SOLMANIA - Comparison of Valproate-Amisulpride and Valproate-Haloperidol in Bipolar I Patients

Exclusion Criteria

• •Having participated in a clinical trial within the three previous months
• •Pregnant or breast-feeding. Female patients should therefore be using reliable contraceptive methods (oral or parenteral contraception, intra-uterine device or surgical sterilisation)
• •Uncontrolled gastro-intestinal, renal, hepatic, endocrine, cardiovascular, pulmonary, immunological or hematological disease
• •Central nervous system (CNS) neoplasm; demyelinating disease; degenerative neurological disorder; active CNS infection; or any progressive disorder that may confound interpretation of the study results
• •Prolactin-dependant tumor
• •Past or current pancreatitis
• •Acute hepatitis, chronic hepatitis, or family history of severe hepatitis, especially drug related, hepatic porphyry
• •Current or recent (within 3 months) DSM IV diagnosis of substance dependence (with the exception of nicotine or caffeine dependence); or substance abuse with stimulants including, but not limited to, cocaine, crack, amphetamines, pseudoephedrine, cold medications with phenylephrine, or other stimulants. Alcohol and marijuana abuse prior to study entry would be acceptable if related to the current manic episode, based on the investigator's judgement
• •Parkinson's disease
• •Phaeochromocytoma
• •History of epilepsy
• •History of allergy or hypersensitivity to haloperidol or benzamides or valproate
• •Treated with fluoxetin within the past 4 weeks
• •Treated with injectable long-acting neuroleptics if, for the patient, the interval between 2 injection periods has not elapsed before pre-inclusion (D-3)
• •Treated with a mood stabiliser (other than valproate) at effective dose for less than 7 days preceding D-3 and for whom a modification is not justified
• •Bradycardia \< 55 beats per minute (bpm)
• •Known hypokaliaemia
• •Congenital prolongation of the QT interval
• •Treated with any of the following medications: Class Ia antiarrhythmic agents such as quinidine, disopyramide/Class III antiarrhythmic agents such as amiodarone, sotalol; Drugs like: beperidil, cisapride, sultopride, thioridazine, intravenous (IV) erythromycin, IV vincamine, halofantrine, pentamidine, or sparfloxacin.
• •Potentially significant alterations of laboratory tests on D0:
• •* ASAT or ALAT \> 2 upper limit of normal (ULN). If ASAT or ALAT values range between 1.5 ULN and 2 ULN, the patient can be randomized and a new test will be performed 7 days after randomization;
• •* Alkaline phosphatase levels or bilirubin levels not within normal reference range.
• •QTc prolongation on D0; QTc Bazett \> 450ms in male patients and QTc \> 470ms in female patients on electrocardiogram (ECG).