Generalized Anxiety Disorder, Major Depressive Disorder
Conditions
Keywords
seroquel XR, quetiapine XR, major depression, generalized anxiety disorder, CBT, co-morbid MDD
Brief summary
The primary objective of the study is to determine whether quetiapine extended-release in combination with cognitive behavioral therapy (CBT) is more effective than CBT plus placebo in treating depressive and anxiety symptoms in patients with both major depression and generalized anxiety disorder. Approximately 64 individuals (adults 18-65) will be randomly assigned to treatment group for 16 weeks. Weekly CBT sessions will be conducted lasting about 45 minutes and weekly visits with the study psychiatrist lasting about 20 minutes in which medication will be discussed. Both clinician administered and self-report measures will be used to compare groups before and after 16 weeks.
Detailed description
This study will evaluate the efficacy of quetiapine extended-release as adjunctive therapy to cognitive behavioral therapy (CBT) compared to CBT plus placebo in the treatment of patients with comorbid major depression and generalized anxiety disorder. We will also evaluate the quality of life in patients with comorbid MDD/GAD, the response and remission rates by treatment group, changes in sleep quality, and tolerability of adjunctive quetiapine to CBT.
Interventions
DRUGseroquel xr
Quetiapine target dosage will be 150 mg/day, beginning at 50 mg/day
BEHAVIORALCBT
16 weeks of treatment
Sponsors
AstraZeneca
Icahn School of Medicine at Mount Sinai
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Provision of written informed consent * A diagnosis of both major depression (single episode or recurrent) and generalized anxiety disorder by Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition (DSM-IV) * Females and/or males aged 18 to 65 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
Exclusion criteria
* Pregnancy or lactation * Any history of psychosis, bipolar disorder, schizophrenia, eating disorders or OCD * 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 enrollment 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 randomization * Substance or alcohol dependence at enrollment (except dependence in full remission, and except for caffeine or nicotine dependence), as defined by DSM-IV criteria * Substance abuse by DSM-IV criteria within 6 months prior to enrollment * 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 randomization of treatment in the present study * Participation in another drug trial within 4 weeks prior to enrollment into this study or longer in accordance with local requirements * A patient with Diabetes Mellitus (DM)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MADRS | baseline and 16 weeks | Montgomery-Åsberg Depression Rating Scale (MADRS) is a 10-item clinician-administered, with overall score ranges from 0 (normal) to 54 (severe depression). Score at 16 weeks as compared to baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HAM-A | baseline and 16 weeks | Hamilton Rating Scale for Anxiety (HAM-A) is a 14-item clinician-administered scale measuring symptoms with total scale from 0 (not present) to 56 (severe) to severe anxiety. |
| Clinical Global Impression Scales for Severity and Improvement | up to 16 weeks | The Clinical Global Impression Scales for Severity and Improvement (CGI-I and CGI-S), both clinician rated, measures overall severity of symptoms and level of improvement on a seven-point scale from 0 (not applicable or not assessed) to 7, where 7 is the most severe. In order for a participant to be considered a treatment responder, he or she must receive a score of 1 (not ill or very much improved) or 2 (borderline mentally ill or much improved). |
| Changes in Sexual Functioning Questionnaire (CSFQ) | baseline and week 16 | Changes in Sexual Functioning Questionnaire (CSFQ) at week 16 as compared to baseline. The CSFQ assesses interest, functioning, and satisfaction in sex on a six-point scale, where 1 is greater than normal and 6 is totally absent, with full range from 5 (greater than normal) to 30 (totally absent). |
Countries
United States
Participant flow
Recruitment details
Participants were recruited through the Mount Sinai faculty referrals, medical center employee newsletter, and advertisements in local newspapers, radio, and craigslist.
Pre-assignment details
Ninety-four participants were screened - 10 participants did not meet study eligibility, 22 elected not to continue. 62 participants were randomized, but 7 never returned for the first visit, leaving 55 participants who began treatment.
Participants by arm
| Arm | Count |
|---|---|
| Seroquel XR Plus CBT Participants were required to take a minimum of one 50 mg pill of quetiapine XR a day with an intended titration schedule reaching 150 mg over the first three weeks, adding one pill per week. . If a participant could not tolerate the increased dose, then dosage was decreased to either one or two pills a day.
All participants who completed the study received 16 sessions of CBT and discontinued medication at 16 weeks. Although conducted weekly, CBT and medication schedules did not always terminate at the same time. | 30 |
| Placebo Plus CBT matching placebo pills plus 16 weeks of Cognitive Behavioral Therapy | 32 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Protocol Violation | 3 | 2 |
| Overall Study | Withdrawal by Subject | 5 | 6 |
Baseline characteristics
| Characteristic | Seroquel XR Plus CBT | Total | Placebo Plus CBT |
|---|---|---|---|
| Age, Continuous | 39.93 years STANDARD_DEVIATION 13.68 | 39.90 years STANDARD_DEVIATION 13.12 | 39.88 years STANDARD_DEVIATION 12.81 |
| Education Advanced | 8 Participants | 12 Participants | 4 Participants |
| Education College | 13 Participants | 28 Participants | 15 Participants |
| Education HS | 4 Participants | 6 Participants | 2 Participants |
| Education Less than HS | 1 Participants | 1 Participants | 0 Participants |
| Education Part college | 3 Participants | 13 Participants | 10 Participants |
| Education Unknown | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants | 4 Participants | 1 Participants |
| Race/Ethnicity, Customized Black | 4 Participants | 8 Participants | 4 Participants |
| Race/Ethnicity, Customized Hispanic | 2 Participants | 5 Participants | 3 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 19 Participants | 41 Participants | 22 Participants |
| Sex: Female, Male Female | 17 Participants | 38 Participants | 21 Participants |
| Sex: Female, Male Male | 13 Participants | 24 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 | 24 / 26 | 11 / 29 |
| serious Total, serious adverse events | 0 / 26 | 0 / 29 |
Outcome results
Primary
MADRS
Montgomery-Åsberg Depression Rating Scale (MADRS) is a 10-item clinician-administered, with overall score ranges from 0 (normal) to 54 (severe depression). Score at 16 weeks as compared to baseline.
Time frame: baseline and 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Seroquel XR Plus CBT | MADRS | Baseline | 27.1 units on a scale | Standard Deviation 5.5 |
| Seroquel XR Plus CBT | MADRS | LOCF (last observation carried forward) | 9.1 units on a scale | Standard Deviation 6.9 |
| Placebo Plus CBT | MADRS | Baseline | 28.6 units on a scale | Standard Deviation 6.5 |
| Placebo Plus CBT | MADRS | LOCF (last observation carried forward) | 15.7 units on a scale | Standard Deviation 11.9 |
Secondary
Changes in Sexual Functioning Questionnaire (CSFQ)
Changes in Sexual Functioning Questionnaire (CSFQ) at week 16 as compared to baseline. The CSFQ assesses interest, functioning, and satisfaction in sex on a six-point scale, where 1 is greater than normal and 6 is totally absent, with full range from 5 (greater than normal) to 30 (totally absent).
Time frame: baseline and week 16
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Seroquel XR Plus CBT | Changes in Sexual Functioning Questionnaire (CSFQ) | Baseline | 15.1 units on a scale | Standard Deviation 6.3 |
| Seroquel XR Plus CBT | Changes in Sexual Functioning Questionnaire (CSFQ) | LOCF | 1.8 units on a scale | Standard Deviation 0.9 |
| Placebo Plus CBT | Changes in Sexual Functioning Questionnaire (CSFQ) | Baseline | 16.6 units on a scale | Standard Deviation 5.7 |
| Placebo Plus CBT | Changes in Sexual Functioning Questionnaire (CSFQ) | LOCF | 14.1 units on a scale | Standard Deviation 6.5 |
Secondary
Clinical Global Impression Scales for Severity and Improvement
The Clinical Global Impression Scales for Severity and Improvement (CGI-I and CGI-S), both clinician rated, measures overall severity of symptoms and level of improvement on a seven-point scale from 0 (not applicable or not assessed) to 7, where 7 is the most severe. In order for a participant to be considered a treatment responder, he or she must receive a score of 1 (not ill or very much improved) or 2 (borderline mentally ill or much improved).
Time frame: up to 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Seroquel XR Plus CBT | Clinical Global Impression Scales for Severity and Improvement | CGI-S Baseline | 4.1 units on a scale | Standard Deviation 0.5 |
| Seroquel XR Plus CBT | Clinical Global Impression Scales for Severity and Improvement | CGI-S LOCF | 2.5 units on a scale | Standard Deviation 1.2 |
| Seroquel XR Plus CBT | Clinical Global Impression Scales for Severity and Improvement | CGI-I Baseline | 3.3 units on a scale | Standard Deviation 1.6 |
| Seroquel XR Plus CBT | Clinical Global Impression Scales for Severity and Improvement | CGI-I LOCF | 1.8 units on a scale | Standard Deviation 1 |
| Placebo Plus CBT | Clinical Global Impression Scales for Severity and Improvement | CGI-I LOCF | 2.4 units on a scale | Standard Deviation 1.1 |
| Placebo Plus CBT | Clinical Global Impression Scales for Severity and Improvement | CGI-S Baseline | 4.3 units on a scale | Standard Deviation 0.5 |
| Placebo Plus CBT | Clinical Global Impression Scales for Severity and Improvement | CGI-I Baseline | 2.7 units on a scale | Standard Deviation 1.9 |
| Placebo Plus CBT | Clinical Global Impression Scales for Severity and Improvement | CGI-S LOCF | 2.9 units on a scale | Standard Deviation 1.2 |
Secondary
HAM-A
Hamilton Rating Scale for Anxiety (HAM-A) is a 14-item clinician-administered scale measuring symptoms with total scale from 0 (not present) to 56 (severe) to severe anxiety.
Time frame: baseline and 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Seroquel XR Plus CBT | HAM-A | Baseline | 16.7 units on a scale | Standard Deviation 5.2 |
| Seroquel XR Plus CBT | HAM-A | LOCF (last observation carried forward) | 5.9 units on a scale | Standard Deviation 3.9 |
| Placebo Plus CBT | HAM-A | LOCF (last observation carried forward) | 9.4 units on a scale | Standard Deviation 7.7 |
| Placebo Plus CBT | HAM-A | Baseline | 17.8 units on a scale | Standard Deviation 4.7 |