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drugs butyrophenones; lithium; phenothiazines; pimozide; promethazine; thioxanthines dopamine agonist withdrawal pathophysiology probably caused by heat generated by muscle rigidity tremor heat production amplified by sarcolemmal depolarization muscle contraction onset days to weeks after initiation of drug encephalopathy clinical muscle rigidity rhabdomyolysis cns extrapyramidal signs; altered consciousness; seizures other neural dysarthria dysphagia; oculogyric crises systemic autonomic instability hyperthermia 38 c cardiac blood pressure lability; tachycardia incontinence tachypnea hyperhidrosis disease course resolution in 2 weeks withshort acting drugs 4 weeks with depo drugs associations often not familial age any age; most often young adults precipitating factors psychoactive drugs within 1 week for short-acting 4 weeks for long-acting lithium; haloperidol; phenothiazines; or especially combinations high doses of neuroleptics cytochrome p4502d mutation allele cyp2d6j homozygous poor hepatic metabolism of drugs associated with nms general dehydration; exhaustion; organic brain damage lab serum ck transient increase in 2 3 levels usually 2,000 to 15,000 leukocytosis hyponatremia some patients csf normal treatment medication bromocriptine; dantrolene; amantadine cooling to 38 c supportive care hydration; reduce fever discontinue predispoasing drugs.