Table 49-2 summarizes typical dosages of these antipsychotic drugs. In the higher dose ranges, parkinsonian features may nonetheless appear. Tardive dyskinesias, however, are infrequent. Common to all the drugs in the class, however, is variable weight gain and aspects of the “metabolic syndrome” including hyperlipidemia and hyperglycemia. With long-term treatment this may accumulate to 20 percent of the patient’s original weight. In a few cases, the newer generation antipsychotics have induced some obsessive-compulsive symptoms. According to Leucht and colleagues who performed a meta-analysis of extrapyramidal symptoms and various drugs, low-potency first-generation antipsychotics (excluding haloperidol) may have comparable complications to the new generation of drugs when dose-equivalent amounts are given. Most clinicians seem not to agree with this perspective. Several series have also suggested that the atypical antipsychosis drugs have a risk of ventricular arrhythmias and sudden death compared to conventional medications. However, the series collected by Ray and colleagues indicates that the frequency of these complications, while increased approximately twofold compared to nonusers, are the same for older and newer drugs when adjusted for medication dose.
The optimal daily dose for treatment of an acute psychotic episode is in the range of 10 to 20 mg daily of haloperidol, the equivalent amount (400 to 800 mg) of a phenothiazine such as chlorpromazine, or escalating doses of the atypical agents, listed in Table 49-2. The administration of much higher doses of phenothiazines or haloperidol is popular with some psychiatrists, but this practice entails serious risks and the advantages have not been demonstrated in controlled trials (see Kane and Marder). Attempts are made to individualize and eventually lower the dosage until the patient’s behavior suggests that a relapse is imminent. Antidepressants and lithium have also been used in those schizophrenic patients with prominent affective symptoms. Electroconvulsive therapy (ECT) is now seldom used except in patients who are catatonic or severely agitated or who have prominent affective symptoms.
To some extent, the extrapyramidal side effects of haloperidol and the phenothiazines can be prevented or at least minimized by the simultaneous parenteral administration of antihistaminic drugs—for example, diphenhydramine, 25 mg tid—and the anticholinergic drugs used in the treatment of Parkinson disease—for example, benztropine, 0.5 to 1 mg bid. However, the latter drugs must be given cautiously for they may interfere with the action of the antipsychotic drugs and, if given in large doses, themselves induce a toxic confusional state. If it becomes necessary to treat the extrapyramidal side effects, it is usually possible to eliminate the anticholinergic drugs after 2 to 3 months without a return of motor symptoms. In chronically medicated patients, 20 to 40 percent of whom develop tardive dyskinesias, an increased dose of the antipsychotic drug may suppress the dyskinesia, but only temporarily. The most dreaded complication of pharmacotherapy is the neuroleptic malignant syndrome. The nature and management of this complication and of the more common problem of tardive dyskinesias are discussed in Chap. 41.
With modern drug therapy and supportive psychiatric management, fully 60 percent of schizophrenic patients will recover sufficiently to return to their homes and become socially adjusted to a varying degree (about half of this group can engage in some occupation). Approximately 30 percent remain severely handicapped and 10 percent remain hospitalized.