Neuroleptic drugs dystonic reaction

Extrapyramidal symptoms (EPS) Dystonic reactions develop primarily with the use of traditional antipsychotics. EPS has occurred during the administration of haloperidol and pimozide frequently, often during the first few days of treatment. Neuroleptic malignant syndrome (NMS) A potentially fatal symptom complex sometimes referred to as NMS has been reported in association with administration of antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, rhabdomyolysis, and acute renal failure. 

EPS include acute dystonic reactions, parkinsonian syndrome, akathisia, tardive dyskinesia, and neuroleptic mahgnant syndrome. Although high-potency conventional antipsychotics are more hkely than low-potency conventional antipsychotics to cause EPS, all first-generation antipsychotic drugs are equally hkely to cause tardive dyskinesia. The atypical antipsychotics cause suhstantially fewer EPS, which is one reason that they are recommended as first-line agents. 

Antipsychotic drugs include the older phenothiazines and butyrophenones, as well as newer atypical drugs. All of these can cause CNS depression, seizures, and hypotension. Some can cause QT prolongation. The potent dopamine D2 blockers are also associated with parkinsonian-like movement disorders (dystonic reactions) and in rare cases with the neuroleptic malignant syndrome, characterized by "lead-pipe" rigidity, hyperthermia, and autonomic instability (see Chapter 29 Antipsychotic Agents Lithium). 

There were no changes in lithium pharmacokinetics when risperidone was substituted open-label for another neuroleptic drug in 13 patients (634). On the other hand, an 81-year-old man had an acute dystonic reaction 4 days after lithium was added to a regimen of risperidone, valproic acid, and benzatropine (635). 

The CYP2D6 genotype is not a determinant of susceptibility to acute dystonic reactions, but may be a contributory factor in neuroleptic drug-induced movement disorders, including tardive dyskinesia (176). 

These include postnatal depression and acute dystonic reactions (which may interfere with normal delivery). Hypotonia can persist for months (569) and may respond to diphenhydramine 5 mg/kg/day. Severe rhinorrhea and respiratory distress in a neonate exposed to fluphenazine hydrochloride prenatally has been reported (484). Neonatal jaundice, hyperbilirubinemia, and melanin deposits in the eyes have occurred when neuroleptic drugs were given during the last trimester or longer during pregnancy. 

Neuroleptic drug poisoning in 86 children has been retrospectively studied in two pediatric hospitals in the USA (1987-1997), with about 9000 and 11 000 annual admissions (617). Most (70%) occurred in children under 6 years of age over two-thirds of the cases (78%) were unintentional. The owner of the medication, when identified (85% of cases), was the grandmother (22%), another family member (21%), the patient (13%), or a non-family caregiver (8%) the most common places where ingestion occurred were the patient s home (64%) or a relative s home (22%). There was a depressed level of consciousness in 91% and a dystonic reaction in 51% there were no deaths. 

In a retrospective study of 116 patients taking neuroleptic drugs, 42% of cocaine users versus 14% of non-users developed dystonic reactions (640). This suggests that the use of cocaine may be a major risk factor for acute dystonic reactions secondary to the use of neuroleptic drugs. 

All basic and advanced life-support measures should be implemented. Gastric decontamination should be performed. Butyrophenones are readily absorbed by activated charcoal. Aggressive supportive care should be instituted. Dystonic reactions respond well to intravenous benztropine or diphenhydramine. Oral therapy with diphenhydramine or benztropine should be continued for 2 days to prevent recurrence of the dystonic reaction. For patients suffering from neuroleptic malignant syndrome, a potentially fatal condition associated with the administration of antipsychotic drugs, dantrolene sodium, and bromocriptine have been used in conjunction with cooling and other supportive measures. Arrhythmias should be treated with lidocaine or phenytoin. Diazepam is the drug of choice for seizures phenytoin is used to prevent recurrence. Hemodialysis and hemoperfu-sion have not been shown to be effective. 

II. Indications. Benztropine is an alternative in adults to diphenhydramine (the drug of choice for children) for the treatment of acute dystonic reactions associated with neuroleptics or metoclopramide. Note It is not effective for tardive dyskinesia or neuroleptic malignant syndrome (see p 22). 

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