ADHD
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.
It has been reported that a five-year-old boy died after being “incinerated” inside a pressurised oxygen chamber while undergoing alternative treatment for ADHD and sleep apnoea. Thomas Cooper was pronounced dead at the scene on Jan 31 at the Oxford Center in Detroit. The following people have been charged in connection with the boy’s death:
- The center’s founder and chief executive, Tamela Peterson, 58, was charged with second-degree murder.
- The facility’s manager Gary Marken, 65, and safety manager Gary Mosteller, 64, were charged with second-degree murder and involuntary manslaughter.
- The operator of the chamber when it exploded, Aleta Moffitt, 60, was charged with involuntary manslaughter and intentionally placing false medical information on a medical records chart.
The boy was undergoing hyperbaric oxygen therapy, which involves breathing pure oxygen in a pressurised chamber.
A hyperbaric chamber at the Oxford Center Credit: David Guralnic
“A single spark it appears ignited into a fully involved fire that claimed Thomas’s life within seconds,” Dana Nessel, Michigan’s Attorney General, explained. “Fires inside a hyperbaric chamber are considered a terminal event. Every such fire is almost certainly fatal and this is why many procedures and essential safety practices have been developed to keep a fire from ever occurring,” she added.
Thomas had been undergoing unapproved treatment for ADHD and sleep apnoea
Ms Nessel accused those charged of putting children’s bodies at risk through unaccredited and debunked treatments for profit. Raymond Cassar, the attorney for centre manager Mr Marken, said the second-degree murder charge comes as “a total shock”. “This was a tragic accident and our thoughts and our prayers go out to the family of this little boy. “I want to remind everyone that this was an accident, not an intentional act. We’re going to have to leave this up to the experts to find out what was the cause of this.”
Ms Nessel said. “The Oxford Center routinely operated sensitive and lethally dangerous hyperbaric chambers beyond their expected service lifetime and in complete disregard of vital safety measures and practices considered essential by medical and technical professionals.”
Approximately 30% of children diagnosed with attention-deficit/hyperactivity disorder (ADHD), the most prevalent mental health disorder in children worldwide, do not respond to conventional pharmaceutical treatments. Previous studies of homeopathic treatment for ADHD have been inconclusive. The objectives of this randomized double-blind placebo-controlled clinical trial were to determine if there
- (a) is an overall effect of homeopathic treatment (homeopathic medicines plus consultation) in the treatment of ADHD;
- (b) are any specific effects the homeopathic consultation alone in the treatment of ADHD;
- (c) are any specific effects of homeopathic medicines in the treatment of ADHD.
Children aged 6-16 years diagnosed with ADHD were randomized to one of three arms:
- Arm 1 (Remedy and Consultation);
- Arm 2 (Placebo and Consultation);
- Arm 3 (Usual Care).
The primary outcome was the change of CGI-P T score between baseline and 28 weeks.
There was an improvement in ADHD symptoms as measured by the Conner 3 Global Index-Parent T-score in the two groups (Arms 1 and 2) that received consultations with a homeopathic practitioner when compared with the usual care control group (Arm 3). Parents of the children in the study who received homeopathic consultations (Arms 1 and 2) also reported greater coping efficacy compared with those receiving usual care (Arm 3). There was no difference in adverse events among the three study arms.
The authors concluded that, in this study, homeopathic consultations provided over 8 months with the use of homeopathic remedy was associated with a decrease in ADHD symptoms in children aging 6-16 years when compared with usual treatment alone. Children treated with homeopathic consultations and placebo experienced a similar decrease in ADHD symptoms; however, this finding did not reach statistical significance when correcting for multiple comparisons. Homeopathic remedies in and of themselves were not associated with any change in ADHD symptoms.
This is an interesting study. It – yet again! – confirms that the effects observed after homeopathic treatments are not due to the remedie but are caused by the interaction with the homeopath. To put it more clearly:
HOMEOPATHIC REMEDIES HAVE NO SPECIFIC EFFECTS; ANY BENEFITS ARE DUE TO THE EFFECTS OF THE THERAPEUTIC ENCOUNTER AND OTHER NON-SPECIFIC EFFECTS.
Guest post by Jan Oude-Aost
ADHD is a common disorder among children. There are evidence based pharmacological treatments, the best known being methylphenidate (MPH). MPH has kind of a bad reputation, but is effective and reasonably safe. The market is also full of alternative treatments, pharmacological and others, some of them under investigation, some unproven and many disproven. So I was not surprised to find a study about Ginkgo biloba as a treatment for ADHD. I was surprised, however, to find this study in the German Journal of Child and Adolescent Psychiatry and Psychotherapy, officially published by the “German Society of Child and Adolescent Psychiatry and Psychotherapy“ (Deutsche Gesellschaft für Kinder- und Jugendpsychiatrie und Psychotherapie). The journal’s guidelines state that studies should provide new scientific results.
The study is called “Ginkgo biloba Extract EGb 761® in Children with ADHD“. EGb 761® is the key ingredient in “Tebonin®“, a herbal drug made by “Dr. Wilma Schwabe GmbH“. The abstract states:
“One possible treatment, at least for cognitive problems, might be the administration of Ginkgo biloba, though evidence is rare.This study tests the clinical efficacy of a Ginkgo biloba special extract (EGb 761®) (…) in children with ADHD (…).“
“Eine erfolgversprechende, bislang kaum untersuchte Möglichkeit zur Behandlung kognitiver Aspekte ist die Gabe von Ginkgo biloba. Ziel der vorliegenden Studie war die Prüfung klinischer Wirksamkeit (…) von Ginkgo biloba-Extrakt Egb 761® bei Kindern mit ADHS.“ (Taken from the English and German abstracts.)
The study sample (20!) was recruited among children who “did not tolerate or were unwilling“ to take MPH. The unwilling part struck me as problematic. There is likely a strong selection bias towards parents who are unwilling to give their children MPH. I guess it is not the children who are unwilling to take MPH, but the parents who are unwilling to administer it. At least some of these parents might be biased against MPH and might already favor CAMmodalities.
The authors state three main problems with “herbal therapy“ that require more empirical evidence: First of all the question of adverse reactions, which they claim occur in about 1% of cases with “some CAMs“ (mind you, not “herbal therapy“). Secondly, the question of drug interactions and thirdly, the lack of information physicians have about the CAMs their patients use.
A large part of the study is based on results of an EEG-protocol, which I choose to ignore, because the clinical results are too weak to give the EEG findings any clinical relevance.
Before looking at the study itself, let’s look at what is known about Ginkgo biloba as a drug. Ginkgo is best known for its use in patients with dementia, cognitive impairment und tinnitus. A Cochrane review from 2009 concluded:
“There is no convincing evidence that Ginkgo biloba is efficacious for dementia and cognitive impairment“ [1].
The authors of the current Study cite Sarris et al. (2011), a systematic review of complementary treatment of ADHD. Sarris et al. mention Salehi et al. (2010) who tested Ginkgo against MPH. MPH turned out to be much more effective than Ginkgo, but Sarris et al. argue that the duration of treatment (6 weeks) might have been too short to see the full effects of Ginkgo.
Given the above information it is unclear why Ginkgo is judged a “possible“ treatment, properly translated from German even “promising”, and why the authors state that Ginkgo has been “barely studied“.
In an unblinded, uncontrolled study with a sample likely to be biased toward the tested intervention, anything other than a positive result would be odd. In the treatment of autism there are several examples of implausible treatments that worked as long as parents knew that their children were getting the treatment, but didn’t after proper blinding (e.g. secretin).
This study’s aim was to test clinical efficacy, but the conclusion begins with how well tolerated Ginkgo was. The efficacy is mentioned subsequently: “Following administration, interrelated improvements on behavioral ratings of ADHD symptoms (…) were detected (…).“ But the way they where “detected“ is interesting. The authors used an established questionnaire (FBB-HKS) to let parents rate their children. Only the parents. The children and their teachers where not given the FBB-HKS-questionnaires, inspite of this being standard clinical practice (and inspite of giving children questionnaires to determine changes in quality of life, which were not found).
None of the three problems that the authors describe as important (adverse reactions, drug interactions, lack of information) can be answered by this study. I am no expert in statistics but it seems unlikely to me to meaningfully determine adverse effects in just 20 patients especially when adverse effects occur at a rate of 1%. The authors claim they found an incidence rate of 0,004% in “700 observation days“. Well, if they say so.
The authors conclude:
“Taken together, the current study provides some preliminary evidence that Ginkgo biloba Egb 761® seems to be well tolerated in the short term and may be a clinically useful treatment for children with ADHD. Double-blind randomized trials are required to clarify the value of the presented data.“
Given the available information mentioned earlier, one could have started with that conclusion and conducted a double blind RCT in the first place!
“Clinical Significance
The trends of this preliminary open study may suggest that Ginkgo biloba Egb 761® might be considered as a complementary or alternative medicine for treating children with ADHD.“
So, why do I care? If preliminary evidence “may suggest“ that something “might be considered“ as a treatment? Because I think that this study does not answer any important questions or give us any new or useful knowledge. Following the journal’s guidelines, it should therefore not have been published. I also think it is an example of bad science. Bad not just because of the lack of critical thinking. It also adds to the misinformation about possible ADHD treatments spreading through the internet. The study was published in September. In November I found a website citing the study and calling it “clinical proof“ when it is not. But child psychiatrists will have to explain that to many parents, instead of talking about their children’s health.
I somehow got the impression that this study was more about marketing than about science. I wonder if Schwabe will help finance the necessary double-blind randomized trial…
[1] See more at: http://summaries.cochrane.org/CD003120/DEMENTIA_there-is-no-convincing-evidence-that-ginkgo-biloba-is-efficacious-for-dementia-and-cognitive-impairment#sthash.oqKFrSCC.dpuf