Treatment of Schizophrenia and Comorbid Cannabis Use Disorder: Comparing Clozapine to Treatment-as-Usual
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Schizophrenia Dual Diagnosis Schizoaffective Disorder Psychotic Disorder Cannabis Abuse |
Drug: Clozapine Drug: Treatment as usual |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Single Blind (Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | Cannabis and Schizophrenia: Effects of Clozapine |
- Days of Cannabis Use as Measured by the Timeline Followback [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
- Brief Psychiatric Rating Scale (BPRS) Total Score [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]This study utilized the 24 item BPRS. Each item is rated a 0 (not present) to 6 (severe) scale. The minimum score for this assessment is 0 and the maximum score is 144.
| Enrollment: | 31 |
| Study Start Date: | October 2000 |
| Study Completion Date: | March 2009 |
| Primary Completion Date: | March 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Clozapine
Clozapine, Clozaril
|
Drug: Clozapine
Clozapine up to 550mg per day
Other Name: Clozaril
|
|
Active Comparator: Treatment as usual
Treatment as usual with any antipsychotic other than Clozapine.
|
Drug: Treatment as usual
Remain on pre-study antipsychotic treatment
|
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.
Eligibility| Ages Eligible for Study: | 18 Years to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| United States, California | |
| West LA VAHCS | |
| Los Angeles, California, United States, 90073 | |
| United States, Missouri | |
| University Missouri | |
| Kansas City, Missouri, United States, 64108 | |
| United States, New Hampshire | |
| Mental Health Center of Greater Manchester | |
| Manchester, New Hampshire, United States, 03101 | |
| United States, South Carolina | |
| University South Carolina | |
| Columbia, South Carolina, United States, 29203 | |
| Principal Investigator: | Alan Green, MD | Dartmouth-Hitchcock Medical Center |
More Information
No publications provided
| Responsible Party: | Dartmouth-Hitchcock Medical Center |
| ClinicalTrials.gov Identifier: | NCT00498550 History of Changes |
| Obsolete Identifiers: | NCT00149955 |
| Other Study ID Numbers: | NCT00149955, R01DA013196, R01 DA013196, DPMCDA |
| Study First Received: | July 6, 2007 |
| Results First Received: | September 28, 2011 |
| Last Updated: | December 15, 2011 |
| Health Authority: | United States: Federal Government |
Keywords provided by Dartmouth-Hitchcock Medical Center:
|
Clozapine Schizophrenia Dual Diagnosis Substance Abuse Cannabis Abuse |
Additional relevant MeSH terms:
|
Marijuana Abuse Psychotic Disorders Mental Disorders Schizophrenia Substance-Related Disorders Schizophrenia and Disorders with Psychotic Features Clozapine Antipsychotic Agents Serotonin Antagonists Serotonin Agents Neurotransmitter Agents |
Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Physiological Effects of Drugs Tranquilizing Agents Central Nervous System Depressants Central Nervous System Agents Therapeutic Uses Psychotropic Drugs GABA Antagonists GABA Agents |
ClinicalTrials.gov processed this record on May 16, 2013