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Navigating the treatment options for comorbid schizophrenia and alcohol use
Schizophrenia is associated with an increased prevalence of alcohol use disorder (AUD),1 which is also associated with relapse and poorer outcomes.2,3 Adherence with (limited) treatment options for this patient population are suboptimal. Furthermore, patients with comorbid AUD are often excluded from pharmacologic trials in schizophrenia. Therefore, this represents an understudied and difficult-to-treat patient population.
Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE), funded by the National Institute of Mental Health, was a large, long comparative series of trials of antipsychotics for the treatment of schizophrenia.4 As effectiveness trials, CATIE did not exclude patients with substance use comorbidity.
Case vignette 1
“Ms Norman” is in her 40s and has a longstanding history of schizoaffective disorder and severe AUD. She binges on alcohol episodically, with several months’ sobriety between periods of heavy drinking. Typically, within several weeks of alcohol cessation, she will experience an exacerbation of psychosis requiring inpatient psychiatric hospitalization. She previously lived independently and was able to have part-time employment. Following a recent illness exacerbation, she experienced a period of homelessness for several months, during which she continued to drink alcohol and dropped out of outpatient psychiatric treatment.
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 risks of first and current hospitalization within the 5 years before study entry for patients with this comorbidity, compared with patients with schizophrenia only. They also compared treatment outcomes with olanzapine versus other antipsychotics in these 2 groups. The authors hypothesized that patients with schizophrenia plus AUD would have worse outcomes than patients with schizophrenia alone and, within each group, the advantages of olanzapine for exacerbations and hospitalizations 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, olanzapine, quetiapine, risperidone, and ziprasidone in 1493 patients with schizophrenia. The primary end point was time to all-cause discontinuation.
Patients were categorized into schizophrenia and AUD and schizophrenia-only groups (based on DSM-IV criteria). The authors excluded 155 patients with nonalcohol substance-use disorders, except for marijuana use, which was permitted. Exacerbation was defined as hospitalization for psychopathology; more than a 25% or 15-point increase in baseline Positive and Negative Syndrome Scale (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; or arrest or incarceration. Times to first and recurrent exacerbations and hospitalizations were compared, including the reasons leading to exacerbations. In the schizophrenia and AUD group, exacerbations and hospitalizations were compared between patients taking olanzapine and those taking other antipsychotics. There were 303 (23%) participants in the schizophrenia and AUD group and 1035 (77%) in the schizophrenia-only group. Patients with schizophrenia and AUD were significantly younger, had a lower body mass index, were more likely to be male, and had a greater number of hospitalizations in the year prior to study entry than those with schizophrenia only. There was little difference in the prevalence of marijuana use between the 2 groups.
Both the time to first exacerbation (median, 5.4 versus 6.4 months; HR, 1.20) and time to first hospitalization (HR, 1.63) were significantly shorter in the schizophrenia and AUD group than the schizophrenia-only group (Figure). A similar finding was observed for recurrent hospitalizations (HR, 1.60), although there was only a trend for between-group differences in recurrent exacerbations. More than half (61%) of patients with schizophrenia and AUD had an exacerbation, compared with 52% in the schizophrenia-only group, and the patients with schizophrenia and AUD 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 plus AUD had a poorer course of illness, with higher risk of disease progression, compared with patients with only schizophrenia. The investigators also found that olanzapine may be associated with longer time to first and recurrent exacerbations compared with other treatments in patients with schizophrenia and AUD comorbidity.
Case vignette 2
“Mr Greggs” is in his 30s with a history of chronic schizophrenia and severe AUD, as well as cannabis use disorder. He is currently serving a 1-year probation for a driving-while-impaired citation. He is adherent with monthly administration of a long-acting injectable antipsychotic but continues to drink alcohol and smoke marijuana regularly. He lives at home with his parents and is chronically unemployed. He has not had a psychiatric hospitalization in many years but remains precontemplative regarding the need for treatment for substance use disorder.
Strengths of the present study included the large number of subjects and the real-world design of the CATIE trial. Potential limitations included the post hoc nature of the analysis as well as the lack of generalizability of findings to patients with schizophrenia and other (nonalcohol) substance use disorders. Future trials are needed to identify effective treatment for this patient population.
The bottom line
Patients with schizophrenia with alcohol use disorder comorbidity versus those without have a worse course of illness, and olanzapine may be associated with a longer time to exacerbations versus other nonclozapine antipsychotics.
Dr Miller is professor, Department of Psychiatry and Health Behavior, Augusta University, Augusta, GA. He is the schizophrenia section chief for Psychiatric TimesTM. The author reports that he receives research support from Augusta University, the National Institute of Mental Health, the Brain & Behavior Research Foundation, and the Stanley Medical Research Institute.
1. Hartz SM, Pato CN, Medeiros H, et al; Genomic Psychiatry Cohort Consortium. Comorbidity of severe psychotic disorders with measures of substance use. JAMA Psychiatry. 2014;71(3):248-254.
2. Bradizza CM, Stasiewicz PR, Dermen KH. Behavioral interventions for individuals dually-diagnosed with a severe mental illness and a substance use disorder. Curr Addict Rep. 2014;1(4):243-250.
3. Jones RM, Lichtenstein P, Grann M, Långström N, Fazel S. Alcohol use disorders in schizophrenia: a national cohort study of 12,653 patients. J Clin Psychiatry. 2011;72(6):775-779.
4. Lieberman JA, Stroup TS, McEvoy JP, et al; Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. 2005;353(12):1209-1223.
5. Pathak S, Jiang Y, DiPetrillo L, Todtenkopf MS, Liu Y, Correll CU. Course of psychosis in schizophrenia with alcohol use disorder: a post hoc analysis of the Clinical Antipsychotic Trials of Intervention Effectiveness in Schizophrenia phase 1 study. J Clin Psychiatry. 2020;81(2):19m12731.❒