Cannabis Abuse, Dual Diagnosis, Psychotic Disorder, Schizoaffective Disorder, Schizophrenia
Conditions
Keywords
Clozapine, Schizophrenia, Dual Diagnosis, Substance Abuse, Cannabis Abuse
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.
Interventions
DRUGClozapine
Clozapine up to 550mg per day
DRUGTreatment as usual
Remain on pre-study antipsychotic treatment
Sponsors
National Institute on Drug Abuse (NIDA)
University of Missouri, Kansas City
VA Medical Center-West Los Angeles
University of South Carolina
Dartmouth-Hitchcock Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Clozapine Clozapine, Clozaril | 15 |
| Treatment as Usual Treatment as usual with any antipsychotic other than Clozapine. | 16 |
| Total | 31 |
Baseline characteristics
| Characteristic | Treatment as Usual | Clozapine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 15 Participants | 31 Participants |
| Age, Continuous | 39.0 years STANDARD_DEVIATION 10.2 | 33.3 years STANDARD_DEVIATION 10 | 36 years STANDARD_DEVIATION 10.3 |
| Region of Enrollment United States | 16 Participants | 15 Participants | 31 Participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Male | 12 Participants | 12 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 15 / 15 | 15 / 16 |
| serious Total, serious adverse events | 4 / 15 | 4 / 16 |
Outcome results
Primary
Average Over Time of Intensity of Cannabis Use (Used to Evaluate Treatment Efficacy)
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.
Time frame: Week 1 to week 12
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clozapine | Average Over Time of Intensity of Cannabis Use (Used to Evaluate Treatment Efficacy) | 0.02 Joints per week |
| Treatment as Usual | Average Over Time of Intensity of Cannabis Use (Used to Evaluate Treatment Efficacy) | 4.56 Joints per week |
p-value: 0.088Mixed Models Analysis