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.
Background:
Stimulants, such as methylphenidate and amphetamines, are currently considered effective medications for treating ADHD. However, approximately one-third of patients do not have an adequate response to these treatments. Additionally, long-term adherence is relatively low, with only about half of the patients still using methylphenidate after six years.
Recently, there has been increasing attention to the concept of microdosing with psychedelic drugs such as psilocybin and LSD. A microdose typically ranges from one-tenth to one-twentieth of a recreational dose and does not produce noticeable perceptual effects or interfere with daily activities.
The Study:
A European research team recently published the findings of the first double-blind, placebo-controlled randomized clinical trial examining the safety and efficacy of repeated low doses of LSD in adults diagnosed with ADHD.
The six-week trial took place at University Hospital in Basel, Switzerland, and Maastricht University, Netherlands. Participants, aged 18 to 65, had clinical diagnoses of ADHD with moderate to severe symptoms.
The team excluded persons with a past or present diagnosis of psychotic disorders, substance use disorders, or other psychiatric or somatic disorders likely to require hospitalization or treatments.
Participants were randomly assigned in a 1:1 ratio to receive either LSD or placebo. Neither study staff nor participants were aware of the assignments until the conclusion of the trial.
During the six-week trial, participants received twice-weekly doses on-site, amounting to a total of 12 doses. Following the first and final doses, participants were asked to determine whether they had been administered LSD or a placebo in order to assess blinding. Four weeks after the conclusion of the microdosing period, participants returned for an evaluation of the treatment's safety and efficacy.
Twenty-seven of the 53 participants were randomized to receive the LSD microdosing treatment in a liquid solution, and 26 to receive placebo. Placebo consisted of the same drinking solution, minus the microdose of LSD.
The average age was 37, and 42% of participants were female. Forty-six of the 53 participants completed the study.
Out of 29 participants, 21 from the LSD group and eight from the placebo group correctly guessed their allocation, totaling 63% overall.
As assessed through the Adult ADHD Investigator Symptom Rating Scale, ADHD symptoms improved by 7.1 points in the LSD group and 8.9 points in the placebo group, with no significant difference between them.
Regarding safety, the LSD group experienced nearly double the adverse events compared to the placebo group. None of the events in either group were classified as serious. The five most frequent adverse events were headache, nausea, fatigue, insomnia, and visual alterations, occurring around three times more frequently in the LSD group than in the placebo group.
The team concluded, “although repeated low-dose LSD administration was safe in an outpatient setting, it failed to demonstrate efficacy compared with placebo in improving ADHD symptoms among adults.”
Conclusion: Microdosing with LSD did not offer significant advantages over placebo in treating ADHD symptoms, despite being physically safe and well tolerated in the trial setting. This suggests that further research is needed to explore alternative treatments for ADHD.
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Attention Deficit Hyperactivity Disorder (ADHD) is a common condition affecting children and adolescents worldwide, characterized by symptoms such as hyperactivity, impulsivity, and inattention. While traditional treatments like medication and behavioral therapy are often used, some individuals are turning to complementary and alternative therapies (CAM) for help. One such option gaining attention is acupuncture. But does it really work for ADHD?
A recent comprehensive study aimed to evaluate the effectiveness of acupuncture in treating ADHD symptoms. Here’s a breakdown of the findings, with a focus on the age groups included in the research and what these findings could mean for ADHD treatment options.
The study in question conducted a systematic review and meta-analysis (SR/MA) of acupuncture trials for ADHD, comparing its effects to traditional treatments such as pharmacotherapy and behavioral therapy. The researchers focused on acupuncture’s impact on core ADHD symptoms like hyperactivity, impulsivity, inattention, and conduct problems, while also exploring how acupuncture might help with other issues, such as learning difficulties and psychosomatic symptoms.
One key feature of this study was the inclusion of a broad age range of participants, specifically children and adolescents. These two groups are the most commonly diagnosed with ADHD, and their responses to treatments can vary significantly. Understanding how acupuncture works for these age groups is critical for evaluating its effectiveness as an ADHD treatment.
Here’s what the study found across the different age groups:
Despite these promising results, the study also highlighted several limitations:
In short, and as is so often the way of evidence-based medicine, we still can’t say with absolute certainty one way or the other. These studies may show promise in improving hyperactivity, impulsivity, inattention, and conduct problems– in both children and adolescents. However, the evidence is not yet strong enough to recommend it as a primary treatment. While it may serve as a helpful complement to standard therapies, especially for those struggling with medication side effects or access to behavioral therapy, more research is needed to establish its effectiveness.
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This New York Times article, “5 Takeaways from New Research about ADHD”, earns a poor grade for accuracy. Let’s break down their (often misleading and frequently inaccurate) claims about ADHD.
The Claim: A.D.H.D. is hard to define/ No ADHD Biomarkers exist
The Reality: The claim that ADHD is hard to define “because scientists haven’t found a single biological marker” is misleading at best. While it is true that no biomarker exists, decades of rigorous research using structured clinical interviews and standardized rating scales show that ADHD is reliably diagnosed. Decades of validation research consistently show that ADHD is indeed a biologically-based disorder. One does not need a biomarker to draw that conclusion and recent research about ADHD has not changed that conclusion.
Additionally, research has in fact confirmed that genetics do play a role in the development of ADHD and several genes associated with ADHD have been identified.
The Claim: The efficacy of medication wanes over time
The Reality: The article’s statement that medications like Adderall or Ritalin only provide short-term benefits that fade over time is wrong. It relies almost entirely on one study—the Multimodal Treatment Study of ADHD (MTA). In the MTA study, the relative advantage of medication over behavioral treatments diminished after 36 months. This was largely because many patients who had not initially been given medication stopped taking it and many who had only been treated with behavior therapy suddenly began taking medication. The MTA shows that patients frequently switched treatments. It does not overturn other data documenting that these medications are highly effective. Moreover, many longitudinal studies clearly demonstrate sustained benefits of ADHD medications in reducing core symptoms, psychiatric comorbidity, substance abuse, and serious negative outcomes, including accidents, and school dropout rates. A study of nearly 150,000 people with ADHD in Sweden concluded “Among individuals diagnosed with ADHD, medication initiation was associated with significantly lower all-cause mortality, particularly for death due to unnatural causes”. The NY Times’ claim that medications lose their beneficial effects over time ignores compelling evidence to the contrary.
The Claim: Medications don’t help children with ADHD learn
The Reality: ADHD medications are proven to reliably improve attention, increase time spent on tasks, and reduce disruptive behavior, all critical factors directly linked to better academic performance.The article’s assertion that ADHD medications improve only classroom behavior and do not actually help students learn also oversimplifies and misunderstands the research evidence. While medication alone might not boost IQ or cognitive ability in a direct sense, extensive research confirms significant objective improvements in academic productivity and educational success—contrary to the claim made in the article that the medication’s effect is merely emotional or perceptual, rather than genuinely educational.
For example, a study of students with ADHD who were using medication intermittingly concluded “Individuals with ADHD had higher scores on the higher education entrance tests during periods they were taking ADHD medication vs non-medicated periods. These findings suggest that ADHD medications may help ameliorate educationally relevant outcomes in individuals with ADHD.”
The Claim: Changing a child’s environment can change his or her symptoms.
The Reality: The Times article asserts that ADHD symptoms are influenced by environmental fluctuations and thus might not have their roots in neurobiology. We have known for many years that the symptoms of ADHD fluctuate with environmental demands. The interpretation of this given by the NY Times is misleading because it confuses symptom variability with underlying causes. Many disorders with well-established biological origins are sensitive to environmental factors, yet their biology remains undisputed.
For example, hypertension is unquestionably a biologically based condition involving genetic and physiological factors. However, it is also well-known that environmental stressors, dietary
habits, and lifestyle factors can significantly worsen or improve hypertension. Similarly, asthma is biologically rooted in inflammation and airway hyper-reactivity, but environmental triggers such as allergens, pollution, or even emotional stress clearly impact symptom severity. Just as these environmental influences on hypertension or asthma do not negate their biological basis, the responsiveness of ADHD symptoms to environmental fluctuations (e.g., improvements in classroom structure, supportive home life) does not imply that ADHD lacks neurobiological roots. Rather, it underscores that ADHD, like many medical conditions, emerges from the interplay between underlying biological vulnerabilities and environmental influences.
Claim: There is no clear dividing line between those who have A.D.H.D. and those who don’t.
The Reality: This is absolutely and resoundingly false. The article’s suggestion that ADHD diagnosis is arbitrary because ADHD symptoms exist on a continuum rather than as a clear-cut, binary condition is misleading. Although it is true that ADHD symptoms—like inattention, hyperactivity, and impulsivity—do vary continuously across the population, the existence of this continuum does not make the diagnosis arbitrary or invalidate the disorder’s biological basis. Many well-established medical conditions show the same pattern. For instance, hypertension (high blood pressure) and hypercholesterolemia (high cholesterol) both involve measures that are continuously distributed. Blood pressure and cholesterol levels exist along a continuum, yet clear diagnostic thresholds have been carefully established through decades of clinical research. Their continuous distribution does not lead clinicians to question whether these conditions have biological origins or whether diagnosing an individual with hypertension or hypercholesterolemia is arbitrary. Rather, it underscores that clinical decisions and diagnostic thresholds are established using evidence about what levels lead to meaningful impairment or increased risk of negative health outcomes. Similarly, the diagnosis of ADHD has been meticulously defined and refined over many decades using extensive empirical research, structured clinical interviews, and validated rating scales. The diagnostic criteria developed by experts carefully delineate the point at which symptoms become severe enough to cause significant impairment in an individual’s daily functioning. Far from being arbitrary, these thresholds reflect robust scientific evidence that individuals meeting these criteria face increased risks for the serious impairments in life including accidents, suicide and premature death.
The existence of milder forms of ADHD does not undermine the validity of the diagnosis; rather, it emphasizes the clinical reality that people experience varying degrees of symptom severity.
Moreover, acknowledging variability in severity has always been a core principle in medicine. Clinicians routinely adjust treatments to meet individual patient needs. Not everyone diagnosed with hypertension receives identical medication regimens, nor does everyone with elevated cholesterol get prescribed the same intervention. Similarly, people with ADHD receive personalized treatment plans tailored to the severity of their symptoms, their specific impairments, and their individual circumstances. This personalization is not evidence of arbitrariness; it is precisely how evidence-based medicine is practiced. In sum, the continuous nature of ADHD symptoms is fully compatible with a biologically-based diagnosis that has substantial evidence for validity, and acknowledging symptom variability does not render diagnosis arbitrary or diminish its clinical importance.
In sum, readers seeking a balanced, evidence-based understanding of ADHD deserve clearer, more careful reporting. By overstating diagnostic uncertainty, selectively interpreting research about medication efficacy, and inaccurately portraying the educational benefits of medication, this article presents an overly simplistic, misleading picture of ADHD.
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