Munich, Germany – Contrary to expectations, the opioid receptor antagonist naltrexone is no better than placebo and can be counterproductive in treating substance use disorder in patients with schizophrenia, according to data released at the 18th European Congress of Psychiatry.

“Because naltrexone is commonly prescribed to nonschizophrenic patients to treat substance abuse, we had thought that it might be a useful adjunctive treatment in schizophrenics with comorbid substance abuse,” Ileana Berman, MD, medical director of community counseling of Bristol County in Taunton, Massachusetts and instructor in psychiatry at Harvard Medical School in Boston, said.

Dr. Berman and colleagues randomized 37 patients with schizophrenia or schizoaffective disorder and an alcohol or other substance abuse disorder to six months’ treatment with naltrexone, 50 mg/d, or placebo.

Comorbid substance abuse frequently occurs in patients with schizophrenia and is associated with a poor prognosis, Dr. Berman observed. In an earlier study that included 85 patients with schizophrenia from a long-term psychiatric hospital, her team found that 48% of the cohort also had a substance abuse disorder and that they responded less to treatment.

There are no established therapies that specifically address the treatment of substance abuse in these patients, and no controlled drug trials have assessed the efficacy of medication on substance abuse and psychiatric symptoms in dual diagnosis patients, she said.

Naltrexone has been used in non-schizophrenic patients for the treatment of substance abuse disorder and has been found to be well tolerated and to decrease substance use and help maintain sobriety.

In the present trial, patients had to have at least two episodes of substance use during the prior three months. Most of them were recruited from a long-term psychiatric institution and had a significant social support system consisting of medication monitoring, social services, and close medical and psychiatric monitoring of their daily activities.

Monthly assessments included the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), Global Assessment Scale (GAF), and the Quality of Life Scale (QLS).

Results showed that all patients improved on all psychiatric assessments. However, patients on naltrexone did worse than patients on placebo by the final assessment of PANSS total (F=5.56, p=0.031) and PANSS general symptom subscale (F=4.72, p=0.044) after controlling for scores on the Michigan Alcohol Screening (MAS) test which were significantly higher in the naltrexone group at baseline.

“Our study contradicted the initial hypothesis that naltrexone will improve clinical symptoms over time,” Dr. Berman commented.

“Because 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,” she said. These patients seem to benefit from appropriate psychotropic treatments for schizophrenia and adequate psychosocial services (case management, residential support, etc.) to ensure compliance with treatment and social integration.

Dr. Berman’s son Jacob, a student who had training in statistics at Moses Brown School in Providence, Rhode Island, performed the data entry, data verification, and statistical analysis.

The study was funded by a grant from the National Alliance for Research in Schizophrenia and Affective Disorders.

Written by Jill Stein
Jill Stein is a Paris-based freelance medical writer.