TABLE 1.

Symptomatic pharmacotherapeutic considerations in dementia with Lewy bodies (DLB)^a

Symptom domain and treatments	Side effects	Comments
Cognitive
Donepezil, rivastigmine, and galantamine	GI symptoms (nausea, vomiting, loose stools, and anorexia)b; sleep problems (somnolence, insomnia, and vivid dreams); autonomic symptoms (postural hypotension, syncope, bradycardia, urinary frequency, drooling, rhinorrhea, and hyperhidrosis); motor symptoms (worsening tremor)	Donepezil and rivastigmine appear to have comparable efficacy (35, 36); galantamine has been less extensively studied. Donepezil and rivastigmine are also potentially effective for neuropsychiatric symptoms and fluctuations; consider high doses if tolerated (37).
Memantine	GI symptoms, confusion, somnolence, hypertension, and dizziness; may worsen hallucinations and delusions (38, 39)	The evidence for efficacy is mixed.c Use with caution in patients with seizures. Do not use with amantadine.
Neuropsychiatric
Selected selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors	GI symptoms; sleep problems (RBD, somnolence, and insomnia); dry mouth, sweating, dizziness, fatigue, headache, sexual dysfunction, tremor, apathy, QTc prolongation, and SIADH	Although commonly used, systematic studies have not been conducted. Evidence to date suggests patients with DLB are very sensitive to side effects (40).
Quetiapine and clozapine	Sedation, headache, confusion, hypotension, dizziness, fatigue, dry mouth, EPS, insomnia, tardive dyskinesia, RLS, urinary retention, dyslipidemia, weight gain, QTc prolongation, and agranulocytosis (clozapine)	Reserve use for severe symptoms refractory to nonpharmacological treatment and cholinesterase inhibitors.
Pimavanserin	Nausea, confusion, and peripheral edema	FDA approved for PD psychosis. There is evidence for efficacy in a mixed sample including patients with AD, PDD, DLB, FTD, or VaD (41).
Motor
Levodopa	Psychosis, orthostatic hypotension, sedation, nausea, and vomiting	Symptomatic benefit is more likely in PDD than in DLB (35).
Zonisamide	Reduced appetite, weight loss, dizziness, and somnolence	Zonisamide might be an effective adjunct to levodopa at 25–50 mg QD (42).
Sleep
Melatonin	Somnolence and headache	Melatonin is the preferred treatment for RBD. It is also potentially effective for insomnia (43).
Armodafinil	Reduced appetite, nausea, loose stools, dry mouth, dizziness, headache, insomnia, and anxiety	Armodafinil is potentially effective for daytime hypersomnia (44).
Autonomic
Midodrine, fludrocortisone, and droxidopa	Supine hypertension (all three), electrolyte disturbances and edema (fludrocortisone), and cardiac arrhythmia (droxidopa)	All three are potentially effective for orthostatic hypotension (45).
Glycopyrrolate and botulinum toxin	Flushing, constipation, vomiting, dry mouth (glycopyrrolate), and weakness (both)	Both are potentially effective for sialorrhea (46, 47).
Psyllium and polyethylene glycol	Nausea, bloating, flatulence, loose stools, and stomach cramps	These are used for constipation in conjunction with dietary modification and increased fluid intake (48).
Mirabegron	Hypertension, constipation, dry mouth, and headache	Mirabegron is an alternative to antimuscarinic agents for urinary frequency and urgency (49).
Sildenafil	Flushing, dyspepsia, headache, hypotension, and syncope (due to systemic vasodilation)	Sildenafil is a short-acting agent (preferable). Caution patient about standing for several hours after administering dose (50).

^aAbbreviations: AD, Alzheimer disease; EPS, extrapyramidal symptoms; FDA, U.S. Food and Drug Administration; FTD, frontotemporal dementia; GI, gastro-intestinal; PD, Parkinson disease; PDD, Parkinson disease with dementia; QD, once daily; RBD, REM sleep behavior disorder; RLS, restless legs syndrome; SIADH, syndrome of inappropriate antidiuretic hormone secretion; VaD, vascular dementia.

^bRisk of GI side effects with transdermal rivastigmine is generally regarded as lower than that with oral rivastigmine.

^cStudies support modest improvements in global efficacy based on Clinician Global Impression of Change scale scores, without improvement in cognition and variable benefit for neuropsychiatric symptoms.