What medications are used to manage restlessness in Alzheimer's disease?

Management of Restlessness in Alzheimer's Disease

For restlessness in Alzheimer's disease, a combination of nonpharmacologic interventions should be tried first, followed by pharmacologic treatments with cholinesterase inhibitors, and if necessary, carefully selected psychotropic medications targeting specific symptoms. 1

Nonpharmacologic Interventions (First-Line)

• Establish a predictable daily routine with consistent exercise, meals, and bedtime schedules 1
• Use distraction and redirection techniques when agitation occurs (the "three R's": repeat, reassure, and redirect) 1
• Simplify tasks by breaking them into manageable steps with clear instructions 1
• Ensure optimal treatment of comorbid conditions that may contribute to restlessness 1
• Create a safe environment with reduced environmental stimuli (minimize glare, noise, household clutter) 1
• Use appropriate lighting to reduce confusion and restlessness at night 1
• Avoid overstimulation and crowded places that can trigger agitation 1
• Register the patient in the Alzheimer's Association Safe Return Program if wandering is a concern 1

Pharmacologic Interventions

First-Line: Cholinesterase Inhibitors

• Cholinesterase inhibitors may improve behavioral symptoms including restlessness 1
• Options include:
  • Donepezil (Aricept): Start with 5 mg once daily, may increase to 10 mg daily after 4 weeks; may cause initial increase in agitation that typically subsides after a few weeks 1
  • Rivastigmine (Exelon): Start with 1.5 mg twice daily, increase by 1.5 mg twice daily every 4 weeks as tolerated to maximum 6 mg twice daily 1
  • Galantamine (Reminyl): Start with 4 mg twice daily with meals, increase to 8 mg twice daily after 4 weeks, may further increase to 12 mg twice daily based on response and tolerability 1

Second-Line: Targeted Psychotropic Medications

When nonpharmacologic approaches and cholinesterase inhibitors fail to adequately control restlessness, consider:

For Restlessness with Depression:

• SSRIs (preferred due to minimal anticholinergic effects) 1:
  • Citalopram (Celexa): Start 10 mg daily, maximum 40 mg daily 1
  • Sertraline (Zoloft): Start 25-50 mg daily, maximum 200 mg daily 1

For Restlessness with Agitation:

• For mild agitation: Begin with structured activities, reassurance, and socialization alongside medication 1
• For severe agitation: Medication plus environmental interventions for safety 1

For Sleep Disturbances Contributing to Restlessness:

• Assess for underlying sleep disorders like restless legs syndrome, which may respond to gabapentin enacarbil 2
• Consider trazodone or melatonin for sleep disturbances 3

Monitoring and Adjustment

• Start psychotropic medications at low doses and increase slowly while monitoring for side effects 1
• After behavioral disturbances have been controlled for 4-6 months, attempt gradual dose reduction to determine if continued pharmacotherapy is needed 1
• Regularly reassess the need for medication and adjust based on response 1

Important Considerations and Pitfalls

• Some behaviors like wandering and pacing may not respond well to drug therapy 1
• Avoid medications with high anticholinergic effects as they can worsen cognition 1
• Be aware that cholinesterase inhibitors may initially increase agitation before improvement occurs 1
• Consider the possibility that restlessness may be due to pain, discomfort, or other medical conditions that should be addressed 1
• Document specific behavioral manifestations, triggers, and interventions attempted for proper assessment and treatment planning 4

Treatment Algorithm

1. Begin with comprehensive nonpharmacologic interventions
2. Add cholinesterase inhibitor if symptoms persist
3. If inadequate response, add targeted psychotropic medication based on specific symptoms
4. Regularly reassess and attempt dose reduction after stabilization