A Study of Quetiapine SR (Seroquel SR) to Treat SSRI-Resistant, Comorbid Panic Disorder Patients

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.

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.