Medications for BPSD

Health staff, carers, and family should identify and modify environmental, physical and psychosocial factors that may increase the likelihood of the person with dementia experiencing distressing behavioural and psychological symptoms. These factors include:

• unmet needs (e.g., pain, hunger, need to eliminate, lack of privacy, lack of meaningful activities, communication)
• lowered stress threshold (e.g., conflicts or poor communication within the family or between staff, carer stress).

People with dementia who develop behavioural and psychological symptoms should be offered a comprehensive assessment at an early opportunity. This should involve their carers and include;

• level of pain or discomfort
• analysis of the behaviour triggers, frequency, timing and presentation
• assessment of physical and mental health
• whether they are experiencing side effects of medication
• physical environmental and interpersonal factors
• an assessment of carer(s) health and communication style when interacting with the person with dementia
• understanding the behaviour as a form of communication.

Agitation / Depression

• People with dementia who experience agitation should be offered a trial of selective serotonin reuptake inhibitor (SSRI) antidepressants (the strongest evidence for effectiveness exists for citalopram) if non-pharmacological treatments are inappropriate or have failed.
• Review with evaluation of efficacy and consideration of de-prescribing should occur after two months. The need for adherence, time to onset of action and risk of withdrawal effects and possible side effects should be explained at the start of treatment.
• Antidepressant medications with anticholinergic effects (e.g., tricyclic antidepressants) should be avoided because they may adversely affect cognition.

1. Citalopram oral 10 mg once daily, gradually increasing after 2–4 weeks if necessary to a maximum of 20 mg once daily.^[3][4]

Adverse effects

• Rare but significant (<0.1%): prolonged QT interval
• Common (>1%): nausea, diarrhoea, agitation, insomnia, drowsiness, tremor, dry mouth, dizziness, headache, sweating, weakness, anxiety, weight gain or loss, sexual dysfunction, rhinitis, myalgia, rash
• Infrequent (0.1–1%): extrapyramidal reactions (including tardive dyskinesia and dystonia), sedation, confusion, palpitations, tachycardia, hypotension, hyponatraemia (usually occurs early in treatment, may be asymptomatic, and is part of SIADH), abnormal platelet aggregation/haemorrhagic complications (e.g. bruising, nose bleeds, GI, vaginal or intracerebral bleeding), mydriasis
• Rare (<0.1%): elevated liver enzymes, hepatitis, hepatic failure, hyperprolactinaemia, e.g. galactorrhoea, blood dyscrasias, akathisia, paraesthesia, taste disturbance.

Practice points

• This medicine is usually taken in the morning
• Avoid in combination with serotonergic agents that may precipitate Serotonergic Syndrome (neuromuscular excitation, diaphoresis, tachycardia, mydriasis, confusion, agitation)
• When stopping SSRI treatment taper over several weeks to avoid withdrawal effects; reduce the daily dose by half no faster than weekly
• Consider checking sodium concentration at baseline, and then soon after starting treatment, especially if at risk for hyponatraemia, e.g. elderly
• Increased suicidal thoughts and behaviour may occur soon after starting antidepressants and should be monitored accordingly
• Sexual dysfunction is an adverse effect that may affect compliance.

Agitation / Psychosis

• People with Alzheimer’s disease, vascular dementia or mixed dementias with mild- to-moderate behavioural and psychological symptoms of dementia should not usually be prescribed antipsychotic medications due to increased risk of cerebrovascular adverse events and death
• The risk of cerebrovascular adverse effects is highest in those with poorly controlled vascular risk factors (atrial fibrillation, hypertension or diabetes) or a history of previous stroke
• Use of these drugs in patients with dementia should be limited to those with intractable agitation or psychosis that has not responded to psychosocial interventions and who have low or moderate risk of stroke
•  If antipsychotics are used for severe behavioural and psychological symptoms of dementia, atypical or second-generation antipsychotics (e.g. risperidone) with low propensity to cause extrapyramidal side effects should be used.
• Risperidone has the strongest evidence for treating psychosis, while Risperidone and olanzapine have the strongest evidence for treating agitation/aggression, with weaker evidence for aripiprazole.
• Risperidone is the only oral medication approved in Australia for use in behavioural disturbances associated with Alzheimer’s type dementia.
  • Other antipsychotics such as quetiapine, olanzapine or aripiprazole if used for BPSD are off label and should only be considered if risperidone is not tolerated or is not appropriate
  • Olanzapine is the only antipsychotic approved for parenteral (intramuscular) use in Australia for patients with BPSD. It is noted that this medication is intended for patients who are orally non-compliant or in an acute emergency setting.
• The following conditions should also be met:
  • There should be a full discussion with the person with dementia and their carers and family about the possible benefits and risks of treatment; in particular, cerebrovascular risk factors
  • Target symptoms should be identified, quantified and documented
  • The effect of comorbid conditions, such as depression, should be considered
  • The dose should be initially low and titrated upwards if necessary
  • If there is no efficacy observed within a relatively short timeframe (usually two to four weeks), treatment should be discontinued

If pharmacotherapy is considered necessary to control hallucinations, delusions or seriously disturbed behaviour, use:

1. Risperidone 0.25mg PO, BD initially. Increase if needed by 0.25mg every 2 or more days. Maximum dose 2mg daily.^[5][6]

Adverse effects

• Common (>1%): sedation, anxiety, agitation, EPSE (below), orthostatic hypotension, tachycardia, blurred vision, mydriasis, constipation, nausea, dry mouth, urinary retention, sexual adverse effects, weight gain, hyperprolactinaemia
• Infrequent or rare: urticaria, Stevens-Johnson syndrome, SIADH, hyperthermia, hypothermia, neuroleptic malignant syndrome (below), anaemia, thrombocytopenia, neutropenia, agranulocytosis, VTE, stroke, ECG changes (reversible, broadened QT interval), arrhythmias, cardiac arrest, sudden death, hepatic fibrosis, priapism, systemic lupus erythematosus, seizures, increased blood glucose, dysarthria, dysphagia, new-onset or worsening obsessive-compulsive symptoms.
• Extrapyramidal side effects (EPSE): Dystonia, akathisia, parkinsonism, tardive dyskinesia
  • Incidence is dose-related
  • Reduce antipsychotic dose to avoid recurrent EPSE when possible
• Neuroleptic Malignant Syndrome
  • A potentially fatal condition characterised by fever, marked muscle rigidity, altered consciousness and autonomic instability
  • usually progresses rapidly over 24–72 hours

Table 1 - Comparison of antipsychotic agents and common adverse effects.

Practice Points:

• Never use first-generation antipsychotics (e.g. Haloperidol) if dementia with Lewy bodies is suspected, or for patients with Parkinson disease.
• Use low starting doses for all psychotropic drugs in people with dementia and increase slowly as necessary. In the early treatment phase, there should be at least weekly review of the target behaviour or symptoms and close observation for adverse effects
• Pharmacological management goal should be lowest effective dose for the shortest period of time.
• Monitor carefully for clinical improvement; consider possible reasons for non-response (e.g. poor compliance, substance misuse, drug interactions, inadequate dose)
• Antipsychotics may increase the risk of pneumonia
• Routine full blood counts and liver function tests are advisable, particularly during the first months of treatment
• Target dosing to the time of most frequent symptoms
• Withdraw antipsychotics slowly to avoid rapid relapse and withdrawal symptoms (tachycardia, sweating, insomnia)
• Check weight, BMI, waist circumference, blood glucose, lipids, BP (and, if clinically indicated, EEG, ECG and prolactin) at baseline and regularly thereafter.

NOTE: Acetylcholinesterase inhibitors should be considered as improvement in cognitive function may have secondary effects in improving neuropsychiatric symptoms of dementia.

https://www.ranzcp.org/clinical-guidelines-publications/clinical-guidelines-publications-library/dementia-antipsychotic-medications-to-care-for-people-with-behavioural-and-psychological-symptoms

https://cheba.unsw.edu.au/clinicians-bpsd-guide-2023