Comorbid Opiate Dependence in Remission, Generalized Anxiety Disorder, Status Post Methadone-Maintenance Treatment
Conditions
Keywords
Generalized Anxiety Disorder, Opiate Dependence, Methadone-Maintenance, Drug Addiction Treatment
Brief summary
This is a 16 week study of the efficacy of quetiapine in treating symptoms of generalized anxiety disorder (GAD) in subjects with comorbid opiate dependence. The study will be conducted in a prospective, randomized, double-blind, and placebo-controlled fashion. Study subjects will be inpatients at a residential drug-treatment facility, enrolled in a 1 year methadone-to-abstinence treatment plan. Subjects will be randomized to receive either quetiapine or placebo in addition to ongoing drug addiction treatment. Subjects will be followed for 16 weeks and a variety of psychometric assessments will be made. Hypothesis One: Compared to placebo, Quetiapine will demonstrate a greater reduction in symptoms of anxiety in subjects with GAD and remitted comorbid opiate abuse. Exploratory Hypotheses: Compared to placebo, Quetiapine will demonstrate a greater improvement in psychosocial functioning and compliance with community norms in subjects enrolled in a residential drug addiction treatment facility.
Interventions
DRUGQuetiapine
Dosage is 50 - 300 mg, once daily, at bedtime.
Sponsors
AstraZeneca
Beth Israel Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Provision of written informed consent * A diagnosis of opiate dependence as defined by Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition (DSM-IV) during the past two years. * A diagnosis of generalized anxiety disorder as defined by Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition (DSM-IV) within the past 6 months. * Males and females aged 21-55 years * Female patients of childbearing potential must be using a reliable method of contraception and have a negative urine human chorionic gonadotropin (HCG) test at enrollment * Able to understand and comply with the requirements of the study * Subjects must be free of illicit drug use for the past 3 months * Subjects must have received methadone maintenance therapy for at least 3 months, and have been at least 2 weeks methadone-free * Good health, as assessed by medical history, physical examination and laboratory tests
Exclusion criteria
* Pregnancy or lactation * Current diagnosis of any Axis I disorder other than GAD, substance dependence in remission, or nicotine dependence * Patients who, in the opinion of the investigator, pose an imminent risk of suicide or a danger to self or others * Known intolerance or lack of response to quetiapine fumarate, as judged by the investigator * Use of any of the following cytochrome P450 3A4 inhibitors in the 14 days preceding enrolment including but not limited to: ketoconazole, itraconazole, fluconazole, erythromycin, clarithromycin, troleandomycin, indinavir, nelfinavir, ritonavir, fluvoxamine and saquinavir * Use of any of the following cytochrome P450 inducers in the 14 days preceding enrollment including but not limited to: phenytoin, carbamazepine, barbiturates, rifampin, St. John's Wort, and glucocorticoids * Administration of a depot antipsychotic injection within one dosing interval (for the depot) before randomisation * Medical conditions that would affect absorption, distribution, metabolism, or excretion of study treatment * Unstable or inadequately treated medical illness (e.g. diabetes, angina pectoris, hypertension) as judged by the investigator * Involvement in the planning and conduct of the study * Previous enrollment or randomisation of treatment in the present study. * Participation in another drug trial within 4 weeks prior enrollment into this study or longer in accordance with local requirements * A patient with Diabetes Mellitus (DM) fulfilling one of the following criteria: * Unstable DM defined as enrollment glycosylated hemoglobin (HbA1c) \>8.5%. * Admitted to hospital for treatment of DM or DM related illness in past 12 weeks. * Not under physician care for DM * Physician responsible for patient's DM care has not indicated that patient's DM is controlled. * Physician responsible for patient's DM care has not approved patient's participation in the study * Has not been on the same dose of oral hypoglycaemic drug(s) and/or diet for the 4 weeks prior to randomization. For thiazolidinediones (glitazones) this period should not be less than 8 weeks. * Taking insulin whose daily dose on one occasion in the past 4 weeks has been more than 10% above or below their mean dose in the preceding 4 weeks Note: If a diabetic patient meets one of these criteria, the patient is to be excluded even if the treating physician believes that the patient is stable and can participate in the study. * An absolute neutrophil count (ANC) of 1.5 x 109 per liter * Positive urine drug screening test for drugs of abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hamilton Anxiety Scale at 16 Weeks | 16 weeks | Hamilton anxiety scale -- a well known quantitative measure for assessment of anxiety |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Beck Depression Inventory at 16 Weeks | 16 weeks | To compare the effect of Quetiapine vs. placebo on symptoms of negative mood in patients with GAD and comorbid opiate abuse in remission. |
Countries
United States
Participant flow
Recruitment details
The study was initiated in 2007 adn terminated in 2010 due to PI's departure. All recrutiement took place at Su Casa residential treatment facility in New York City. All recruitment was done by the PI.
Pre-assignment details
The subjects were individuals with opiate addiction on agonist therapy. After recruitement subjects underwent methadone taper as inpatients. Most subjects left the study because they signed out of the Su Casa Program and did not complete their methadone taper.
Participants by arm
| Arm | Count |
|---|---|
| Quetiapine Subjects on MMTP receiving quetiapine | 9 |
| Placebo Subjects on methadone maintenance receiving placebo while inpatients in a methadone treatment facility Su Casa | 5 |
| Total | 14 |
Baseline characteristics
| Characteristic | Placebo | Quetiapine | 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 | 5 Participants | 9 Participants | 14 Participants |
| Age Continuous | 45 years STANDARD_DEVIATION 9 | 43 years STANDARD_DEVIATION 7 | 43.8 years STANDARD_DEVIATION 9 |
| Region of Enrollment United States | 5 participants | 9 participants | 14 participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 4 Participants | 7 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Hamilton Anxiety Scale at 16 Weeks
Hamilton anxiety scale -- a well known quantitative measure for assessment of anxiety
Time frame: 16 weeks
Population: Data was not analyzed: PI left the institution and the study was terminated
Secondary
Beck Depression Inventory at 16 Weeks
To compare the effect of Quetiapine vs. placebo on symptoms of negative mood in patients with GAD and comorbid opiate abuse in remission.
Time frame: 16 weeks
Population: Data were not analyzed. PI left institution, and did not respond to attempts top contact him.