Substance abuse frequently occurs in schizophrenia and has a poor prognosis. In 85 patients with schizophrenia from a long-term psychiatric hospital we previously examined the clinical impact of substance abuse and found that 48% of patients had comorbid substance use disorders and that they responded less to treatment. Naltrexone has been used in patients without schizophrenia for the treatment of substance use disorder. Consequently, we conducted a double-blind controlled study of adjunctive treatment with naltrexone or placebo in patients with schizophrenia with co-morbid substance use disorders to determine whether naltrexone would improve outcome.

Thirty-seven patients entered the study and were randomized to placebo vs. naltrexone 50mg/day. The monthly assessments included the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), Global Assessment Scale (GAF), and the Quality of Life Scale (QLS). We used an analysis of variance of the change scores between final visit and baseline with the last visit carried over.

All patients improved in PANSS and QLS but those on naltrexone improved less with a statistically significant group difference between the PANSS total (F=6.5, p≤0.03) and general symptom change scores (F=4.2, p≤0.04) when weighted for the Michigan Alcohol Screening (MAS).

Both groups of patients improved in this controlled setting where patients refrained from substance abuse; those on naltrexone improved less, however. As patients with schizophrenia have pervasive neuroreceptor deficits, it is possible that they have deficits in the opioid system suggesting that the addition of the opioid-blocker naltrexone may be counterproductive.