JAMA Neurology: The Effect of Methylphenidate on Apathy in Patients with Alzheimer's Disease--ADMET-2 Randomized Clinical Trial

Apathy is one of the most common neuropsychiatric symptoms in patients with Alzheimer's disease (AD)
.

This multicenter randomized placebo-controlled clinical trial was conducted in 9 U.
S.
clinics and 1 Canadian clinic specializing in the treatment of dementia from August 2016 to July 2020
.

• Of the 200 participants, 99 were assigned to the methylphenidate group and 101 were assigned to the placebo group
  .
  
• The median age (interquartile range) of the study participants was 76 years (71-81 years); 68 (34%) were women and 131 (66%) were men
  .
  
• Compared with the placebo group, patients taking methylphenidate had a greater decline in adverse reaction apathy scores from baseline to 6 months (mean difference, − 1.
  25; 95% CI, − 2.
  03, − 0.
  47; P=0.
  002)
  .
  
• The largest decrease in the NPI apathy score occurred in the first 100 days.
  Compared with placebo, participants without apathy symptoms had a significant risk ratio of methylphenidate treatment (hazard ratio, 2.
  16; 95% confidence interval, 1.
  19-3.
  91; P=0.
  01)
  .
  
• After 6 months, compared with placebo, the odds ratio for methylphenidate to obtain an improvement rating in terms of changes in the overall clinical impression of the Alzheimer's disease collaborative study was 1.
  90 (95%CI, 0.
  95-3.
  84; P=0.
  07)
  .
  
• Using longitudinal model estimation, the average change from baseline to 6 months was 1.
  43 (95% confidence interval 1.
  00-2.
  04; P=0.
  048)
  .
  
• Cognitive measures and quality of life did not differ significantly between the different groups
  .
  
• Of the 17 serious adverse events that occurred during the study, none were related to the study drug
  .
  
• There was no significant difference in safety between the treatment groups
  .