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.     

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.     

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.     

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.     

High-dose pyridoxine in tardive dyskinesia.

The clinical similarities of tardive dyskinesia and 1-dopa intoxication lend support to the post-synaptic hypersensitivity hypothesis in tardive dyskinesia. Pyridoxine, a co-factor in the decarboxylation of dopa, reverses the movement disorder of l-dopa intoxication. Although early studies of pyridoxine in tardive dyskinesia have not been encouraging, the results of the present study suggest that high doses of pyridoxine may reduce the frequency and severity of involuntary movements in tardive dyskinesia.     

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.     

Bereitschaftspotential in tardive dyskinesia

The bereitschaftspotential or motor readiness potential is a slow negative electroencephalographic wave occurring 150-1500 ms prior to the onset of a voluntary movement. It was measured in 33 subjects: 11 normal controls, 11 medicated schizophrenics with no tardive dyskinesia or evidence of drug-induced parkinsonism, and 11 patients with tardive dyskinesia. The bereitschaftspotential amplitude was more than two times larger in patients with tardive dyskinesia than in normal controls or schizophrenic patients without tardive dyskinesia. The increased amplitude correlated with the degree of severity of the tardive dyskinesia as measured on the Abnormal Involuntary Movement Scale (AIMS). The finding of the increased bereitschaftspotential amplitude in tardive dyskinesia, taken together with earlier findings of low amplitude in Parkinson's disease, suggests that this potential may reflect the level of dopaminergic activity in the basal ganglia.     

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.     

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.     

Electroencephalogram in tardive dyskinesia

The electroencephalogram was studied in affective disorder and schizophrenic patients both with and without tardive dyskinesia. There were no significant differences in electroencephalographic changes among the groups. The majority of electroencephalographic abnormalities appear to be drug induced. Tardive dyskinesia is not associated with specific changes in the electroencephalogram.     

Quetiapine in tardive dyskinesia

Tardive dyskinesia (TD) is a potentially irreversible side-effect of antipsychotic medication. Some atypical antipsychotics, by virtue of their better side-effect profile, seem to have an ability to reverse TD. The importance of trying to treat TD has become more urgent in view of the medico-legal implications of Article 3 of the Human Rights Act, 1998 which states that ''no one shall be subjected to inhuman or degrading treatment or punishment'': interpretation of this article was successfully used to win a large out-of-court settlement for a patient with TD in our region. Though clozapine has been used in cases with TD, its role is limited, due to the risk of agranulocytosis. We write about three cases with TD who responded well to quetiapine (Seroquel © , AstraZeneca), and suggest that more robust research be carried out to investigate the initial promise. (Int J Psych Clin Pract 2002; 6: 175-177 )