine which patients eventually converted to schizophrenia or bipolar disorder.2 Overall, for patients with substance abuse disorders, the conversion rate to schizophrenia or bipolar disorder was 32.2%.2 The rates for substance abusers to convert to either schizophrenia and bipolar disorder were 26.0% and 8.4%, respectively.2

The substance most frequently implicated in drug-inducing psychosis was cannabis, which had an overall conversion rate of 47.4% to either schizophrenia or bipolar disorder.2 Although alcohol was the most commonly abused substance (it was used by more than one-third of participants), it was only responsible for converting 22.1% to either schizophrenia or bipolar disorder.2

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“We hope that clinicians will glean from our study that patients with alcohol or substance-induced psychoses are very much at risk of developing schizophrenia or bipolar disorder afterwards,” said Carsten Hjorthøj, PhD, MSc, senior researcher and head of psychosis research at Copenhagen University in Denmark, in an interview with Psychiatry Advisor.

“They should note that while the initial period after the substance-induced psychosis confers the greatest risk, that patients will still be at risk of schizophrenia or bipolar disorder even several years after the substance-induced psychosis.”

What to Watch for in Substance Abusers

Risk factors varied for substance abusers to convert to schizophrenia vs bipolar disorder, although a history of mental illness and self-harm were strong indicators for either disorder. Conversion to schizophrenia included risk factors such as young age, male sex, and history of substance abuse, eating disorder, or personality disorder.2 For bipolar disorder, risk factors for conversion included history of anxiety, depression, and personality disorder; female sex; and age >51 years.2 The registry study found that it took 3.1 years for substance-induced psychosis to convert to schizophrenia and 4.4 years to convert to bipolar disorder.2

In another registry-based longitudinal study of 6217 inmates in Sweden, Rognli and colleagues also found cannabis use to be a predictor of later primary psychosis development (odds ratio [OR], 2.62; 95% CI, 1.39-4.96).3

The largest factor, however, contributing to later psychosis was using multiple drugs (OR, 9.55; 95% CI, 3.42-26.67), prior psychiatric hospitalizations (OR, 3.22; 95% CI, 2.27-4.54), and non-drug-induced hallucinations (OR, 4.00; 95% CI, 2.82-5.67).3

“It seems that cannabis is the substance most strongly related to later development of schizophrenia, while amphetamine is more related to the acute drug-induced psychosis,” explained psychologist Eline Borger Rognli, PhD, from Oslo, Norway, in a separate interview with Psychiatry Advisor.

“However, amphetamine use seems to increase the risk for later schizophrenia. It seems to be the sum of type of drug (cannabis and amphetamine most importantly), amount used (age of onset, frequency of use, cumulative exposure, strength of psychoactive component/[tetrahydrocannabinol (THC)] concentration), and genetic and environmental vulnerability.”

What Distinguishes Primary Psychosis from Drug-induced Psychosis?

People with primary psychosis are usually diagnosed at a younger age than are people with drug-induced psychosis.2 Also, those with substance abuse tend to have a family history of substance abuse.2 Ascertaining the diagnosis should aid in the treatment plan.

In a study of 48 patients (n=25 primary psychosis; n=23 drug-induced psychosis), Mauri and colleagues sought to discern differences between those who were admitted for primary psychosis with comorbid drug abuse and those who were admitted for substance-induced psychosis.4 Although patients who had comorbid drug abuse had higher baseline scores than patients with drug-induced psychosis, at 5.48 vs 4.39, respectively, on the Unusual Content of Thought item from the Brief Psychiatric Rating Scale, the patients did not differ in the other Brief Psychiatric Rating Scale items at the 5-year follow-up. Both groups had comparable rates of developing schizophrenia. Even when the patients with comorbid substance abuse stopped taking drugs, their symptoms did not improve.4

Close Follow-up Is Essential

Until more rigorous and longer trials provide definitive evidence on the course of substance-induced psychosis, clinicians will need to be vigilant with patients who have presented with a drug-induced psychotic episode. “Frequent check-ups with probes for severe mental illness may be warranted; it may also be a good idea, with the patient’s permission, of course, to involve family and possibly friends in a ‘how to detect early warning signs’ intervention,” advised Dr Hjorthøj.

Summary and Clinical Applicability

Mounting evidence suggests that patients who first present with a drug-induced psychotic episode tend to be at substantial risk of developing schizophrenia or bipolar disorder. Cannabis is the substance most frequently implicated in conversion from substance-induced psychosis to either schizophrenia or bipolar disorder. Clinicians need to follow-up frequently and for several years after the initial presentation of drug-induced psychosis.