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 Chap. 4) and the movement disorder of Huntington chorea. It has been widely used in critical care practice to reduce the duration of delirium but at least one randomized trial has failed to show that it is any different than treatment with placebo (Girard et al).
Treatment of Neuroleptic Side Effects
As indicated earlier, acute dystonic spasms usually respond to cessation of the offending drug and to the administration of diphenhydramine. 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 well, but the tardive dyskinesias stand apart because they may persist for months or years and may be permanent.
Oral, lingual, and laryngeal dyskinesias of the tardive type are affected relatively little by any antiparkinsonian drugs. Amantadine in doses of 50 to 100 mg tid has been useful in a few of the cases of post-phenothiazine dyskinesia. Other drugs such as benztropine have been tried in the treatment of regional and more generalized tardive dyskinesia with uncertain results. Nevertheless, there is a tendency for most of the obstinate forms to subside slowly even after several years of unsuccessful therapy. Once a tardive syndrome has been identified, an immediate tapering of the offending medication is recommended, though the efficacy of this strategy has not been evaluated prospectively, and furthermore there is risk of exacerbation of psychotic symptoms. Substitution of the offending medication with one of the second generation “atypical” antipsychotic medications is a reasonable strategy, though the reduced dyskinetic effects of these medications is only relative.
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, as well as a few instances reported with the newer antipsychosis drugs. Its incidence has been calculated to be only 0.2 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 hyperthermia, rigidity, stupor, unstable blood pressure, diaphoresis, and other signs of sympathetic overactivity, high serum creatine kinase (CK) values (up to 60,000 units), and, in some cases, renal failure because of myoglobinuria. The syndrome was first observed in patients treated with haloperidol, but since then other neuroleptic drugs have been incriminated, particularly the highly potent thioxanthene derivatives and the phenothiazines—chlorpromazine, fluphenazine, 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 specifically olanzapine, are also capable of inducing the syndrome but the risk in comparison to the first generation of antipsychotic drugs has not been established.