Newer Antipsychotics Play an Important Role in the Management of Late-Onset Schizophrenia

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Selecting Drug Therapy a Challenge

Pharmacological treatment of schizophrenia in older adults presents some interesting challenges for prescribers because of physiological changes associated with aging.[4] Antipsychotics are typically metabolised by cytochrome P450 (CYP) isoenzymes in the liver. For example, quetiapine is primarily metabolised by the isoenzyme CYP3A4.[5] Clearance of drugs metabolised by CYP3A4 appears to decline with age. Thus, plasma concentrations of quetiapine may be elevated in older patients, placing them at risk for adverse effects due to increased 1-adrenoceptor blockade.[6] In addition, CYP3A4 activity may be induced by other drugs such as carbamazepine or barbiturates, possibly leading to plasma quetiapine concentrations that are lower than expected.[6]

Elderly patients are at increased risk for adverse effects from antipsychotic agents that block dopaminergic, 1-adrenergic, muscarinic or histaminergic receptors (see table 1). Traditional antipsychotics such as haloperidol are effective in managing delusions and hallucinations, but elderly patients are more prone to develop adverse effects of dopamine receptor blockade, including extra-pyramidal symptoms (EPS) such as parkinsonism and tardive dyskinesia. Older patients also appear to be at particular risk of developing urinary incontinence or being injured from a fall.[6]

Drug interactions are also a concern in the elderly. Co-administration of an antipsychotic that blocks muscarinic receptors (e.g. chlorpromazine, thioridazine) with either benzatropine† or procyclidine (used to treat EPS) places the elderly patient at particular risk for anticholinergic adverse effects such as confusion, delirium, tachycardia and falls (see table 1). The newer antipsychotics may cause orthostatic hypotension due to 1-adrenergic blockade (e.g. clozapine, quetiapine; also, olanzapine and risperidone with rapid dose escalation),[10] and caution is warranted when these agents are used in conjunction with antihypertensives in elderly patients.[7] Of particular concern may be the prazosin and terazosin which are commonly used in the elderly. Clinically relevant drug interactions with the atypical antipsychotics have been reviewed in-depth elsewhere.[7,11]

† Benzatropine is not available in Spain; quetiapine is not available in Denmark and France; sertindole has been withdrawn from use in those countries where it was formerly available; ziprasidone is still undergoing clinical development and has not yet been launched; zotepine is available only in Austria, Germany, Japan, South Korea and the UK.

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