Alcohol Abuse, Psychotic Disorder, Schizoaffective Disorder, Schizophrenia, Substance Abuse
Conditions
Keywords
Quetiapine, Seroquel, Schizophrenia, Dual Diagnosis, Substance Abuse, Alcohol Abuse
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.
Interventions
DRUGQuetiapine
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.
Sponsors
Augusta University
AstraZeneca
Dartmouth-Hitchcock Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Number of Drinking Days Per Week | 12 Weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Symptoms | 12 Weeks | 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. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from two urban study sites, one in New England, the other in the Southeast, primarily through clinician referral, over two years. All participants gave informed consent.
Pre-assignment details
Prior to starting quetiapine, all participants first completed a screening assessment to establish diagnosis, amount of alcohol (and other drugs) consumed, and current medications and medical status. This data was used to characterize the group and assess whether they met eligibility criteria for the study.
Participants by arm
| Arm | Count |
|---|---|
| QUET 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. | 23 |
| Total | 23 |
Baseline characteristics
| Characteristic | QUET |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants |
| Age, Continuous | 35.8 years STANDARD_DEVIATION 9.9 |
| Region of Enrollment United States | 23 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 13 / 16 |
| serious Total, serious adverse events | 3 / 16 |
Outcome results
Primary
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.
Time frame: 12 Weeks
Population: Only those participants who received at least 4 weeks of treatment with quetiapine were included in this analysis. Site differences resulted in only the 11 participants from Site 1 to be included in the analysis. Participants from Site 2 were all admitted to the study directly from the hospital which could have affected their alcohol consumption.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| QUET | Mean Number of Drinking Days Per Week | 2.7 Drinking Days per Week | Standard Deviation 2.3 |
Secondary
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.
Time frame: 12 Weeks
Population: Only those participants who received at least 4 weeks of treatment with quetiapine were included in this analysis. Site differences resulted in only the 11 participants from Site 1 to be included in this analysis. Participants from Site 2 were all admitted to the study directly from the hospital, which could have affected their behavior.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| QUET | Clinical Symptoms | 65.5 Units on a scale | Standard Deviation 16.5 |