Only stimulants, atomoxetine reduce core ADHD symptoms in adults, meta-analysis shows

Key takeaways:

• Stimulants and atomoxetine had short-term benefits in adults with ADHD, but long-term efficacy remains under-investigated.
• Atomoxetine was less tolerable than placebo.

In a large network meta-analysis of pharmacological, psychological and neurostimulatory ADHD interventions, only stimulants and atomoxetine were associated with short-term reductions in core symptoms among adults.

However, the findings showed that atomoxetine was less tolerable than placebo.

To the researchers’ knowledge, this was the first network meta-analysis that compared pharmacological and nonpharmacological treatments in adults with ADHD.

“Our work should inform upcoming guidelines, such as those from the American Professional Society of ADHD and Related Disorders, providing guidance to health care professionals and empowering individuals with ADHD in making informed decisions about their health,” Edoardo G. Ostinelli, MD, senior researcher in the department of psychiatry at the University of Oxford, and colleagues wrote in The Lancet Psychiatry.

Ostinelli and colleagues examined data from 113 randomized controlled trials encompassing 14,887 patients aged 18 years or older with ADHD (45.6% women).

In the trials, pharmacological treatments were administered for at least 1 week, and psychological interventions involved at least four sessions. For neurostimulation trials, the duration of treatment was “any length deemed appropriate,” the researchers wrote.

The primary outcomes were changes in core symptom severity based on patient- and clinician-reported scales at timepoints closest to 12 weeks (efficacy), as well as all-cause discontinuation (acceptability).

Overall, the analysis included trials on 63 pharmacological therapies, 28 psychological therapies, 10 neurostimulation therapies and 97 control conditions.

At 12 weeks, there was a greater reduction in core ADHD symptoms with atomoxetine (standardized mean difference, –0.38 for patient reports and –0·51 for clinician reports) and stimulants (SMD, 0.39 for patient reports, –0.61 for clinician reports) vs. placebo.

In contrast, cognitive behavioral therapy, cognitive remediation, mindfulness, psychoeducation and transcranial direct current stimulation were only associated with better clinician-reported outcomes vs. placebo, not self-reported outcomes.

In terms of acceptability, the therapeutics were similar to placebo except for atomoxetine (OR = 1.43; 95% CI 1-14-1.8) and guanfacine (OR = 3.7; 95% CI, 1.22-11.19), which were less acceptable, according to the researchers.

Ostinelli and colleagues acknowledged there were limitations to the study, like the fact that few trials included data past 26 weeks.

“Our study provides the most comprehensive comparative evidence on the effects of pharmacological and nonpharmacological therapies for ADHD in adults to date,” they wrote. “Clinical decision-making should be based on a careful weighing of

benefits and harms, considering the findings from this [network meta-analysis] and other sources of evidence. Overall, further longer-term studies on alternative medications, non-pharmacological strategies, and their combinations available to date are needed to better inform the care of ADHD in adults.”