Pharmacologic agents used in the management of neuropsychiatric symptoms in dementia

Medication category

Daily dose

Adverse-effect monitoring

Comments

Second-generation antipsychotics (SGAs)

Risperidone

(LAI, ODT, liquid)

Initial: 0.25 mg once daily to bid

Titration: 0.25-0.5 mg every 3-7 days

Max: 2 mg

– Sedation

– Postural hypotension

– Falls

– Anticholinergic adverse effects (dry mouth, constipation, confusion)

– EPS, particularly parkinsonian signs and symptoms (rigidity, bradykinesia, shuffling gait, masked facies, tremor)

– Olanzapine and quetiapine more sedating than risperidone or aripiprazole

– Best supported SGA for NPSs

– Most likely SGA to cause EPS

Olanzapine

(IM, ODT)

Initial: 2.5-5 mg at bedtime

Titration: 2.5-5 mg every 3-7 days

Max: 10 mg

– Most likely SGA to cause metabolic adverse effects

– Availability in rapidly dissolving preparation advantageous in noncompliance

Quetiapine

Initial: 12.5 mg bid

Titration: 12.5-25 mg every 3-7 days

Max: 150 mg

– Used for Parkinson disease dementia and dementia with Lewy bodies at lower doses due to high sensitivity to EPS

– In those with psychosis and Parkinson disease dementia, if possible, first reduce dopaminergic agents

Aripiprazole

Initial: 2-5 mg daily

Titration: 2-5 mg every 3-7 days

Max: 10 mg

– Most likely SGA to cause akathisia (restlessness)

First-generation antipsychotics (FGAs)

Haloperidol

(IM, IV, LAI, liquid)

Initial: 0.25 mg bid

Titration: 0.5 mg bid every 3-7 days

Max: 1.5 mg bid

– Haloperidol more likely to cause EPS than SGAs

– Gold standard for delirium

– Can be given IM in ED when other formulations unavailable or IV in ICU; monitor ECG for QTc prolongation, especially when dosage ≥3 mg/day

SSRI antidepressants

Citalopram

Initial: 5-10 mg daily

Titration: 10 mg every 7 days

Max: 20 mg

– Headache

– Nausea (give with food to ↓GI upset)

– Diarrhea

– Sweating

– Insomnia

– Hyponatremia

– Risk of GI bleed

– QTc prolongation at higher doses of citalopram

– Risk of falls, fractures, and osteoporosis

– Citalopram is the best supported SSRI for NPS; monitor ECG for QTc prolongation, especially when dosage ≥20 mg/day

– In FTD patients, SSRIs are first-line agents, particularly for repetitive behaviors

Escitalopram

Initial: 5 mg daily

Titration: 5 mg every 7 days

Max: 10 mg

Sertraline

Initial: 25 mg daily

Titration: 25 mg every 7 days

Max: 100 mg

Anticonvulsants

Carbamazepine

Initial: 50 mg daily

Titration: 50 mg every 7-14 days, bid to tid

Max: 500 mg

– Sedation

– Ataxia/falls

– Neutropenia

– Hyponatremia

– ↑ Liver function tests

– Skin rash

– Risk of drug-drug interactions

– Monitor drug level

Agents for sleep

Lorazepam

(IM, IV, liquid)

Initial: 0.25-0.5 mg at bedtime

Titration: 0.25-0.5 mg every 3-7 days

Max: 2 mg

BZPs:

– Sedation

– Confusion/cognitive impairment

– Ataxia/falls

– Disinhibition

Trazodone:

– Postural hypotension

– Dry mouth

– Constipation

– BZPs for short-term use only

– BZPs carry risk of tolerance/dependence, falls, worsening cognition, and withdrawal upon discontinuation; their use should be limited to situations that may require rapid onset of action while under close observation

– Trazodone can be used in FTD, in 25 mg bid to tid starting dose to 100-300 mg daily

Zopiclone

Initial: 3.75 mg at bedtime

Titration: 3.75 mg every 3-7 days

Max: 15 mg

Trazodone

Initial: 25 mg at bedtime

Titration: 25 mg every 3-7 days

Max: 100 mg

Cholinesterase inhibitors

Donepezil

Initial: 2.5-5 mg daily

Titration: 2.5-5 mg every 4-6 weeks

Max: 10 mg (23 mg slow release)

– GI upset (nausea/vomiting/diarrhea)

– Loss of appetite

– ↓ GI adverse effects with patch

– Insomnia, hypervivid dreams

– Bradycardia

– Urinary incontinence

– Muscle cramps

– ChEIs are first-line agents for psychosis in Parkinson disease dementia and dementia with Lewy bodies

– ChEIs can be beneficial in apathy

– Take with food to minimize GI upset

– Rotate patch site

– In FTD, ChEIs are contraindicated

Rivastigmine

Initial: 1.5 mg bid

Titration: 1.5 mg every 4 weeks

Max: 12 mg

Initial: 4.6 mg patch

Titration: 9.5 mg every 4 weeks

Max: 13.3 mg

Galantamine

Initial: 8 mg daily

Titration: 8 mg every 4 weeks

Max: 24 mg

Extended-release formulation

bid, 2 times a day; BZP, benzodiazepine; ChEI, cholinesterase inhibitor; ECG, electrocardiogram; ED, emergency department; EPS, extrapyramidal symptoms; FGA, first-generation antipsychotic; FTD, frontotemporal dementia; GI, gastrointestinal; ICU, intensive care unit; IM, available as intramuscular formulation; IV, available as intravenous formulation; LAI, available as long-acting injectable formulation; NPS, neuropsychiatric symptom; ODT, available as orally dissolving/disintegrating tablet; SGA, second-generation antipsychotic; SSRI, selective serotonin reuptake inhibitor; tid, 3 times a day.