Quetiapine and the Dopaminergic Epigenetic Control

Inclusion criteria

For inclusion in the study subjects must fulfil all of the following criteria:

• Provision of written informed consent
• A diagnosis of schizophrenia by Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition (DSM-IV)
• Able to understand and comply with the requirements of the study
• Age 18 - 65 years

Exclusion criteria

Any of the following is regarded as a criterion for exclusion from the study:

• Any DSM-IV Axis I disorder not defined in the inclusion criteria
• 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 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 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 inclusion
• Substance or alcohol dependence at enrolment (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 enrolment
• 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 enrolment in the present study.
• Participation in another drug trial within 4 weeks prior enrolment into this study or longer in accordance with local requirements
• Actual treatment with clozapine or clozapine treatment during the previous three month. Other antipsychotic drugs will be allowed, if intake can be terminated during the two day wash out period.
• Previous history of major head injuries or neurological disorders
• Intake of homocysteine lowering vitamins (folate, B12, B6)
• Renal failure
• Intake of nutritional derivatives which influence epigenetic patterns (butyrate from milk products, tea polyphenol or epigallo-catechin-3-gallate which inhibits DNMT)