#363 Making a difference in indifference? Medications for apathy in dementia

• Results statistically different unless indicated. Comparisons versus placebo.
• Two systematic reviews (4-7 RCTs, 346-1341 patients) from the last 5 years of treating apathy in mild-moderate Alzheimer’s dementia over 2-24 weeks.^1,2
• Methylphenidate (immediate-release 10mg BID). Reporting most inclusive systematic review (4 RCTs, 346 patients):²
  • Apathy (mix of informant- and clinician-rated)
    • 72-point apathy scale (Baseline ~50; 3.3-point change clinically significant).^3-6
      • 6 point improvement versus 1 point (placebo) at ≤12 weeks.²
    • 12-point apathy scale (Baseline ~7; 1-2 point change clinically significant).^2,3,5,7
      • No difference versus placebo at <12 weeks.²
      • 4.5 point improvement versus 3.1 (placebo) at 24 weeks.²
  • Clinicians’ global impression:
    • Any improvement: 46% versus 34% (placebo).²
  • Mini-mental state exam:
    • No difference.²
  • Any adverse events or dropouts due to adverse events:
    • No difference.²
• Antipsychotics (2 RCTs, 421-649 patients):¹
  • Apathy: No difference.
• Antidepressants:
  • SSRIs (2 RCTs, 43-83 patients, neither required apathy diagnosis):¹
    • Apathy: Inconsistent results.^8,9
  • Bupropion (One RCT not in systematic reviews, 108 patients) versus placebo:¹⁰
    • Apathy: No difference.
    • Quality of Life (52-point scale): 1.2 points worse versus 0.4 better (placebo).
• Limitations: Small studies; one cross-over RCT (26 patients) negatively skewed meta-analyzed results;⁵ apathy a secondary outcome in antidepressant and antipsychotic RCTs; trial exclusion criteria (examples: cardiac abnormalities, uncontrolled hypertension, agitation) limit generalizability and safety data.

• No improvement in apathy with cholinesterase inhibitors alone versus placebo,² but 60-100% of RCT methylphenidate patients used cholinesterase inhibitors.^1,2
• Methylphenidate associated with weight loss, behavioural changes, insomnia, and cardiovascular harms.¹¹
• Depression and apathy often overlap and can be difficult to distinguish in practice.¹²
• Non-pharmacologic options include sensory stimulation (example music therapy) and pet therapy based on low-quality evidence of benefit.¹³