A multi-institutional collaborative study was conducted concerning the course of pregnancy and delivery and the incidence of abnormal infants delivered of epileptic women. Of 657 women receiving antiepileptic drugs, 73% delivered live infants, 14% had miscarriage or stillbirth, and 13% underwent induced abortion. In contrast to the above findings, 80% of 162 patients not receiving antiepileptic drugs delivered live infants and 4% had miscarriage or stillbirth. The latter outcome was significantly increased in the medicated patients. In this series, 63 (9.9%) of 638 live births were malformed, 55 (11.5%) being from medicated mothers and 3 (2.3%) from nonmedicated mothers. The incidence of fetal malformation in medicated mothers was thus five times as high as that in nonmedicated mothers. Cleft lip and/or palate and malformations involving the cardiovascular system were found frequently in the infants from medicated mothers. General background factors that might exert teratogenic effects on pregnant patients with epilepsy were studied, and the potential toxicity of antiepileptic drugs to the fetus was also analyzed. In this regard, consideration should be given to whether the patient has partial epileptic seizures, whether the patient herself exhibits any malformation, or whether her previous pregnancy resulted in an abnormal outcome. The incidence of fetal malformation was the highest (12.7%) in the medicated patients who had epileptic seizures during the pregnancy. It is presumed on the basis of the results of analysis of the data that a combination of more than three drugs and a daily dose greater than a certain minimal level is likely to produce malformed infants.

A preliminary double-blind controlled study on the prophylactic effect of carbamazepine on recurrent manic-depressive psychotics was conducted with 22 patients using an inert placebo in ten subjects as a control drug. Carbamazepine in the dosage of 200-600 mg was administered for 1 year. Among the 22 carbamazepine subjects, carbamazepine was found to be effective in 60% of the cases and inert placebo in 22.2% (U-test, P less than 0.10). It is suggested that carbamazepine is a useful drug for the prophylaxis of manic-depressive illness.

No abstract

A multi-institutional study comparing the antimanic effect of carbamazepine (CBZ) and lithium carbonate (Li) was performed using a double-blind group comparison design in a series of 105 patients with bipolar disorders. CBZ and Li were given for four weeks using a fixed-flexible method at an equipotent dose ratio of 1:1, starting from an initial dosage of 400 mg with a maximum dosage of 1200 mg. The final global improvement rate, based on the number of cases showing moderate to marked amelioration of manic symptoms, was 62% in the CBZ group and 59% in the Li group, with no significant difference being found between the two groups. Incidence of cutaneous side-effects was significantly higher in the CBZ group. The mean daily dosage and serum level of CBZ in the fourth week were 674 +/- 239 mg and 7.3 +/- 2.4 micrograms/ml respectively; these were within the therapeutic range. The daily dose and serum level of Li, however, were 710 +/- 239 mg and 0.46 +/- 0.22 mEq/l, and the Li level seemed to be too low to compare its therapeutic effect with that of CBZ. Prior to the present study, approximately 80% of the patients in both groups had been receiving antipsychotic medication, equivalent to 8.0 mg of haloperidol on average, without favorable response. This medication was maintained unchanged during treatment. While the shortcomings of the present study limit the interpretation of the data, it may be suggested that the usefulness of CBZ as a drug for the treatment of manic states is comparable to that of Li.

A multi-institutional double-blind study comparing the therapeutic effect of adjunctive carbamazepine and placebo with standard neuroleptic treatment was performed on 162 patients with DSM-III diagnosis of schizophrenic (n = 127) or schizoaffective disorders (n = 35) who had excited states or aggressive/violent behavior that responded unsatisfactorily to neuroleptic treatment. The patients participated in a 4-week trial of carbamazepine plus neuroleptics (n = 82) or placebo plus neuroleptics (n = 80). The sum of patients with marked and moderate improvement was modestly larger in the carbamazepine group (48 vs. 30%, P less than 0.05). There was no significant difference between the carbamazepine and placebo groups in the changes of total BPRS scores, although the carbamazepine group showed more improvement on the items suspiciousness, uncooperativeness and excitement. The results suggest that carbamazepine, when used in combination with neuroleptics, is a useful drug for the treatment of excited states of patients with schizophrenic and schizoaffective disorders.