Panic Disorder
Conditions
Keywords
SSRI Resistant, Seroquel SR, Seroquel XR, Panic Disorder, Comorbid Panic Disorder, Quetiapine SR, Quetiapine XR
Brief summary
The primary objective of this study is to test the hypothesis that a SSRI plus quetiapine SR (Seroquel SR) will result in superior early (first 1-3 weeks of treatment) stabilization of panic symptoms in SSRI-resistant, comorbid Panic Disorder patients versus a SSRI plus placebo.
Detailed description
This was a single-site, double-blind, placebo-controlled (PLAC), randomized, parallel group (2 groups), 8-week, quetiapine extended release (XR) coadministration trial. SSRI resistance was determined either historically or prospectively. Patients were randomized if they remained moderately ill (CGI-S score ≥ 4). Change in the PDSS scale total score was the primary efficacy outcome measure. Responders were identified as those with a ≥50 % decrease from their baseline PDSS score. In the early weeks of therapy, XR was flexibly and gradually titrated from 50 to 400 mg/day. Conclusions: This proof-of-concept RCT did not support the efficacy of this treatment strategy for SSRI-resistant PD. Quetiapine XR was generally well-tolerated. Important limitations were the small sample size, and the relatively low average dose of quetiapine XR used.
Interventions
DRUGquetiapine XR
Subjects will receive daily dosing at night, with a flexible dosing schedule, 50-400 mg.
DRUGplacebo
Subjects will receive daily dosing at night with caplets matching the appearance of the active drug. However, caplets will not contain any active medication.
Sponsors
AstraZeneca
Indiana University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Provision of written informed consent * Diagnosis of Panic Disorder by DSM-IV TR and confirmed by MINI plus interview * Females and males ages 18-65 years old * Female patients of childbearing potential must by 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 * Have a CGI illness severity score = or \> 4 * Patients with comorbid major depression, dysthymia or other anxiety problems are eligible to participate as well.
Exclusion criteria
* Pregnancy or lactation * Any DSM-IV TR Axis I disorder not mentioned in the inclusion requirements * Suicidal or danger to self or others * Known intolerance to quetiapine fumarate or intolerance to SSRI therapy * 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 * Opiates, amphetamine, barbiturate, cocaine, cannabis, or hallucinogen abuse by DSM-IV TR criteria within 4 weeks prior to enrollment * Medical conditions that would affect absorption, distribution, metabolism, or excretion of study treatment * Unstable or inadequately treated medical illness (e.g. 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 enrollment into this study or longer in accordance with local requirements * A patient with a diagnosis of Type I or Type II Diabetes Mellitus (DM) * An absolute neutrophil count (ANC) of 1.5 x 109 per liter * A lifetime history of a pre-existing CNS/neurological disorder e.g. epilepsy, TBI, brain tumor * Patient with severe personality disorders * Patients who have started a new course of psychotherapy (CBT, supportive, insight-oriented) within 1 month of the screening visit * Patients unwilling to refrain from participation in psychotherapy during the 9-week period of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Total Panic Disorder Severity Scale (PDSS) Scores | Baseline and the end of 8 weeks of treatment | Possible total scores on the PDSS range from 0-28. The outcome measure represents the change, between baseline and the end of 8 weeks of treatment, in the the total PDSS scores. Lower scores indicate less severe panic disorder symptoms. A negative mean change in the scores at the end of 8 weeks represents a decrease in severity of panic disorder symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Scores in Measurements of Depressive Symptoms (Hamilton Depression Rating Scale, HAM-D), Generalized Anxiety Symptoms (Hamilton Anxiety Rating Scale, HAM-A) and the Sleep Quality Item of the Pittsburgh Sleep Quality Index (PSQI). | Comparing baseline and the end of 8 weeks of treatment | Subjects scores on secondary efficacy measures were measured, comparing baseline and the end of 8 weeks of treatment, including the Hamilton Depression Rating Scale, HAM-D, which has 21 items, with scores ranging from 0-66; the Hamilton Anxiety Rating Scale, HAM-A, which has 14 items, with scores ranging from 0-56; and the sleep quality item of the PSQI, a four-point scale rating sleep quality as very good, fairly good, fairly bad or very bad. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Quetiapine Quetiapine SR: Subjects will receive daily dosing at night, with a flexible dosing schedule, 50-400 mg. | 13 |
| Placebo Placebo: Subjects will receive daily dosing at night with caplets matching the appearance of the active drug. However, caplets will not contain any active medication. | 13 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 |
| Overall Study | Intercurrent illness | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | Quetiapine | Placebo | 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 | 13 Participants | 13 Participants | 26 Participants |
| Age, Continuous | 35.5 years STANDARD_DEVIATION 9.6 | 35.5 years STANDARD_DEVIATION 16.8 | 35.5 years STANDARD_DEVIATION 13.2 |
| Clinical Global Impression-Severity Scale (CGI-S) | 4.8 units on a scale STANDARD_DEVIATION 0.8 | 4.4 units on a scale STANDARD_DEVIATION 0.7 | 4.6 units on a scale STANDARD_DEVIATION 0.8 |
| Hamilton Anxiety Rating Scale (HAM-A) | 21.2 units on a scale STANDARD_DEVIATION 6.8 | 17 units on a scale STANDARD_DEVIATION 5.2 | 19.1 units on a scale STANDARD_DEVIATION 6 |
| Hamilton Depression Rating Scale (HAM-D) | 14.6 units on a scale STANDARD_DEVIATION 6.2 | 11.5 units on a scale STANDARD_DEVIATION 5.1 | 13.1 units on a scale STANDARD_DEVIATION 5.7 |
| Panic Disorder Severity Scale | 14.8 units on a scale STANDARD_DEVIATION 3.6 | 13.7 units on a scale STANDARD_DEVIATION 3 | 14.3 units on a scale STANDARD_DEVIATION 3.3 |
| Pittsburgh Sleep Quality Index (PSQI) sleep hours | 6.2 hours slept per night STANDARD_DEVIATION 1.3 | 6.7 hours slept per night STANDARD_DEVIATION 1.6 | 6.5 hours slept per night STANDARD_DEVIATION 1.5 |
| Pittsburgh Sleep Quality Index (PSQI) sleep quality | 2.9 units on a scale STANDARD_DEVIATION 0.6 | 2.3 units on a scale STANDARD_DEVIATION 0.6 | 2.6 units on a scale STANDARD_DEVIATION 0.6 |
| Region of Enrollment United States | 13 participants | 13 participants | 26 participants |
| Sex: Female, Male Female | 10 Participants | 8 Participants | 18 Participants |
| Sex: Female, Male Male | 3 Participants | 5 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 13 | 5 / 13 |
| serious Total, serious adverse events | 0 / 13 | 0 / 13 |
Outcome results
Primary
Change in Mean Total Panic Disorder Severity Scale (PDSS) Scores
Possible total scores on the PDSS range from 0-28. The outcome measure represents the change, between baseline and the end of 8 weeks of treatment, in the the total PDSS scores. Lower scores indicate less severe panic disorder symptoms. A negative mean change in the scores at the end of 8 weeks represents a decrease in severity of panic disorder symptoms.
Time frame: Baseline and the end of 8 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine SR | Change in Mean Total Panic Disorder Severity Scale (PDSS) Scores | -5.3 units on a scale | Standard Deviation 4.7 |
| Placebo | Change in Mean Total Panic Disorder Severity Scale (PDSS) Scores | -5.6 units on a scale | Standard Deviation 4.8 |
Secondary
Change in Scores in Measurements of Depressive Symptoms (Hamilton Depression Rating Scale, HAM-D), Generalized Anxiety Symptoms (Hamilton Anxiety Rating Scale, HAM-A) and the Sleep Quality Item of the Pittsburgh Sleep Quality Index (PSQI).
Subjects scores on secondary efficacy measures were measured, comparing baseline and the end of 8 weeks of treatment, including the Hamilton Depression Rating Scale, HAM-D, which has 21 items, with scores ranging from 0-66; the Hamilton Anxiety Rating Scale, HAM-A, which has 14 items, with scores ranging from 0-56; and the sleep quality item of the PSQI, a four-point scale rating sleep quality as very good, fairly good, fairly bad or very bad.
Time frame: Comparing baseline and the end of 8 weeks of treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Quetiapine SR | Change in Scores in Measurements of Depressive Symptoms (Hamilton Depression Rating Scale, HAM-D), Generalized Anxiety Symptoms (Hamilton Anxiety Rating Scale, HAM-A) and the Sleep Quality Item of the Pittsburgh Sleep Quality Index (PSQI). | Increase in PSQI sleep quality scores | 1.3 units on a scale | Standard Deviation 0.5 |
| Quetiapine SR | Change in Scores in Measurements of Depressive Symptoms (Hamilton Depression Rating Scale, HAM-D), Generalized Anxiety Symptoms (Hamilton Anxiety Rating Scale, HAM-A) and the Sleep Quality Item of the Pittsburgh Sleep Quality Index (PSQI). | Decrease in HAM-D scores | 5.0 units on a scale | Standard Deviation 5.2 |
| Quetiapine SR | Change in Scores in Measurements of Depressive Symptoms (Hamilton Depression Rating Scale, HAM-D), Generalized Anxiety Symptoms (Hamilton Anxiety Rating Scale, HAM-A) and the Sleep Quality Item of the Pittsburgh Sleep Quality Index (PSQI). | Decrease in HAM-A scores | 6.8 units on a scale | Standard Deviation 8.1 |
| Placebo | Change in Scores in Measurements of Depressive Symptoms (Hamilton Depression Rating Scale, HAM-D), Generalized Anxiety Symptoms (Hamilton Anxiety Rating Scale, HAM-A) and the Sleep Quality Item of the Pittsburgh Sleep Quality Index (PSQI). | Decrease in HAM-D scores | 3.8 units on a scale | Standard Deviation 3.6 |
| Placebo | Change in Scores in Measurements of Depressive Symptoms (Hamilton Depression Rating Scale, HAM-D), Generalized Anxiety Symptoms (Hamilton Anxiety Rating Scale, HAM-A) and the Sleep Quality Item of the Pittsburgh Sleep Quality Index (PSQI). | Decrease in HAM-A scores | 5.5 units on a scale | Standard Deviation 4.7 |
| Placebo | Change in Scores in Measurements of Depressive Symptoms (Hamilton Depression Rating Scale, HAM-D), Generalized Anxiety Symptoms (Hamilton Anxiety Rating Scale, HAM-A) and the Sleep Quality Item of the Pittsburgh Sleep Quality Index (PSQI). | Increase in PSQI sleep quality scores | 1.3 units on a scale | Standard Deviation 1 |