Cochrane for Clinicians

Putting Evidence into Practice

Use of Amphetamines for Attention-Deficit/Hyperactivity Disorder in Adults


Am Fam Physician. 2019 Sep 1;100(5):278-279.

Author disclosure: No relevant financial affiliations.

Clinical Question

Are amphetamines safe and effective in adults with attention-deficit/hyperactivity disorder (ADHD)?

Evidence-Based Answer

Amphetamines provide a clinician-rated 30% or greater reduction in ADHD symptoms when compared with placebo (number needed to treat = 5).1 (Strength of Recommendation: B, based on inconsistent or limited-quality patient-oriented evidence.)

Practice Pointers

ADHD is a neurodevelopmental disorder with a mean onset at six years of age. Approximately one-third of affected children will carry the disorder into adulthood; the current prevalence of ADHD in U.S. adults is 4.4%.2 ADHD symptoms present differently in adults than in children. Hyperactivity and impulsivity in adults often appear as restlessness, talkativeness, and emotional dysregulation (i.e., irritability, emotional lability, and emotional reactivity). Inattention manifests similarly in childhood and adulthood. The use of amphetamines for the treatment of adult ADHD has increased, and this Cochrane review analyzed their safety and effectiveness.1

The review included 19 randomized controlled trials (2,521 adults with ADHD) comparing dextroamphetamine, lisdexamfetamine (Vyvanse), or mixed amphetamine salts with placebo. Studies lasted on average 5.3 weeks (range: one to 20 weeks), with only three studies (N = 542) lasting more than eight weeks. The participants had a mean age of 35.3 years, and most (57.2%) were men; 78.8% had combined-type ADHD. The primary outcome was the severity of ADHD symptoms, assessed by clinicians or participants using the standardized ADHD Rating Scale-IV (ADHD-RS-IV). Secondary outcomes included clinical impressions of ADHD symptom severity and improvement at study end based on the Clinical Global Impression Severity and Impression Scales (CGI-S and CGI-I, respectively); percentage of participants with a 30% reduction in ADHD symptoms (measured by the ADHD-RS-IV) and/or a CGI-I score of 1 or 2; global functioning based on the CGI-S; symptoms of depression

Author disclosure: No relevant financial affiliations.


show all references

1. Castells X, Blanco-Silvente L, Cunill R. Amphetamines for attention deficit hyperactivity disorder (ADHD) in adults. Cochrane Database Syst Rev. 2018;(8):CD007813....

2. National Institute of Mental Health. Attention-deficit/hyperactivity disorder (ADHD). November 2017. Accessed September 17, 2018.

3. Adler LA, Goodman D, Weisler R, et al. Effect of lisdexamfetamine dimesylate on sleep in adults with attention-deficit/hyperactivity disorder. Behav Brain Funct. 2009;5:34.

4. Weisler RH, Greenbaum M, Arnold V, et al. Efficacy and safety of SHP465 mixed amphetamine salts in the treatment of attention-deficit/hyperactivity disorder in adults: results of a randomized, double-blind, placebo-controlled, forced-dose clinical study. CNS Drugs. 2017;31(8):685–697.

5. Martin PT, Corcoran M, Zhang P, et al. Randomized, double-blind, placebo-controlled, crossover study of the effects of lisdexamfetamine dimesylate and mixed amphetamine salts on cognition throughout the day in adults with attention-deficit/hyperactivity disorder. Clin Drug Investig. 2014;34(2):147–157.

6. Kollins SH, English JS, Itchon-Ramos N, et al. A pilot study of lisdexamfetamine dimesylate (LDX/SPD489) to facilitate smoking cessation in nicotine-dependent adults with ADHD. J Atten Disord. 2014;18(2):158–168.

7. Kay GG, Michaels MA, Pakull B. Simulated driving changes in young adults with ADHD receiving mixed amphetamine salts extended release and atomoxetine. J Atten Disord. 2009;12(4):316–329.

8. Frick G, Yan B, Adler LA. Triple-bead mixed amphetamine salts (SHP465) in adults with ADHD: results of a phase 3, double-blind, randomized, forced-dose trial [published online April 1, 2017]. J Atten Disord. Accessed September 17, 2018.

9. Biederman J, Fried R, Hammerness P, et al. The effects of lisdexamfetamine dimesylate on the driving performance of young adults with ADHD: a randomized, double-blind, placebo-controlled study using a validated driving simulator paradigm. J Psychiatr Res. 2012;46(4):484–491.

10. National Institute for Health and Care Excellence Attention deficit hyperactivity disorder: diagnosis and management. NICE guideline [NG87]. March 2018. Accessed September 17, 2018.

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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