Archives ofDisease in Childhood 1991; 66: 91-92 91 Arch Dis Child: first published as 10.1136/adc.66.1.91 on 1 January 1991. Downloaded from Neuroleptic malignant syndrome

Neuroleptic malignant syndrome is one of a number of com- acting drugs such as bromocryptine and curare. Laboratory plications of treatment with neuroleptic medication. While investigation often demonstrates raised creatine phosphoki- common side effects include sedation, irritability, and nase and serum potassium concentrations indicative of apathy, the most worrying disorders are the extrapyramidal skeletal muscle necrosis, although absence of positive labor- dystonic reactions. These reactions may broadly be classi- atory indices is compatible with the diagnosis, as these are fied as acute, late onset, and withdrawal emergent.' secondary or non-specific.6 There are two common acute reactions: parkinsonism and Neuroleptic malignant syndrome occurs in 05-1% of akathisia. Parkinsonism is produced by neuroleptic action patients on antipsychotic treatment, can strike at any age, on nigrostriatal dopamine receptors with characteristic and can be rapidly fatal.7 Such reactions have been reported involuntary tremor, skeletal muscle rigidity, and bradykine- as being commoner in infants, particularly with associated sia. Features are similar to those of Parkinson's disease, exhaustion, dehydration, or fever.8 Brain damaged indi- where depletion of pigmented cells in the substantia nigra viduals are thought to be more susceptible to the results in reduced dopaminergic activity, and imbalance syndrome.9 Anticholinergics are of little use.6 The syn- between dopaminergic and cholinergic neuronal systems. drome's development is unrelated to dosage or duration of Benztropine, and to a lesser extent benzhexol and orphenad- medication.7 Piperazine and butyrophenone are major tran- rine, inhibit neuronal reuptake of dopamine and block cho- quillisers that are particularly associated with the neurolep- linergic muscarinic receptors, thereby alleviating these par- tic malignant syndrome in childhood, although any anti- kinsonian symptoms. psychotic medication may precipitate the condition.7 Akathisia is the other common and troublesome acute Symptoms of neuroleptic malignant syndrome may sponta- extrapyramidal side effect. It consists of a subjective sensa- neously remit despite continued neuroleptic medication, tion of overwhelming restlessness that frequently manifests with later fatal recurrence.'0 It is particularly important to as repeated pacing about.2 differentiate between commoner extrapyramidal side The main late onset reaction to neuroleptic medication, effects, which characteristically respond to anticholinergic tardive dyskinesia, consists of rhythmic spontaneous move- medication, and neuroleptic malignant syndrome which ments of mouth and tongue, occasionally with choreiform may be worsened by antiparkinsonian agents but is helped

movements in the limbs. It is irreversible once established. by dopamine-2 agonists like bromocriptine. http://adc.bmj.com/ Risk of this complication is related to the patient's age, Treatment consists of stopping medication, rehydration, duration of treatment and dose, presence of brain damage, measures to reduce fever, adequate monitoring, and support and the chronic use ofantiparkinsonian drugs. The mechan- of cardiovascular, respiratory, renal and other vital func- ism is not fully understood, but may be due to dopaminergic tions, and specific antidote medications-for example, dan- hypersensitivity in the nigrostriatal system with relative trolene or bromocriptine." reduction in cholinergic functioning. Medication should be Successful simultaneous administration of the neuroleptic stopped if possible. Increased dosage will decrease dopami- and bromocriptine has been undertaken, thereby circum- nergic activity but is more harmful in the long term.3 venting the 'catch 22' situation of an individual with inca- on September 27, 2021 by guest. Protected copyright. Withdrawal emergent symptoms are adverse drug reac- pacitating psychosis as well as neuroleptic malignant tions which manifest only when medication has been with- syndrome. 12 drawn. Clinical presentation is characterised by involuntary movements and ataxia that may only remit once medication has been reintroduced.4 Conclusion Clinicians must be alert to the possibility of rare but serious side effects to neuroleptic medication in childhood and ado- Neuroleptic malignant syndrome lescence. Certain factors, including the individual's age and The most serious of the adverse reactions to neuroleptic coexisting brain damage, may predispose to the conditions. medication is the neuroleptic malignant syndrome. This Clinical presentation is similar to adulthood, but may more comprises an idiosyncratic reaction to the neuroleptic recog- readily be misattributed to non-organic or other physical nised by its characteristic clinical features of altered sensor- causes. ium, muscular rigidity, hyperpyrexia of unknown origin, Early accurate diagnosis is essential in order to ensure and autonomic dysfunction. The extreme peripheral appropriate treatment and the individual's physical safety. muscle spasm had once been considered sufficient to generate the dramatic rise in body temperature. This view JEREMY TURK was supported by in vitro muscle biopsy studies and benefi- BRYAN LASK cial effects of dantrolene. However it is now thought more Department of Psychological Medicine, Hospital for Sick Children, likely that, at least in the early stages, the hyperpyrexia has a Great Ormond Street, central origin arising from sudden disturbance of dopa- London WCIN 3J7H minergic pathways within hypothalamic thermoregulatory centres. In support of this view is work demonstrating pro- Dr Turk is currently funded as a Wellcome Research Training Fellow longed hyperthermia following phenothiazine injection into in the department of child psychiatry, Institute of Child Health, animal rostral hypothalamus, and the usefulness of centrally London. 92 Turk, Lask

1 Campbell M, Green WH, Deutsch SI. Child and adolescent psychopharmaco- 7 Knight ME, Roberts RJ. Phenothiazine and butyrophenone intoxication in logy. London: Sage Publications, 1985. children. Pediatr Clin North Am 1986;33:299-309. 2 Kolb LC. Pharmacological therapy. Modern clinicalpsychiatry. London: Saun- 8 Corless JD, Buchanan DS. Phenothiazine intoxication in children. JAMA Arch Dis Child: first published as 10.1136/adc.66.1.91 on 1 January 1991. Downloaded from ders, 1977:829-54. 1%5;194:565-7. 3 Bird J, Harrison G. Drug therapy. Examination notes in psychiatry. Bristol: 9 Diamond JM, Hayes DD. A case of neuroleptic malignant syndrome in a Wright, 1984:209-31. mentally retarded adolescent. J Adolesc Health Care 1986;7:419-422. 4 Polizos P, Engelhardt DM, Hoffman SP, Waizer J. Neurological conse- 10 McCarthy A, Bourke S, Fahy J, Binchy I, Fitzgerald MX. Fatal recurrence of quences ofpsychotropic drug withdrawal in schizophrenic children. Jowunal neuroleptic malignant syndrome. Br J Psychiatry 1988;152:558-9. of Autism and Childhood Schizophrenia 1973;3:247-53. 11 Granato JE, Stern BJ, Ringel A, et al. Neuroleptic malignant syndrome: suc- 5 Caroff SN. The neuroleptic malignant syndrome. J Clin Psychiaty 1980;41: cesful treaunent with dantrolene and bromocryptine. Ann Neurol 1983;14: 79-83. 89-90. 6 Abbott RJ, Loizou LA. Neuroleptic malignant syndrome. Br i Psychiatry 12 Goldwasser HG, Hooper JF, Spears NM. Concomitant treatment ofneurolep- 1986;148:47-51. tic malignant syndrome and psychosis. Br I Psychiatry 1989;154:102-4. http://adc.bmj.com/ on September 27, 2021 by guest. Protected copyright.