Search

The author describes the development of a neurotoxicity syndrome in a 68 year old women treated for 1½ years with lithium for recurrent depressions. The syndrome developed after 10 mgr. haloperidol per day was added, during a manic episode, for 10 days. The lithium levels were 0.71 ± 0.19 MEq/L. After 19 days all medications were discontinued. The neurotoxicity consisted succes-sivily of confusion, somnolence, agitation, extrapyramidal symptoms, cerebellair ataxia and EEG abnormalities. After 10 weeks memory impairmments were still present. At four months, memory function was restored. After five months, the patient was discharged without residual symptoms. The patient reported amnesia for the first six weeks of the syndrome. The author points out that while patients may develop tolerance to lithium maintenance after several years, they still may develop a neurotoxicity syndrome when haloperidol is added to treat a manic episode.

During an asymptomatic phase platelet MAO activity was examined in 28 unipolar patients, 8 of whom previously had developed mania during clomipramine treatment for depression. The platelet MAO activity was not lower in these switchers than in 20 unipolar patients who did not become manic during a similar clomipramine treatment. High but nonsignificant correlations were found among platelet MAO activity and age of onset of mania, duration of clomipramine treatment before the switch, and the duration of manic behavior. These clinical variables correlated significantly amongst themselves. The high and normal platelet MAO activities of these patients neither support nor rule out a Bipolar I diagnosis. This study supports the pharmacologic basic of the induction of mania during clomipramine treatment.

1. Central dopamine turnover may be lowered in patients with unipolar endogenous depression particularly when associated with retardation. 2. Nomifensine selectively activates the central dopaminergic system and may be of special therapeutic value in patients with motor inhibition. 3. A double-blind comparison of clomipramine and nomifensine was carried out in patients with recurrent unipolar depression. Biochemical and clinical assessments were carried out weekly for 4 weeks. 4. The mean homovanillic acid level in cisternal liquor of those patients who responded to nomifensine, was significantly lower than the mean level of the total group. 5. The factor "retardation" on the Hamilton Depression Scale was improved more with nomifensine than with clomipramine.

Manic behavior during randomly assigned treatment with clomipramine (chlorimipramine) or amitriptyline hydrochloride developed in seven of 50 hospitalized unipolar depressed patients. Six of the 25 clomipramine-treated patients became manic. Only one patient in the amitriptyline-treated group developed manic behavior. The switch into mania occurred at the mean age of 63, much later than the reported age of risk for mania. Significant correlations were observed between the age at onset of mania, the number of days of clomipramine treatment, and the duration of the manic episode. We hypothesize that such a switch into mania in unipolar patients is triggered by the psychopharmacological effect of clomipramine through an alleged change in activity of the central dopamine and serotonin systems.