Clinical trial NCT00619892: A Study of Quetiapine SR (Seroquel SR) to Treat SSRI-Resistant, Comorbid Panic Disorder Patients
Official title: An 8-week, Randomized, Double-Blind, Placebo-Controlled Trial of Seroquel SR Co-administration for SSRI-Resistant, Comorbid Panic Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Panic Disorder
Keywords: SSRI Resistant
Seroquel SR
Seroquel XR
Panic Disorder
Comorbid Panic Disorder
Quetiapine SR
Quetiapine XR
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2008-02-21
Enrollment: 26
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 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Mean Total Panic Disorder Severity Scale (PDSS) Scores
timeFrame: Baseline and the end of 8 weeks of treatment
Secondary outcomes:
measure: 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).
timeFrame: Comparing baseline and the end of 8 weeks of treatment
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: University Hospital Outpatient Center, Psychiatry
state: Indiana
Study officials:
affiliation: Indiana University
name: Andrew W. Goddard, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Goddard AW, Mahmud W, Medlock C, Shin YW, Shekhar A. A controlled trial of quetiapine XR coadministration treatment of SSRI-resistant panic disorder. Ann Gen Psychiatry. 2015 Sep 15;14:26. doi: 10.1186/s12991-015-0064-0. eCollection 2015.