Marietta H. Klapper

Tolerability and efficacy of clozapine combined with lithium in schizophrenia and schizoaffective disorder.

The safety and tolerability of clozapine combined with lithium were investigated because of potential additive risks as well as frequent usage in clinical practice. Ten hospitalized schizophrenic and 10 schizoaffective patients receiving clozapine maintenance therapy with partial therapeutic response were studied in a randomized controlled trial. CGI and PANSS outcome ratings were employed and a cognitive battery was administered at baseline and after 4 weeks of lithium and placebo administration. Barnes and UKU side effect ratings and laboratory safety data were obtained. Combined lithium-clozapine treatment was well tolerated except for reversible neurotoxic reactions in two schizophrenic patients. Safety measures showed no significant variations, even during lithium toxicity. Total WBC and absolute granulocyte counts increased with lithium and declined with placebo. Schizoaffective patients improved with lithium on CGI and PANSS total and negative symptom scales and the cognitive measures, whereas schizophrenic patients did not. Lithium added to clozapine in treatment regimens for hospitalized, treatment-resistant, schizoaffective patients appears to afford potential benefit without harmful effects; for schizophrenic patients, however, it did not afford improvement but posed a risk of lithium toxicity.

Manic symptoms: An indication for bilateral ECT

As a follow-up to pilot observations that six manic patients who failed to respond to unilateral electroconvulsive therapy (ECT) recovered rapidly when switched to bilateral treatment, a retrospective study was conducted. Twenty-five patients who responded after switchover from unilateral to bilateral ECT, 25 age- and sex-matched controls, and 25 concurrent controls who responded to right unilateral ECT alone were evaluated. Demographic variables and DSM-III diagnosis did not discriminate between the groups, nor were they different in terms of electroencephalographic (EEG) findings, neuropsychological test results, numbers of ECT, and duration of seizure discharges. Standard assessments of psychopathology performed by independent psychiatrists showed no differences in ratings of psychosis or depressive phenomena. However, scales assessing manic symptoms showed highly significant differences with many more features of unrestrained behavior, elevated mood, hurried speech, and other typical features of mania in the patients who were switched from unilateral to bilateral ECT. Although there were no differences in prescribed drugs, the use of prn medications for sleep was greater in the experimental-switched patients than in controls. Patients who responded to unilateral ECT alone exhibited virtually no manic features, whereas those who demonstrated these characteristics failed to respond to unilateral ECT but benefited when switched to bilateral treatment.

Topographic EEG studies of mania

QEEG findings from 39 hospitalized manic patients were accomplished after a drug free period and following pharmacotherapy with lithium or carbamazepine alone or lithium combined with carbamazepine, haloperidol or risperidone. A subsample of 10 drug-free manic patients was compared with normal controls, which revealed lower qEEG amplitudes in the left anterior and midtemporal regions in the patients. Comparisons of drug therapies showed increased delta amplitudes and total power with lithium compared with carbamazepine. Increased fast frequencies were observed in the lithium and carbamazepine plus lithium groups compared with carbamazepine alone. Comparisons of the three drug combination groups revealed increased alpha and beta 1 amplitudes, most with risperidone and least with carbamazepine. Anterior delta and beta 2 amplitudes and interhemispheric coherence were increased directly proportional to plasma lithium levels. Nonresponders to treatment were identified at baseline by increased generalized theta amplitudes. After treatment, the nonresponders had higher amplitudes in the left temporal areas. Numerous qEEG associations with individual ratings of manic symptoms were found, more at baseline than after treatment. In general levels of psychopathology were negatively correlated with qEEG amplitudes. The qEEG findings appear to implicate dominant temporal lobe dysfunctions in mania.