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

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to examine the efficacy of quetiapine (Seroquel) in reducing substance use in persons diagnosed with schizophrenia. The primary hypothesis is that quetiapine treatment will be associated with a decrease in substance use.

Detailed Description
-----------------
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.

Official Title
-----------------
Efficacy of Quetiapine in Treating Patients With Active Substance Use Disorder and Schizophrenia

Conditions
-----------------
Schizophrenia, Schizoaffective Disorder, Psychotic Disorder, Substance Abuse, Alcohol Abuse

Intervention / Treatment
-----------------
* Drug: Quetiapine


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Quetiapine<br>After patients provided informed consent and completed baseline measures, quetiapine was initiated in all participants and titrated up to a target dose of 600 mg (in divided daily doses) over two weeks as the previous antipsychotic medication was slowly tapered and discontinued. Participants met with study physicians weekly to assess tolerability and response to the medication. Concomitant medications were held constant. After the initial titration period, quetiapine was dosed in a flexible manner up to 800 mg /day, with dose adjustments based on symptomatic response and side effects. | Drug: Quetiapine<br>* After patients provided informed consent and completed baseline measures, quetiapine was initiated in all participants and titrated up to a target dose of 600 mg (in divided daily doses) over two weeks as the previous antipsychotic medication was slowly tapered and discontinued. Participants met with study physicians weekly to assess tolerability and response to the medication. Concomitant medications were held constant. After the initial titration period, quetiapine was dosed in a flexible manner up to 800 mg /day, with dose adjustments based on symptomatic response and side effects.<br>* Other names: Seroquel;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Number of Drinking Days Per Week | Timeline Follow-back (TLFB) procedure was used at screening and baseline to establish current substance use, and it was also used weekly during the course of the study to assess continued alcohol and other substance use. TLFB cosisted of using a calendar and sasking participants to report alcohol and other drug use since last visit. At the screening visit, the TLFB was done for the four weeks prior to the visit. | 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Symptoms | The main outcome measure of clinical symptoms was the Positive and Negative Symptoms Scale. This is a 30 item scale for assessing patients diagnosed with schizophrenia. Each item is rated on a 1 (absent) to 7 (extreme) scale. The minimum total score is 30 and the maximum is 210. | 12 Weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Quetiapine, Seroquel, Schizophrenia, Dual Diagnosis, Substance Abuse, Alcohol Abuse