February 10, 2026

Large Cohort Study Reports Association Between Eye Disorders and ADHD

Refractive errors, such as myopia (nearsightedness), hyperopia (farsightedness), and astigmatism (distorted vision due to irregular curvature of the eye or lens), are common worldwide. These conditions affect 12%, 5%, and 15% of children, and rise significantly in adults to 26.5%, 31%, and 40%. Additionally, strabismus (misalignment of the eyes) and amblyopia (reduced vision in one eye from uneven image formation, often linked to strabismus) occur globally at rates of 2% and 1.4%, respectively. 

Visual impairment can affect children’s concentration in school, and studies suggest a link between eye disorders and ADHD. 

To investigate this relationship, two researchers – one based in the US and the other in Israel –carried out a nationwide retrospective cohort study using electronic medical records of all insured individuals aged 5 to 30 who were part of Maccabi Health Services, Israel’s second largest health maintenance organization, between 2010 and 2022. 

Of over 1.6 million insured members (2010–2020), inclusion/exclusion criteria and propensity score matching for age and sex were applied, along with a one-year wash-out period between the first eye diagnosis and ADHD diagnosis. In total, 221,707 cases were matched with controls without eye disorders at a 1:2 ratio, resulting in a cohort of 665,121 participants.  

Overall, those with any previous eye diagnosis were 40% more likely to have a subsequent ADHD diagnosis. This was slightly higher for females (45%) than for males (35%). It was also slightly higher for children and adolescents (42%) than for adults (37%).  

More specifically: 

  • Myopia (425,000+ participants): 30% higher ADHD rate. 
  • Hyperopia (120,000+) and astigmatism (175,000+): over 50% higher ADHD rate. 
  • Strabismus (13,000+): over 60% higher ADHD rate. 
  • Amblyopia (14,000+): 40% higher ADHD rate. 

The authors concluded that eye disorders are associated with ADHD. They noted these associations were more marked in females and children and adolescents, although, as noted above, those differences were small. They recommended that primary care providers and neurologists consider risk stratification for early screening, and that ophthalmologists refer high-risk patients for ADHD evaluation. 

 

 

Asaf Israeli and Eedy Mezer, “Association between eye disorders and the development of ADHD/ADD: a nationwide retrospective cohort study,” Eye (2026), https://doi.org/10.1038/s41433-025-04227-w

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Adult ADHD and Comorbid Somatic Disease

Adult ADHD and Comorbid Somatic Disease

Although there has been much research documenting that ADHD adults are at risk for other psychiatric and substance use disorders, relatively little is known about whether ADHD puts adults at risk specifically for somatic medical disorders.  

Given that people with ADHD tend toward being disorganized and inattentive, and that they tend to favor short-term over long-term rewards, it seems logical that they should be at higher risk for adverse medical outcomes.  But what does the data say?

In a systematic review of the literature, Instances and colleagues have provided a thorough overview of this issue.  Although they found 126 studies, most were small and were of "modest quality".   Thus, their results must be considered to be suggestive, not definitive for most of the somatic conditions they studied.  

Also, they excluded articles about traumatic injuries because the association between ADHD and such injuries is well established. Using qualitative review methods, they classified associations as being a) well-established; b) tentative, or c) lacking sufficient data.

Only three conditions met their criteria for being a well-established association: asthma, sleep disorders, and obesity.  

They found tentative evidence implicating ADHD as a risk factor for three conditions: migraine headaches, celiac disease, and diseases of the circulatory system.  

These data are intriguing, but cannot tell us why ADHD people are at increased risk for somatic conditions. One possibility is that suffering from ADHD symptoms can lead to an unhealthy lifestyle, which leads to increased medical risk. Another possibility is that the biological systems that are dysregulated in ADHD are also dysregulated in some medical disorders.  For example, we know that there is some overlap between the genes that increase the risk for ADHD and those that increase the risk for obesity. We also know that the dopamine system has been implicated in both disorders.

Instances and colleagues also point out that some medical conditions might lead to symptoms that mimic ADHD. They give sleep-disordered breathing as an example of a condition that can lead to the symptom of inattention.    

But this seems to be the exception, not the rule. Other medical conditions co-occurring with ADHD seem to be true comorbidities, rather than the case of one disorder causing the other. Thus, primary care clinicians should be alert to the fact that many of their patients with obesity, asthma, or sleep disorders might also have ADHD.  

By screening such patients for ADHD and treating that disorder, you may improve their medical outcomes indirectly via increased compliance with your treatment regime and an improvement in health behaviors. We don't yet have data to confirm these latter ideas, as the relevant studies have not yet been done.

April 5, 2021

The Role of Serotonin in ADHD and Its Many Comorbidities

Serotonin is a key chemical in the body that helps regulate mood, behavior, and also many physical functions such as sleep and digestion. It has also been linked to how ADHD (attention-deficit/hyperactivity disorder) develops in the brain. This study looks at how serotonin may be involved in both the mental health and physical health conditions that often occur alongside ADHD.

It is well-established that ADHD is more than just trouble focusing or staying still. For many, it brings along a host of other physical and mental health challenges. It is very common for those with ADHD to also have other diagnosed disorders. For example, those with ADHD are often also diagnosed with depression, anxiety, or sleep disorders. When these issues overlap, they are called comorbidities. 

A new comprehensive review, led by Dr. Stephen V. Faraone and colleagues, delves into how serotonin (5-HT), a major brain chemical, may be at the heart of many of these common comorbidities.

Wait! I thought ADHD had to do with Dopamine–Why are we looking at Serotonin?

Serotonin is a neurotransmitter most often linked to mood, but its role in regulating the body has much broader implications. It regulates sleep, digestion, metabolism, hormonal balance, and even immune responses. Although ADHD has long been associated with dopamine and norepinephrine dysregulation, this review suggests that serotonin also plays a central role, especially when it comes to comorbid conditions.

The Study:

  • Objective: To systematically review which conditions commonly co-occur with ADHD and determine whether serotonin dysfunction might be a common thread linking them.

  • Method: The authors combed through existing literature up to March 2024, analyzing evidence for serotonin involvement in each comorbidity associated with ADHD.

  • Scope: 182 psychiatric and somatic conditions were found to frequently occur in people with ADHD.

Key Findings

  • 74% of Comorbidities Linked to Serotonin: Of the 182 comorbidities identified, 135 showed evidence of serotonergic involvement—91 psychiatric and 44 somatic (physical) conditions.

  • Psychiatric Comorbidities: These include anxiety disorders, depression, bipolar disorder, and obsessive-compulsive disorder—all of which have long-standing associations with serotoninergic dysfunction.

  • Somatic Comorbidities: Conditions like irritable bowel syndrome (IBS), migraines, and certain sleep disorders also showed a significant serotonergic link.

This research suggests that serotonin dysregulation could explain the diverse and sometimes puzzling range of symptoms seen in ADHD patients. It supports a more integrative model of ADHD—one that goes beyond the brain’s attention, reward and executive control circuits and considers broader physiological and psychological health.

future research into the role of serotonin could help develop more tailored interventions, especially for patients who don't respond well to stimulant medications. Future studies may focus on serotonin’s role in early ADHD development and how it interacts with environmental and genetic factors.

The Take-Away: 

This study is a strong reminder that ADHD is a complex, multifaceted condition. Differential diagnosis is crucial to properly diagnosing and treating ADHD. Clinicians' understanding of the underlying link between ADHD and its common comorbidities may help future ADHD patients receive the individualized care they need. By shedding light on serotonin’s wide-reaching influence, this study may provide a valuable roadmap for improving how we diagnose and treat those with complex comorbidities in the future. 

July 14, 2025

Analysis of ADHD Comorbidities and Additional Healthcare Costs

Claims-based real-world data can reveal population-level trends in health among people with neurodevelopmental disorders. This new study examined the prevalence, demographics, and chronic comorbidities of adults and of children and adolescents with ADHD in a large national health plan. It also compared healthcare use and costs between those with and without ADHD. 

A research team in the United States conducted an observational cohort study using claims data from more than 1.9 million adults and nearly 500,000 children and adolescents, comparing individuals diagnosed with ADHD to those without the diagnosis. 

ADHD was diagnosed in 4% of adults and in 5% of children and adolescents. 

Comorbidities By The Numbers: 

Disruptive childhood disorders are behavioral problems marked by ongoing defiance, uncooperativeness, and aggression that affect a child's daily life and relationships. The main types, oppositional defiant disorder (ODD) and conduct disorder (CD), involve persistent anger and argumentativeness in ODD, and more severe actions like aggression, cruelty, and criminal behavior in CD. Without treatment, these common childhood disorders can continue into adulthood and raise the risks of substance use, violence, incarceration, and early death. 

Disruptive childhood disorders were twenty times more frequent among children and adolescents with ADHD than among those without ADHD diagnosis, and fifteen times more frequent among adults with ADHD. 

Bipolar disorder was twelve times more common among children and adolescents with ADHD than those without ADHD, and seven times more common among adults with ADHD. 

Schizophrenia was eleven times more prevalent among children and adolescents with ADHD than those without ADHD, and three-and-a-half times more common among adults with ADHD. 

Anxiety was nine times more frequent among children and adolescents with ADHD than among those without ADHD diagnosis, and more than five times more frequent among adults with ADHD. 

Depression was eight times more common among children and adolescents with ADHD than those without ADHD, and more than five times more common among adults with ADHD. 

Suicidal ideation was eight times more prevalent, and suicide attempt seven times more prevalent, among children and adolescents with ADHD than those without ADHD. Both suicidal ideation and suicide attempt were five times more common among adults with ADHD. 

Gender dysphoria was almost six times more frequent among children and adolescents with ADHD than among those without ADHD diagnosis, and five times more frequent among adults with ADHD.  

Eating disorders were over four times more common among children and adolescents with ADHD than those without ADHD, and five times more common among adults with ADHD. 

Substance-related disorders were over six times more prevalent, and alcohol use disorder was six times more prevalent among children and adolescents with ADHD than those without ADHD, and four and three times more prevalent among adults with ADHD. 

Increased Costs of Medical Care:

These comorbidities and ADHD led to higher medical costs. Children and adolescents with ADHD spent $610 more annually on healthcare than those without, while adults with ADHD had $1,684 higher average yearly expenditures than non-ADHD adults. 

The Take-Away:

This large claims-based analysis of a national commercial insurer found ADHD diagnoses in roughly 4% of adults and 5% of children. It documented substantially higher rates of co-occurring behavioral-health conditions and markedly greater healthcare utilization and expenditures among those with ADHD. The authors report increased odds for several co-occurring diagnoses, as well as higher per-member-per-month (PMPM) spending and per-thousand-per-month (PTPM) utilization, largely driven by greater use of behavioral health services. 

Importantly, these results come from cross-sectional, claims data within a commercially insured population: they describe associations, not causal relationships, and may not generalize to uninsured, publicly insured, or otherwise different populations. These findings, therefore, warrant cautious interpretation and highlight the need for longitudinal and more representative studies to clarify drivers of the increased burden and to inform care and policy.

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

Brain Stimulation Therapy Shows No Benefit for ADHD in New Meta-analysis

ADHD is a neurodevelopmental condition rooted in delayed or atypical maturation of the prefrontal cortex  (the brain region that governs self-regulation). This maturational lag underlies the hallmark difficulties with attention, hyperactivity, and impulsivity, and also impairs what researchers call executive function: the cognitive toolkit we rely on for working memory, impulse control, mental flexibility, emotional regulation, and the ability to tolerate delays in reward. 

The Background:

Standard treatments work through two main routes. Stimulant and non-stimulant medications are considered very safe and effective treatments, but are not without risk of side effects and are not appropriate for every ADHD patient. Behavioral and psychosocial interventions can improve self-regulation and social functioning, but they require sustained effort and produce variable results. These limitations have kept the search for better alternatives active. 

One candidate that has drawn growing attention is transcranial direct current stimulation (tDCS). The technique is appealingly simple: a weak electrical current is applied to the scalp through small electrodes, modulating the excitability of neurons in the underlying cortex without requiring surgery, anesthesia, or significant discomfort. Its safety profile and ease of use have made it attractive to researchers. 

The Study: 

A newly published meta-analysis set out to give the technique its most rigorous test yet, pooling results from randomized controlled trials, including crossover designs, that compared active tDCS against sham stimulation in people with ADHD across all age groups. 

The Results: 

The findings were consistently null. Across seven trials enrolling 303 participants, tDCS produced no significant reduction in overall ADHD symptom severity compared with sham. Breaking symptoms into their components made no difference: neither hyperactivity/impulsivity nor inattention improved. Turning to executive function, 18 studies with 872 participants found no meaningful gain in inhibitory control, and 12 studies with 506 participants found the same for working memory. Smaller bodies of evidence, including three studies on cognitive flexibility (122 participants) and two on hot executive function, the motivational and emotional dimension of self-regulation (86 participants),  similarly came up empty. Variation in outcomes across studies was small to moderate, and there was no evidence of publication bias skewing the picture. 

The authors’ conclusion was succinct: tDCS was well tolerated but “did not demonstrate significant overall efficacy for core ADHD symptoms or executive functions.” 

July 2, 2026