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Table 58-1 Neurologic side effects of the neuroleptic-antipsychotic drugs
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PERIOD OF REACTION CLINICAL FEATURES MAXIMUM RISK PROPOSED MECHANISM TREATMENT
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Acute dystonias
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Spasm of muscles of tongue, face, neck, back Bradykinesia, rigidity, masked facies, shuf ing gait, variable tremor Perioral tremor, exed posture; usually reversible Motor restlessness with anxiety or agitation
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1 5 days
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Dopamine excess Acetylcholine excess
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Parkinson syndrome
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5 30 days (may persist)
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Dopamine blockade
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Antiparkinson agents are diagnostic and curative (IM or IV, then PO) Antiparkinson agents (PO); dopamine agonists risky Antiparkinson agents: reduce dose of neuroleptic Reduce dose or change drug; low doses of propranolola; antiparkinson agents or benzodiazepines may help Stop neuroleptic; antiparkinson agents usually fail; bromocriptine and dantrolene often help; expert supportive care crucial, ICU best Prevention best; treatment unsatisfactory; slow, spontaneous remission
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Rabbit syndrome
Months or years
Unknown
Akathisia
1 60 days (commonly persists)
Adrenergic excess
Neuroleptic malignant syndrome
Catatonia, stupor, fever, unstable pulse and blood pressure, myoglobinemia, elevated CPKb; can be fatal Oral-facial dyskinesia, choreoathetosis, often slowly reversible, rarely progressive
Weeks
Unknown
Tardive dyskinesia
6 24 months (worse on withdrawal)
Dopamine excess
IM, intramuscularly; IV, intravenously; PO, per os (orally); ICU, intensive care unit a There may be an increased risk of hypotension on interaction between high doses of propranolol and some antipsychotic agents; clonidine may also be effective at doses of 02 to 08 mg/day but carries a high risk of hypotension, and tolerance (loss of ef cacy) may develop b CPK, creatine-phosphokinase in serum, released from hypertonic muscle Adapted from Baldessarini RJ, Cole JO: Chemotherapy, in Nicholi AM Jr (ed): The Harvard Guide to Modern Psychiatry, 2nd ed, Cambridge, MA, Harvard University Press, 1988, with permission
PART 6
PSYCHIATRIC DISORDERS
Table 58-2 Newer antipsychotic drugs with limited extrapyramidal side effects
TARGET OR BRAND MEDICATION NAME INITIAL DOSE MAXIMAL DOSE POTENTIAL SIDE EFFECTSa
Olanzapine Quetiapine Clozapine Risperidone Ziprasidone Aripiprazole Amisolpride
Zyprexa Seroquel Clozaril Risperidol Geodon Abilify Solian
5 mg 25 mg bid 125 mg bid 1 mg bid 20 mg 5 mg 100 mg
10 mg 300 mg 300 mg 3 mg bid 160 mg 30 mg 1000 mg
Orthostatic hypotension, transaminase elevation, hyperprolactinemia Orthostatic hypotension, cataracts, transaminase elevation Agranulocytosis, transient fever, anticholinergic activity, hyperglycemia Orthostatic hypotension Less weight gain than others in this class Prolongation of QT interval Less weight gain than others in this class Prolongation of QT interval
All have the potential to cause tardive dyskinesias and neuroleptic malignant syndrome (see Table 58-1), but these complications are less frequent than with phenothiazines and haloperidol Weight gain is common with this class of drugs
infrequent Common to all the drugs in the class is variable weight gain With long-term treatment this may accumulate to 20 percent of the patient s original weight Hypercholesterolemia and diabetes then often emerge and may require additional treatment In a few cases the newer generation antipsychotics have induced some obsessive-compulsive symptoms Finally, it might be commented that according to Leucht and colleagues who performed a meta-analysis of extrapyramidal symptoms and various drugs, that low potency rst-generation antipsychotics (excluding haloperidol) may have comparable complications to the new generation of drugs when dose-equivalent amounts are given Not all clinicians agree with this perspective The optimal daily dose for treatment of an acute psychotic episode is in the range of 10 to 20 mg daily of haloperidol or the equivalent amount (400 to 800 mg) of a phenothiazine such as chlorpromazine or escalating doses of the newer agents as listed in Table 58-2 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 Longacting piperazine phenothiazines, given subcutaneously every week or two, are used in patients who are unable to take oral medication or refuse to do so Extrapyramidal side effects are troublesome and tardive dyskinesias may be even more problematic (page 94) 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, or, in exceptional instances, where there has been no response to medication 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 eg, diphenhydramine (Benadryl), 25 mg tid and the anticholinergic drugs used in the treatment of Parkinson disease eg, benztropine mesylate (Cogentin), 05 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, may themselves induce a toxic confusional state If it becomes necessary to treat the extrapyramidal side effects, it is usu-
ally possible to eliminate the anticholinergic drugs after 2 to 3 months without a return of 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 tardive dyskinesias have been discussed on pages 94 95 Supportive psychotherapy (repeated explanation, reassurance, encouragement) is of course necessary, as in any prolonged illness, and the family needs the same type of help The physician should be understanding and sympathetic but also rm and professional The general purpose of psychotherapy is to help the patient get a grasp on reality and to strengthen his self-esteem and psychologic defenses Psychoanalytic therapy has little to offer as a primary mode of treatment Outcome With modern drug therapy and supportive psychiatric management, fully 60 percent of schizophrenic patients will recover suf ciently to return to their homes and become socially adjusted to a varying degree (about half of this group can engage in some occupation) About 30 percent remain helpless and severely handicapped and 10 percent remain hospitalized
DELUSIONAL DISORDER (PARANOIA)
The term paranoid ( para beside, nous mind) literally means a mind beside itself It designates patients who show xed suspicions, persecutory delusions, dominant ideas or grandiose trends logically elaborated and with due regard for reality once the false interpretation or premise has been accepted Further characteristics that differentiate pure paranoia from typical schizophrenia are formally correct conduct, adequate emotional reactions, and coherence of the train of thought (Rosanoff) In other words, in pure paranoia (delusional disorder in DSM-IV), there is supposed to be no mental defect other than the delusional system no dementia, hallucinations, or emotional disturbance In past years, a large group of the mentally ill was classi ed as paranoid But with advancing knowledge of mental illness, fewer and fewer have been left in this category The trouble that psychiatrists have taken to couch this de nition in negatives implies that paranoia is frequently a feature of
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