Approach to pharmacological management of agitation, aggression or psychosis of dementia

Behavioural and psychological symptoms of dementia are often temporary and can usually be prevented and treated with nonpharmacological management. Communication abilities often decline as dementia progresses, and changed or challenging behaviour is often caused by unmet needs unlikely to be helped by drugs (eg need to toilet, distress from pain or loneliness, frustration). If behaviour is adequately assessed and its cause is promptly addressed, drugs are unnecessary for most patients with dementia who experience symptoms of agitation, aggression or psychosis.

Drugs used to treat agitation, aggression or psychosis of dementia appear to be less effective than nonpharmacological management. These limitations must be balanced against the serious harms associated with psychotropic use in people with dementia. Only consider using a drug to treat agitation, aggression or psychosis of dementia if nonpharmacological management has not alleviated symptoms and the patient is distressed or considered a threat to themselves or others. It is preferable to seek expert advice (eg from a specialist or a specialist centre¹) before starting a drug.

If a drug is used for agitation, aggression or psychosis of dementia:

• use the lowest effective dose for the shortest period of time
• avoid polypharmacy
• use it in combination with nonpharmacological management.

If a drug appears to be ineffective, reassess behavioural and psychological symptoms and consider seeking expert advice—do not continue to trial drugs to manage the behaviour.

The evidence base to guide drug use for behavioural symptoms of dementia is mainly from common dementia subtypes (Alzheimer disease, mixed Alzheimer disease and vascular dementia, and to a lesser extent, dementia with Lewy bodies and dementia in Parkinson disease). Use caution before applying the advice below to other dementias (eg frontotemporal dementia).

For advice on neuropsychiatric symptoms associated with Parkinson disease, see here.

Patients who have dementia with Lewy bodies can experience severe sensitivity reactions and worsening of motor symptoms in response to antipsychotics. The drugs of choice for agitation, aggression or psychosis in these patients are rivastigmine or donepezil. There is insufficient evidence to guide antipsychotic therapy in dementia with Lewy bodies—use antipsychotic therapy with caution. If antipsychotic therapy is used, low-dose quetiapine is preferred because it may be less likely to cause the aforementioned adverse effects.

If an antipsychotic cannot be used or has been ineffective, a selective serotonin reuptake inhibitor (SSRI) antidepressant may be considered for agitation or aggression (not psychosis) of dementia. However, the evidence base to support SSRIs for agitation and aggression of dementia is significantly weaker than for antipsychotics. Although antidepressants appear to be safer than antipsychotics (they are associated with significantly lower mortality rates), they are associated with other adverse effects including hyponatraemia and falls. Of all the SSRIs, citalopram has the strongest evidence for agitation and aggression of dementia—if it is used, monitor for adverse effects and review response to treatment at 2 to 3 months and consider stopping if effectiveness is limited.

Avoid using benzodiazepines to treat agitation, aggression and psychosis of dementia—there is limited evidence of benefit and they are associated with serious adverse effects including cognitive decline, urinary incontinence, falls, hip fractures and dependence². Benzodiazepine use has also been associated with increased all-cause mortality. If an antipsychotic or an antidepressant cannot be used, a benzodiazepine with a (comparatively) short half-life and no active metabolites (eg oxazepam) may be considered for agitation, aggression or psychosis of dementia for a maximum of 2 weeks—closely monitor the patient for adverse effects.

Other drugs have insufficient evidence to recommend their use for agitation, aggression or psychosis of dementia.

Do not use sodium valproate to treat agitation, aggression or psychosis of dementia. Limited evidence suggests it does not improve these symptoms and is associated with a higher rate of adverse effects, some of which are serious—a Cochrane review concluded that further research on sodium valproate for agitation, aggression or psychosis of dementia may not be justified³⁴ .

If the patient poses an immediate threat to themselves or others and immediate tranquilisation is required with a parenterally administered drug, see Pharmacological management for acute behavioural disturbance in older people or Pharmacological management for acute behavioural disturbance in adults for advice.