3 Clinical psychopharmacology3.4 Therapeutics
3.4.1.2.4 Age
2 min read1 figure
Written by Resident Doctor Committee · Published
Principles
Age changes body composition, protein binding, liver enzymes and renal function, so it alters distribution, free drug and clearance; weight alone cannot predict exposure.
Reduced physiological reserve means older people develop delirium or hypotension at drug levels younger adults tolerate.
Doses are based on physiology and frailty, not chronological age.
Children and older people are underrepresented in trials, so much prescribing is off-label.
Children and adolescents
Growth, puberty and clearance change at different rates, and some children need higher doses per kilogram than adults.
Adverse effects and placebo response can differ from adults, so adult data do not transfer.
Fluoxetine is the first antidepressant NICE recommends for moderate to severe childhood depression, alongside psychological therapy; its UK licence starts at age 8.
Suicidality needs close monitoring early in treatment and in anyone under 25.
Stimulants need growth monitoring on age- and sex-referenced charts, and antipsychotics need weight, metabolic and prolactin monitoring.
Working age and reproductive life
Enzyme inducers can reduce hormonal contraceptive effectiveness, and hyperprolactinaemia can impair fertility.
Under the valproate Pregnancy Prevention Programme, starting valproate under 55 generally needs two specialists to document that no effective or tolerated alternative exists, or that reproductive risks do not apply.
Older people
Change with age | Consequence |
|---|---|
Renal function often declines | Lithium, gabapentinoids, amisulpride and metabolites accumulate |
Less muscle mass and creatinine production | A normal-looking creatinine can hide renal impairment |
Less body water, more fat | Lithium concentrations rise; diazepam distributes more widely and acts longer |
Lower hepatic mass and blood flow | High-extraction drugs are cleared less and have higher bioavailability |
Oxidation may decline; glucuronidation is relatively preserved | Lorazepam or oxazepam is preferred to diazepam when a benzodiazepine is needed |
Low albumin in frailty or illness | Highly bound drugs have a higher free fraction |
Adverse effects in later life
Effect | Causes and features |
|---|---|
Falls | Sedation, hypotension, blurred vision, parkinsonism, ataxia, nocturia; hip fracture carries roughly 20 to 30% one-year mortality |
Antimuscarinic burden | Cognitive impairment, delirium, urinary retention, constipation, angle closure; cumulative exposure is associated with dementia |
Hyponatraemia | SSRIs, carbamazepine, diuretics; presents with confusion, falls or seizures |
Cardiac | Bradycardia, conduction disease, QT prolongation; presentations may be atypical |
Falls risk is assessed with gait, falls history and lying and standing blood pressure.
People at risk of hyponatraemia need a baseline and early repeat sodium.
Dosing and deprescribing
Start low and titrate cautiously to an effective, tolerated dose.
Age alone should not block effective treatment, including ECT, because severe depression risks suicide, malnutrition and immobility.
Deprescribing means reducing or stopping drugs whose harms or lack of indication outweigh benefit, usually one at a time with a planned taper.