Which ADHD interventions are effective? An umbrella review

This umbrella review assessed the effects of and related evidence certainty of interventions for attention deficit/hyperactivity disorder (ADHD) across an individual’s lifespan, and to develop a continuously updated web platform for people with lived experience of ADHD as a method to disseminate living evidence synthesis for shared decision making. Six databases were searched from inception to 19 January 2025. Study authors were contacted for additional information when necessary.

Systematic reviews that used meta-analyses of randomised controlled trials were eligible, if they compared a drug or non-drug intervention with a passive control in individuals with a diagnosis of ADHD. Primary outcomes were severity of ADHD symptoms, analysed by rater type (clinician-rated, parent-rated, teacher-rated, or self-rated) and time point (short term (12 weeks, or study endpoint), medium term (26 weeks), and long term (52 weeks)),acceptability (participants dropping out for any reason), and tolerability (participants dropping out owing to any side effects). Secondary outcomes included daily functioning, quality of life, comorbid symptoms, and key side effects (decreased sleep and appetite). All eligible meta-analyses were re-estimated with a standardised statistical approach. Methodological quality was assessed using AMSTAR-2. Evidence certainty was evaluated using an algorithmic version of the GRADE framework, adapted for drug and non-drug interventions.

115 of 414 full text articles were deemed eligible and 299 were excluded; the eligible articles comprised 221 unique combinations of participants, interventions, comparators, and outcomes. For each combination, the most recent and methodologically robust meta-analysis was selected for re-estimation, which gave 221 re-estimated meta-analyses in total, derived from 47 meta-analytic reports.

• In the short term, alpha-2 agonists, amphetamines, atomoxetine, methylphenidate, and viloxazine showed medium to large effect sizes in reducing the severity of ADHD symptoms in children and adolescents, with moderate to high certainty evidence.
• Methylphenidate showed consistent benefits across raters (standardised mean difference >0.75, 95% confidence interval (CI) 0.56 to 1.03; moderate or high certainty evidence).
• These interventions showed lower tolerability than the placebo, but this effect was not significant for methylphenidate and atomoxetine.
• In adults, atomoxetine, cognitive behavioural therapy, methylphenidate (and, when restricting analyses to high quality trials, amphetamines) showed at least moderate certainty evidence of efficacy on ADHD symptoms, with medium effect sizes.
• Methylphenidate, amphetamines, and atomoxetine had worse tolerability than placebo (methylphenidate, risk ratio 0.50, 95% CI 0.36 to 0.69; amphetamines, 0.40, 0.22 to 0.72; atomoxetine, 0.45, 0.35 to 0.58).
• Acupuncture showed large effect sizes for ADHD symptoms, but with low certainty evidence.
• Cognitive behavioural therapy in children and adolescents showed large effect sizes for ADHD symptoms, but with low certainty evidence.
• Mindfulness in adults showed large effect sizes for ADHD symptoms, but with low certainty evidence.
• No high certainty, long term evidence was found for any intervention.
• An online platform showing effects and evidence certainty of each intervention across age groups, time points, and outcomes (https://ebiadhd-database.org/) was developed.

The authors concluded that this review provides updated evidence to inform patients, practitioners, and guideline developers how best to manage ADHD symptoms. The online platform should facilitate the implementation of shared decision making in daily practice.

ADHD is a condition that receives much attention at present. It is far from easy to treat, and, as with all such conditions, numerous forms of so-called alternative medicine (SCAM) are claimed to be effective. Here is a (most likely incomplete) list (in fact, it is difficult to find a SCAM that is not claimed to be useful):

• Essential Fatty Acid Supplementation, specifically Omega-3 and Omega-6 fatty acids (often from fish oil or primrose oil.
• Elimination Diets, e.g. elimination of certain substances, such as artificial food colorings/additives (like the Feingold diet), refined sugar, or alleged allergens.
• Supplementation with various micronutrients, particularly Zinc, Iron, Magnesium, and broad-spectrum multivitamins/multiminerals.
• Ginkgo Biloba.
• Korean Red Ginseng.
• Bacopa Monnieri (Brahmi) an Ayurvedic herb.
• Pycnogenol, French Maritime Pine Bark Extract.
• St. John’s Wort.
• Passionflower.
• Neurofeedback, also known as EEG biofeedback or brain training. 
• Mindfulness.
• Meditation.
• Chiropractic.
• Osteopathy.
• Yoga.
• Tai Chi.
• Homeopathy.
• Acupuncture.
• Hypnotherapy. 

Of these SCAMs, just 2 are supported by some evidence. I stress ‘some’, because the authors of the above paper point out that, despite large effect sizes, the evidence should be rated as being uncertain. This seems to indicate that the primary studies are less than reliable.

What lessons can be learnt from all this? For me the two main ones are these:

IN SCAM, THERE IS MUCH MORE HYPE THAN RELIABLE EVIDENCE.

THE LESS TREATABLE A CONDITION IS, THE MORE SCAMs CLAIM EFFICACY.