Clinical trial NCT00671853: Quetiapine Extended Release (XR) in Bipolar Patients With Comorbid Generalized Anxiety Disorder (GAD)
Official title: Quetiapine XR in the Treatment of Comorbid Generalized Anxiety Disorder in Bipolar Depression With or Without Substance Use Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bipolar Disorder
Anxiety
Anxiety Disorders
Substance Use Disorders
Keywords: Bipolar Disorder
Anxiety
Anxiety Disorders
Substance Use Disorders
Lead sponsor: University Hospitals Cleveland Medical Center
Sponsor class: OTHER
Collaborators: name: National Alliance for Research on Schizophrenia and Depression
name: AstraZeneca
First posted: 2008-05-05
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective is to test the hypothesis that Quetiapine XR (Extended Release) monotherapy and adjunctive therapy is effective in the acute treatment of bipolar depression and comorbid generalized anxiety disorder in patients with bipolar disorder with or without a substance use disorder. The secondary aim is to generate an estimate of effect size to power a definitive large-scale, multi-site collaborative R01 and to configure the use of the primary and secondary outcome measures in the definitive large-scale study.

Detailed description: 120 subjects aged 18 and up with Diagnostic and Statistical Manual -IV Generalized Anxiety Disorder and Bipolar Disorder type I or II as identified by extensive clinical interview and the Mini-International Neuropsychiatric Interview (MINI) will be enrolled and randomized. Assignment to each arm will be balanced for BP I vs BP II; male vs female; and with vs without SUD. Potential participants will be recruited by means of Institutional Review Board -approved advertising or from the clinical psychiatric infrastructure.

This study is a randomized, double-blind, placebo-controlled, 8-week comparison of quetiapine sustained-release monotherapy or adjunctive mood stabilizer therapy vs. placebo in the acute treatment of comorbid generalized anxiety disorder in patients with bipolar disorder with or without a substance use disorder. Subjects will be assessed weekly for mood changes and side effects.

Eligibility criteria: Inclusion Criteria:

* Diagnostic and Statistical Manual-IV diagnosis of bipolar I or II disorder, and currently depressed as confirmed by the MINI-Plus at Screening.
* Diagnostic and Statistical Manual-IV diagnosis of lifetime GAD;
* Hamilton Depression Rating Scale -17 items total score ≥ 18;
* Hamilton Anxiety Rating Scale total score ≥ 18;
* Be male or female at least 18 year old and not older than 65.

Exclusion Criteria:

* Pregnancy or breast feeding.
* Severe medical or neurological problems.
* Severe personality disorder.
* Currently suicidal risk judged by physician.
* Known history of intolerance or hypersensitivity to any of the medications involved in the study.
* Treatment with quetiapine at any dose in the 6 months prior to randomization.
* Known lack of response to quetiapine in a dosage of at least 50 mg for 4 weeks at any time, as judged by the investigator.
* Dependence on opiate, phencyclidine (PCP), and/or barbiturate.
* Acute mania as determined by a score \> 12 on the Young Mania Rating Scale at baseline.
* Concurrent obsessive compulsive disorder.
* 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 enrolment or randomisation of treatment in the present study.
* Participation in another drug trial within 4 weeks prior enrolment into this study or longer in accordance with local requirements
* A patient with diabetes mellitus (DM) fulfilling one of the following criteria: a. Unstable DM defined as enrollment glycosylated hemoglobin (HbA1c) .8.5% b. Admitted to hospital for treatment of DM or DM related illness within the past 12 weeks c. Not under physician care for DM d. Physician responsible for patient's DM care has not indicated that the patient's DM is controlled f. Physician responsible for patient's DM care has not approved the patient's participation in the study g. Has not been on the same dose of oral hypoglycemic drug(s) and/or diet for the 4 weeks before randomization. For thiazolidinediones (glitazones) this period should not be less than 8 weeks before randomization h. 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 patient with DM 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.

Primary outcomes:
measure: Change in the 17 Item Hamilton Rating Scale for Depression (HAM-D-17) Score
timeFrame: Week 0 - Week 8
Secondary outcomes:
measure: Response Rate (≥ 50% Improvement) on Hamilton Rating Scale for Depression (HAM-D-17)
timeFrame: Week 0 - Week 8
measure: Remission Rate (≤ 7) on Hamilton Rating Scale for Depression (HAM-D-17)
timeFrame: Week 0 - Week 8
measure: Change in Clinical Global Impressions of Improvement or Severity (CGI-I or S) Score
timeFrame: Week 0 - Week 8
measure: Change in the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) Score
timeFrame: Week 0 - Week 8
measure: Change in Hamilton Rating Scale for Anxiety (HAM-A)
timeFrame: Week 0 - Week 8
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
Study officials:
affiliation: University Hospitals Cleveland Medical Center
name: Keming Gao, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gao K, Wu R, Kemp DE, Chen J, Karberg E, Conroy C, Chan P, Ren M, Serrano MB, Ganocy SJ, Calabrese JR. Efficacy and safety of quetiapine-XR as monotherapy or adjunctive therapy to a mood stabilizer in acute bipolar depression with generalized anxiety disorder and other comorbidities: a randomized, placebo-controlled trial. J Clin Psychiatry. 2014 Oct;75(10):1062-8. doi: 10.4088/JCP.13m08847.