In the previous period of grant support lithium (Li) was compared with carbamazepine (CBZ) for the acute and maintenance treatment of mania in patients who received no other adjuvant medications. The results of that study indicated that neither Li nor CBZ were very effective under these circumstances. Sixty-eight percent of patients wert dropped after 6 to 8 weeks of treatment for inadequate therapeutic response. Some differences were identified between the drugs, mainly in the greater degree of sedation and improved behavioral control with CBZ during the first five weeks of the study. Otherwise the two drugs yielded essentially the same therapeutic benefits. No significant toxicity was encountered. We now propose to compare Li-CBZ combined with Li-HAL in the acute and maintenance treatment of mania using essentially the same research design. Patients will again be treated for 8 weeks after which those who are unimproved or still meet study entrance criteria will be dropped from the study. The remainder will be followed for up to one year on double blind medications. At the end of that time patients who have been stable for at least 3 months will be tapered off CBZ or HAL and followed for up to a year on Li alone unless there is clinical worsening or recurrence.
The aims of the study are to test hypotheses that Li-CBZ combined is a viable short and long term treatment for manic patients as compared with the standard Li-HAL. If this be so, then exposure to neuroleptics, which is a particular hazard in bipolar patients, can be significantly reduced. We will examine outcome of short and long term treatment in relation to sex, age at onset, other demographic variables, manic proneness, rapid cycling, EEG abnormalities and clinical characteristics. Safety data from the SAFTEE general inquiry, neurological ratings, clinical EEG, EKG and laboratory tests of hematologic, hepatic, renal and thyroid functions will be compared in the two treatment groups. Brain Surface Activity Mapping (BSAM) and neuropsychological assessments will be completed at baseline and after short and long term treatment to compare the two treatment groups and to relate to the degree of therapeutic response. Multivariate analysis will be employed to identify the characteristics of patients who respond favorably or unfavorably to the two treatments. Long term prophylaxis will also be evaluated in term of survival time on the study and continued status on Li alone after withdrawal of CBZ and FM.
| 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. (1996) Comparison of therapeutic modalities for mania. Psychopharmacol Bull 32:623-7 |
| Small, J G; Klapper, M H; Marhenke, J D et al. (1995) Lithium combined with carbamazepine or haloperidol in the treatment of mania. Psychopharmacol Bull 31:265-72 |
| Milstein, V; Milstein, M J; Small, I F (1995) Radiographic screening for ECT: use and usefulness. Convuls Ther 11:38-44 |
| 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 |
