Longterm Treatment

In reviews of nearly 30 controlled prospective studies involving several thousand schizophrenic patients, the mean overall relapse rate was 58% for patients withdrawn from antipsychotic drugs and given a placebo versus only 16% of those who continued on drug therapy. Daily dosage in chronic cases often can be lowered to 50—200 mg of chlorpromazine or its equivalent without signs of relapse, but rapid dose reduction or discontinuation appears to increase risk of exacerbation or relapse. Flexible therapy in which dosage is adjusted to changing current requirements can be useful and can reduce the incidence of adverse effects.

If the modern or atypical antipsychotic agents have superiority to older neuroleptics, this advantage is most important in the long-term treatment of chronic or recurrent psychotic illnesses, where it is standard practice to continue maintenance treatment with moderate and well-tolerated doses of an antipsychotic agent indefinitely, as long as the clinical indications, benefits, and tol-erability remain clear. The only agent with securely proven superiority is clozapine. Nevertheless, there is some evidence that modern atypical antipsychotics may yield superior results in long-term treatment, if only due to superior tolerability and adherence to treatment.

Maintenance with injections of the decanoate ester of fluphenazine or haloperidol every 2-4 weeks, or with long-acting risperidone microspheres every 2—3 weeks, can be very effective. However, an expectation of superiority of long-acting injected antipsychotics is not well supported by available studies, most of which involve randomization of patients who already are largely cooperative with long-term oral treatment.

Special Populations

The treatment of some symptoms and behaviors associated with delirium or dementia is another accepted use for the antipsychotic drugs. They may be administered temporarily while a specific and correctable structural, infectious, metabolic, or toxic cause is vigorously sought. They sometimes are used for prolonged periods when no correctable cause can be found. There are no drugs of choice or clearly established dosage guidelines for such indications, although older neurolep-tics of high potency are preferred. Modern atypical agents have not established their place in the management of delirium or dementia. In patients with delirium without likelihood of seizures, frequent small doses (e.g., 2-6 mg) of haloperidol or another potent antipsychotic may be effective in controlling agitation. Agents with low potency should be avoided because of their greater tendency to produce sedation, hypotension, and seizures, and those with central anticholinergic effects may worsen confusion and agitation.

A challenging special population is Parkinson's disease patients with psychotic symptoms related to dopaminergic therapy (see Chapter 20). Standard neuroleptics, risperidone (even in small doses), and olanzapine often produce unacceptable worsening of bradykinesia-akinesia. Clozapine is relatively well tolerated and effective, though more complicated to use. Use of moderate doses of newer agents with very low risk of parkinsonism (aripiprazole, quetiapine, ziprasidone) requires further study.

Most antipsychotics are rapidly effective in the treatment of mania and often are used con-comitantly with the institution of lithium or anticonvulsant therapy (see below).

Antipsychotic drugs may have a limited role in the treatment of severe depression, especially in patients with striking agitation or psychotic features; addition of an antipsychotic to an antidepressant in this setting may yield results approaching those obtained with ECT. Antipsychotic agents ordinarily are not used for the treatment of anxiety disorders. The use of clozapine in patients with schizophrenia and a high risk of suicidal behavior may reduce the risk of suicide attempts. Clozapine is the first drug to be FDA-approved for an antisuicide indication.

Drug treatment of childhood psychosis and other behavioral disorders of children is confused by diagnostic inconsistencies and a paucity of controlled trials. Antipsychotics can benefit children with disorders characterized by features that occur in adult psychoses, mania, autism, or Tourette's syndrome. Low doses of the more potent or modern atypical agents usually are preferred in an attempt to avoid interference with daytime activities or performance in school. Attention deficit disorder, with or without hyperactivity, responds poorly to antipsychotic agents, but often if the condition is not comorbid with bipolar disorder, responds very well to stimulants and some antidepressants. The recommended doses of antipsychotic agents for school-aged children with moderate degrees of agitation are lower than those for acutely psychotic children, who may require daily doses similar to those used in adults (Table 18—3). Doses of modern atypical antipsy-chotic agents for children and adolescents with psychotic or manic illness usually are started at the lower end of the range prescribed for adults.

Poor tolerance of the adverse effects of the antipsychotic drugs often Limits the dose in elderly patients. One should proceed cautiously, using small, divided doses of agents with moderate or high potency, with the expectation that elderly patients will require doses that are one-half or less of those needed for young adults. The potential risk of stroke associated with risperidone and olanza-pine in elderly patients should be considered.

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