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June 19, 2025
Background:
In Iceland, treatment with ADHD medication can only be initiated by psychiatrists or pediatricians with experience in diagnosing neurodevelopmental disorders. The diagnostic evaluation is most often carried out by a psychologist or psychiatrist, and must be confirmed by a psychiatrist.
Some previous studies have suggested a small but significant increased risk of psychosis or mania associated with ADHD medication, while others have not.
Iceland has a single-payer national healthcare insurance system that tracks virtually its entire population. An Icelandic research team accessed two administrative databases with nationwide coverage – the Icelandic Prescription Medicines Register and the Icelandic Hospital Discharge Register – to explore this relationship among all adults from 2010 through 2022.
They included three categories of ADHD medications prescribed in Iceland: amphetamines, including dexamphetamine and lisdexamphetamine; methylphenidate; and atomoxetine. In Iceland, methylphenidate or atomoxetine must be prescribed and tried first before switching to lisdexamphetamine or dexamphetamine.
Method:
Diagnoses of mania or psychosis recorded in electronic health records were used to identify individuals who were admitted to a psychiatric ward within one year of starting treatment with a specific class of ADHD medication. First-onset psychosis or mania was defined as the emergence of these conditions in individuals with no prior history, diagnosis, or hospitalization for psychosis or mania.
A total of 16,125 adults began using an ADHD medication for the first time during the 13-year study period.
Methylphenidate was the most used ADHD medication among those admitted for psychosis or mania (25 out of 61; 41%), reflecting its status as the most frequently prescribed stimulant during the study period. It was followed by amphetamines (21 out of 61; 34.4%) and atomoxetine (15 out of 61; 24.6%).
Half of those hospitalized had previously received a diagnosis of substance use disorder. One in nine (11%) of those hospitalized acknowledged misuse of the type of ADHD medication they had been prescribed.
Within a year of discharge, 42 out of the 61 patients (68.9%) had been prescribed an ADHD medication again. Among those, one in four (11 out of 42; 26%) were readmitted for psychosis or mania within the following year.
The team noted, “It is concerning that most patients (68.9%) in our study resumed ADHD drug treatment within a year of hospital discharge … However, some studies have reported that the use of psychostimulants or atomoxetine to treat ADHD in individuals with psychotic disorders did not increase the risk of hospitalisation for psychosis if used concurrently with antipsychotic medication or that such use might even reduce this risk.”
Findings:
By comparison with the general population, adults initiating ADHD medications had eight times the relative risk of being admitted for psychosis or mania within the first year.
The absolute risk was low: 0.38% overall for those initiating ADHD medication. Adjusting for the general population risk of hospitalization for first-onset psychosis or mania, more than 300 patients would need to be initiated to ADHD medication to generate one hospital admission for psychosis or mania.
The team conceded, “Confounders of real-life clinical settings, such as non-disclosed ADHD drug abuse or misuse or some degree of substance abuse, may have influenced our findings.”
A further, unmentioned, limitation is that the team did not perform any of the usual adjustments for confounding variables, critically including co-occurring (comorbid) psychiatric disorders known to be common with ADHD, and likely to have a major effect on the relative risk of hospitalization.
Given the very small increase in risk along with the methodological flaws, the team’s suggestion of a “potential causal role of ADHD drugs in the development of first-onset psychosis or mania” is unsubstantiated and speculative. This is especially so given other studies suggesting no increased risk for psychosis due to these medications.
In any event, causation cannot be established through observational studies.
Ragna Kristin Gudbrandsdottir, Engilbert Sigurdsson, Þorsteinn Ivar Albertsson, Halldora Jonsdottir, and Oddur Ingimarsson, “Risk of hospitalisation for first-onset psychosis or mania within a year of ADHD medication initiation in adults with ADHD,” BMJ Mental Health (2025), 28: 1–7, https://doi.org/10.1136/bmjment-2024-301521.
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:
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.
Acid-suppressive medications, including proton pump inhibitors (PPIs) and histamine-2 (H2) receptor antagonists, are often prescribed during pregnancy to treat heartburn and gastroesophageal reflux disease.
Research shows changes in the gut microbiome can negatively affect neurodevelopment. Since acid-suppressive medications alter gut microbiota, maternal use during pregnancy may impact offspring’s neurodevelopment. Because PPIs and H2 receptor antagonists readily cross the placental barrier, they could potentially influence fetal neurodevelopment.
The link between prenatal exposure to acid-suppressive medications and major neuropsychiatric disorders is not well understood. With the use of these medications during pregnancy rising, it is important to assess their impact on children's long-term neurodevelopment. This study examined whether maternal use of acid-suppressive drugs is associated with increased risk of neuropsychiatric disorders in children, using a large, nationwide birth cohort from South Korea.
South Korea operates a single-payer health insurance system, providing coverage for over 97% of its citizens. The National Health Insurance Service (NHIS) maintains a comprehensive database with sociodemographic details, medical diagnoses, procedures, prescriptions, health examinations, and vital statistics for all insured individuals.
A Korean research team analyzed data from over three million mother-child pairs (2010–2017) to assess the risks of prenatal exposure to acid-suppressing medications. They applied propensity scoring to adjust for maternal age, number of children, medical history, and outpatient visits before pregnancy, to minimize confounding factors. That narrowed the cohort to just over 800,000 pairs, with half in the exposed group.
With these adjustments, prenatal exposure to acid-suppressing medications was associated with 14% greater likelihood of being subsequently diagnosed with ADHD.
Yet, when 151,737 exposed births were compared to the same number of sibling controls, no association was found between prenatal exposure and subsequent ADHD, which suggests unaccounted familial and genetic factors influenced the preceding results.
The Take-Away:
Evidence of these medications negatively affecting pregnancies is mixed, mostly observational, and generally reassuring when these medications are used appropriately. Untreated GERD and gastritis, however, have known risks and associations with the development of various cancers. With no evidence of an association with ADHD (or for that matter any other neuropsychiatric disorder), there is no current evidence-based reason for expectant mothers to discontinue use of acid-suppressing medications.
For years, a persistent concern has shadowed the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD): Does the medication eventually stop working? Patients often report that their symptoms seem to return despite consistent use, leading to "dose escalation" or "medication holidays." A new systematic review from Sam Cortese’s team published in CNS Drugs finally puts these concerns to the test by synthesizing decades of empirical research.
Before diving into the findings, you must understand two often-confused phenomena:
The review analyzed 17 studies covering over 10,000 individuals, and the results provide a much-needed reality check for the clinical community.
The researchers found preliminary evidence that acute tolerance (tachyphylaxis) can occur within a 24-hour window.
The most important finding is that tolerance does not commonly develop to the therapeutic effects of ADHD medication in the long term. In one landmark study following children for up to 10 years, only 2.7% of participants lost their response to methylphenidate without a clear external explanation. Doses, when adjusted for natural body growth, remained remarkably stable over years of treatment.
Consistent with the lack of therapeutic tolerance, the body does not become tolerant to the physical side effects of stimulants. Increases in heart rate and blood pressure typically persist for as long as the medication is taken. This underscores why clinicians must continue monitoring cardiovascular health throughout the entire duration of treatment.
If it’s Not Tolerance, What Is It?
If "tolerance" isn't real, why do some patients feel their medication is failing? The review suggests clinicians look at these alternative explanations:
Why This Matters
These results provide clinicians the confidence to tell patients that their medication is unlikely to "wear out" permanently. Rather than immediately increasing a dose when symptoms flare, the first step should be a "clinical deep dive" into the patient's lifestyle, stress levels, and adherence.
For researchers, the review highlights a major gap: most existing studies are small, dated, or of low quality. There is a dire need for robust, longitudinal studies that track both the brain's response and the patient's environment over several years.
For people with ADHD, while your body might get "used to" the initial "buzz" of a stimulant within hours, its ability to help you focus and manage your life remains remarkably durable over the years.
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