by Justin Jackson , Medical Xpress

Credit: Unsplash/CC0 Public Domain

Stimulants and atomoxetine are the only effective interventions to reduce short-term adult ADHD symptoms, yet show limited evidence for long-term outcomes and quality of life improvements, according to a study by the University of Oxford’s Department of Psychiatry at Warneford Hospital.

According to the CDC, approximately 2%–5% of adults experience attention-deficit/hyperactivity disorder (ADHD) symptoms such as inattention, hyperactivity, and impulsivity. The wide range in their estimates reflects limited or nonexistent tracking data for ADHD at a national level.

Ongoing debates center on whether pharmacological and non-pharmacological interventions can effectively manage long-term outcomes. Existing guidelines emphasize medication but suggest non-pharmacological support if medications are not well tolerated or if adherence is difficult.

Although pharmacological treatments such as stimulants and non-stimulants like atomoxetine are the cornerstone of treatment in adults, concerns about tolerability and side effects have led to increased interest in non-pharmacological therapies.

Cognitive behavioral therapy (CBT), mindfulness, and neurostimulation are among the leading non-pharmacological treatments. These alternatives lack robust comparative data, particularly regarding their efficacy relative to established pharmacological treatments.

In the paper titled “Comparative efficacy and acceptability of pharmacological, psychological, and neurostimulatory interventions for ADHD in adults: a systematic review and component network meta-analysis,” published in The Lancet Psychiatry, researchers assessed pharmacological, psychological, and neurostimulatory intervention outcomes.

Investigators searched multiple databases and included 113 randomized controlled trials involving a total of 14,887 participants with at least one week’s duration for medications and multiple sessions for psychological therapies. Pharmacological therapies encompassed stimulants, atomoxetine, bupropion, clonidine, guanfacine, modafinil, and viloxazine.

Non-pharmacological strategies included psychological therapies such as CBT and mindfulness, as well as neurostimulatory approaches like transcranial direct current stimulation.

Standardized mean differences were calculated for the severity of ADHD core symptoms, both self-rated and clinician-rated. Results were sorted by time points of up to 52 weeks and examined for acceptability as measured by all-cause treatment discontinuation. Secondary outcomes included emotional dysregulation, executive dysfunction, and quality of life.

Stimulants and atomoxetine demonstrated the highest efficacy in reducing ADHD symptoms at 12 weeks, supported by both self-reported (-0.39) and clinician-reported scales (-0.61). Atomoxetine also worked well, though slightly less so than stimulants (-0.38 and -0.51) across scales.

Interventions such as CBT and mindfulness revealed an intriguing disconnect between clinicians and patients. On clinician-reported scales, both treatments were more effective than placebo, but not on self-reported measures.

Non-pharmacological therapies in the studies could not be fully blinded, potentially introducing bias leading to the disconnect in reported results. While it is unclear which—if not both—introduced bias, the contrast to the agreement seen in the blinded versions is a great example of why bias elimination is such a crucial aspect of research whenever it is possible.

Most interventions were comparable to placebo for all-cause discontinuation (including lack of efficacy, side effects, personal preference, or other factor,) except atomoxetine (OR 1.43) and guanfacine (OR 3.70), which were rated less acceptable due to higher dropout rates. Atomoxetine, guanfacine, and modafinil had higher discontinuation rates than placebo specifically due to adverse effects.

Evidence beyond 12 weeks was sparse, with only five trials contributing data at 52 weeks. CBT, neurofeedback, and relaxation therapy showed some efficacy in reducing symptoms in the long term, though small sample sizes limited confidence in the findings.

Stimulants were the only intervention showing small-to-moderate emotional dysregulation benefits at 12 and 52 weeks. No interventions demonstrated efficacy for executive dysfunction, and none significantly improved quality of life.

This review offers the most comprehensive investigation to date on adult ADHD interventions, and unfortunately, it suggests that there is still a tremendous unmet need waiting to be addressed.

More information: Edoardo G Ostinelli et al, Comparative efficacy and acceptability of pharmacological, psychological, and neurostimulatory interventions for ADHD in adults: a systematic review and component network meta-analysis, The Lancet Psychiatry (2024). DOI: 10.1016/S2215-0366(24)00360-2

Journal information:The Lancet Psychiatry

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