Cochrane for Clinicians

Putting Evidence into Practice

Pharmacologic Interventions for Apathy in Patients with Alzheimer Disease


Am Fam Physician. 2019 Jan 1;99(1):14-15.

Author disclosure: No relevant financial affiliations.

Clinical Question

Is methylphenidate (Ritalin) safe and effective for reducing apathy in patients with Alzheimer disease (AD)?

Evidence-Based Answer

Methylphenidate may improve apathy in select patients with AD (mean difference [MD] = –4.99 on the apathy evaluation scale [AES]; 95% confidence interval [CI], –9.55 to –0.43), although the clinical significance associated with these findings remains unclear and the evidence is considered low quality. The risk of developing an adverse effect is no more likely with methylphenidate than with placebo (relative risk [RR] = 1.28; 95% CI, 0.67 to 2.42).1 (Strength of Recommendation: B, based on limited-quality patient-oriented evidence.)

Practice Pointers

AD is a debilitating, prevalent, and costly condition affecting 5.7 million Americans.2 Behavioral and psychological symptoms of dementia such as apathy are common and among the most troubling aspects of dementia care. Apathy is a state of reduced motivation affecting goal-directed cognitive activity, goal-directed behavior, and the accompanying emotional response.3 Apathy is a highly prevalent and persistent behavioral and psychological symptom of dementia and is associated with disability, poor health, caregiver burden, and mortality.4,5 The objective of this review was to assess the safety and effectiveness of pharmacotherapies for the treatment of apathy in patients with AD.

This Cochrane review included 21 randomized controlled trials (published between 1998 and 2017) involving 6,384 participants.1 The authors looked for any placebo-controlled trials investigating pharmacologic treatments in persons with AD or mixed AD (i.e., AD with vascular pathology) reporting an effect on apathy. Of the 21 trials, only four reported apathy as a primary outcome measure; three of these featured an examination of methylphenidate, whereas one featured modafinil (Provigil). Apathy outcomes were measured using the AES or the neuropsychiatric inventory apathy subscale (NPIa). The AES is scored

Author disclosure: No relevant financial affiliations.


show all references

1. Ruthirakuhan MT, Herrmann N, Abraham EH, Chan S, Lanctôt KL. Pharmacological interventions for apathy in Alzheimer's disease. Cochrane Database Syst Rev. 2018;(5):CD012197....

2. Alzheimer's Association. 2018 Alzheimer's disease facts and figures. Alzheimers Dement. 2018;14(3):367–429.

3. Robert P, Onyike C, Leentjens AF, et al. Proposed diagnostic criteria for apathy in Alzheimer's disease and other neuropsychiatric disorders. Eur Psychiatry. 2009;24(2):98–104.

4. van der Linde RM, Matthews FE, Dening T, Brayne C. Patterns and persistence of behavioural and psychological symptoms in those with cognitive impairment: the importance of apathy. Int J Geriatr Psychiatry. 2017;32(3):306–315.

5. Steinberg M, Shao H, Zandi P, et al.; Cache County Investigators. Point and 5-year period prevalence of neuropsychiatric symptoms in dementia: the Cache County Study. Int J Geriatr Psychiatry. 2008;23(2):170–177.

These are summaries of reviews from the Cochrane Library.

This series is coordinated by Corey D. Fogleman, MD, Assistant Medical Editor.

A collection of Cochrane for Clinicians published in AFP is available at



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