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Methamphetamine use makes hallucinations and other psychotic symptoms substantially more likely among addicts, particularly for those abusing other substances, a longitudinal study affirmed.

The odds of psychotic symptoms were 5.3-fold higher during periods of meth use (P<0.001), Rebecca McKetin, PhD, of the Australian National University in Canberra, and colleagues found.

That risk was dose-dependent and further doubled by frequent marijuana or alcohol use, the group reported online in JAMA Psychiatry (formerly the Archives of General Psychiatry).

"Clinicians need to be vigilant for signs of methamphetamine use among patients who present with psychosis and to appreciate the role that methamphetamine plays in the generation of psychotic symptoms," they wrote.

The stimulant, also known as meth or speed, produces a transient psychotic reaction very similar to acute paranoid schizophrenia and sometimes bizarre behavior and thought disorder.

While that association is well-established, the evidence came only from case reports and cross-sectional studies and it couldn't be certain that the link was causal, not just preexisting psychosis, the group explained.

"This is not a trivial consideration because drug use is concentrated among segments of the population that have a high risk for psychosis, namely young men, and individuals with comorbid risk factors for psychosis (e.g., a history of mental disorders and adverse life events)," they wrote.

Their study used a fixed-effects analysis comparing periods of exposure and non-exposure to overcome confounding by premorbid factors.

It included 278 individuals ages 16 and older in the larger Australian Methamphetamine Treatment Evaluation Study (MATES) cohort who met DSM-IV criteria for methamphetamine dependence at baseline but had no history of schizophrenia or mania.

The average participant had been using the drug for 13 years prior to study entry.

Structured interviews about substance use in the prior month at baseline, 3 months, 1 year, and 3 years indicated methamphetamine use during 58% of those months, with a median of 8 days of use during a month when they used it.

Drug testing on hair samples from a subset suggested only 6% falsely reported abstinence.

Fully 60% of the participants reported psychotic symptoms -- defined by a clinically significant score of 4 or more points on the Brief Psychiatric Rating Scale for suspiciousness, unusual thought content, or hallucinations -- during at least one of the 4 months of observation. Severity was typically moderate.

The likelihood of psychotic symptoms was a low 7% in months without meth use and low levels of cannabis and alcohol use (less than 16 days).

It rose to 48%, though, with 16 days or more of methamphetamine use and to 61% to 69% when adding frequent cannabis or alcohol use.

After adjustment for use of those other drugs, the dose-dependent link to methamphetamine remained:

• 4.0-fold higher risk of psychotic symptoms for 1 to 15 days of use versus none in the prior month (95% confidence interval 2.5 to 6.5)
• 11.2-fold higher risk of psychotic symptoms for 16 or more days of use versus abstinence in the past month (95% CI 5.9 to 21.1)

Frequent cannabis and/or alcohol use (16 days of use in the past month) further increased the odds of psychotic symptoms (cannabis: OR, 2.0 [95% CI 1.1 to 3.5]; alcohol: OR, 2.1 [95% CI 1.1 to 4.2]).

Concurrent changes in health and social functioning, such as unemployment, unstable housing, and disability, didn't appear to account for the association. Further adjustment for these factors attenuated the odds without eliminating their significance.

The researchers cautioned that while a small proportion of the patients reported psychotic symptoms during periods of abstinence, the study couldn't determine how chronic the psychotic symptoms were and whether meth increased longer-term vulnerability to psychosis.

Another limitation was inability to rule out confounding from unmeasured factors that went along with methamphetamine use, such as sleep deprivation.

Moreover, the analysis couldn't prove the direction of causality and its results may not generalize to occasional stimulant abuse or the general population.

"Dependent methamphetamine users, by virtue of many years of stimulant use and a range of common risk factors of drug dependence and psychotic disorders, are likely to be more prone to psychosis than the general population," the group warned.

"Moreover, mental health disorders are particularly high among drug users who seek treatment, elevating the likelihood of psychotic phenomena among this sample of participants (who were primarily treatment seekers) compared with drug users in the community."

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