Reversible and irreversible tardive dyskinesia: a case report.
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Biomedical subjects
Publications and source records attributed to G Chouinard.
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The plasma prolactin (PRL) levels of 35 chronic schizophrenic patients undergoing long-term maintenance treatment with neuroleptic drugs were measured before and after either neuroleptic withdrawal or a switch to a fixed dose of chlorpromazine 900 mg/day. In both men and women there tended to be a significant correlation between the initial log plasma PRL level while on neuroleptic maintenance treatment and the dosage received converted to chlorpromazine equivalents. Neuroleptic withdrawal in ech of 19 cases was followed by a decline in PRL plasma levels. Switching to chlorpromazine 900 mg/day (16 cases) produced either increases or decreases in PRL plasma levels that were significantly correlated with the change in neuroleptic dosage converted to chlorpromazine equivalents. Thus there was no evidence of tolerance to the PRL-elevating effect of neuroleptics in these patients who had been treated for many years with neuroleptics.
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Tardive dyskinesia is thought to result from neostriatal dopaminergic receptor supersensitivity induced by chronic treatment with neuroleptics. The authors suggest that dopaminergic supersensitivity also occurs in the mesolimbic region after chronic neuroleptic exposure, resulting in the development of a supersensitivity psychosis. Neuroleptic-induced supersensitivity psychosis is illustrated by data from 10 patients that demonstrate the syndrome's clinical and pharmacologic characteristics. An implication of neuroleptic-induced mesolimbic supersensitivity is that the tenaency toward psychotic relapse in such patients is determined by more than just the normal course of the illness.
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In a double-blind placebo-controlled study, deanol acetamidobenzoate, administered in doses up to 1.5 g q.d. for three weeks to chronic schizophrenic patients presenting moderate to severe tardive dyskinesia, failed to alleviate the dyskinetic movements. However, there was a tendency for a significant increase in the schizophrenic symptoms of the deanol-treated group relative to the control group. The ineffectiveness of deanol in alleviating tardive dyskinesia is consistent with its inability to enhance brain acetylcholine synthesis. The worsening of the schizophrenic symptoms may possibly result from an interference by deanol with central cholinergic function.
In a double-blind controlled study lasting 4 weeks 25 newly admitted severely depressed patients were randomly assigned to tryptophan-nicotinamide or imipramine or tryptophan-nicotinamide-imipramine combination. Nicotinamide was given to reduce peripheral breakdown of tryptophan. Although there were no substantial differences between the three treatments, the efficacy of tryptophan-nicotinamide tended to diminish after 2 weeks when the dose of tryptophan was increased from 4 g/day to 6 g/day and that of nicotinamide from 1.0 g/day to 1.5 g/day. The therapeutic response of patients treated with tryptophan-nicotinamide was significantly correlated with the rise in plasma tryptophan. For the tryptophan-nicotinamide-imipramine group, however, therapeutic response and rise in plasma tryptophan were negatively correlated, implying that tryptophan levels were too high in some patients. The data suggest that tryptophan-nicotamide may be as effective as imipramine in unipolar patients providing the dose is kept within the therapeutic window, and that at low doses it could also potentiate the action of tricyclic antidepressants. Bipolar patients seem to require higher doses of tryptophan than unipolar patients.
The authors found a 31% incidence of tardive dyskinesia among 261 schizophrenic outpatients treated with neuroleptics. Multiple linear logistic regression analysis revealed a higher incidence of tardive dyskinesia among elderly patients, those with longer records of hospitalization, those for whom neuroleptic medication had little therapeutic effect, and those treated with fluphenazine. Patients manifesting tardive dyskinesia tended to have fewer parkinsonian symptoms than those without the disorder, especially when tremors and akathisia were excluded from consideration. Multiple linear regression analysis indicated that brain-damaged patients and male patients were more susceptible to severe forms of the disorder, even though these factors were not implicated in its initial appearance.
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