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Neuroleptic Malignant Syndrome
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This is the most dreaded complication of phenothiazine and haloperidol use; rare instances have been reported after the institution or the withdrawal of L-dopa and similar dopaminergic agents Its incidence has been calculated to be only 02 percent of all patients receiving neuroleptics (Caroff and Mann), but its seriousness is underscored by a mortality rate of 15 to 30 percent if not recognized and treated promptly It may occur days, weeks, or months after neuroleptic treatment is begun The syndrome consists of rigidity, stupor, unstable blood pressure, variable hyperthermia, diaphoresis and other signs of autonomic dysfunction, high serum creatine kinase (CK) values (up to 60,000 units), and, in some cases, renal failure due to myoglobinuria The syndrome was rst observed in patients treated with haloperidol, and since then other neuroleptic drugs have been incriminated, particularly the highly potent thioxanthine derivatives and the phenothiazines chlorpromazine, uphenazine, and thioridazine but also, on rare occasions, the less potent drugs that are used to control nausea, such as promethazine It has become evident that the newer antipsychotic drugs, and speci cally olanzapine, are also capable of inducing the syndrome but the risk in comparison to the rst generation of antipsychotic drugs has not been established If treatment of the neuroleptic malignant syndrome is started early, when consciousness is rst altered and the temperature is rising, bromocriptine in oral doses of 5 mg tid (up to 20 mg tid) will terminate the condition in a few hours If oral medication can no longer be taken because of the patient s condition, dantrolene, 025 to 30 mg intravenously, may be lifesaving Once coma has supervened, shock and anuria may prove fatal or leave the patient in a vegetative state The rigors during high fever may cause muscle damage and myoglobinuria, and the circulatory collapse may lead to hypoxic-ischemic brain injury
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Haloperidol (Haldol) is the only member of this group approved for use as an antipsychotic in the United States It has much the same therapeutic effects as the phenothiazines in the management of acute psychoses and shares the same side effects as the phenothiazines, but exhibits little or no adrenergic blocking action It is an effective substitute for the phenothiazines in patients who are intolerant of the latter drugs, particularly of their autonomic effects It is also one of the main drugs for the treatment of Gilles de la Tourette syndrome (the other being pimozide; see page 95) and the movement disorder of Huntington chorea
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Treatment of Neuroleptic Side Effects
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As indicated earlier, acute dystonic spasms usually respond to diphenhydramine (Benadryl) Administration of antiparkinsonian drugs of the anticholinergic type (trihexyphenidyl, procyclidine, and benztropine) may hasten recovery from some of the acute symptoms The purely parkinsonian syndrome usually improves as
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Meningitis, heat stroke, lithium intoxication, catatonia, and acute dystonic reactions gure in the differential diagnosis Of course, neuroleptic medication must be discontinued as soon as any of the severe extrapyramidal reactions are recognized It has been common practice to avoid future administration of the offending neuroleptic, but the risk of using another class of antipsychotic agents has not been fully addressed The neuroleptic malignant syndrome bears an uncertain relationship to malignant hyperthermia by way of its clinical aspects but also in its response to bromocriptine and dantrolene (see later) Malignant hyperthermia is an inherited disorder that, in susceptible individuals, is triggered by inhalation anesthetics and skeletal muscle relaxants (page 1272) This disorder was described before the introduction of neuroleptic drugs and in a small proportion of cases has been related to a mutation of the ryanodine receptor gene on chromosome 19q A genetic factor is also suspected to underlie the neuroleptic malignant syndrome (a polymorphism in the D2 receptor gene; see Suzuki et al), possibly provoked by fatigue and dehydration There is no evidence that the occurrence of one of these syndromes confers a susceptibility to the other It hardly needs to be pointed out that the antipsychotic drugs have been much overused This would be suspected just from the frequency with which they are being prescribed These medications have speci c indications, noted earlier and in Chaps 56, 57, and 58, and the physician should be certain of the diagnosis and the indication for their use That the neuroleptic drugs can produce tardive dyskinesia in nonpsychotic patients is reason enough not to prescribe them for nervousness, apprehension, anxiety, mild depression, insomnia, and the many normal psychologic reactions to trying environmental circumstances These drugs are not curative but only suppress or partially alleviate symptoms, and they should not serve as a substitute for, or divert the physician from, the use of other measures for the relief of abnormal mental states
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