Extended-release methylphenidate for attention deficit hyperactivity disorder (ADHD) in adults

This review sought to assess the beneficial and harmful effects of extended-release formulations of methylphenidate in adults diagnosed with ADHD.

The review authors included 24 randomised controlled trials (RCTs), 21 of which were conducted in an outpatient setting and 3 in prisons, mostly in North America and Europe. A total of 5066 participants with a formal diagnosis of ADHD took part in the studies. The median age of the participants was 36 years old. Twelve trials were sponsored by industry, four were publicly funded with industry involvement, and seven were publicly funded; the funding source of one study was unclear. The median trial duration was eight weeks.

Extended-release methylphenidate versus placebo (up to 26 weeks)

The evidence was very uncertain about the effect of extended-release methylphenidate on the following outcomes.

  • Functional outcome of ‘Days missed at work’ at 13-week follow-up: mean difference (MD) −0.15 days, 95% confidence interval (CI) −2.11 to 1.81; 1 trial, 409 participants.
  • Self-rated ADHD symptoms: standardised mean difference (SMD) −0.37, 95% CI −0.43 to −0.30; 16 trials, 3799 participants.
  • Serious adverse events: risk ratio (RR) 1.43, CI 95% CI 0.85 to 2.43; 14 trials, 4078 participants.
  • Self-rated quality of life: SMD −0.15, 95% CI −0.25 to −0.05; 6 trials, 1888 participants.
  • Investigator-rated ADHD symptoms: SMD −0.42, 95% CI −0.49 to −0.36; 19 trials, 4183 participants.
  • Peer-rated (e.g. family members) ADHD symptoms: SMD −0.31, 95% CI −0.48 to −0.14; 3 trials, 1005 participants.
  • Any adverse event: RR 1.27, 95% CI 1.19 to 1.37; 14 trials, 4214 participants.

Only one trial (419 participants) had follow‐up data at 52 weeks and two trials (314 participants) included active comparators; hence, long‐term and comparative evidence are limited.

The review authors concluded that the benefits and harms of extended-release methylphenidate remain uncertain. The certainty of the evidence is very low for all outcomes due to high risk of bias, the short durations of the trials, and limitations to the generalisability of the results.

The evidence is current to February 2021.

Read the full review here on the Cochrane Library.