Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder

Comorbid alcohol/substance use disorder (SUD) in schizophrenia is a major concern, both in
view of the high frequency of SUD among patients with schizophrenia and the difficulty in
managing such patients. Though antipsychotic medications are effective in reducing symptoms
and impairment in persons with schizophrenia, the typical antipsychotic agents are of limited
value in controlling alcohol/substance use in these patients. Extrapyramidal, dysphoric side
effects of conventional neuroleptics may actually promote the use of substances in an attempt
to counteract these effects.

Novel antipsychotics have radically altered treatment expectations and outcomes for patients
with severe forms of schizophrenia. With the greater availability of novel agents in clinical
practice, it has been noted that these benefits have also extended to specific subgroups of
patients including patients with comorbid SUD. Several retrospective studies have
demonstrated a decrease in comorbid substance use in patients with schizophrenia treated with
clozapine. There is little data available, however, on the efficacy of quetiapine in patients
with schizophrenia and comorbid SUD. Its receptor profile, including a weak Dopamine2 (D2)
receptor blocking ability and substantial effects at noradrenergic receptors, makes it a
logical antipsychotic to use in the comorbid population.

The study is an open-label investigation of the efficacy of quetiapine in a group of 30
patients with schizophrenia and comorbid substance use disorder. Patients diagnosed with
schizophrenia or schizoaffective disorder and a comorbid substance use disorder are switched
to quetiapine for 12 weeks. We hypothesize that quetiapine treatment will be associated with
a decrease in substance use. Moreover, we further hypothesize that measures of symptoms,
cognition and quality of life will also improve over baseline assessments in patients treated
with quetiapine. Data suggesting a beneficial effect of quetiapine will have to be confirmed
in a prospective double-blind study. This pilot investigation will provide preliminary data
and effect sizes that will be used in the design of this subsequent investigation.

Inclusion Criteria:

- Age 18-65

- Schizophrenia or schizoaffective disorder

- Meets Structured Clinical Interview for Diagnostic and Statistical Manual of Mental
Disorders, Fourth Edition (SCID) criteria for a substance use disorder (alcohol use
disorder [AUD]; abuse or dependence)

- Active substance use on at least 8 days during the 4 weeks prior to randomization.

- Current treatment with antipsychotic medication.

- Able to provide informed consent, or in the case of patients with legal court
appointed guardians willing to give assent, with the consent of the guardian.

- Not actively suicidal.

Exclusion Criteria:

- Current treatment with, decanoate antipsychotic, clozapine, or doses of quetiapine not
approved by the team of investigators. Individuals treated with depot antipsychotic
must wait until the end of their injection cycle before starting on study medication.

- Currently pregnant, planning to become pregnant, or unwilling to use an acceptable
form of birth control.

- Currently residing in a residential program designed to treat substance use disorders.

- Treatment at baseline with a psychotropic agent proposed to curtail substance use.

- Patients who, in the opinion of the investigator, are judged unsuitable to participate
in the study.

- Unable to take part in the assessments in a meaningful way

- Hypersensitivity/intolerance to quetiapine

- Serious, unstable medical condition

- Participation in clinical trial of an investigational drug within 30 days of baseline
visit, or concurrent participation in a treatment study of a psychosocial intervention