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.
- 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
- 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
- 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
- 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
- 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
- An absolute neutrophil count (ANC) of 1.5 x 109 per liter
- Positive urine drug screening test for drugs of abuse