Schizophrenia is associated with an increased prevalence of alcohol use disorders (AUD),1 which is associated with relapse2 and poorer outcomes.

Schizophrenia is associated with an increased prevalence of alcohol use disorders. A post-hoc analysis of the clinical course of the 2 disorders is an important change in this understudied and often overlooked population.

Schizophrenia is associated with an increased prevalence of alcohol use disorder (AUD),1 which is associated with relapse2 and poorer outcomes.3 Unfortunately, adherence with (limited) treatment options for this patient population are suboptimal. Furthermore, patients with comorbid AUD are often excluded from clinical pharmacologic trials in schizophrenia. Therefore, this represents and understudied and difficult-to-treat patient population.

The NIMH-funded Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) was a large, long comparative trial of antipsychotics for the treatment of schizophrenia.4 As an effectiveness trial, CATIE did not exclude patients with substance use comorbidity.

Pathak and colleagues5 reported on a post-hoc analysis of the course of illness in patients with schizophrenia and AUD from the CATIE study. They assessed time to first and recurrent exacerbation, and risk of first and current hospitalization in these patients within the 5 years before study entry, compared with patients with schizophrenia only. They also compared treatment outcomes with olanzapine versus other antipsychotics in these 2 groups. The authors hypothesized that schizophrenia + AUD would have a worse outcome than patients with schizophrenia, and within each group the advantages of olanzapine for exacerbations and hospitalizations in the CATIE study would be retained.

Data for the study were obtained from the publicly available, limited access CATIE study dataset from the NIMH. Briefly, CATIE was an 18-month double-blind, randomized trial of perphenazine and olanzapine, quetiapine, risperidone, and ziprasidone in 1493 patients with schizophrenia.The primary endpoint was time to all-causes discontinuation.

Patients were categorized into schizophrenia + AUD (based on DSM-IV criteria) and schizophrenia-only groups. The authors excluded 155 patients with non-alcohol substance use disorders, except for marijuana use, which was permitted. Exacerbation was defined as hospitalization for psychopathology; > 25% or 15-point increase in baseline PANSS total score; or significant worsening of key PANSS items, clinically significant aggression or suicidal/homicidal ideation, use of rescue medication, emergency department visit, discontinuation due to lack of efficacy, and arrest or incarceration. Time to first and recurrent exacerbations and hospitalizations were compared between the 2 subject groups, including the reasons leading to exacerbations. In the schizophrenia + AUD group, exacerbations and hospitalizations were compared between olanzapine and the other antipsychotics. Data were analyzed using Cox proportional hazards and Andersen-Gill models. Kaplan-Meier plots were presented for time to first even analyses.

There were 303 (23%) partipants in the schizophrenia + AUD group and 1035 (77%) in the schizophrenia group. Patients with schizophrenia + AUD were significantly younger (aged 38 versus aged 41 years), had a lower BMI (29 versus 30), were more likely to be male (87% versus 70%), and had a greater number of hospitalizations in the year prior to study entry (0.9 versus 0.6) than those with schizophrenia only. There was little difference in the prevalence of marijuana use between the 2 groups (6% versus 8%).

The time to first exacerbation (5.4 versus 6.4 months, HR = 1.20) and time to first hospitalization (HR = 1.63) were both significantly shorter in schizophrenia + AUD than schizophrenia only. A similar finding was observed for recurrent hospitalizations (HR = 1.60), although there was only a trend for between-group differences in recurrent exacerbations (HR = 1.16). Over half (61%) of patients with schizophrenia + AUD had an exacerbation, compared with 52% in the schizophrenia-only group, and these patients were more likely to have an exacerbation resulting in hospitalization for psychopathology, due to aggression or suicidal/homicidal ideation, or arrest or incarceration.

Overall, perphenazine, quetiapine, risperidone, and ziprasidone were all associated with a significantly shorter time to first exacerbation compared with olanzapine (HRs = 1.81-2.80). A similar pattern of findings was observed for time to first hospitalization.

The authors concluded that patients with schizophrenia + AUD had a poorer course of illness with higher risk of disease progression compared to patients with schizophrenia without AUD comorbidity. They also found that olanzapine may be associated with longer time to first and recurrent exacerbations compared to other treatment in patients with schizophrenia and AUD comorbidity. Strengths of the present study include the large number of subjects and the “real-world” design of the CATIE trial. Potential limitations include the post-hoc nature of the analysis, and the lack of generalizability of findings to patients with schizophrenia and other (non-alcohol) substance use disorders. Future trials are needed to identify effective treatment for this patient population.

Originally published at psychiatic times