Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical evaluation and pharmacological treatment of Gilles de la Tourette's syndrome (TS) and other hyperkinesias in Hvidovre Hospital is reviewed. Pimozide still seems to be the most effective single drug in the treatment of Tourette symptoms. Anticholinergics most often in combination with one or two other drugs are still the most effective drug in the treatment of dystonia. Clozapine is an effective alternative in the treatment of tremor.
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PMID:Clinical evaluation and pharmacological treatment of Gilles de la Tourette's syndrome and other hyperkinesias. 135 7

Clozapine, an atypical neuroleptic, does not cause extrapyramidal symptoms of Parkinsonism and dystonia and appears to have a reduced or absent capacity to produce tardive dyskinesia. 37 subjects, most with chronic schizophrenia, were treated with clozapine and TD outcome was analyzed. A subset of these subjects underwent plasma and CSF studies. TD response was heterogenous, but a proportion of patients improved with clozapine treatment. Neurochemical data differed from published reports of classical neuroleptics with the most robust effect produced by clozapine seen in CSF norepinephrine levels. Other neurochemical data and implications for the mechanism of clozapine in TD are reviewed.
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PMID:Clozapine pharmacology and tardive dyskinesia. 247 47

Clozapine has had a uniquely favorable motor system side effect profile since its initial evaluations. This has been convincingly corroborated by many double blind, single blind, and open studies treating acute and chronic psychosis. The acute extrapyramidal syndromes of dystonia, akathisia and parkinsonism infrequently occur, whereas these syndromes develop in up to 75% of patients receiving traditional neuroleptics. Tardive dyskinesia can be suppressed with higher doses of clozapine given over extended periods. However, an antipsychotic effect can be achieved in many patients at doses below the dyskinesia suppressing level. There is no established causative relationship between clozapine and tardive dyskinesia, but there is a theoretical basis that this may occur. Preliminary data suggest clozapine has mild antiparkinsonian effects as well as efficacy in controlling dopamine agonist-induced psychosis without aggravating parkinsonism. A much wider use of clozapine will further characterize the magnitude of differences compared to other neuroleptics, and identify additional indications for this special compound.
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PMID:Clozapine: neuroleptic-induced EPS and tardive dyskinesia. 268 32

Since the introduction of chlorpromazine in the 1950s, neuroleptic medications have been the mainstay of treatment of schizophrenia and other psychotic disorders. These medications do not always lead to complete remission of symptoms but they have allowed many patients to lead more productive and satisfying lives away from the restrictions of chronic hospitalisation. However, neuroleptics are associated with a number of adverse effects that can compromise their effectiveness. Extrapyramidal adverse effects include acute dystonic reactions, neuroleptic-induced Parkinsonism and akathisia. They can often be treated with neuroleptic dose reduction, addition of anticholinergic or beta-blocking agents, or medication change. Later-onset movement disorders such as tardive dyskinesia or dystonia require careful evaluation and may be treated with dose reduction or change of neuroleptic to an atypical agent. Potentially fatal reactions such as agranulocytosis and neuroleptic malignant syndrome can rarely occur and often require significant medical intervention. Clozapine offers some advantages over 'typical' neuroleptics but has a unique adverse effect profile which includes agranulocytosis.
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PMID:Adverse effects of antipsychotic drugs. 790 81

Among the tardive dyskinesia syndromes, dystonia can be the most difficult to treat. It may be severe to the point of being disabling, yet the patients may require antipsychotic medications for an even more disabling psychosis. Clozapine, an atypical neuroleptic drug that lacks extrapyramidal effects, may be the drug of choice for such patients. This report describes three patients with significant dystonia, previously disabled by their psychoses, who have been successfully managed with clozapine plus other agents for > 3 years.
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PMID:Clozapine treatment of psychosis in patients with tardive dystonia: report of three cases. 791 39

We report a patient with severe axial tardive dystonia who has had dramatic improvement for 4 years after treatment with the atypical antipsychotic drug clozapine (625 mg/day). Clozapine differs from conventional neuroleptics in that it has higher affinity for D1 and lower affinity for D2 dopamine receptors than do conventional antipsychotics, which are relatively selective D2 antagonists. We propose that repetitive stimulation of the D1 receptor by endogenous dopamine, resulting in sensitization of the D1-mediated striatal output in the presence of D2 receptor blockade, is a fundamental mechanism mediating tardive dyskinesia, including the dystonic type. According to this hypothesis, it is primarily the D1 antagonist action of clozapine that accounts for its inability to cause tardive dyskinesia as well as its therapeutic effect in tardive dystonia. Regardless of its mechanism of action, the sustained improvement observed in this case suggests that clozapine should be tried in cases of severe refractory tardive dystonia.
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PMID:Treatment of severe axial tardive dystonia with clozapine: case report and hypothesis. 796 12

The effects of the atypical neuroleptic clozapine were studied in an inbred line of Syrian golden hamsters with generalized dystonia, i.e. a frequent movement disorder in humans. The effects of clozapine were compared with those of the classical neuroleptic, haloperidol. Clozapine, 7.5-20 mg/kg i.p., potently reduced the severity of dystonic attacks in the mutant hamster model, but induced marked sedation at these doses. Lower doses were ineffective. Haloperidol, 0.5 mg/kg i.p., significantly reduced the severity of dystonia without marked sedation. The finding that clozapine possesses antidystonic potency similar to that of haloperidol in a genetic model of dystonia might suggest that this atypical neuroleptic is an effective alternative in the treatment of dystonic patients who respond to neuroleptics, particularly because of the clinical evidence that clozapine is almost devoid of extrapyramidal adverse effects.
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PMID:The atypical neuroleptic, clozapine, exerts antidystonic activity in a mutant hamster model. Comparison with haloperidol. 828 96

Levodopa-induced dyskinesias result in considerable functional impairment for patients and formidable therapeutic challenges for physicians. A practical method of treating such dyskinesias is first to classify the levodopa dyskinesias according to their temporal profile after drug administration, namely, into predictable (interdose, biphasic and 'off-period') and unpredictable ('on-off') dyskinesias. Treatment of each type of dyskinesia requires a different and relatively specific therapeutic strategy. With progression of Parkinson's disease, the threshold for interdose dyskinesia lowers, while the threshold for antiparkinsonian efficacy is unchanged; therefore, the strategy is to maintain levodopa concentrations between these 2 thresholds and avoid high concentrations. Frequent small doses of liquid levodopa preparations may be indicated. Clozapine appears to increase the threshold for dyskinesia. However, its usefulness is limited primarily by dose-related sedation and by dose-unrelated agranulocytosis. Buspirone and fluoxetine may have specific antidyskinetic benefit. Surgical treatment may aid selected patients, although criteria for selection are not fully established. The biphasic dyskinesias occur just before and just after an oral dose of levodopa. They result when levodopa concentrations fall below or rise above the threshold for therapeutic efficacy; therefore, the strategy is to maintain concentrations as nearly constant as possible above that threshold. Dopamine agonists such as subcutaneous apomorphine combined with domperidone may be particularly helpful. Thalamic stimulation can also benefit selected patients. 'Off-period' dyskinesias occur at times of predicted low concentrations of levodopa. The treatment strategy is to provide sufficient levodopa or dopaminergic stimulation during those intervals. Dopamine agonists (e.g. bromocriptine at night) may help the characteristic early foot dystonia. Anticholinergic agents may also help. The unpredictable ('on-off') dyskinesias are first analysed to establish a pattern of response. Then, on the basis of that pattern, they are treated by maintaining levodopa concentrations or dopaminergic tone during the periods that would ordinarily be 'off.' Administration of liquid levodopa preparations, addition of dopaminergic agents, restriction of treatment during the morning hours as well as restriction of the majority of dietary protein in the evening meal may provide a period of predictable good function early in the day. Clozapine, even early in treatment, appears to reduce the incidence of these dyskinesias. Rescue with apomorphine during a malignant prolonged 'off' phase is particularly valuable.
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PMID:Methods of managing levodopa-induced dyskinesias. 882 14

The treatment of refractory major depression, including the psychotic subtype, is a therapeutic challenge. Three cases of resistant psychotic depression were treated with clozapine monotherapy, an atypical antipsychotic drug effective in treatment-resistant schizophrenia and mania. Both psychotic and mood symptoms responded well to clozapine monotherapy, although response was delayed in one case. Tardive dyskinesia improved markedly, and tardive dystonia improved moderately in one patient. No patient relapsed during a follow-up period of 4-6 years of clozapine treatment. Clozapine was well-tolerated with few side effects. These observations suggest controlled trials of clozapine in the treatment of psychotic depression that fails to respond to electroconvulsive therapy or typical neuroleptics plus tricyclic antidepressants are indicated. The same is true for the use of clozapine in maintenance treatment for psychotic depression in those cases in which typical neuroleptic drugs are required, in order to reduce the risk of tardive dyskinesia and dystonia.
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PMID:Acute and long-term effectiveness of clozapine in treatment-resistant psychotic depression. 887 71

Although the new generation of atypical antipsychotic agents could some day eliminate concerns about tardive dyskinesia (TD), this disorder remains a significant clinical problem for both patients and physicians. Fortunately, many, if not most, cases of TD are mild. For patients with mild to moderate TD, therapeutic efforts are primarily directed at minimizing neuroleptic exposure or, when possible, changing to atypical agents. Most cases of TD do not seem to progress, suggesting that the risk of remaining on typical neuroleptics is probably small. Patients with moderate to severe forms of TD present greater challenges. These patients frequently require medication to suppress their dyskinesias. A variety of suppressive agents have been tried with limited success. No treatment strategy has emerged that is clearly superior or even successful in most patients. Increasing doses of typical neuroleptics may be useful for short-term suppression; however, the long-term efficacy and risk of this strategy have not been studied carefully. Data on atypical neuroleptics are scant. Clozapine's short-term suppressive effects seem, at best, weak, but patients may improve with long-term treatment. Medications with relatively few side effects that may have suppressive efficacy for some patients include calcium channel blockers, adrenergic antagonists, and vitamin E. Gamma-amino-butyric acid agonists agents and dopamine depleters are frequently useful, but have troubling side effects of their own. A variety of other medications have been employed, but are not well studied. For patients with tardive dystonia, anticholinergic agents or botulinum toxin has been particularly effective. Efforts to understand the neurobiology of TD may shed light on this persistent clinical conundrum.
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PMID:Treatment of tardive dyskinesia. 936 97


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