Frailty and medication for mental health

There is no significant evidence that individuals with depression and frailty benefit from antidepressants.¹⁰³ One SR also found no evidence of benefits for people with frailty taking antidepressants (fluoxetine, clomipramine).¹⁰⁴

The evidence is poor regarding benefits and harm, therefore prescribers and people over 65 years with frailty should discuss the use of antidepressants, considering the lowest effective dose and the duration of treatment. Due to poor efficacy, these should be reviewed after two to four weeks to assess the benefits and side effects.¹⁰⁵

Trials of different types of antidepressants were examined in older adults with depression, or with neuropsychiatric symptoms of dementia. They reviewed the benefit in relation to the adverse effects, which include more frequent fatigue, nausea, constipation, dizziness, and diarrhoea, and proposed that a reduction in antidepressants in frail older adults could decrease the risk of polypharmacy and medication side effects.

One SR found significantly fewer deaths among people taking AChEI compared to placebo.¹⁰⁴ People taking AChEI (galantamine, donepezil) suffered significantly more neurological adverse effects (agitation, tremor, confusion, depression, abnormal gait, and dizziness), than people taking placebo. There was little difference in functional status between placebo and AChEI. There was no significant difference in adherence to treatment.

For cognitive function, measured by Severe Impairment Battery (SIB), one trial reported a significant difference, in favour of galantamine over placebo. When Mini Mental State Examination (MMSE) was used to measure cognitive function, another trial reported significant superiority of donepezil compared with placebo at 8,16 and 20 weeks.¹⁰⁴

Therefore, prescribers and people over 65 years with frailty, should discuss the benefits of taking AChEIs, (including cognitive benefits) compared to the risk of adverse GI and neurological effects (e.g. agitation, tremor, confusion, depression, aggression, vertigo, abnormal gait, and dizziness). Stopping established treatment with AChEIs for Alzheimer’s dementia may lead to loss of cognition or function which may not be regained if the medication is restarted, so the risks and benefits of deprescribing should be considered carefully.¹⁰⁶

The efficacy and safety of anticonvulsants (carbamazepine, valproate) was compared with placebo in frail older patients with Alzheimer’s disease and aggressive / agitated behaviour,¹⁰⁴ and the evidence is limited. Prescribers and people over 65 years with frailty (and/or their proxy) should balance the limited benefits of prescribing anticonvulsants against the considerable neurological adverse effects (agitation, tremor, confusion, depression, aggression, vertigo, abnormal gait, dizziness). 

The efficacy and safety of a range of antipsychotics (including risperidone, haloperidol, quetiapine, fluvoxamine) was reviewed in frail older adults with Alzheimer’s Disease and psychotic symptoms.¹⁰⁴ The evidence for effectiveness was limited for improving agitation, anergia and some behavioural and psychological symptoms. Overall, there was little evidence of benefit for a range of outcomes, e.g. cognitive function, treatment of thought disturbance, dementia outcomes, reduction in deaths.

The evidence highlighted that antipsychotics have adverse effects, including a significant worsening in extrapyramidal symptoms. There was some evidence that people with frailty treated with antipsychotics had significantly more neurological adverse events (e.g. somnolence, agitation, abnormal gait, insomnia and convulsions).

Antipsychotics are frequently prescribed to reduce symptoms of stress and distress in people with dementia. However, these drugs have limited benefits, and older patients are particularly vulnerable to their adverse effects. ¹⁰⁷ Antipsychotics are also associated with an adverse cardiovascular profile and an increased risk of metabolic disorders, and these may need additional electrocardiogram (ECG) and biochemistry monitoring. Long-term use is associated with cerebrovascular events and death in people with dementia.³² They should only be used when alternative non-pharmacological measures have failed, and their use should be re-evaluated on a regular basis. Evidence suggests that discontinuation may not cause significant deterioration in symptoms.

The list below sets out the recommendations on reviewing the evidence, and a considered judgment process.

Recommendations when managing frailty and depression or dementia