Common neuropsychiatric symptom clusters in dementia and pharmacologic strategies

NPSs in dementia

Pharmacologic options

“Better-not-to-use” pharmacologic options

Agitation/aggression

– Serotonergic antidepressants (eg, citalopram, sertraline, trazodone)

– Shorter-acting BZPs (eg, lorazepam, oxazepam)

– Anticonvulsants (eg, carbamazepine, valproic acid) if comorbid bipolar disorder

– SGAs (eg, risperidone, olanzapine, quetiapine, aripiprazole)

– FGAs (eg, haloperidol)

– Do not use SGAs/FGAs as first choice

– Avoid highly anticholinergic FGAs/SGAs (eg, chlorpromazine, perphenazine, clozapine)

– Avoid highly dopamine-blocking FGAs and SGAs in parkinsonism-related dementias (eg, haloperidol, risperidone)

– Limit use of anticonvulsants (eg, carbamazepine, valproic acid) if no comorbid bipolar disorder

– ChEIs may worsen agitation; do not use in FTD

– Avoid BZDs/sedative-hypnotics as first choice

Apathy

– ChEIs (eg, donepezil, rivastigmine, galantamine)

– Antidepressants

– Psychostimulants (eg, methylphenidate, modafinil)

– FGAs/SGAs may worsen apathy

– Antidepressants at high doses may worsen apathy

Psychosis

– ChEIs (eg, donepezil, rivastigmine, galantamine)

– SGAs

– FGAs

– Limit use of FGAs and most of SGAs (except quetiapine) in dementia with Lewy bodies and Parkinson disease dementia due to worsening of EPSs in dose-dependent fashion

– Limit use of FGAs/SGAs in prolonged QTc syndrome (except aripiprazole)

Depression

– Antidepressants (eg, citalopram, escitalopram, sertraline, venlafaxine, bupropion, mirtazapine)

– Avoid highly anticholinergic antidepressants (eg, clomipramine, amitriptyline, doxepin)

Disinhibition

– Antidepressants (eg, citalopram, trazodone)

– Antiandrogens (eg, medroxyprogesterone acetate)

– GnRH analogues (eg, leuprolide)

– SGAs/FGAs (eg, quetiapine, haloperidol)

– BZPs may worsen disinhibition

– Dopamine agonists may worsen disinhibition

Sleep disturbances

– Antidepressants (eg, mirtazapine, trazodone)

– Shorter-acting BZPs/sedative-hypnotics, if necessary, for a brief period of time (eg, lorazepam, oxazepam, temazepam, zopiclone)

– Avoid BZDs/sedative-hypnotics as first choice

– Do not use long-acting BZPs (eg, diazepam, chlordiazepoxide, flurazepam) due to drug accumulation, active metabolites

BZP, benzodiazepine; ChEI, cholinesterase inhibitor; EPS, extrapyramidal symptom; FGA, first-generation antipsychotic; FTD, frontotemporal dementia; GnRH, gonadotropin-releasing hormone; NPS, neuropsychiatric symptom; SGA, second-generation antipsychotic.