What Works for Adults With ADHD?

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Medications demonstrated effectiveness for core symptoms of attention-deficit/hyperactivity disorder (ADHD) in adults without evidence of whether quality of life (QOL) is improved, and nonpharmacologic interventions could be rated effective by clinicians but not by patients, in findings from the first component network meta-analysis (CNMA) of the array of treatments offered to adults with ADHD.¹

"Given the concerns around the safety of ADHD medications, there is a pressing need to better understand the comparative efficacy and tolerability or safety of medications and nonpharmacological interventions for the management of ADHD in adults," observed Edoardo Ostinelli, MD, and colleagues.

The investigators conducted the CNMA to compare benefits and harms of available interventions from 113 randomized controlled trials (RCTs) identified from multiple data bases, from inception through September 2023. The trials evaluated pharmacologic treatments (63 trials with 6875 participants); psychological therapies (28 trials with 1116 participants); neurostimulatory therapy and neurofeedback (10 trials with 194 participants); and control conditions (97 trials with 5770 participants).

The trial controls could be either active or placebo, and were double-blinded if evaluating medication, cognitive training, or neurostimulation alone. Medication trials also had to have maximum planned doses correspond to international guidelines, and duration of at least 1 week. Trials with psychological therapies had to provide at least 4 sessions and trials of neurostimulation had to apply the regimens established in originating studies.

The primary outcomes of the CNMA were severity of ADHD core symptoms at time points close to 12 weeks, as measured on clinician-rated scales and/or patient self-rating, and acceptability of the intervention, inferred from discontinuation rates. Secondary outcomes included these measures at longer term, as well as emotional dysregulation, executive dysfunction, and quality of life.

A unique aspect of the CNMA study was to include individuals with lived experience in its planning and implementation; Ostinelli et al found this particularly helpful in formulating study questions and selecting outcomes.

"Collaborating with individuals with lived experience of ADHD has been a crucial aspect of our work, ensuring their voices are heard and meaningfully influence our research," Ostinelli told Psychiatric Times.

"Given the abundance of available findings, we first asked a panel of people with lived experience of ADHD to select which outcomes they wished to visualize based on what matter to them, and data availability—without knowledge of the results," Ostinelli explained. "We then presented the findings to them without disclosing the treatment names. Their insights and feedback provided significant value and helped shape our manuscript."

In the primary outcome of ADHD core symptoms at 12 weeks, Ostinelli et al reported that atomoxetine and stimulant medications were statistically significantly superior to placebo on both clinician rating and patient self-report. Relaxation therapy was less effective than placebo on self-reported scales. Cognitive behavioral therapy, cognitive remediation, mindfulness, psychoeducation, and transcranial direct current stimulation were superior to placebo on clinician ratings but not self-reported scales.

"There are several potential explanations for the misalignment between clinician and patient ratings," Ostinelli commented. "Further research is needed to determine whether this discrepancy is due to outcome reporting bias or if different types of raters simply measure distinct aspects of the condition."

Acceptability of interventions were generally similar for adults, with stimulants rated more acceptable than placebo; however, both atomoxetine and stimulants were less tolerated than placebo.

In a secondary efficacy outcome of reducing emotional dysregulation, atomoxetine and stimulants were superior to placebo at 12 weeks, but not at 26 weeks. No other active intervention was found efficacious for emotional dysregulation, albeit with only 3 RCTs identified. The investigators highlighted this area for future research.

"As difficulty with regulation of emotions is often a highly impairing symptoms that some argue should be regarded as part of the core symptoms of ADHD, additional evidence to support its management is a pressing need," Ostinelli et al urge.

On another secondary outcome of executive function, the CNMA found that active interventions, apart from mindfulness, did not differ from placebo on processing speed at 12 weeks. They noted that their findings differed from studies in children with ADHD, with neither medication nor cognitive training demonstrating efficacy for improving executive function in adults.

"Given the high frequency and impairing nature of executive dysfunction associated with ADHD in adults, effective interventions and support are urgently needed," the investigators declared.

Although Ostinelli et al found little evidence of any active intervention improving QOL at 12 weeks for adults, they acknowledge that a longer timeframe is probably necessary to measure this outcome and point out that there are few data at longer time points. The lack of evidence for improvement in QOL in adults differs from findings in children, they note, with another meta-analysis finding evidence that medication for ADHD improved QOL in children in short to medium term.²

"With the similar effects of continuing and discontinuing medications on reported quality of life in a few randomized discontinuation trials, available evidence does not support medications as standalone treatments in providing satisfactory benefits on the quality of life of adults with ADHD," Ostinelli et al indicated.

To the question of whether this CNMA will influence clinician's choice of treatment modality for adults with ADHD, Ostinelli acknowledged the hesitancy of some clinicians to prescribe treatments with which they are not fully confident. He emphasized, however, the importance of providing personalized medicine grounded in the available evidence and anticipates that this CNMA will inform clinical decision making.

"This underscores the need to enhance education and provide ongoing professional development on ADHD treatments," Ostinelli said. "Initiatives such as establishing a network of dedicated research clinics and hubs should be promoted to improve access to treatment while also leveraging their contributions to advance future health care."

Dr Bender reports on medical innovations and advances in practice and edits presentations for news and professional education publications. He previously taught and mentored pharmacy and medical students, and he provided and managed pharmacy care and drug information services.

References

1. Ostinelli EG, Schulze M, Zangani C, et al. Comparative efficacy and acceptability of pharmacological, psychological, and neurostimulatory interventions for ADHD in adults: a systematic review and component network meta-analysis. Lancet Psychiatry 2025;12(1):32-43.

2. Bellato A, Perrott NJ, Marzulli L, et al. Systematic review and meta-analysis: effects of pharmacological treatment for attention-deficit/hyperactivity disorder on quality of life. J Am Acad Child Adolesc Psychiatry. May 30, 2024. Online ahead of print.