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

This new review assessed the efficacy and harms (adverse effects) of immediate release (IR) methylphenidate (MPH) for treating ADHD in adults.

The review authors included 10 randomised controlled trials (RCTs) comparing IR MPH with placebo, an osmotic-release oral system (OROS) of MPH (an extended-release formulation), an extended-release formulation of bupropion, lithium and Pycnogenel® (maritime pine bark extract). A total of 497 adults with ADHD took part in the trials, and the duration of follow-up ranged from 6 to 18 weeks.

Results for IR MPH versus placebo

The review authors found very low-certainty evidence that, compared with placebo, IR MPH may reduce clinician-rated symptoms of ADHD (1 trial, 146 participants), participant-rated symptoms of ADHD (SMD −0.59, 95% CI −1.25 to 0.06; 2 trials, 138 participants), and clinicians’ impression of the severity of ADHD symptoms (MD −0.57 (assessed with the Clinical Global Impression-Severity scale, scored from 1 (very much improved) to 7 (very much worse), 95% CI −0.85 to −0.28; 2 trials, 139 participants). However, the evidence is very uncertain. They also found low-certainty evidence that, compared with placebo, IR MPH may slightly impact clinicians’ impression of improvement of ADHD symptoms (1 trial, 49 participants). However, they found no clear evidence of an effect on anxiety (1 trial, 19 participants) or depression (1 trial, 19 participants). The review authors also found that IR MPH increase the risk of gastrointestinal complications (RR 1.96, 95% CI 1.13 to 2.95) and loss of appetite (RR 1.77, 95% CI 1.06 to 2.96) (4 trials, 344 participants).

Results for IR MPH versus lithium

The review authors found very low-certainty evidence from one trial (46 participants) that, compared with lithium, IR MPH may have little to no effect on symptoms of ADHD, anxiety or depression. Additionally, the trial reported adverse events in five participants given IR MPH (diarrhoea, headache, orthostatic hypotension) and nine participants given lithium (chest discomfort, diarrhoea, nausea, headache). The one study included in this comparison did not assess participant-rated symptoms of ADHD, or clinical impression of severity or improvement.

Conclusions

Compared with placebo or lithium, the evidence of the effects of IR MPH on symptoms of ADHD in adults is uncertain (low and very low-quality evidence). Additionally, adults treated with IR MPH are at increased risk of gastrointestinal and metabolic harms compared with placebo. The review authors concluded that clinicians should consider whether it is appropriate to prescribe IR MPH, given its limited efficacy and increased risk of harms.

Read the full review here on the Cochrane Library.