Managing tardive dyskinesia.

Tardive dyskinesia, a delayed side effect of neuroleptic drugs, requires early recognition and a systematic treatment plan. An outline is presented which offers guidelines for management strategies and drug treatments, along with a summary of recent developments.     

Clenbuterol-induced tardive dyskinesia.

A 73-year-old man with a history of obstructive lung disease who received clenbuterol 20 mg b.i.d. over 5 years developed dyskinetic movements mainly of the respiratory muscles, closely resembling neuroleptic-induced dyskinesias. Despite drug withdrawal, abnormal movements persisted unchanged. Treatment with reserpine successfully controlled the dyskinetic movements. Clinicians should be aware of this potentially harmful effect of long-term clenbuterol therapy.     

Sulpiride in tardive dyskinesia.

The abnormal involuntary movements in tardive dyskinesia can be reduced by the dopamine antagonist drugs, phenothiazines and butyrophenones, but most cause an increase in Parkinsonian signs. Sulpiride, a benzamide derivative, and selective antagonist of D2 receptors had a significantly beneficial effect on most of 15 patients (p less than 0.01). In 12 patients the improvement was marked. The reduction of abnormal movements was observed even with low doses, and it was not necessary to increase the dose of sulpiride above 600 mg daily. There were no significant side effects during the trial nor during an additional three months of treatment.     

Prevalence of tardive dyskinesia.

Forty-four epidemiologic studies on tardive dyskinesia were evaluated as to whether they provided information on diagnostic criteria, objective scale and assessment, interobserver reliability, period of observation, and specific interhospital coordination. Studies which met these standards were reviewed for data on class of neuroleptic therapy, dose, duration, continuity of treatment, extrapyramidal toxicity, spontaneous dyskinesias, other drugs and treatment modalities, age and sex. A higher prevalence of tardive dyskinesia has been consistently noted in the elderly and in females. No other predisposing factors for tardive dyskinesia have been conclusively demonstrated thus far. Prevalence of tardive dyskinesia is estimated at 24-56% in chronic neuroleptic users.     

Treatment of tardive dyskinesia.

The pathogenesis of tardive dyskinesia is distinct from and may be functionally opposite to that of parkinsonism. The former is thought to be related to central nervous system dopaminergic hyperactivity, while the latter is known to be related to dopamine deficiency. An effective schema for the treatment of tardive dyskinesia includes avoiding antiparkinsonian medication and prescribing deanol, an acetylcholine precursor, while continuing or increasing phenothiazine dosages.     

Oxiperomide in tardive dyskinesia.

Tardive dyskinesia can be suppressed by dopaminergic receptor blockers, but often at the cost of a reciprocal increase in Parkinsonism. Oxiperomide, a dopaminergic antagonist that has been shown to reduce levodopa-induced dyskinesias without producing an equal aggravation of Parkinsonism, was evaluated in a blind placebo-controlled trial in 10 patients with tardive dyskinesia. It decreased tardive dyskinesia significantly (p less than 0.01) without significantly provoking or increasing Parkinsonism. There was no relationship between either tardive dyskinesia or Parkinsonism and eye blinking rates. These results can be interpreted as additional evidence for the existence of more than one population of dopamine receptors involved in controlling extrapyramidal function. Although oxiperomide is only a palliative suppressing agent in tardive dyskinesia, as the symptoms returned when the drug was stopped, it is an interesting agent in the search for selective dopaminergic receptor blockers.     

Amisulpride-induced tardive dyskinesia

Tardive dyskinesia (TD) is a movement disorder that develops during the course of long-term treatment with neuroleptic agents and is characterized primarily by choreiform and athetotic movements. We report the case of a 34-year-old man suffering from schizophrenia, disorganized type. He received amisulpride (400 mg daily) and the result was much improvement. 20 months later, he was presented with TD, which resolved almost completely after change of treatment to 1200 mg quetiapine without any relapsing. To our knowledge, his is the first case report in the literature of tardive dyskinesia induced by amisulpride.     

Laryngeal tardive dyskinesia

Neuroleptic treatment frequently induces movement disorders, the tardive dyskinesias. These are frequently seen in the orobuccolingual region. Although the beginning of neuroleptic treatment can cause acute dystonia and breathing difficulty, chronic neuroleptic treatment has only rarely been shown to affect the laryngeal musculature. Laryngeal abnormal movements were assessed in 12 patients receiving chronic neuroleptic treatment who showed orobuccolingual abnormal movements. The Abnormal Involuntary Movement Scale was systematically assessed in all patients. Clinical examination revealed that 8 had speech disorders, 8 had breathing difficulties, and 5 had swallowing disorders. Laryngeal endoscopy showed that 10 of the patients had intermittent partial obstruction of the glottis, due to repetitive abnormal adduction of the vocal cords. Percutaneous electromyography of the thyroarytenoid muscles showed spontaneous irregular and prolonged muscular contractions, while the patients were at rest and when speaking. The patients were not aware of these movements. In view of this finding, laryngeal dyskinesia should be considered and studied as a possible side-effect of chronic neuroleptic use.     

Factors related to tardive dyskinesia.

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.     

Neuroleptic-induced tardive dyskinesia

Prolonged exposure to neuroleptic drugs induces tardive dyskinesia which may be persistent or permanent. Predisposing factors to tardive dyskinesia are not apparent although the aging brain appears more vulnerable. The drug treatment of tardive dyskinesia is at present unsatisfactory. Preventive measures, other than limiting neuroleptic use have not been established. The pathophysiology of tardive dyskinesia may relate to cerebral dopamine overactivity. However, although this may be a primary change responsible for tardive dyskinesia alterations in other neuronal systems such as acetylcholine, 5HT or GABA may be involved.     

Sodium valproate in tardive dyskinesia.

Recent findings suggest that tardive dyskinesia may involve GABA-ergic influences in addition to dopaminergic receptor hypersensitivity and relative cholinergic hypofunction. Sodium valproate, which may increase brain GABA, moderately recuded tardive dyskinesia with doses of 900--3000 mg/day, as measured by a tremorgraph and rating scales. There was no correlation between dosage, blood levels, or clinical response. Although the symptoms were not completely controlled, valproate and other GABA-ergic agents may be useful compounds in studying and treating tardive dyskinesia.