Should we prescribe immediate-release methylphenidate (Ritalin) to adults with attention-deficit/hyperactivity disorder (ADHD)?
In adults with ADHD, immediate-release methylphenidate improves symptoms of hyperactivity, impulsiveness, and inattentiveness compared with placebo. Short-term adverse effects such as weight loss and decreased appetite do not appear to be serious. However, larger studies of longer duration are needed to evaluate for cardiovascular outcomes. (Strength of Recommendation: B, based on inconsistent or limited-quality patient-oriented evidence.)
ADHD is a common diagnosis in primary care, with an estimated prevalence of 4.4% in the adult population.1 An estimated 35% of children with ADHD still meet criteria for ADHD as adults.2 Many more children will no longer meet criteria for ADHD as adults, but will continue to manifest some of the core symptoms (i.e., hyperactivity, inattentiveness, or impulsiveness). Compared with control patients, adults with ADHD are more likely to have other psychiatric comorbidities (e.g., anxiety, bipolar disorder, substance abuse), interpersonal impairments, and difficulty with employment.2
This Cochrane review included 11 randomized, double-blind, placebo-controlled trials examining the effectiveness of immediate-release methylphenidate in 474 participants. Compared with placebo, methylphenidate decreased symptoms of hyperactivity with a standardized mean difference (SMD) of −0.60 (95% confidence interval [CI], −1.11 to −0.09); inattentiveness with an SMD of −0.66 (95% CI, −1.02 to −0.30); and impulsiveness with an SMD of −0.62 (95% CI, −1.08 to −0.17). Looking at the overall change in condition, the pooled studies demonstrated an SMD of −0.72 (95% CI, −1.12 to −0.32), favoring methylphenidate over placebo.
The effects of treatment with methylphenidate on anxiety and depression symptoms were equivocal; some studies showed benefit, whereas others demonstrated no effect. Subgroup analysis showed high-dose methylphenidate (more than 0.9 mg per kg per day) to be no more effective than low-dose methylphenidate (0.9 mg per kg per day or less) in treating hyperactivity, impulsiveness, or inattentiveness.
The main adverse effects of methylphenidate use in children also pertain to adults. Decreased appetite was reported in six studies, and significant weight loss was reported in three studies. Insomnia, jitteriness, sweating, and tremor also occurred. There were reports of significantly elevated blood pressure and heart rate in some of the studies, but none revealed an increased risk of cardiovascular events or death. The number of patients studied is too small and the length of the trials is too short to detect a clinically important increase in cardiovascular events, if one exists.
This Cochrane review concluded that, compared with placebo, immediate-release methylphenidate is an effective treatment for adults with ADHD, but the review had some limitations. The study participants were limited to individuals from the United States, Canada, and the Netherlands without significant comorbid psychiatric issues, so caution must be used when generalizing the results to other populations. Because the trials span approximately 35 years, there is some variation in the assessment tools used and the diagnosis rates. The size (the largest included 146 participants) and duration (the longest was 17 weeks) of the trials impose serious limitations for detecting long-term adverse effects and the effectiveness of methylphenidate over time. Despite these limitations, the included trials provide evidence in support of current recommendations that methylphenidate be considered first-line therapy in the management of adult ADHD.3