May 22, 2024

Meta-analysis from Worldwide Data Finds Greater Co-occurrence of Epilepsy and ADHD Than Expected

Noting that the degree of comorbidity (co-occurrence) between epilepsy and ADHD “has never been quantified based on a systematic review with meta-analysis,” a Chinese study team based at Wuhan university has just reported findings based on doing just that. 

Their systematic search of the peer-reviewed medical literature yielded 17 studies examining the prevalence of epilepsy among persons with ADHD, and 49 studies measuring the prevalence of ADHD among persons with epilepsy.

According to the Apple dictionary app, epilepsy is “a neurological disorder marked by sudden recurrent episodes of sensory disturbance, loss of consciousness, or convulsions, associated with abnormal electrical activity in the brain.” Its lifetime prevalence in the general population is about 0.76%, or about one in every 130 persons.

Meta-analysis of 17 studies with a combined total of over 900,000 participants spread over twelve countries on five continents yielded an epilepsy prevalence estimate of 3.4% among individuals with ADHD, or well over four times the prevalence in the general population. There was no sign of publication bias, but variability (heterogeneity) among studies was extremely high.

The worldwide prevalence of ADHD in children, on the other hand, is about 7.2%, affecting roughly one in fourteen.

Meta-analysis of 49 studies with a combined total of 172,206 persons from 16 countries on five continents reported an ADHD prevalence of just over 22% among persons with epilepsy. However, heterogeneity among studies was extremely high, and there was very strong evidence of publication bias. 

Using the trim-and-fill correction for publication bias yielded a reduced estimate of 16%, which is still over twice the prevalence in the general population.

Furthermore, the authors noted, “Given that the large sample studies in this study are basically population-based studies and the small sample studies are hospital-based studies, there is also the possibility of Berkson’s bias. Specifically, patients with comorbidities are more likely to need help or seek medical advice. This possibility would yield a higher comorbidity rate in hospital-based studies.”

And that is exactly what emerged from subgroup analysis. The prevalence of ADHD in epilepsy among the hospital-based studies was 27.1%, over twice the 13.2% prevalence reported from the 13 population-based studies. The largest population-based study, a U.S. study with over 114,000 participants, yielded a prevalence of only 3.5%.

The authors cautioned that the very high degree of heterogeneity between studies indicates “it is inappropriate to consider the summary effect as representative of the real effect.”

Shun, Wang & Yao, Baozhen & Haiju, Zhang & Xia, Liping & Yu, Shiqian & Peng, Xia & Xiang, Dan & Liu, Zhongchun. (2023). Comorbidity of epilepsy and attention-deficit/hyperactivity disorder: a systematic review and meta-analysis. Journal of Neurology. 270. 1-13. 10.1007/s00415-023-11794-z.

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Precision Matters: A Response to the Evolving Language of ADHD

Language is powerful. The words we choose not only reflect our understanding of the world but also actively shape it. Recently, this truth has been at the center of a growing debate in the mental health field regarding how we talk about ADHD.  

In a recent paper published in The Lancet Psychiatry titled “The Power of Words: Respectful Language in ADHD Research,” French and colleagues advocated for a shift toward "neurodiversity-affirmative language”. Rooted in the social model of disability, their proposal encourages researchers to abandon traditional medical terminology, e.g., words like disorder and deficit, in favor of more neutral terms such as condition and challenge.  

My colleague, Dr. Michael Miller, and I read this with great interest. We completely agree that revising language is essential to good science and that, both as researchers and as human beings, we are ethically bound to speak respectfully. However, we felt compelled to write a response. In our new paper, we argue that while language must evolve, it must do so scientifically. 

The Two Prerequisites for Language Change 

If we are going to fundamentally shift our scientific lexicon, two requirements must be met: 

  1. A clear consensus among those with lived experience that the current language is harmful and that new language is needed. 
  1. A commitment to scientific accuracy and precision in the new terms. 

Currently, the proposal by French and colleagues meets neither requirement. While they claim consensus is accumulating that certain terms are disrespectful, they provide zero empirical evidence that this view is shared by the community of individuals living with ADHD. Even proponents of patient-centered language admit there is surprisingly little data supporting specific language changes. 

More alarmingly, the recommended changes severely dilute the scientific accuracy of our field. Let’s look at two examples. 

Why a "Deficit" is Not Just a “Challenge" 

French and colleagues suggest replacing the term deficit with challenge. On the surface, challenge sounds softer and more affirming. But scientifically, these words are not interchangeable. 

For decades, the term deficit has been defined by a specific performance metric that falls substantially below an expected level. It is a measurable reality. A challenge, on the other hand, refers to a new or difficult task that tests someone's ability.  

Every single human being is "challenged" by complex neuropsychological tests, but only some individuals who face that challenge demonstrate scientifically significant deficits. If we relabel measurable deficits as universal challenges, we sacrifice the exactness required to communicate scientific findings and accurately measure the effects of life-changing treatments. 

ADHD is a Disorder, Not Just a "Condition" 

Another proposal is to replace the word disorder with condition

In mainstream psychiatry, a disorder is a clinically significant disturbance that causes distress or disability. The word purposefully separates natural human variation from the suffering (pathos) that gives pathology its meaning.  

Condition is a completely neutral term. Pregnancy is a condition. Being tall is a condition. Calling ADHD a condition distances the diagnosis from the profound suffering it can cause.   

French et al. argue against framing ADHD as a disorder because it exists on a spectrum without a clear cutoff, its manifestation is context-dependent, and its definition evolves. But if we apply that logic across all of medicine, the concept of disease unravels: 

  • Are hypertension and osteoporosis no longer diseases because they rely on dimensional thresholds? 
  • Is asthma no longer a disease because its manifestation depends heavily on environmental context? 
  • Was multiple sclerosis not a disease before modern imaging allowed us to physically see brain lesions? 

The Real-World Danger of Imprecise Language 

This is not merely an academic debate over semantics. The language we use has real-world implications. In the United States and across the globe, our healthcare, educational, and legal systems run on precise medical language. Terms like impairment, dysfunction, and disorder are legally and administratively required to justify support services, workplace accommodations, specialized educational therapies, and medications. The language of pathology in diagnostic manuals regulates the flow of these resources. 

If we reclassify ADHD as a neutral condition characterized only by challenges, we risk erecting massive bureaucratic barriers. Imprecise language could easily be used by institutions or insurance companies to deny vital care to the people who need it most. 

The Need for Lexical Discipline 

Attempting to characterize a clinical disorder entirely through its strengths happens in a scientific vacuum. We cannot ignore the vast body of rigorous evidence confirming that ADHD meets the long-standing criteria used by mental health science to identify clinical disorders. 

As professionals, our respect for the ADHD community demands a commitment to language that is clear, correct, and evidence-based. To build genuine consensus about how we talk about ADHD, we need meaningful, collaborative dialogue that integrates compelling empirical data and rigorous theory. 

This standard of "lexical discipline" is not just a technical preference.  It is a vital mechanism through which science and the mental health professions uphold their duty to society. 

July 14, 2026

Finding the Sweet Spot: Comprehensive Meta-Analysis Reveals the Limits of ADHD Medication Dosing

The First Comprehensive Dose-effect Network Meta-analysis of ADHD Medications:

For many ADHD patients, getting properly diagnosed and starting meds is only half the battle. The next step is figuring out the exact right dose. Historically, clinical guidelines have provided scant guidance on this critical step. This lack of direction can inadvertently foster two extremes in clinical practice: therapeutic inertia (settling for a subtherapeutic dose that leaves symptoms undertreated) or uncritical escalation (driving doses higher and higher beyond licensed limits without meaningful benefit).

To clear up this pharmacological gray area, an international team of researchers published the first comprehensive dose-effect network meta-analysis of ADHD medications in The Lancet Psychiatry. By pulling together a massive vault of clinical trial data, they mapped out exactly how efficacy and tolerability shift as doses increase.

The Study:

Traditional meta-analyses evaluate head-to-head, pairwise data, comparing one drug at a specific dose directly against a placebo. However, this study utilized an advanced Bayesian hierarchical network model using restricted cubic splines.

This mathematical framework allowed the researchers to combine both direct trial data and indirect evidence simultaneously across 113 double-blind randomized controlled trials (RCTs). In total, the study evaluated data from 14,138 children/adolescents and 11,016 adults. By standardizing various formulations into basic equivalents (e.g., converting amphetamines to dextroamphetamine equivalents), they created a clear, unified map of dose ranges.

The Results: 

The study yielded distinct dose-response curves depending on the patient's age and the specific medication class. Rather than a linear trend in which "more medicine equals more benefit," most treatments reach a clear statistical plateau or ceiling.

For Children and Adolescents (under 18)

In the pediatric population, medications hit clear peak efficacy boundaries:

  • Methylphenidate: Average efficacy peaked at roughly 45 mg/day. Beyond this, curves suggested a minor dip in efficacy, though with wide credible intervals (high uncertainty).
  • Amphetamines: Reached their peak average benefit at approximately 25 mg/day
  • Guanfacine: Maxed out its clinical benefit at around 4mg/day.

For both amphetamines and guanfacine, escalating the dosage past these points resulted in U-shaped curves, meaning further dose hikes yielded diminishing group-level symptom reduction.

For Adults (18 and older)

Adult profiles showed slightly different trajectories:

  • Amphetamines: Reached a distinct clinical plateau at roughly 50 mg/day. Pushing the dose higher did not improve average symptom relief.
  • Methylphenidate: Interestingly, adult data showed a continuous increase in efficacy across the observed dose range, though with diminishing incremental improvements as it approached 50 mg/day. The researchers noted this lack of a distinct plateau might be due to sparse trial data in higher-dose adult brackets.

The ultimate goal of this landmark analysis is to guide shared decision-making between clinicians, patients, and families. The results send a dual message to the medical community:

  1. Avoid Therapeutic Inertia: Clinicians should not hesitate to optimize doses and titrate upward from low starting doses if a patient's ADHD symptoms remain insufficiently controlled. Subtherapeutic dosing remains a widespread issue that impairs long-term treatment adherence.
  2. Rethink Routine Escalation: At the patient-group level, there is no compelling statistical evidence that routinely pushing past FDA-licensed maximum limits provides additional clinical benefit—but it reliably exposes patients to higher risks of side effects and reduced tolerability.
The Takeaway:

A medication's true efficacy hinges on its tolerability, typically measured by how often patients discontinue treatment due to severe side effects. For amphetamines, this dropout risk scales linearly with dosage, notably exceeding placebo in children above 25 mg/day and becoming prominent in adults past 50 mg/day. In contrast, methylphenidate shows no clear dose-dependent dropout risk in pediatric patients, whereas adults face a steep risk curve: increasing the dose from 60 mg/day to 90 mg/day raises the dropout risk from 7.3% to 10.0% for only modest symptom relief. Finally, youth taking guanfacine experience a sharp climb in discontinuation risks, reaching a 9.8% median risk at 4 mg/day before data limitations obscure further trends.  

The authors strongly emphasize that these findings represent group averages. Because individual metabolism, genetics, and comorbidities vary widely, some specific patients may legitimately require and tolerate higher off-label doses. However, if an unusually high dose is needed, the study suggests it should prompt a careful clinical pause, either to reassess for co-occurring conditions (like anxiety, autism, or sleep disorders) or to manage realistic expectations regarding what the medication can achieve.

July 10, 2026

What is The Pharmaceutical Supply Chain? Addressing The ADHD Medication Shortage

The persistent shortage of ADHD medications has been more than a simple annoyance for patients at the pharmacy; the inconsistent availability of these medications has had deep impacts on the daily lives of those struggling without them. While public discourse has pointed fingers at over-prescribing or at restrictive DEA quotas, a recent economic evaluation in JAMA Health Forum suggests we’ve been looking in the wrong direction for an answer to what is causing this. 

The reality of the shortage is less about increased demand and more about a fragile, globalized supply chain that snapped at a critical link. 

Debunking the "Quota Myth":

The prevailing narrative suggested that the Drug Enforcement Administration (DEA) was stifling production by refusing to raise quotas. However, the data tells a different story. In 2022, manufacturers collectively met only about 70% of their allotted production quotas. 

So we know that the problem wasn't that this DEA quota ceiling was too low. In fact, most manufacturers couldn't even reach it. Even when accounting for exports and domestic retail, production remained significantly below the legal limit. Even if the DEA had doubled its quotas, these medications still likely wouldn't have magically appeared on pharmacy shelves. 

The most striking finding in the study is the correlation between the shortage and a sharp decline in the import of raw Active Pharmaceutical Ingredients (APIs).  For the past decade, Germany has accounted for over 85% of US amphetamine imports. In 2022, these imports dropped by approximately 36.7%.  When the API doesn't arrive at the factory, production for medium and small manufacturers grinds to a halt. Unlike larger pharmaceutical giants, these smaller players often lack the inventory cushion or flexibility to quickly pivot to a new supplier. 

When the primary supply of amphetamine-based stimulants (like Adderall) faltered, it triggered a secondary crisis. Patients and clinicians, seeking alternatives, shifted toward lisdexamfetamine (Vyvanse) and methylphenidate (Ritalin/Concerta). 

  • Substitution Strain: This sudden migration of millions of patients created a domino effect, eventually leading to shortages in those medications as well. 
  • The Tolerance Gap: As any clinician knows, these stimulants are not perfect substitutes. Switching a stabilized patient to a different class of medication often leads to a trial-and-error period that may be characterized by poor tolerability or reduced efficacy. 

If we view this shortage purely through a regulatory or clinical lens, we miss the underlying cause of the crisis. The pharmaceutical industry has become a victim of its reliance on "just-in-time manufacturing” and highly concentrated sourcing.  Because over 30% of APIs for the US market are produced in just one or two facilities globally, the system isn't just inefficient; it’s brittle. We are, in a sense, trapped in a system that prioritizes cost-reduction over the resilience required for public health. 

The researchers suggest several policy shifts to prevent a repeat of this supply chain failure: 

  1. Increased Transparency: The FDA should require manufacturers to disclose their specific API suppliers. 
  1. Risk Assessment: Identifying "vulnerable" drugs that rely on fewer than three production facilities worldwide. 
  1. Regulatory Flexibility: Streamlining the process for manufacturers to switch API suppliers during a documented national shortage. 

The ADHD medication shortage wasn't a failure of clinical oversight or a sudden surge in "TikTok-driven diagnoses”, as many have suggested. It was a failure of logistics. It reminds us that the path from a lab in Germany to a patient's hand in the US is far more precarious than we realized. 

July 6, 2026