Quetiapine Compared With Placebo in the Management of Fibromyalgia

Fibromyalgia causes widespread muscle pain, tender points on the body, and fatigue. It
affects 3-6% of Americans, mostly middle-aged women, and as many as 30% of patients are
unable to maintain full-time employment. Conventional analgesics rarely reduce the pain,
and even strong narcotics rarely eliminate it. This is a double-blind placebo-controlled
25-week crossover study of 42 patients. The first appointment will assess patients'
eligibility to participate. For the first 12 weeks after screening, 21 will be on Seroquel
XR 200 mg and 21 will be on placebo. After one week of washout, they will switch to the
other compound for the next 12 weeks. Participants will be 18 years or older, meet the
American College of Rheumatology criteria for fibromyalgia and will have not satisfactorily
responded to their previous treatment. The primary outcome measure will be the mean change
from baseline to endpoint in the FIQ total score. Secondary efficacy measures will be the
CGI (Clinical Global Impression), PSQI (Pittsburgh Sleep Quality Index), BDI (Beck
Depression Inventory), STAI (State-Trait Anxiety Inventory) and SF-12 (Short-Form 12 Health
Inventory), as well as individual items of the FIQ (Fibromyalgia Impact Questionnaire).

Inclusion Criteria:

- Provision of written informed consent

- A diagnosis of fibromyalgia according to the following American College of
Rheumatology 1990 Criteria for the Classification of Fibromyalgia

- History of widespread pain has been present for at least three months (defined as:
Pain in both sides of the body; Pain above and below the waist with additional, axial
skeletal pain must be present. Low back pain is considered lower segment pain)

- Pain in 11 of 18 tender point sites on digital palpation

- Females and males from age 18 to age 60 inclusive

- 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

- Unsatisfactory response to previous treatment as indicated by a score equal to or
greater than 4 on the FIQ

Exclusion Criteria:

- Pregnancy or lactation

- Patients who, in the opinion of the investigator, pose an 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 randomisation

- 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
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. 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 enrollment into this study
or longer in accordance with local requirements

- A patient with Diabetes Mellitus (DM) fulfilling one of the following criteria:

- Unstable DM defined as enrollment glycosylated hemoglobin (HbA1c) >8.5%

- Admitted to hospital for treatment of DM or DM related illness in past 12 weeks.

- Not under physician care for DM

- Physician responsible for patient's DM care has not indicated that patient's DM
is controlled.

- Physician responsible for patient's DM care has not approved patient's
participation in the study

- Has not been on the same dose of oral hypoglycaemic drug(s) and/or diet for the
4 weeks prior to randomization. For thiazolidinediones (glitazones) this period
should not be less than 8 Weeks.

- 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

- An absolute neutrophil count (ANC) of less than or equal to 1.5 x 10^9 per liter

- dementia

- Patients identified as meeting criteria for the Metabolic Syndrome, defined by
meeting any 3 of the following:

- Waist circumference greater than 40 inches (men) or 35 inches (women)

- Triglycerides greater than 150 mg/dl

- HDL cholesterol less than 40 mg/dl (men) or 50 mg/dl (women)

- High blood pressure greater than 130/ greater than 85

- Fasting glucose greater than 110 mg/dl