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December 17, 2021
A team of Spanish researchers performed a systematic search of the medical literature and found 28 studies that could be included in a series of meta-analyses of specific measures of sleep impairment. Except for a single meta-analysis with eight studies and 1,713 participants, however, all involved just three to five studies apiece, with anywhere from 121 to just over a thousand participants.
The team examined three sorts of measures:
· Subjective measures, based on self-reporting by ADHD patients.
· Polysomnography is an objective sleep study in which the subject is wired up and studied by technicians in a lab, usually overnight, monitoring multiple body functions, such as brain activity, eye movements, muscle activation, and heart rhythm.
· Actigraphy, a non-invasive objective means of monitoring sleep. The subject wears an actimetry monitor, which is usually worn like a wristwatch on the non-dominant arm. Because it is minimally intrusive, the subject may wear it for a week or more while engaging in normal activities.
In the subjective measures, adults with ADHD generally reported substantially higher sleep impairments than non-ADHD controls. In the largest meta-analysis, covering eight studies and 1,713 participants, adults with ADHD reported moderately longer latency times for falling asleep than controls. In meta-analyses of five studies with between 834 and 1,130 participants, they also reported moderately poorer sleep quality, more frequent night awakenings, being moderately less rested upon awakening in the morning, and moderate-to-strongly greater daytime sleepiness. There was no significant difference in perceived sleep duration.
Polysomnography measures, on the other hand, failed to confirm these subjective impressions. No significant differences were found between adults with ADHD and controls for the initial latency period until onset of sleep, sleep efficiency, waking after the onset of sleep, total sleep time, stage one or stage two sleep, slow-wave sleep, REM (rapid eye movement) sleep, and latency period until REM sleep.
As mentioned above, polysomnography is conducted in lab settings, and therefore inevitably diverges from normal patterns of behavior. Actigraphy helps bridge that gap, by monitoring normal behavior, though with more limited types and precision of data analysis.
And indeed, a meta-analysis of four studies with 222 participants confirmed self-reports that sleep efficiency was moderate to strongly lower in adults with ADHD and that the latency period until the onset of sleep was markedly longer. On the other hand, it found no significant difference in true sleep.
The researchers also looked at prevalence statistics. Whereas the prevalence of sleep-onset insomnia in the general population has been reported in the range of 13 to 15 percent, a meta-analysis of four studies with 466 participants found fully two-thirds of adults with ADHD reporting insomnia, a greater than four-to-one ratio. Similarly, a meta-analysis of three studies with 458 participants found one-third reporting daytime sleepiness, which is twice the rate reported in the general population.
There was no sign of publication bias in any of these results. The authors cautioned, however, about the small number of studies involved, stating this "compromises the generalizability of the findings." Also, some studies included patients undergoing pharmacological treatment for ADHD, "increasing the risk of confounding results."
Moreover, "Sleep onset latency and sleep efficiency were not significantly impaired in the polysomnography, which was incongruent with the actigraphy results. This may be due to a difference in the evaluation context. Whereas polysomnography is considered the gold-standard measure to objectively assess sleep architecture, actigraphy shows a more ecological approach, with the evaluation being conducted in a more naturalistic context for a longer period. However, actigraphy has more environmental influence, which can compromise the data recorded and the interpretation of the results, whereas, in polysomnography, multiple variables can be controlled in the laboratory setting to increase the internal validity of the results. On the contrary, polysomnography studies can produce artifacts due to the unusual circumstances in the setting, so results may need to be interpreted with caution."
The authors concluded, "The results found in the present study show the relevance of addressing sleep concerns in adult populations diagnosed with neurodevelopmental conditions."
Jorge Lugo, Christian Fadeuilhe, Laura Gisbert, Imanol Setiena, Mercedes Delgado, Montserrat Corrales, Vanesa Richarte, Josep Antoni Ramos-Quiroga, "Sleep in adults with autism spectrum disorder and attention-deficit/hyperactivity disorder: A systematic review and meta-analysis," EuropeanNeuropsychopharmacology (2020),https://doi.org/10.1016/j.euroneuro.2020.07.004.
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.
The Background:
Concerns remain about how ADHD and methylphenidate (MPH) use might affect children's health and growth, and especially how it may affect their adult height. While some studies suggest disrupted growth and a possible biological mechanism, the impact of ADHD prevalence and MPH use is still unclear. Children with ADHD may develop unhealthy habits – irregular eating, low physical activity, and poor sleep – that can contribute to obesity and reduced height. MPH’s appetite-suppressing effect can lead to skipped meals or overeating. Since growth hormone is mainly released during deep sleep, chronic sleep deprivation could plausibly slow growth and impair height development; however, a clear link between ADHD, MPH use, overweight, and shorter stature has never been firmly established.
The Study:
South Korea has a single payer health insurance system that covers more than 97% of its population. A Korean research team used the National Health Insurance Service database to perform a nationwide population study to explore this topic further.
The study involved 34,850 children, of whom 12,866 were diagnosed with ADHD. Of these children, 6,816 (53%) had received methylphenidate treatment, while 6,050 (47%) had not. Each patient with ADHD was precisely matched 1:1 by age, sex, and income level to a control participant without ADHD. The sex ratio was comparable in all groups.The team used Body Mass Index (BMI) as an indicator of overweight and obesity.
The Results:
The researchers found that being diagnosed with ADHD was associated with 50% greater odds of being overweight or obese as young adults, and over 70% greater odds of severe obesity (BMI > 30) compared to matched non-ADHD controls, regardless of whether or not they were medicated.
Those diagnosed with ADHD, but not on methylphenidate, had 40% greater odds of being overweight or obese, and over 55% greater odds of becoming severely obese, relative to matched non-ADHD controls.
Methylphenidate users had 60% greater odds of being overweight or obese, and over 85% greater odds of becoming severely obese, relative to matched non-ADHD controls.
There were signs of a dose-response effect. Less than a year’s exposure to methylphenidate was associated with roughly 75% greater odds of becoming severely obese, whereas exposure over a year or more raised the odds 2.3-fold, relative to matched non-ADHD controls. Using MPH increased the prevalence of overweight from 43.2% to 46.5%, with a greater prevalence among those using MPH for more than one year (50.5%).
It is important to note that most of this effect was from ADHD itself, with methylphenidate only assuming a predominant role in severe obesity among those with longer-term exposure to the medicine.
As for height, children with ADHD were no more likely to be short of stature than matched non-ADHD controls. Being prescribed methylphenidate was associated with slightly greater odds (7%) of being short of stature, but there was no dose-response relationship.
Conclusion:
The team concluded, “patients with ADHD, particularly those treated with MPH, had a higher BMI and shorter height at adulthood than individuals without ADHD. Although the observed height difference was clinically small in both sexes and age groups, the findings suggest that long-term MPH exposure may be associated with growth and body composition, highlighting the need for regular monitoring of growth.” They also point out that “Despite these findings, the clinical relevance should be interpreted with caution. In our cohort, the mean difference in height was less than 1 cm (eg, maximum −0.6 cm in females) below commonly accepted thresholds for clinical significance.” Likewise, increases in overweight/BMI were small.
One problem with interpreting the BMI/obesity results is that some of the genetic variants that cause ADHD also cause obesity. If that genetic load increases with severity of ADHD than the results from this study are confounded because those with more severe ADHD are more likely to be treated than those with less severe ADHD.
Due to these small effects along with the many study limitations noted by the authors, these results should be considered alongside the well-established benefits of methylphenidate treatment.
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