A comparison study of quetiapine medication and psychological therapy versus placebo tablets and psychological therapy in patients who are deemed at risk of developing a psychotic disorder.

Exclusion Criteria35

• Any of the following is regarded as a criterion for exclusion from the study:
• Pregnancy or lactation
• Patients who, in the opinion of the investigator, pose an imminent risk of suicide or a danger to self or others, as operationalised with a current Comprehensive Assessment of At Risk Mental States (CAARMS) aggression/dangerous behaviour severity score of 5-6 or current CAARMS suicidality/self-harm score of 5-6
• 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 enrolment 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 enrolment including but not limited to: phenytoin, carbamazepine, barbiturates, rifampicin, St. John’s Wort, and glucocorticoids.
• Administration of a depot antipsychotic injection within one dosing interval (for the depot) before randomisation.
• Medical conditions that would affect absorption, distribution, metabolism, or excretion of study treatment
• Unstable or inadequately treated medical illness (e.g. congestive heart failure, angina pectoris, hypertension) as judged by the investigator.
• Involvement in the planning and conduct of the study
• Previous enrolment or randomisation of treatment in the present study
• Participation in another drug trial within 4 weeks prior to enrolment 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 enrolment 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 randomisation. 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
• Note: If a diabetic patient meets one of these criteria, the patient is to be excluded even if the treating physician believes that the patient is stable and can participate in the study.
• An absolute neutrophil count (ANC) of 1.5 x 109 per liter.
• Past history of a treated or untreated psychotic or manic episode of one week duration or longer, as rated using the CAARMS
• Organic brain disease, e.g. epilepsy, inflammatory brain diseases
• (Liver Function Tests) LFTs and Kreatinine and electrolytes (U+Es) outside the normal range
• Current treatment with lithium, methyl phenidate or ketamine
• Intelligence Quotient (IQ) < 70, as recorded in medical history
• Current or past antipsychotic treatment longer than 1 week (seven days).
• Present or past diagnosis of a schizophrenic, schizophreniform, schizoaffective, delusional, bipolar, or mood disorder with psychotic features according to the Diagnostic and Statistical Manual of Mental Disorders (DSM) IV
• Diagnosis of delirium, dementia, amnestic or cognitive disorder, mental retardation, serious developmental disorder, autism spectrum disorders
• Magnetic resonance imaging (MRI) or Electroencephalograph (EEG) abnormalities, as recorded in medical history
• Participation in other clinical trials, which could interfere with the present trial
• Contraindication accordant to Summary of Product Characteristics (SMPC): Known intolerance of the active pharmaceutical ingredient or another ingredient of verum or placebo
• Drugs with anticipated interactions (in accordance to SMPC)
• Hospitalisation due to legal or regulatory devices