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The antipsychotics are used to treat all forms of the schizophrenias as well as psychotic ideation in organic brain psychoses, delirium and dementia, drug-induced psychoses, psychotic depression, and mania They are also effective in Tourette s disorder They quickly lower the arousal (activity) level and, perhaps indirectly, gradually improve socialization and thinking The improvement rate is about 80% Patients whose behavioral symptoms worsen with use of antipsychotic drugs may have an undiagnosed organic condition such as anticholinergic toxicity Symptoms that are ameliorated by these drugs include hyperactivity, hostility, aggression, delusions, hallucinations, irritability, and poor sleep Individuals with acute psychosis and good premorbid function respond quite well The most common cause of failure in the treatment of acute psychosis is inadequate dosage, and the most common cause of relapse is noncompliance Although typical antipsychotics are efficacious in the treatment of so-called positive symptoms of schizophrenia such as hallucinations and delusions, atypical antipsychotics are thought to have efficacy in reducing both positive symptoms and negative symptoms such as withdrawal, psychomotor retardation, and poor interpersonal relationships Antidepressant drugs may be used in conjunction with neuroleptics if significant depression is present Resistant cases may require concomitant use of lithium, carbamazepine, or valproic acid The addition of a benzodiazepine drug to the neuroleptic regimen may prove helpful in treating the agitated or catatonic psychotic patient who has not responded to neuroleptics alone lorazepam, 1 2 mg orally, can produce a rapid resolution of catatonic symptoms and may allow maintenance with a lower neuroleptic dose Electroconvulsive therapy (ECT) has also been effective in treating catatonia

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The dosage range is quite broad For example, risperidone, 05 1 mg orally at bedtime, may be sufficient for the elderly person with mild dementia, whereas up to 6 mg/d may be used in a young patient with acute schizophrenia For quick response, an atypical antipsychotic may be started in combination with a benzodiazepine (eg, risperidone oral solution, 2 mg, or olanzapine, 10 mg orally, and lorazepam, 2 mg orally, every 2 4 hours as needed) In an acutely distressed, psychotic patient one might use haloperidol, 10 mg intramuscularly, which is absorbed rapidly and achieves an initial tenfold plasma level advantage over equal oral doses Psychomotor agitation, racing thoughts, and general arousal are quickly

For both typical and atypical neuroleptic agents, a range of side effects has been reported The most common anticho-

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linergic side effects include dry mouth (which can lead to ingestion of caloric liquids and weight gain or hyponatremia), blurred near vision, urinary retention (particularly in elderly men with enlarged prostates), delayed gastric emptying, esophageal reflux, ileus, delirium, and precipitation of acute glaucoma in patients with narrow anterior chamber angles Other autonomic effects include orthostatic hypotension and sexual dysfunction problems in achieving erection, ejaculation (including retrograde ejaculation), and orgasm in men (approximately 50% of cases) and women (approximately 30%) Delay in achieving orgasm is often a factor in medication noncompliance Electrocardiographic changes occur frequently, but clinically significant arrhythmias are much less common Elderly patients and those with preexisting cardiac disease are at greater risk The most frequently seen electrocardiographic changes include diminution of the T wave amplitude, appearance of prominent U waves, depression of the ST segment, and prolongation of the QT interval Thioridazine has been given an FDA warning for dose-related QTc delay and risk of fatal cardiac arrhythmias As noted above, ziprasidone can produce QTc prolongation An ECG prior to treatment in some patients may be indicated In some critical care patients, torsades de pointes has been associated with the use of high-dose intravenous haloperidol (usually > 30 mg/24 h) Associations have been suggested between the atypical neuroleptics and new-onset diabetes, hyperlipidemia, QTc prolongation, and weight gain (Table 25 6) The FDA has particularly noted the risk of hyperglycemia and new-onset diabetes in this class of medication that is not related to weight gain Monitoring of weight, fasting blood sugar and lipids prior to initiation of treatment and at regular intervals thereafter is an important part of medication monitoring Neuroleptic medications in general may have metabolic and endocrine effects, including weight gain, hyperglycemia, infrequent temperature irregularities (particularly in hot weather), and water intoxication, that may be due to inappropriate ADH secretion Lactation and menstrual irregularities are common (antipsychotic drugs should be avoided, if possible, in breast cancer patients because of potential trophic effects of elevated prolactin levels on the breast) Both antipsychotic and antidepressant drugs inhibit sperm motility Bone marrow depression and cholestatic jaundice occur rarely; these are hypersensitivity reactions, and they usually appear in.

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