Olanzapine may be more effective than other antipsychotics for patients with schizophrenia, alcohol use disorder

Patients with schizophrenia and alcohol use disorder experienced a worse illness course than those with only schizophrenia, according to results of a post hoc analysis published in Journal of Clinical Psychiatry.

Researchers found that olanzapine may be associated with a longer time to first and recurrent exacerbations vs. other antipsychotics among this patient population.

“Despite recognition that [alcohol use disorder] can complicate the course of illness in schizophrenia, treatment options for these patients are limited, and it has been difficult to evaluate a link between alcohol drinking and symptom worsening in this unique patient population,” Sanjeev Pathak, MD, vice president of clinical research at Alkermes Inc., and colleagues wrote. “Clinical trials conducted for the regulatory approval of pharmacologic treatments in schizophrenia exclude those with comorbid [alcohol use disorder]. As a consequence, clinical trial data in this population are sparse, and further research is needed to identify effective treatments for this clinically relevant yet understudied population.”

The NIMH funded a prospective, multiphase study called Clinical Antipsychotic Trials of Intervention Effectiveness in Schizophrenia (CATIE), which was one of the largest and longest comparative effectiveness trials of antipsychotics as schizophrenia treatment. The CATIE study was open to patients with schizophrenia and comorbid conditions, such as drug, alcohol and tobacco use. A prior analysis of phase 1 CATIE data showed that illicit substance use, excluding alcohol use disorder, attenuated the reduction in time to all-cause olanzapine-associated discontinuation. Another secondary analysis of individuals with alcohol use disorder at baseline revealed no differences between any of the evaluated antipsychotics.

To evaluate phase 1 CATIE data, Pathak and colleagues categorized patients without substance abuse, except marijuana use, in the month before study entry into those with a history of alcohol use disorder within 5 years before study entry and those without alcohol use disorder per DSM-IV criteria. They compared time to first and recurrent exacerbations and hospitalizations between disease states and between olanzapine and perphenazine, quetiapine, risperidone and ziprasidone.

Pathak and colleagues included data of 1,338 patients, of whom 22.6% had schizophrenia and alcohol use disorder and 77.4% had only schizophrenia. Results showed that time to first exacerbation of schizophrenia was significantly shorter among those with alcohol use disorder vs. those with schizophrenia-only (median, 5.4 months vs. 6.4 months; HR = 1.2; 95% CI, 1.01-1.42). They observed similar results for first hospitalization (HR = 1.63; 95% CI, 1.2-2.22) and recurrent hospitalizations (HR = 1.6; 95% CI, 1.18-2.15). Among both groups, the most common factors of exacerbation were an increase in symptom severity and lack of efficacy. Among patients with schizophrenia and alcohol use disorder related or unrelated to marijuana, the researchers found that perphenazine, quetiapine, risperidone and ziprasidone were associated with significantly shorter time to first exacerbation vs. olanzapine.

“Additional large, randomized, controlled trials with greater patient numbers are needed in patients with schizophrenia and a dual diagnosis of comorbid [alcohol use disorder] or other substance use disorder,” the researchers wrote. – by Joe Gramigna

Disclosures: Pathak is an employee of Alkermes Inc. and may own stock/options in the company. Please see the study for all other authors’ relevant financial disclosures.