Treatment Considerations for Schizophrenia and Comorbid Substance Use Disorder

BRIEF COMMUNICATION

The abuse of alcohol by patients with schizophrenia is a remarkably common phenomenon, and occurs 3 times more often than in the general population.¹ Comorbid alcohol use disorder is associated with worsening symptoms and is deleterious to the course and outcome of schizophrenia, with medication nonadherence as a probable “final common pathway.” There is evidence that clozapine, in contrast to other antipsychotics-including risperidone-limits alcohol use in dual diagnosis patients with schizophrenia and substance use comorbidity.²

It has been hypothesized that the efficacy of clozapine on alcohol use in dual diagnosis patients may be attributable to its broad pharmacologic effects, including weak dopamine D2 receptor antagonism. Green and colleagues³ performed a 6-month randomized trial of long-acting injectable (LAI) versus oral risperidone in patients with schizophrenia and comorbid alcohol use disorder.

The authors hypothesized that LAI risperidone would be more likely than oral risperidone to decrease alcohol use because the LAI preparation results in lower average steady-state blood concentrations than oral risperidone, and thus lower D2 receptor occupancy, and also encourages increased medication adherence.

Patients with schizophrenia or schizoaffective disorder and current comorbid alcohol use disorder were recruited from 1 of 4 sites (community mental health and Veterans Affairs clinics) in the US. All participants were aged 18 to 65 years; were psychiatrically stable (taking antipsychotic medication and had no change in psychotropic medications in the past months); and had use of alcohol on at least 5 days during the 4 weeks prior to randomization.

Other current substance use disorders were not exclusionary. Excluded from the study were patients on clozapine, 2 or more concurrent antipsychotics, or a LAI antipsychotic; currently treated with agents to curtail substance use; currently in a residential program for substance use; intolerance or allergy to risperidone; or currently pregnant or unwilling to use and acceptable form of birth control.

One-hundred fifty patients with schizophrenia or schizoaffective disorder and comorbid alcohol use disorder were consented, and 95 patients were randomized to receive either LAI risperidone every 2 weeks (n = 46, target dose = 37.5 mg, max dose = 50 mg) or daily oral risperidone (n=49, target dose=4 mg, max dose=6 mg), with study visits every 2 weeks for 6 months.

Concomitant psychotropic medications were maintained without changes (as much as possible) and other psychosocial treatments were allowed. Use of other antipsychotic medications, however, was not allowed outside the period of switching antipsychotics to risperidone. Psychiatric symptoms, alcohol use, and treatment utilization were assessed by blinded raters.

Participants were predominantly males with a mean age of 42, an average of 2 heavy drinking days per week (5 or more drinks per day), and minimal illicit drug use. Sixty-eight patients (72%) remained in the study for 6 months. In an efficacy analysis, heavy drinking significantly worsened over time in the oral risperidone group. Heavy drinking days per week decreased by 0.1 days in the LAI risperidone group and increased by 0.7 days in the oral risperidone group.

The difference between the 2 groups was significant at the trend level (p = 0.054). The 2 groups were also significantly different with regards to number of drinking days per week, with fewer days in the LAI risperidone group. However, there were no differences in alcohol use between the 2 groups as measured by intensity or the Alcohol Use Scale. Patients taking LAI had lower blood levels of the active metabolite of risperidone compared to the oral group.

The authors concluded that there was a significant increase in heavy drinking in the oral risperidone group over the course of the study, but a decrease in heavy drinking in the LAI risperidone group was not clearly found. Potential limitations of the trial included a relatively small sample size, the loss of statistical power due to patients stopping assigned medication, potential effects of subjects already taking oral risperidone at study entry, and the open-label nature of the study.

The bottom line
This trial suggests that patients with schizophrenia and comorbid alcohol use disorder continue some drinking despite treatment with either LAI or oral risperidone. However, injectable risperidone may be a better choice than oral risperidone for these dual-diagnosis patients.

Disclosures:

Dr Miller is Associate Professor in the department of psychiatry and health behavior at Georgia Regents University in Augusta. He is the Schizophrenia Section Editor for Psychiatric Times. [Full bio]

References:

1. Regier DA, Farmer ME, Rae DS, et al. Comorbidity of mental disorders with alcohol and other drug abuse: results from the Epidemiologic Catchment Area (ECA) Study. JAMA. 1990;264:2511-2518.
2. Buckley P, McCarthy M, Chapman P, et al. Clozapine treatment of comorbid substance abuse in patients with schizophrenia. Schizoph Res. 1999;36:272.
3. Green AI, Brunette MF, Dawson R, et al. Long-acting injectable vs oral risperidone for schizophrenia and co-occuring alcohol use disorder: a randomized trial. J Clin Psychiatry. 2015;76:1359-1365.