The goals of this project are to compare and contrast the therapeutic effectiveness and safety of acute and maintenance treatment with lithium (Li), carbamazepine (CBZ) and lithium combined with carbamazepine (Li-CBZ) in patients with DSM III bipolar disorders presenting in manic or mixed phases. One-hundred twenty patients will be randomly assigned to one of the three treatments on a double-blind basis. PRN neuroleptics will be permitted for the control of severely disturbed or dangerous behavior and to facilitate compliance for the first six weeks of the study, but not afterwards. Patients who achieve remission on randomly assigned medications will be followed for six to 42 months with maintenance of double-blind conditions. Patients who fail to respond, deteriorate on study medications or experience significant adverse reactions within the first eight weeks of treatment will be crossed over to either Li or CBZ and followed during long-term treatment if stabilization is achieved, which will also be double-blind. Clinical ratings of manic, depressive and psychotic symptomatology and inventories of characteristics said to be typical of patients with complex partial epilepsy will be obtained before the study and at intervals throughout. Laboratory data to be obtained repeatedly before and during the study will include neuropsychological tests, clinical EEG studies and quantitative EEG assessments. Plasma levels of Li and CBZ and its 10,11-epoxide will be monitored and maintained within accepted therapeutic ranges. Safety data will be obtained using the SAFTEE general and specific inquiries, EKG and laboratory tests of hematologic, hepatic, renal and thyroid functions. Patients will be dropped from the study whenever criteria are met for affective relapse or recurrence. Data analysis will compare therapeutic responses in the three treatment groups during acute treatment, stabilization and followup. Outcome will also be evaluated in terms of the clinical rating scale variables, timing of remission and duration on the study protocol. Response to the three treatments will be examined in relation to sex, age at onset, other demographic variables, manic proneness, numbers of previous episodes, rapid cycling, EEG and neuropsychological test findings and other characteristics. Multivariate analyses will be utilized to identify patient characteristics that are predictive of favorable response to each of the three treatments.
| Small, J G; Milstein, V; Malloy, F W et al. (1998) Topographic EEG studies of mania. Clin Electroencephalogr 29:59-66 |
| Small, J G; Klapper, M H; Milstein, V et al. (1991) Carbamazepine compared with lithium in the treatment of mania. Arch Gen Psychiatry 48:915-21 |
| Small, J G; Milstein, V (1990) Lithium interactions: lithium and electroconvulsive therapy. J Clin Psychopharmacol 10:346-50 |
| Small, J G (1990) Anticonvulsants in affective disorders. Psychopharmacol Bull 26:25-36 |
| Small, J G; Klapper, M H; Kellams, J J et al. (1988) Electroconvulsive treatment compared with lithium in the management of manic states. Arch Gen Psychiatry 45:727-32 |
| Small, J G; Milstein, V; Miller, M J et al. (1988) Neurophysiological evidence for actions of ECT. Psychopharmacol Bull 24:391-5 |
| Small, J G; Milstein, V; Small, I F et al. (1987) Computerized EEG profiles of haloperidol, chlorpromazine, clozapine and placebo in treatment resistant schizophrenia. Clin Electroencephalogr 18:124-35 |
| Milstein, V; Small, J G; Small, I F (1986) Electrically induced seizures (ECT). Compr Ther 12:68-72 |
