BNF for Children 2011-2012

BNFC 2011–2012 4.2.1 Antipsychotic drugs 173Renal impairment Start with small doses of antipsychoticdrugs in severe renal impairment because ofincreased cerebral sensitivity. Pericyazine should beavoided in renal impairment.Pregnancy Extrapyramidal effects have been reportedoccasionally in the neonate when antipsychotic drugsare taken during the third trimester of pregnancy.Breast-feeding There is limited information availableon the short- and long-term effects of antipsychotics onthe breast-fed infant. Animal studies indicate possibleadverse effects of antipsychotic medicines on the developingnervous system. Treatment with antipsychoticswhilst breast-feeding should be avoided unless absolutelynecessary.Side-effects Extrapyramidal symptoms are the mosttroublesome. They occur most frequently with thepiperazine phenothiazines (such as perphenazine, prochlorperazine,and trifluoperazine), the butyrophenones(such as haloperidol), and the depot preparations. Theyare easy to recognise but cannot be predicted accuratelybecause they depend on the dose, the type of drug, andon individual susceptibility.Extrapyramidal symptoms consist of:. parkinsonian symptoms (including tremor), whichmay appear gradually (but less commonly than inadults);. dystonia (abnormal face and body movements) anddyskinesia, which appear after only a few doses;. akathisia (restlessness), which characteristicallyoccurs after large initial doses and may resemblean exacerbation of the condition being treated; and. tardive dyskinesia (rhythmic, involuntary movementsof tongue, face, and jaw), which usuallydevelops on long-term therapy or with high dosage,but it may develop on short-term treatment withlow doses—short-lived tardive dyskinesia mayoccur after withdrawal of the drug.Parkinsonian symptoms remit if the drug is withdrawnand may be suppressed by the administration of antimuscarinicdrugs (section 4.9.2). However, routineadministration of such drugs is not justified becausenot all children are affected and because they mayunmask or worsen tardive dyskinesia.Tardive dyskinesia is of particular concern because itmay be irreversible on withdrawing therapy and treatmentis usually ineffective. In children, tardive dyskinesiais more likely to occur when the antipsychoticis withdrawn. However, some manufacturers suggestthat drug withdrawal at the earliest signs of tardivedyskinesia (fine vermicular movements of the tongue)may halt its full development. Tardive dyskinesia mayoccur and treatment must be carefully and regularlyreviewed.Hypotension and interference with temperature regulationare dose-related side-effects.Neuroleptic malignant syndrome (hyperthermia, fluctuatinglevel of consciousness, muscle rigidity, andautonomic dysfunction with pallor, tachycardia, labileblood pressure, sweating, and urinary incontinence) is arare but potentially fatal side-effect of some antipsychoticdrugs. Discontinuation of the antipsychotic isessential because there is no proven effective treatment,but cooling, bromocriptine, and dantrolene have beenused. The syndrome, which usually lasts for 5–7 daysafter drug discontinuation, may be unduly prolonged ifdepot preparations have been used.Other side-effects include: drowsiness; apathy; agitation,excitement and insomnia; convulsions; dizziness; headache;confusion; gastro-intestinal disturbances; nasalcongestion; antimuscarinic symptoms (such as drymouth, constipation, difficulty with micturition, andblurred vision; very rarely angle-closure glaucoma);cardiovascular symptoms (such as hypotension, tachycardia,and arrhythmias); ECG changes (cases of suddendeath have occurred); venous thromboembolism; endocrineeffects such as menstrual disturbances, galactorrhoea,gynaecomastia, impotence, and weight gain;blood dyscrasias (such as agranulocytosis and leucopenia),photosensitisation, contact sensitisation andrashes, and jaundice (including cholestatic); cornealand lens opacities, and purplish pigmentation of theskin, cornea, conjunctiva, and retina.Overdosage: for poisoning with phenothiazines andrelated compounds, see Emergency Treatment of Poisoning,p. 31.Classification of antipsychotics The phenothiazinederivatives can be divided into 3 main groups.Group 1: chlorpromazine, levomepromazine(methotrimeprazine), and promazine, generallycharacterised by pronounced sedative effects andmoderate antimuscarinic and extrapyramidal sideeffects.Group 2: pericyazine and pipotiazine, generallycharacterised by moderate sedative effects, markedantimuscarinic effects, but fewer extrapyramidalside-effects than groups 1 or 3.Group 3: perphenazine, prochlorperazine, and trifluoperazine,generally characterised by fewer sedativeeffects, fewer antimuscarinic effects, but morepronounced extrapyramidal side-effects thangroups 1 and 2.Drugs of other chemical groups resemble the phenothiazinesof group 3 in their clinical properties. Theyinclude the butyrophenones (e.g. haloperidol);diphenylbutylpiperidines (e.g. pimozide); thioxanthenes(flupentixol and zuclopenthixol); and thesubstituted benzamides (e.g. sulpiride).For details of the newer antipsychotic drugs amisulpride,aripiprazole, clozapine, olanzapine, quetiapine,and risperidone, see under Atypical AntipsychoticDrugs, p. 177.Choice As indicated above, the various drugs differsomewhat in predominant actions and side-effects.Selection is influenced by the degree of sedationrequired and the child’s susceptibility to extrapyramidalside-effects. However, the differences between antipsychoticdrugs are less important than the great variabilityin response; moreover, tolerance to secondary effectssuch as sedation usually develops. The atypical antipsychoticdrugs may be appropriate if extrapyramidal sideeffectsare a particular concern (see under AtypicalAntipsychotic Drugs, p. 177). Clozapine is used forschizophrenia when other antipsychotic drugs are ineffectiveor not tolerated.4 Central nervous system