Treatment of Schizophrenia and Comorbid Cannabis Use Disorder: Comparing Clozapine to Treatment-as-Usual

Phase 4

Completed

• Conditions: Schizophrenia; Psychotic Disorder; Cannabis Abuse; Schizoaffective Disorder; Dual Diagnosis
• Interventions: Drug: Treatment as usual; Drug: Clozapine

• Registration Number: NCT00498550
• Lead Sponsor: Dartmouth-Hitchcock Medical Center

Brief Summary

Many individuals with schizophrenia also suffer from marijuana addiction. Clozapine, an atypical antipsychotic medication, may prove useful at preventing drug relapse in schizophrenic individuals who are seeking treatment for marijuana addiction. The purpose of this study is to compare the effectiveness of clozapine, vs. treatment-as-usual with other oral antipsychotics at reducing marijuana use in schizophrenic individuals.

Detailed Description

Individuals with schizophrenia have a high risk of becoming addicted to drugs; between 13 to 42% of schizophrenics are addicted to marijuana. These individuals often have difficulties adhering to a substance abuse treatment program, and have an increased chance of marijuana relapse. Marijuana use by schizophrenics has also been associated with clinical exacerbations, noncompliance with antipsychotic medications, poor global functioning, and increased rehospitalization rates. While antipsychotic medications are often effective in controlling symptoms of schizophrenia, they are not always effective in preventing substance abuse. Clozapine, an atypical antipsychotic drug, is currently used to treat schizophrenia. Preliminary research has shown that clozapine is more successful at reducing drug relapse rates in individuals with schizophrenia, as compared to other antipsychotic medications, including olanzapine and risperidone. The purpose of this study is to compare the effectiveness of clozapine as compared to other oral antipsychotic treatment, including combinations of up to two antipsychotics, in reducing marijuana use in schizophrenic individuals.

This study will enroll individuals with schizophrenia who are currently taking any oral antipsychotic other than clozapine, including those taking up to two oral antipsychotic, and who are also addicted to marijuana. The study will begin with a 1-week assessment phase, during which all participants will continue taking olanzapine or risperidone. Participants will undergo a physical examination and have blood drawn for laboratory tests. Information pertaining to their medical, psychiatric, and substance use history will also be collected. Urine tests and breathalyzers will be used to screen for the presence of alcohol and drugs. Following the assessment phase, participants will be randomly assigned to switch to clozapine or remain on their prestudy antipsychotic for 12 weeks. Participants remaining on their prestudy antipsychotic treatment will continue to receive the same dose for the entire study. Participants taking clozapine will initially receive a daily dose of 12.5 mg, which will be increased to a maximum of 400 mg per day, as tolerated. Study visits will take place once a week. At each visit, medication side effects, physical and psychological symptoms, substance use, treatment services received, and living situation will be assessed. Blood will be drawn for laboratory tests. Drug and alcohol levels will be monitored three times a week through urine and breathalyzer tests. Quality of life questionnaires will be administered once a month.

Study Timeline

• Study Start: 2000-10
• Study First Submitted: 2007-07-06
• Study First Submitted QC: 2007-07-06
• Study First Posted: 2007-07-10
• Primary Completion: 2009-03
• Study Completion: 2009-03
• Results First Submitted: 2011-09-28
• Results First Submitted QC: 2011-12-15
• Results First Posted: 2012-01-19
• Status Verified: 2019-02
• Last Update Submitted: 2019-02-28
• Last Update Posted: 2019-03-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 31

Inclusion Criteria

• Meets Diagnostic and Statical Manual of Mental Disorders IV (DSM-IV) diagnostic criteria for schizophrenia or schizoaffective disorder
• Meets diagnostic criteria for marijuana use disorder, as determined by a rating of 3 or higher on the Drug Use Scale (Abuse or Dependence)
• Used marijuana on 5 or more days during the 3 weeks prior to study entry
• Taking any oral antipsychotic other than clozapine in the month prior to study entry. (Patients may take a second oral antipsychotic medication, if approved by the Medication Adjustment Group)
• If female, willing to use effective contraception throughout the study

Exclusion Criteria

• Unable to take clozapine for medical reasons, including previous clozapine-induced granulocytopenia, myeloproliferative disorder, white blood cell count less than 3500/mm3, or history of seizures
• Currently taking clozapine
• Currently taking other psychotropic medications for the treatment of substance use (e.g., disulfiram, naltrexone, acamprosate, inderol, tegretol, topiramate, and pramipexole)
• Participated in a clinical trial of an investigational drug within 30 days of study entry
• Currently participating in a psychosocial intervention clinical trial
• Has medical or legal problems that may entail a jail or hospital stay during the study
• Has a developmental disability that would make study participation difficult
• Currently enrolled in a live-in treatment program for substance use disorders
• Pregnant or plans to become pregnant during the study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment as usual	Treatment as usual	Treatment as usual with any antipsychotic other than Clozapine.
Clozapine	Clozapine	Clozapine, Clozaril

Primary Outcome Measures

Name	Time	Method
Average Over Time of Intensity of Cannabis Use (Used to Evaluate Treatment Efficacy)	Week 1 to week 12	Intensity of cannabis use is obtained for each week retrospectively as the number of joints smoked during the prior week (assessed by the Timeline Followback Scale). Mixed models are used to obtain estimates of efficacy from the partial data provided by each subject while adherent to assigned treatment (under the 'missing at random' assumption). The 'explanatory' estimands (target of the mixed model estimation) are defined in terms of population quantities that would have occurred had all subjects remained on assigned treatment throughout the study. The point estimate for each arm is reported under Number.

Trial Locations

Locations (4)

University Missouri; 🇺🇸 Kansas City, Missouri, United States

West LA VAHCS; 🇺🇸 Los Angeles, California, United States

University South Carolina; 🇺🇸 Columbia, South Carolina, United States

Mental Health Center of Greater Manchester; 🇺🇸 Manchester, New Hampshire, United States