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September 13, 2024
A meta-analysis of short-term, placebo-controlled, randomized clinical trials (Cortese et al. 2018), looking at both efficacy and safety, supported prescribing stimulants – methylphenidate use in children and adolescents and amphetamine use in adults – as first-choice medications.
However, these were short-term studies, and they focused on relieving ADHD symptoms. What about longer-term outcomes, especially looking more broadly at functional impairment and overall quality of life?
Sweden has a single-payer health insurance system that encompasses virtually every resident and is linked to national registers that enable researchers to conduct nationwide population studies.
A joint Finnish-Swedish research team used Sweden’s registers to study outcomes for all individuals of working age, 16 to 65 years old, living in Sweden who had received a diagnosis of ADHD from 2006 through 2021. The resulting study cohort encompassed 221,714 persons with ADHD.
The team adjusted for the following confounding variables: Genetics, baseline severity of symptoms, baseline comorbidities, temporal order of treatments (which medication was used as first, second, third, and so forth, including also nonuse of ADHD medications), time since cohort entry, and time-varying use of psychotropic drugs, including antidepressants, anxiolytics, hypnotics, mood stabilizers (carbamazepine, valproic acid, and lamotrigine), lithium, antipsychotics, and drugs for addictive disorders.
With these adjustments, they discovered that amphetamine treatment was associated with a roughly 25% reduction in psychiatric hospitalization relative to unmedicated ADHD. Lisdexamphetamine was associated with a roughly 20% reduction, dexamphetamine with a 12% reduction, and methylphenidate with a 7% reduction. All four medications are stimulants.
None of the non-stimulant medications – atomoxetine, guanfacine, clonidine – had any significant effect on psychiatric hospitalization. Nor did modafinil a drug that is not FDA approved for ADHD but is sometimes used when other drugs fail.
Amphetamine was also associated with the greatest reduction in suicide attempts or deaths, with a roughly 40% decline relative to unmedicated ADHD. Dexamphetamine was associated with a roughly 30% decline and lisdexamphetamine with a roughly 25% decline. The stimulant methylphenidate was only associated with an 8% reduction, and modafinil had no significant effect.
Surprisingly, non-stimulant medications were associated with significant increases in suicide attempts or deaths: 20% for atomoxetine, 65% for guanfacine, and almost double for clonidine.
Amphetamine and lisdexamphetamine also reduced the risk of nonpsychiatric hospitalization by more than a third compared to unmedicated ADHD. Dexamphetamine was associated with a risk reduction of more than 25%, methylphenidate with 20% lesser risk.
The non-stimulant atomoxetine was associated with a roughly 15% reduction in risk of nonpsychiatric hospitalization. But neither guanfacine nor clonidine had any significant effect.
Turning to work disability, atomoxetine was the only ADHD medication associated with a reduction – a roughly 10% improvement. All other medications had no significant effect.
The team concluded, “In this cohort study of adolescents and adults with ADHD, the use of medications for ADHD, especially lisdexamphetamine and other stimulants, was associated with decreased risk of psychiatric hospitalizations, suicidal behavior, and nonpsychiatric hospitalizations during periods when they were used compared with periods when ADHD medication was not used. Non-stimulant atomoxetine use was associated with decreased risk of work disability.”
Heidi Taipale, Jakob Bergström, Katalin Gèmes, Antti Tanskanen, Lisa Ekselius, Ellenor Mittendorfer-Rutz, and Magnus Helgesson, “Attention-Deficit/Hyperactivity Disorder Medications and Work Disability and Mental Health Outcomes,” JAMA Network Open (2024), 7(3):e242859, https://doi.org/10.1001/jamanetworkopen.2024.2859.
Cortese S, Adamo N, Del Giovane C, et al., “Comparative efficacy and tolerability of medications for attention- deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis,” Lancet Psychiatry (2018) 5(9):727-738, https://doi.org/10.1016/S2215-0366(18)30269-4.
With the growth of the Internet, we are flooded with information about attention deficit hyperactivity disorder from many sources, most of which aim to provide useful and compelling "facts" about the disorder. But, for the cautious reader, separating fact from opinion can be difficult when writers have not spelled out how they have come to decide that the information they present is factual.
My blog has several guidelines to reassure readers that the information they read about ADHD is up-to-date and dependable. They are as follows:
Nearly all the information presented is based on peer-reviewed publications in the scientific literature about ADHD. "Peer-reviewed" means that other scientists read the article and made suggestions for changes and approved that it was of sufficient quality for publication. I say "nearly all" because in some cases I've used books or other information published by colleagues who have a reputation for high-quality science.
When expressing certainty about putative facts, I am guided by the principles of evidence-based medicine, which recognizes that the degree to which we can be certain about the truth of scientific statements depends on several features of the scientific papers used to justify the statements, such as the number of studies available and the quality of the individual studies. For example, compare these two types of studies. One study gives drug X to 10 ADHD patients and reported that 7 improved. Another gave drug Y to 100 patients and a placebo to 100 other patients and used statistics to show that the rate of improvement was significantly greater in the drug-treated group. The second study is much better and much larger, so we should be more confident in its conclusions. The rules of evidence are fairly complex and can be viewed at the Oxford Center for Evidenced Based Medicine (OCEBM;http://www.cebm.net/).
The evidenced-based approach incorporates two types of information: a) the quality of the evidence and b) the magnitude of the treatment effect. The OCEBM levels of evidence quality are defined as follows (higher numbers are better:
Non-randomized, controlled studies. In these studies, the treatment group is compared to a group that receives a placebo treatment, which is a fake treatment not expected to work.
It is possible to have high-quality evidence proving that a treatment works but the treatment might not work very well. So it is important to consider the magnitude of the treatment effect, also called the "effect size" by statisticians. For ADHD, it is easiest to think about ranking treatments on a ten-point scale. The stimulant medications have a quality rating of 5 and also have the strongest magnitude of effect, about 9 or 10.Omega-3 fatty acid supplementation 'works' with a quality rating of 5, but the score for the magnitude of the effect is only 2, so it doesn't work very well. We have to take into account patient or parent preferences, comorbid conditions, prior response to treatment, and other issues when choosing a treatment for a specific patient, but we can only use an evidence-based approach when deciding which treatments are well-supported as helpful for a disorder.
A Chinese research team performed two types of meta-analyses to compare the risk of suicide for ADHD patients taking ADHD medication as opposed to those not taking medication.
The first type of meta-analysis combined six large population studies with a total of over 4.7 million participants. These were located on three continents - Europe, Asia, and North America - and more specifically Sweden, England, Taiwan, and the United States.
The risk of suicide among those taking medication was found to be about a quarter less than for unmediated individuals, though the results were barely significant at the 95 percent confidence level (p = 0.49, just a sliver below the p = 0.5 cutoff point). There were no significant differences between males and females, except that looking only at males or females reduced sample size and made results non-significant.
Differentiating between patients receiving stimulant and non-stimulant medications produced divergent outcomes. A meta-analysis of four population studies covering almost 900,000 individuals found stimulant medications to be associated with a 28 percent reduced risk of suicide. On the other hand, a meta-analysis of three studies with over 62,000 individuals found no significant difference in suicide risk for non-stimulant medications. The benefit, therefore, seems limited to stimulant medication.
The second type of meta-analysis combined three within-individual studies with over 3.9 million persons in the United States, China, and Sweden. The risk of suicide among those taking medication was found to be almost a third less than for unmediated individuals, though the results were again barely significant at the 95 percent confidence level (p =0.49, just a sliver below the p = 0.5 cutoff point). Once again, there were no significant differences between males and females, except that looking only at males or females reduced the sample size and made results non-significant.
Differentiating between patients receiving stimulant and non-stimulant medications once again produced divergent outcomes. Meta-analysis of the same three studies found a 25 percent reduced risk of suicide among those taking stimulant medications. But as in the population studies, a meta-analysis of two studies with over 3.9 million persons found no reduction in risk among those taking non-stimulant medications.
A further meta-analysis of two studies with 3.9 million persons found no reduction in suicide risk among persons taking ADHD medications for 90 days or less, "revealing the importance of duration and adherence to medication in all individuals prescribed stimulants for ADHD."
The authors concluded, "exposure to non-stimulants is not associated with a higher risk of suicide attempts. However, a lower risk of suicide attempts was observed for stimulant drugs. However, the results must be interpreted with caution due to the evidence of heterogeneity ..."
Raising children is not easy. I should know.
As a clinical psychologist, I've helped parents learn the skills they need to be better parents. And my experience raising three children confirmed my clinical experience.
Parenting is a tough job under the best of circumstances, but it is even harder if the parent has ADHD.
For example, an effective parent establishes rules and enforces them systematically. This requires attention to detail, self-control, and good organizational skills. Given these requirements, it is easy to see how ADHD symptoms interfere with parenting. These observations have led some of my colleagues to test the theory that treating ADHD adults with medication would improve their parenting skills. I know about two studies that tested this idea.
In 2008, Dr. Chronis-Toscano and colleagues published a study using a sustained-release form of methylphenidate for mothers with ADHD. As expected, the medication decreased their symptoms of inattention and hyperactivity/impulsivity. The medication also reduced the mother's use of inconsistent discipline and corporal punishment and improved their monitoring and supervision of their children.
In a 2014 study, Waxmonsky and colleagues observed ADHD adults and their children in a laboratory setting once when the adults were off medication and once when they were on medication. They used the same sustained-release form of amphetamine for all the patients. As expected, the medications reduced ADHD symptoms in the parents. This laboratory study is especially informative because the researchers made objective ratings of parent-child interactions, rather than relying on the parents' reports of those interactions. Twenty parents completed the study. The medication led to less negative talk and commands and more praise by parents. It also reduced negative and inappropriate behaviors in their children.
Both studies suggest that treating ADHD adults with medication will improve their parenting skills. That is good news. But they also found that not all parenting behaviors improved. That makes sense. Parenting is a skill that must be learned. Because ADHD interferes with learning, parents with the disorder need time to learn these skills. Medication can eliminate some of the worst behaviors, but doctors should also provide adjunct behavioral or cognitive-behavioral therapies that could help ADHD parents learn parenting skills and achieve their full potential as parents.
The Background:
ADHD and epilepsy are the two most common neurological disorders in children and adolescents. Additionally, they appear as co-diagnoses more often than chance would predict. Roughly a quarter of children with epilepsy also have ADHD, and children with ADHD face a 2.5-times greater risk of developing epilepsy than their peers.
Clinicians have long suspected that carrying both diagnoses compounds cognitive difficulties, but no rigorous quantitative review has mapped out exactly how much, or in what ways. This new meta-analysis now fills that gap.
The Study:
The team pooled data from peer-reviewed studies that included children and adolescents diagnosed with both conditions alongside at least one comparison group: children with neither condition, children with epilepsy alone, or children with ADHD alone. To capture the breadth of thinking skills, they constructed a general intelligence factor drawing on six cognitive domains:
The Results:
Across eleven studies (995 participants), children and adolescents with both conditions scored moderately lower on general intelligence than those with epilepsy alone. The same pattern held across all six cognitive domains. Seven studies (785 participants) comparing the dual-diagnosis group with those who had ADHD alone found an equally consistent moderate deficit, replicated in every domain.
The clearest signal emerged when researchers compared children and adolescents carrying both diagnoses to typically-developing peers. Seven studies covering 427 individuals revealed a substantially larger gap in general intelligence, with the effects of the two conditions appearing to be roughly additive, meaning the combined burden was approximately equal to the sum of each condition's individual impact. This pattern held across five of the six domains.
The Interpretation:
The results come with meaningful caveats. Variability across individual studies was moderate in the first two comparisons and high in the third, reflecting real differences in how studies were designed, which populations they sampled, and how they measured cognition. While there was no sign of publication bias in the first group, it was not assessed in two of the three analyses.
The authors describe “a widespread profile of cognitive dysfunction” in children and adolescents with both epilepsy and ADHD, while underscoring that the substantial variability between studies warrants caution in drawing overly precise conclusions. The findings nonetheless carry practical weight: children managing both conditions may need more intensive cognitive screening and support than current clinical practice routinely provides.
The focus on children and adolescents with ADHD often revolves around behavioral issues and academic difficulties, but the social struggles are real. Around 60% of youth with ADHD experience meaningful difficulties in social skills, reading social cues, and forming reciprocal relationships with peers. Over time, these struggles can raise the risk of anxiety and depression.
Medication remains the primary treatment for ADHD, with stimulants like methylphenidate (Ritalin) being the most commonly prescribed. While effective at reducing core symptoms such as inattention and impulsivity, medication has not been shown to improve social behavior or peer relationships.
The Background:
Exercise has recently emerged as a promising adjunctive therapy. A newly published meta-analysis examined whether structured physical activity can specifically improve social functioning in young people with ADHD. It builds on a previous review from 2015, addressing gaps that earlier work left open: social outcomes were rarely treated as a primary focus, and no prior analysis had systematically compared exercise types or asked how much exercise is actually needed to see benefits.
The Study:
The analysis included 13 randomized controlled trials involving 703 participants aged 6 to 18, all clinically diagnosed with ADHD. Only exercise programs lasting at least four weeks were considered. Studies that combined exercise with other therapies, such as psychotherapy, were excluded to isolate exercise's specific effects.
The researchers used a technique called network meta-analysis, which allows different interventions to be compared against one another even when they haven't been tested head-to-head, alongside dose-response modeling to identify how much exercise produces the greatest benefit.
Results:
The most striking results came from closed-skill exercise: across four studies involving 92 participants, it was associated with a very large reduction in social dysfunction. Open-skill exercise, by contrast, showed no measurable improvement across four studies with 91 participants. Multicomponent exercise (the group combining elements of both open- and closed-skill) reported large gains in two smaller studies with 33 participants.
Mind-body exercise showed a moderate benefit across three studies involving 44 participants.
The dose-response analysis offered a practically useful finding: 30 to 60 minutes of moderate-intensity exercise per day appeared to produce the best outcomes, with a minimum of roughly 15 to 30 minutes daily needed to achieve any meaningful benefit.
The Take-Away:
The results are encouraging but should be interpreted carefully. The number of studies in each category was small (two to three studies each), and sample sizes were modest, meaning the findings may not hold up as more evidence accumulates. The absence of publication bias is reassuring, as is the use of rigorous methodology, but this remains an early-stage evidence base. Larger, well-designed trials are needed before firm clinical recommendations can be made.
For now, the findings position structured physical activity (particularly closed-skill and multicomponent exercise) as a plausible complement to existing ADHD treatment, specifically targeting the social difficulties that medication tends not to address. The practical dose guidance is a useful starting point: around half an hour of moderate daily exercise as a minimum, with an hour as the apparent sweet spot. As low-risk additions to a treatment plan go, that’s a relatively accessible bar for most families to consider alongside professional guidance.
Exercise has attracted growing attention as an intervention for ADHD. As a potential treatment option for ADHD, it is, of course, highly appealing because it can be low- to no-cost, widely accessible, and free of the side effects that can accompany medication. From previous studies, we know that certain types of exercise may be more effective than others, but do we actually know enough for clinicians to prescribe physical activity as a treatment for ADHD?
The First Study: Effects on Core ADHD Symptoms
Despite encouraging findings in individual studies, researchers have lacked clear guidance on which types of exercise work best, at what intensity, and for how long. A meta-analysis by Chen et al. set out to address this by pooling data from 20 randomized controlled trials (RCTs) involving 841 children and adolescents aged 4–18, all of which compared exercise interventions against non-exercising control groups.
The results were cautiously optimistic. Across standardized symptom scales, exercise produced a small improvement in ADHD symptoms overall. Objective cognitive tests showed a moderate improvement. Emotional and behavioral outcomes, however, showed no significant change.
To understand what was driving differences between studies, the researchers broke results down by exercise type. Therapeutic and alternative exercises (targeted movements and specific techniques such as those prescribed by physical therapists) were associated with moderate symptom improvements. Mind-body practices (such as yoga or tai chi) showed small-to-moderate gains. Conventional aerobic exercise yielded smaller effects, while skill-based competitive sports showed no measurable benefit. Notably, the variability between individual studies remained high throughout, meaning these categories should be interpreted with some caution.
Results:
The authors recommend that clinicians and parents consider incorporating therapeutic or alternative exercise sessions twice a week, each lasting 60–90 minutes, as a supplemental strategy alongside existing ADHD treatment. They stop short of calling this definitive, noting that future research should clarify how exercise produces its effects and how it might best be combined with medication or behavioral therapy.
The Second Study: Effects on Inhibitory Control
A second meta-analysis, by Zhang et al., zoomed in on a specific and particularly relevant cognitive challenge in ADHD: inhibitory control. Inhibitory control refers to the ability to suppress impulsive responses and tune out irrelevant distractions. This capacity underlies much of the restlessness, interrupting, and difficulty staying on task that characterize the condition.
This analysis drew on 34 studies with over 1,300 participants spanning all age groups, making it broader in scope than the Chen et al. review. Overall, exercise was associated with a moderate improvement in inhibitory control. When the analysis was restricted to RCTs alone, this finding held up. When studies with a high risk of bias were excluded, however, the effect size dropped to small-to-moderate.
One notable null result: three studies that used EEG to measure brain activity during inhibitory tasks found no significant effects on the neural signatures most closely tied to this process. This suggests exercise may influence behavior without necessarily changing the underlying brain mechanisms researchers expected, or that current methods aren't yet sensitive enough to detect such changes.
The dosing question produced some of the more practically useful findings. Single exercise sessions yielded only borderline small improvements. Sustained exercise programs, by contrast, showed moderate improvements, and programs with sessions three times per week produced large gains and had the strongest effect between the two meta-analyses. Exercise intensity and total program duration, perhaps interestingly, were not significant factors.
Results:
The authors are measured in their conclusions: exercise shows a real but modest benefit for inhibitory control, and frequency appears to matter more than intensity. They caution against overstating the case for exercise as treatment for ADHD overall, as it did not significantly affect hyperactivity or impulsivity as standalone outcomes, and its neural effects remain unclear.
The Broader Picture :
Ultimately, these two meta-analyses support exercise as a meaningful supplemental intervention for ADHD, particularly for attention and cognitive control, while urging realistic expectations. Neither suggests exercise should replace established treatments. Both are limited by high variability across the underlying studies, and both call for better-designed research to sharpen the guidance available to clinicians and families.
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