Clinical trial NCT01639872: Clozapine for Cannabis Use in Schizophrenia
Official title: Clozapine for Cannabis Use Disorder in Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Schizophrenia
Cannabis Abuse
Cannabis Dependence
Dual Diagnosis
Keywords: Schizophrenia
Cannabis Abuse
Cannabis Dependence
Dual Diagnosis
Clozapine
Risperidone
Lead sponsor: Dartmouth-Hitchcock Medical Center
Sponsor class: OTHER
Collaborators: name: University of South Carolina
name: Michigan State University
name: University of Miami
name: University of Massachusetts, Worcester
First posted: 2012-07-13
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Many individuals with schizophrenia also suffer from marijuana addiction that worsens their problems related to schizophrenia. Most of the medications prescribed for schizophrenia have no effect on reducing marijuana use. Preliminary data suggests that clozapine, an atypical antipsychotic, may limit marijuana use in people diagnosed with schizophrenia, but it is not commonly used due to its side effects and is reserved for people who do not respond to other antipsychotic medications.

In the proposed study, 132 individuals who are diagnosed with both schizophrenia and a cannabis use disorder will be randomized to a 12-week treatment course with either clozapine or risperidone (another commonly prescribed antipsychotic medication) to test the hypothesis that patient treated with clozapine will have decreased cannabis use as compared to patients treated with risperidone.

Should this study indicate that clozapine will lessen marijuana use in persons diagnosed with schizophrenia more than risperidone, it will provide evidence needed to begin to shift clinical practice toward its use in this population.

Detailed description: Cannabis use disorder (CUD), which is up to ten times more common in patients with schizophrenia (SCZ) than in the general population, worsens the course of this severe psychiatric disorder. Since SCZ occurs in 1% of the population, the co-occurrence of CUD in 13% to 42% of people with this disorder presents society with an important public health problem. Unfortunately, most antipsychotics available for treatment of patients with SCZ do not appear to limit their cannabis use. Moreover, the one antipsychotic that preliminary data suggest may well limit cannabis use in these patients, clozapine (CLOZ), is not used for this purpose; it is reserved for patients whose psychosis is treatment resistant.

The overarching idea behind this proposal, however, is that CLOZ's use is being unreasonably restricted and should be made more widely available for patients with SCZ who have a co-occurring CUD but whose psychosis is not necessarily treatment resistant. This notion is supported by our preliminary clinical and animal data on the effects of CLOZ, as well as our neurobiological model of the basis of cannabis use in patients with SCZ that provides a pharmacologic rationale for this effect of CLOZ.

Even given all the arguments favoring the potential benefits of CLOZ in patients with SCZ and CUD, however, its side effect profile will likely limit its use until a fully powered study demonstrates its ability to decrease cannabis use in patients with SCZ. This proposal aims to launch such a study. If, as we hypothesize, this study confirms and extends our previous preliminary data of the effects of CLOZ in patients with SCZ and CUD, it will provide a strong impetus to expand the use of CLOZ in this population.

In the proposed study, 132 patients who are comorbid for both SCZ and CUD will be randomized to a 12-week treatment course with either CLOZ or risperidone (RISP) to test the hypothesis that patients treated with CLOZ will have decreased cannabis use as compared to patients treated with RISP. In addition, the study will determine whether patients treated with CLOZ will have improvements in psychiatric symptoms, quality of life neuropsychological functions as compared to those taking RISP. We will also explore whether patients taking CLOZ show improved reward responsiveness as compared to those taking RISP. Finally, this study will explore whether those patients with the val/val genotype at the Catechol-O-methyltransferase (COMT) Val158Met locus are more likely to decrease cannabis use during CLOZ treatment than are those without the val/val COMT genotype.

Should this study indicate that CLOZ will lessen cannabis use in patients with SCZ more than RISP, it will provide evidence needed to begin to shift clinical practice toward its use in these patients.

Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of schizophrenia
* Clinical diagnosis of a cannabis use disorder (abuse or dependence)

Exclusion Criteria:

* Pregnant,trying to become pregnant or nursing
* History of a seizure disorder
* Current treatment with clozapine or risperidone
* Contraindication to treatment with clozapine or risperidone

Primary outcomes:
measure: Average Over Time of Intensity of Cannabis Use (Used to Evaluate Treatment Efficacy)
timeFrame: 12 weeks
measure: Average Over Time of Frequency of Cannabis Use
timeFrame: 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Garden Grove
country: United States
facility: CNS Network Inc
state: California
city: Oakland
country: United States
facility: Pacific Research Partners
state: California
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Worcester
country: United States
facility: Unversity of Massachusetts Medical School
state: Massachusetts
city: Grand Rapids
country: United States
facility: Michigan State University / Cherry Street Health Services
state: Michigan
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Raleigh
country: United States
facility: University of North Carolina/UNC Center for Excellence in Community Mental Health
state: North Carolina
city: Columbia
country: United States
facility: University of South Carolina
state: South Carolina
city: Rutland
country: United States
facility: Rutland Regional Medical Center
state: Vermont
Study officials:
affiliation: Dartmouth College
name: Alan I Green, MD
role: STUDY_CHAIR
References: