Clinical question
In patients with dementia, how safe and effective are stimulants, antidepressants, and antipsychotics for treating apathy?
Bottom line
Methylphenidate may improve apathy scores by a small but potentially clinically meaningful amount compared with placebo (eg, 5 points more on a 72-point scale at about 12 weeks). Methylphenidate does not impact cognition. Antipsychotics and antidepressants do not improve apathy compared with placebo.
Evidence
Results are statistically different unless indicated; comparisons are versus placebo. Two systematic reviews (4 to 7 RCTs, N=346 to 1341) published in 2018 and 2022 examined treating apathy in patients with mild to moderate Alzheimer dementia over 2 to 24 weeks.1,2
Methylphenidate (immediate release, 10 mg twice daily): reporting systematic review with the most recent RCTs included (4 RCTs, N=346).2
- Apathy (mix of informant and clinician rated): On a 72-point scale (baseline about 50; a 3.3-point change is clinically significant)3,4 there was a 6-point improvement versus 1 point at 12 or fewer weeks. On a 12-point scale2 (baseline about 7; a 1- to 2-point change is clinically significant)5 there was no difference at 8 weeks or less, but a 4.5- versus 3.1-point improvement at 24 weeks.
- Clinicians’ global impression: any improvement was 46% with methylphenidate versus 34% with placebo.
- There was no difference in Mini-Mental State Examination score.
- There were no differences in any rates of adverse events or dropouts due to adverse events.
Antipsychotics (2 RCTs, N=421 to 649)1: no difference.
Antidepressants:
Limitations: Small studies; 1 crossover RCT (N=26) negatively skewed meta-analyzed results7; apathy is a secondary outcome in antidepressant and antipsychotic RCTs; trial exclusion criteria (eg, cardiac abnormalities, uncontrolled hypertension, agitation) limit generalizability and safety data.
Context
There was no improvement in apathy among patients taking cholinesterase inhibitors alone versus placebo,2 but 60% to 100% of patients in RCTs taking methylphenidate also took cholinesterase inhibitors.1,2
Methylphenidate was associated with weight loss, behavioural changes, insomnia, and cardiovascular harms.8
Nonpharmacologic options include sensory stimulation (eg, music therapy), cognitive stimulation, and pet therapy, based on low-quality evidence of benefit.9
Implementation
Apathy in older adults can be related to multiple disorders including dementia or depression; distinguishing between them is challenging. Depression may affect both short- and long-term memory, whereas in dementia, short-term memory loss is predominant. A prior mood disorder, hopelessness, and dysphoric or tearful affect suggest depression, while indifference and lack of emotion suggest apathy.10 Side effects of methylphenidate such as behavioural changes and weight loss were more common but did not reach a statistical difference in apathy clinical trials compared with placebo.2,4,6 Monitoring for new or worsening symptoms is advised.
Notes
Tools for Practice articles in CFP are adapted from peer-reviewed articles at http://www.toolsforpractice.ca and summarize practice-changing medical evidence for primary care. Coordinated by Dr G. Michael Allan and Dr Adrienne J. Lindblad, articles are developed by the Patients, Experience, Evidence, Research (PEER) team and supported by the College of Family Physicians of Canada and its Alberta, Ontario, and Saskatchewan Chapters. Feedback is welcome at toolsforpractice@cfpc.ca.
Footnotes
Competing interests
None declared
- Copyright © 2024 the College of Family Physicians of Canada
In this issue
Jump to section
Related Articles
Cited By...
- No citing articles found.