Pharmacologic Treatment of Neuropsychiatric Symptoms of Dementia

First, consider removing potentially offending medication (anticholinergic, sedating, benzodiazepines, etc.) 120,122

Antipsychotic black box warning

• Absolute increased risk of death is 1-2%, even when considering increased comorbidities in population receiving antipsychotics 123
• American Psychiatric Association recommends an attempt to taper off antipsychotics in dementia within four months, provided no history of adverse reaction to taper 124

Anxiety

• Citalopram 30mg QD was shown to reduce irritability, anxiety, and delusions compared to placebo in AD patients by 9 weeks 125
• Memantine was shown to have benefit on behavioral symptoms in several meta-analyses of Alzheimers dementia patients 126

Psychotic symptoms (delusions / hallucinations)

• Citalopram 30mg was shown to reduce hallucinations and delusions in AD patients by 9 weeks 125
• Risperidone
• Acetylcholinesterase inhibitors for visual hallucinations

Agitation / aggression

• Citalopram 30mg QD was shown to reduce irritability, anxiety, and delusions compared to placebo in AD patients by 9 weeks 125
• Risperidone most effective out of antipsychotic studies, followed by aripiprazole and olanzapine though antipsychotics confer increased cerebrovascular risks, mortality, and extrapyramidal symptoms. Quetiapine has been found to have negative studies
• Memantine not shown to be helpful with significant aggressive behaviors in a double-blind placebo controlled trial with moderate-severe Alzheimers patients 127

Depression

• Unfortunately, A Cochrane review found no strong evidence for antidepressants as treatment of depression in dementia, including subgroup analyses of SSRIs, venlafaxine, mirtazapine, and TCAs 128
  • There is some evidence that antidepressants may increase remission rates 128
• Because depression and dementia share significant overlap in symptoms (apathy, amotivation, cognitive deficits, etc.), if studies isolate core symptoms of depression such as sadness, pessimism, and low self-esteem, some evidence may exist for mirtazapine (but not sertraline) 129

Apathy

• Apathy is associated with significantly worse functioning and more impairment than cognitive status alone would suggest, with strongest effects in mild dementia, leading to worse patient quality of life and increased distress of caregivers; prevalence is correlated with dementia severity (27.8% in patients w/ CDR 0.5; 58.8% in patients with CDR 2) 130
• Best pharmacologic results for apathy treatment in dementia were found in acetylcholinesterase inhibitors, with some evidence for memantine, less for stimulants and atypical antipsychotics, and no evidence for antidepressants and anticonvulsants 131

Night-time behaviors (waking and getting up at night)

• a Cochrane review found insufficient evidence of any drug trials to treat sleep in patients with moderate-severe AD. Melatonin up to 10mg and ramelteon were ineffective; low-quality evidence for trazodone 50mg to improve nocturnal sleep time and sleep efficiency 132