Methylphenidate and atomoxetine use do not increase a pregnant woman’s risk for miscarriage or congenital anomalies in the fetus, finds a new systematic review and meta-analysis published in JAMA Network Open.¹

The review included 10 studies involving 16.5 million pregnant women from 6 countries. It is the first study to compare pregnant women with ADHD who took methylphenidate or atomoxetine with pregnant women with ADHD who did not take these medications, as well as with pregnant women who did not have ADHD or take these medications.

The study, which helps to fill in the gaps of a still-evolving research landscape, has critical implications for millions of women of reproductive age. Medications for ADHD including atomoxetine and methylphenidate are classified by the FDA as “pregnancy category C,” indicating a lack of controlled studies. As a result, no definitive guidelines yet exist for prescribers, though recent research has demonstrated that many ADHD medications are safe for use in pregnancy. In 2020, a qualitative review of eight studies found “no convincing evidence to indicate that prenatal exposure to ADHD medication results in clinically significant adverse effects.”² In 2023, a large population-based register study concluded that taking ADHD medication, including stimulants, while pregnant does not impact the neurodevelopment or growth of the fetus.³

Historically, some research has suggested that using certain ADHD medications during pregnancy may pose risks to the fetus. One such study from 2018 found a slight association between the use of methylphenidate (though not amphetamine) and some cardiac malformations in infants.⁴

More recent research focused on maternal health has revealed that continued use of ADHD medication during pregnancy may have protective effects for mothers. A 2022 study published in Frontiers in Reproductive Health found that women with ADHD who were unmedicated during pregnancy were significantly more likely than their non-ADHD counterparts to experience adverse health outcomes including depressive episodes, postpartum depression, gestational hypertension, and cardiac disease. Pregnant women with ADHD who took medication, stimulants or non-stimulants, demonstrated lower risks of these conditions.⁵

ADHD and Pregnancy: Further Research Needed

According to a recent ADDitude survey, just 2% of readers who have been pregnant reported taking ADHD medication during their pregnancies. For some, this was true because their pregnancy pre-dated their ADHD diagnosis; others said they were concerned about the impact of ADHD medications on fetal health. While some readers found the hormonal changes of pregnancy led to an improvement in ADHD symptoms, many encountered the opposite.

“I went through both pregnancies and breastfeeding without my ADHD medication and it was very difficult, especially when I was working while continuing college classes,” says Chrissy, an ADDitude reader in Pennsylvania. “Brain fog and tiredness loomed over me the entire time, which became frustrating and depressing at times, despite staying on my depression medication.”

“I was diagnosed after the birth of my second child,” recounts Daniela, an ADDitude reader in Italy who now takes medication. “So, I was a mess during my first pregnancy with more forgetfulness, more mood swings, and raging paranoia.”

While the new JAMA Network study contributes an important piece to the puzzle of ADHD medication use during pregnancy, the full picture remains incomplete. The investigators explain the study’s limitations include the nonspecific definition of “congenital anomaly” and potential confounding variables related to ADHD severity. “Further studies are needed to support pregnant women with ADHD in facing a comfortable pregnancy,” the authors write.

Sources

¹di Giacomo E, Confalonieri V, Tofani F, Clerici M. Methylphenidate and Atomoxetine in Pregnancy and Possible Adverse Fetal Outcomes: A Systematic Review and Meta-Analysis. JAMA Netw Open. 2024;7(11):e2443648. doi:10.1001/jamanetworkopen.2024.43648

²Li  L, Sujan  AC, Butwicka  A,  et al.  Associations of prescribed ADHD medication in pregnancy with pregnancy-related and offspring outcomes: a systematic review.  CNS Drugs. 2020;34(7):731-747. doi:10.1007/s40263-020-00728-2

³Madsen, K. B., Robakis, T. K., Liu, X., Momen, N., Larsson, H., Dreier, J. W., … Bergink, V. (2023). In utero exposure to ADHD medication and long-term offspring outcomes. Molecular Psychiatry, 1–8. doi: 10.1038/s41380-023-01992-6

⁴Huybrechts KF, Bröms G, Christensen LB, et al. Association Between Methylphenidate and Amphetamine Use in Pregnancy and Risk of Congenital Malformations: A Cohort Study From the International Pregnancy Safety Study Consortium. JAMA Psychiatry. 2018;75(2):167–175. doi:10.1001/jamapsychiatry.2017.3644

⁵Walsh, C. J., Rosenberg, S. L., & Hale, E. W. (2022). Obstetric complications in mothers with ADHD. Frontiers in reproductive health, 4, 1040824. https://doi.org/10.3389/frph.2022.1040824

Stimulant medication may normalize certain brain regions impacted by ADHD in children, according to a cross-sectional neuroimaging study of 7,126 children aged 9 to 10 recently published in Neuropsychopharmacology.¹

Study participants were divided into three groups. The “no-med ADHD” group included 1,002 children with severe ADHD symptoms who were not taking stimulant medication. The “stim low-ADHD” group included 273 children whose ADHD symptoms were mild and well-managed with stimulant medication. The “TDC” group included 5,378 typically developing controls.

ADHD symptoms experienced by the no-med ADHD group were associated with brain structure abnormalities not seen in the TDC or stim low-ADHD group, including:

• lower cortical thickness in the insula (INS), a brain area associated with saliency detection or the ability to prioritize information
• less grey matter volume in the nuclear accumbens (NAc), a brain area associated with reward processing and motivation

Children in the stim low-ADHD group showed no significant differences in these brain areas compared to controls. This contrast in structural MRIs suggests that stimulant medication may work to normalize some (but not all) brain regions and improve symptoms in children with ADHD.

Stimulant medication was not associated with improvement in all brain regions. Among those not impacted were the following:

• the caudate (CAU), a brain area responsible for motor control
• the amygdala (AMY), a brain area responsible for emotions

“This result is consistent with previous studies,” the researchers wrote. “Reduced volume in children with ADHD in the CAU is one of the most replicated findings in sMRI studies. No effect of stimulant medications was found in the CAU in the participants with ADHD in several cross-sectional studies. Along the same lines, longitudinal studies on children pointed to the improvement of volumes in the CAU associated with age but not stimulant medications… and two previous studies also pointed out there was no effect of stimulant medications on the AMY.”

Non-stimulant medication did not significantly impact brain structure.

A separate validation analysis included 273 participants with high ADHD symptoms who were taking stimulant medication; the results were consistent with the main study and still suggested that stimulant medication had a positive and noticeable effect on the brain structure of children in this group compared to the no-med ADHD group, even though both groups had high symptom severity at the time of the study.

“These findings are important for the treatment of children with ADHD using stimulant medication,” the researchers wrote.

Stimulant Medication & the ADHD Brain

Stimulants are the first-line treatment for ADHD in children aged 6 and older, teens, and adults. However, some people with ADHD discontinue medication due to side effects. The most common side effects reported by caregivers in ADDitude’s 2023 treatment survey were appetite suppression, irritability or moodiness, and sleep problems.

“Our current medication treatments for ADHD work quite well, but unfortunately, many children stop the treatment or stop taking medication,” said Jonathan Posner, M.D., in his 2020 ADDitude webinar, “Secrets of the ADHD Brain: How Brain Imaging Helps Us Understand and Treat Attention Deficit.” “In fact, the majority of teenagers with ADHD will stop treatment within two years.”

Understanding the parts of the brain that are impacted by stimulant medication can help refine treatment and determine “which of those changes are responsible for symptom improvement versus side effects,” Posner said.

“One of the things that brain imaging has shown is that the development of the brain in children with ADHD seems to be somewhat delayed,” Posner said. “But the overall course of development in children with ADHD versus without ADHD is very similar. It’s almost as if the ADHD brain is a couple of years behind. The very optimistic part of this is that it ultimately does catch up for most children with ADHD.”

For the majority of patients, ADHD symptoms do continue into adulthood, and the prevalence of ADHD in adults is rising. ^{2, 3} However, the present study confirmed Posner’s observations and found that children with even severe ADHD caught up developmentally for the region of the brain responsible for prioritizing information.

MRI scans showed greater cortical thickness in the INS region for the stim-low ADHD group and TDC group compared to the no-med ADHD group. However, data from a two-year follow-up analysis showed these differences were no longer present. Development of the INS is complicated, the researchers noted, but they suggested that “the No-Med group has delayed INS development at baseline, which eventually catches up to the other children.” Researchers theorize that stimulant medication may speed up this process and will continue to follow up with children over the next few years.

Limitations & Future Research

Participant data was obtained from the Adolescent Brain Cognitive Development (ABCD) study, an ongoing study since 2019 that will follow children over 10 years. Data was obtained via structural MRIs and symptom questionnaires and analyzed using linear mixed-effects models (LMM). The study included measures of cortical thickness, cortical area, cortical and subcortical volumes, and total intracranial volume.

The ABCD study lacked diagnostic information for ADHD; therefore, researchers grouped participants using latent class analysis (LCA) and 18 ADHD symptoms from the K-SADS — a moderately reliable test of affective disorders and schizophrenia. Children with bipolar disorders and anxiety disorders, oppositional defiant disorder, obsessive-compulsive disorders, and conduct disorders were excluded from the study.

Results indicate that stimulant medication may enhance brain structure and alleviate ADHD symptoms; however, this study was cross-sectional and did not establish clear causation. Information on the mean dose and duration of participants’ stimulant medication use was missing from the study. Additionally, researchers warned that the study did not fully capture the association between brain structure and ADHD severity. The stim-low ADHD group was much smaller than the other two groups, which may have hindered the study’s results. The two-year follow-up (in line with ABCD study release 4.0) included fewer participants (3,992 after exclusion criteria). Results should be interpreted with caution.

Future research should further incorporate supplemental data on stimulant use, study stimulant use by patients with severe ADHD, and include more longitudinal data.

Sources

¹Wu, F., Zhang, W., Ji, W. et al. (2024). Stimulant medications in children with ADHD normalize the structure of brain regions associated with attention and reward. Neuropsychopharmacol, 49, 1330–1340. https://doi.org/10.1038/s41386-024-01831-4

²U.S. Centers for Disease Control and Prevention. (2024, October 4). ADHD in adults: an overview.
https://www.cdc.gov/adhd/articles/adhd-across-the-lifetime.html

³American Psychiatric Association. (2019, November 15). ADHD increasing among adults.
https://www.psychiatry.org/news-room/apa-blogs/adhd-increasing-among-adults

Emotional dysregulation is an invisible string linking sensory processing, anxiety, and ADHD in children, according to new research that explores the relationship between sensory processing subtypes and self-regulation in children with neurodevelopmental disorders. Researchers found that, while some sensory subtypes were associated with elevated anxiety and others with elevated ADHD symptomatology, all sensory processing subtypes were associated with higher emotional dysregulation compared with sensory-typical children.

The study, published in Nature, enrolled 117 participants from a community-based specialty clinic; all participants were children aged 8 to 12 years old with various neurodevelopmental diagnoses, including autism and ADHD.¹ The researchers uncovered five distinct sensory processing profiles in this group:

• Typical Sensory Processing (30% of the sample)
• Sensory Under-Responsive (20%): Child often does not respond to verbal information or what is around them
• Sensory Over-Responsive (19%): Child is bothered by wearing certain garments or by loud sounds
• Sensory Seeking (19%): Child has a persistent desire for fast movement and often cannot stop touching things or people
• Mixed Sensory Processing (11%): A combination of the above, depending on context or the stimuli

The study highlights the “wide range of heterogeneity in sensory experiences among populations with neurodevelopmental concerns,” say the study’s authors.

Elevated Emotional Dysregulation, Anxiety, ADHD

The researchers investigated the prevalence of behavioral and emotional regulation challenges in the group as a whole and in different sensory subtypes. They also considered the following comorbidities:

• 62% of the group exhibited ADHD symptoms
• 39% exhibited emotion dysregulation
• 19% exhibited anxiety

They also studied patterns associated with specific sensory subtypes:

• Children in the sensory over-responsive subtype reported significantly elevated anxiety levels.
• Children in the sensory seeking and sensory under-responsive subtypes reported the highest levels of ADHD behaviors.
• All subtypes, apart from typical sensory processing, reported elevated levels of emotion dysregulation.

These findings offer insights into the complicated relationship between sensory processing and self-regulation challenges, which researchers hope will help clinicians better serve neurodivergent children through targeted interventions that address overlapping symptomology.

“Not many people realize that the sensory systems are foundational to development, functioning and wellbeing. Differences in sensory processing may undermine the acquisition of skills of a higher order – from behavior to learning,” explains Candace Peterson MS, OTRL, in her ADDitude article. “What Is Your Child’s Sensory Profile?” “This is why sensory challenges in kids often manifest in school, show up as behavior problems, and make daily living difficult.”

An ADDitude reader who struggles with sensory over-responsiveness explains: “Sounds seem to overstimulate me the most frequently and easily. It feels like the sounds are physically pushing me into a corner and squishing me.” Another reader with sensory over-responsiveness says clothing tags and seams are her “mortal enemies.” “On good days, they’re a slight annoyance,” she says. “On bad days, it feels like they’ve come alive with tiny needles for fingers, incessantly poking at me, causing repeated stings.”

Sources

¹Brandes-Aitken, A., Powers, R., Wren, J. et al. Sensory processing subtypes relate to distinct emotional and behavioral phenotypes in a mixed neurodevelopmental cohort. Sci Rep 14, 29326 (2024). https://doi.org/10.1038/s41598-024-78573-2

The diagnostic criteria for ADHD are largely based on studies of young white boys — and do not reflect the lived experiences of many adults with the condition. This gap between clinical guidance and real-life symptoms has contributed to a decades-long problem with misdiagnosis, missed diagnoses, and inadequate treatment for individuals who slipped under the ADHD radar in childhood.

ADHD persists into adulthood for up to 90% of children with the condition, however, only 33% of pediatricians, 30% of family practitioners, 25% of nurse practitioners, and 22% of internists said that they received adequate training on ADHD in medical school, according to data presented by the American Professional Society of ADHD and Related Disorders (APSARD) at its 2024 conference. APSARD is now working to remedy this obstacle to care with the first-ever guidelines for the diagnosis and treatment of ADHD in adults. In 2023, it established a 27-member task force that is devising clinical practice guidelines for the diagnosis and treatment of ADHD in adults. According to David Goodman, M.D., who is leading the medical subcommittee for the task force, the adult ADHD guidelines have the greatest chance at widespread adoption if they are research-based, clinically informed, and patient-focused. APSARD hopes to publish the guidelines in 2025.

Continue reading “The State of Adult ADHD Today” to learn more.

2. ADHD Medication Use Lowers the Risk of Death, Hospitalization

Treating ADHD with medication can lower the overall risk of mortality by 19% and overdose by 50%. It also reduces hospitalizations, both psychiatric and non-psychiatric, according to two large-scale Swedish studies.^{1, 2} These findings highlight the importance of ADHD medication use for long-term health and longevity, underscoring the urgent need to end the stimulant shortage that has prevented U.S. patients with ADHD from consistently accessing medication since the Fall of 2022.

Continue reading “ADHD Medication Use Lowers the Risk of Death, Hospitalization” to learn more.

3. Massive Study Ties Leaded Gasoline Exposure to 150 Million Mental Health Diagnoses in U.S.

Leaded gasoline and exposure to its exhaust may help explain an estimated 151 million U.S. cases of psychiatric disorders, including ADHD, depression, and anxiety, according to a new cross-sectional study spanning the last 75 years.

Exposure to leaded gasoline from car exhaust was tied to population-wide cases of mental health disorders from 1940 to 2015 in the study, published in December in the Journal of Child Psychology and Psychiatry.³ It estimated that more than half of the current U.S. population was exposed to harmful levels of lead in childhood, resulting in profound effects on their mental health, personality traits, and overall well-being. People born between 1966 and 1986 (referred to as Generation X) experienced the highest rate of lead exposure and are at the greatest risk for anxiety, depression, ADHD, and personality changes.

Continue reading “Massive Study Ties Leaded Gasoline Exposure to 150 Million Mental Health, ADHD Diagnoses in U.S.” to learn more.

4. High and Low Estrogen Exacerbate ADHD Symptoms in Females

The impact of rising and falling hormone levels on ADHD symptoms is compounded for females beginning in puberty, according to the multiple hormone sensitivity theory explained in a review article published in January in Hormones and Behavior.⁴ The theory offers valuable insight into how hormones — namely, high and low estrogen levels — may influence ADHD symptoms in females across the lifespan, including during the menstrual cycle, puberty, pregnancy, and menopause.

Per the theory, females may be more likely to engage in risk-taking and reward-seeking behaviors in the days leading up to ovulation. These behaviors coincide with a steady rise in estrogen levels that drops off during ovulation. In contrast, withdrawal and/or depletion of estrogen at a cycle’s end may be characterized by increased negative affect, avoidant behaviors, and reduced executive functioning.

Continue reading “High and Low Estrogen Exacerbate ADHD Symptoms in Females: New Theory.” to learn more.

5. ADHD Medication Costs Soar

ADHD medication costs have nearly doubled or tripled for doses of Ritalin, Concerta, and Focalin since the Adderall shortage began in October 2022, according to a report published in USA Today in late 2023. The newspaper analyzed the prices that retail community pharmacies pay for common ADHD prescriptions. For specific dosages of methylphenidate (i.e., Ritalin and Concerta), the average price paid by small to mid-sized independent and chain pharmacies nearly doubled from late 2022 to December 2023. The average cost of certain versions of dexmethylphenidate (Focalin) more than doubled during that period.

Continue reading “ADHD Medication Costs Soar: Price Report” to learn more.

6. ADHD Traits May Have Provided an Evolutionary Advantage

ADHD traits such as distractibility and impulsivity may have benefited our ancestors as they foraged for food, and they continue to play a crucial role in how people with ADHD adapt and survive, suggests research published in February in the journal Proceedings of the Royal Society B Biological Sciences.⁵

“We speculate that ADHD serves as an adaptive specialization for foraging, thus explaining its widespread prevalence and continued persistence in the human population,” the researchers said. “This tendency to explore while foraging might extend to other behaviors such as cycling more frequently between information sources in the classroom or sources of stimulation in the home environment.”

Continue reading “ADHD Traits May Have Provided an Evolutionary Advantage” to learn more.

7.

In June, the Justice Department charged two top officers at the telehealth company Done Global with allegedly distributing Adderall and other stimulants for ADHD to patients who officials said did not merit a proper diagnosis. While health officials warned that the “disruption” to Done could affect as many as 50,000 adult patients⁶, many of whom were already impacted by the ongoing ADHD medication shortage, this criminal action highlights another important issue: the limited access to clinical care for people with ADHD in the United States.

Continue reading “Done ADHD Investigation Sparks Worry of Inadequate Care” to learn more.

8. Boredom Triggers High Stress Response in Impulsive People

Boredom causes a heightened stress response in impulsive people, as evidenced by the elevated cortisol levels documented in research published in Physiology & Behavior in October.⁷ The research deepens the scientific community’s understanding of the interplay between impulsivity and boredom, suggesting that this relationship may be mediated by the hypothalamic-pituitary-adrenal (HPA) axis.

“This research suggests that the lived experience of boredom feels more intense and aversive for people who are highly impulsive, transforming into an overwhelming need to escape that boredom,” explained Matt Parker, Ph.D., the study’s senior author and a neuroscientist at the University of Surrey.

Continue reading “Boredom Triggers High Stress Response in Impulsive People: New Study” to learn more.

9. DEA OKs Expanded Production of the ADHD Medication Vyvanse

Vyvanse and its generic equivalents (lisdexamfetamine dimesylate) became more readily available at pharmacies following a decision in September by the Drug Enforcement Administration (DEA) to allow expanded production of the stimulant medication used to treat ADHD and moderate-to-severe binge-eating disorder (BED) in adults. The DEA approved a 24% production increase in response to the ongoing stimulant shortage.

“These adjustments are necessary to ensure that the United States has an adequate and uninterrupted supply of lisdexamfetamine to meet legitimate patient needs both domestically and globally,” the DEA said in a letter on September 5.

Continue reading “Vyvanse Shortage Update: DEA OKs Expanded Production of the ADHD Medication” to learn more.

10. ADHD Medication Prescriptions Spiked Ahead of Adderall Shortage

Prescriptions for ADHD medications increased significantly during the COVID-19 pandemic, especially for women and for adults aged 20-39, according to a study published in January in JAMA Psychiatry. The most significant increases were found among prescriptions for adults aged 20-39, up 81% for non-stimulants and 30% for stimulants; and for women, up 59% for non-stimulants and 25% for stimulants.⁸ By contrast, researchers found a decrease or no change in rates of prescriptions during the pandemic for medications used to treat other behavioral health disorders, including anxiety, depression, and opioid use disorders.

Continue reading “ADHD Medication Prescriptions Spiked Ahead of Adderall Shortage: New Report” to learn more.

Sources

¹Li, L., Zhu, N., Zhang, L., et al. (2024). ADHD Pharmacotherapy and Mortality in Individuals With ADHD. JAMA. https://doi.org/10.1001/jama.2024.0851

²Tipale, H., Bergström, J., Gèmes, K., et al. (2024). Attention-Deficit/Hyperactivity Disorder Medications and Work Disability and Mental Health Outcomes. JAMA Netw Open. 7(3):e242859. https://doi.org/10.1001/jamanetworkopen.2024.2859

³McFarland, M.J., Reuben, A. and Hauer, M. (2024). Contribution of Childhood Lead Exposure to Psychopathology in the US Population Over the Past 75 Years. J Child Psychol Psychiatr.https://doi.org/10.1111/jcpp.14072

⁴Eng, A.G., Nirjar, U., Elkins, A.R., Sizemore, Y.J., Monticello, K.N., Petersen, M.K., Miller, S.A., Barone, J., Eisenlohr-Moul, T.A., & Martel, M.M. (2024). Attention-Deficit/Hyperactivity Disorder and the Menstrual Cycle: Theory and Evidence. Hormones and Behavior. 158(105466).https://doi.org/10.1016/j.yhbeh.2023.105466

⁵Barack, D.L., Ludwig, V.U., Parodi, F., Ahmed, N., Brannon, E.M., Ramakrishnan, A.M., and Platt, M.L. (2024). Attention Deficits Linked with Proclivity to Explore While Foraging. Proceedings of the Royal Society B Biological Sciences. https://doi.org/10.1098/rspb.2022.2584

⁶CDC. Disrupted Access to Prescription Stimulant Medications Could Increase Risk of Injury and Overdose. June 13, 2024. https://emergency.cdc.gov/han/2024/han00510.asp

⁷ Clay, J.M., Badariotti, J.I., Kozhushko, N., Parker, M.O. (2024). HPA Activity Mediates the Link Between Trait Impulsivity and Boredom. Physiology & Behavior. 284, 114637. https://doi.org/10.1016/j.physbeh.2024.114637

⁸Chai, G., Xu, J., Goyal S, et al. (2024). Trends in Incident Prescriptions for Behavioral Health Medications in the US, 2018-2022. JAMA Psychiatry. https://doi.org/10.1001/jamapsychiatry.2023.5045

Leaded gasoline and exposure to its exhaust may help explain an estimated 151 million U.S. cases of psychiatric disorders, including ADHD, depression, and anxiety, according to a new cross-sectional study spanning the last 75 years published in the Journal of Child Psychology and Psychiatry.¹

Exposure to leaded gasoline from car exhaust was tied to population-wide cases of mental health disorders from 1940 to 2015 by researchers from Duke University, Florida State University, and the Medical University of South Carolina. They estimated that more than half of the current U.S. population was exposed to harmful levels of lead in childhood, resulting in profound effects on their mental health, personality traits, and overall well-being. People born between 1966 and 1986 (referred to as Generation X) experienced the highest rate of lead exposure and are at the greatest risk for anxiety, depression, ADHD, and personality changes.

“Research on lead as a developmental neurotoxicant is robust,” says Joel Nigg, Ph.D., a clinical psychologist and a professor in the departments of psychiatry and behavioral sciences at Oregon Health & Science University. “Its correlation with ADHD is also well established. Even low levels of exposure have an effect on ADHD.”², ³

Nigg was the principal investigator on several studies suggesting that lead exposure has a causal role in ADHD. One study published in Psychological Science found that children with ADHD who had the HFE C282Y gene mutation exhibited significantly more symptoms of hyperactivity and impulsivity than did children with ADHD who lacked the mutation.⁴

“Because the C282Y gene helps to control the effects of lead in the body, and the mutation was spread randomly in the children, it is difficult to explain these findings unless lead is, in fact, part of the cause of ADHD, not just associated with it. Numerous animal studies also support a link,” he says.

Leaded Gasoline Exposure Is a Public Health Crisis

Nigg’s study and others have linked lead exposure to life-long mental, physical, and behavioral issues; lowered IQ points; and personality changes.⁵, ⁶, ⁷, ⁸ However, the findings from the Journal of Child Psychology and Psychiatry’s study highlight the historic and pervasive effects of lead exposure on the cognitive and psychological health of a staggering slice of the U.S. population.

“Lead’s potential contribution to psychiatry, medicine, and children’s health may be larger than previously assumed,” the researchers wrote.

The study analyzed lead levels in children’s blood collected for the CDC’s National Health and Nutrition Examination Surveys (NHANES) and correlated that with historic leaded-gasoline data. The researchers calculated “mental illness points” based on the fraction of changes in the mental health of Americans born in different years and the population elevations of mental health symptoms associated with lead exposure.

The researchers identified a cumulative increase of 602 million general psychopathology points across the population, corresponding to an estimated 151 million additional mental disorders. They found that lead exposure heightened the risks for anxiety, depression, and ADHD; increased neuroticism, associated with negative emotionality; and decreased conscientiousness, reflecting less self-control and goal-oriented behavior.

While the study’s results do not prove causation, the researchers say that their findings will provide doctors with insights about their patients’ symptoms and underscore the need for expanded lead testing in patients and the recognition of lead poisoning as a neurodevelopmental disorder within a psychiatric diagnostic framework.

Leaded Gasoline Exposure: Next Steps

Lead was added to gasoline in the 1920s to improve engine performance. During the early childhood years of Generation X, leaded gasoline became the predominant fuel type in the U.S. In the mid-1970s, the U.S. Environmental Protection Agency (EPA) began phasing out leaded gasoline, but a U.S. ban did not go in effect for on-road vehicles until 1996. Lead is still found in some paints, children’s toys, and deteriorating water pipes.

According to The CDC, high levels of lead exposure can lead to seizures, vomiting, memory loss, and even death. Exposure to even small amounts of lead can be harmful. Children 6 years or younger are most vulnerable to lead poisoning, which can cause development and growth delays, hearing and speech problems, difficulty learning and paying attention, and serious illness and death.

Symptoms of lead poisoning can be hard to recognize in children. The CDC recommends discussing possible lead exposure with a child’s healthcare provider and testing children ages 1 to 5 for lead if they:

• Live in a home built before 1978
• Receive Medicaid services
• Are an immigrant, refugee, or adopted from another country
• Live near a known source of lead, such as a lead smelter or mine

Sources

¹McFarland, M.J., Reuben, A. and Hauer, M. (2024). Contribution of Childhood Lead Exposure to Psychopathology in the US Population Over the Past 75 Years. J Child Psychol Psychiatr.https://doi.org/10.1111/jcpp.14072

²Sanders, T., Liu, Y., Buchner, V., Tchounwou, P.B. (2009). Neurotoxic Effects and Biomarkers of Lead Exposure: A Review. Rev Environ Health. https://doi.org/10.1515/reveh.2009.24.1.15

³Nigg, J. T., Knottnerus, G. M., Martel, M. M., Nikolas, M., Cavanagh, K., Karmaus, W., & Rappley, M. D. (2008). Low Blood Lead Levels Associated with Clinically Diagnosed Attention-Deficit/Hyperactivity Disorder and Mediated by Weak Cognitive Control. Biological Psychiatry. 63(3), 325–331. https://doi.org/10.1016/j.biopsych.2007.07.013

⁴Nigg, J. T., Elmore, A. L., Natarajan, N., Friderici, K. H., & Nikolas, M. A. (2016). Variation in an Iron Metabolism Gene Moderates the Association Between Blood Lead Levels and Attention-Deficit/Hyperactivity Disorder in Children. Psychological Science.https://doi.org/10.1177/0956797615618365

⁵Reuben, A., Schaefer, J.D., Moffitt, T.E., Broadbent, J., Harrington, H., Houts, R.M., Ramrakha, S., Poulton, R., Caspi, A. (2019). Association of Childhood Lead Exposure With Adult Personality Traits and Lifelong Mental Health. JAMA Psychiatry. https://doi.org/10.1001/jamapsychiatry.2018.4192

⁶Heidari, S., Mostafaei, S., Razazian, N. et al. (2022). The Effect of Lead Exposure on IQ Test Scores in Children Under 12 Years: A Systematic Review and Meta-Analysis of Case-Control Studies. Syst Rev. https://doi.org/10.1186/s13643-022-01963-y

⁷Roy, A., Bellinger, D., Hu, H., Schwartz, J., Ettinger, A.S., Wright, R.O., Bouchard, M., Palaniappan, K., Balakrishnan, K. (2009). Lead Exposure and Behavior Among Young Children in Chennai, India. Environ Health Perspect. https://doi.org/10.1289/ehp.0900625

⁸Schwaba, T., Bleidorn, W., Hopwood, C.J., Gebauer, J.E., Rentfrow, P.J., Potter, J., Gosling, S.D. (2021). The Impact of Childhood Lead Exposure on Adult Personality: Evidence from the United States, Europe, and A Large-Scale Natural Experiment. Proc Natl Acad Sci USA. https://doi.org/10.1073/pnas.2020104118

Enlisting in the military just became easier for people with ADHD.

The restrictions on ADHD and other medical conditions historically used to disqualify potential recruits from joining the military have been lifted by the U.S. Department of Defense (DOD) under its Medical Accession Records Pilot (MARP) program. According to MARP’s new guidelines, people with ADHD and learning disorders, such as dyslexia, can enlist without a waiver if they have not received treatment for the conditions within the past year.

Historically, ADHD disqualified candidates unless they secured a military waiver to allow enlistment, a lengthy, multi-step, and largely imprecise process. Candidates were also required to go without treatment for ADHD for at least three years prior to enlistment.

When the MARP program began in 2022, it listed 38 medical conditions that no longer required waivers for enlistment. Earlier this year, the DOD increased the number to 51. Removing the waiver requirement accelerates the enlistment process and frees up medical evaluators to review candidates with more complex medical histories.

“Nearly 77% of youth between the ages of 17 and 24 need some type of waiver to qualify for military service,” said Dr. Katie Helland, DOD director of military accession policy, at a Pentagon news briefing on October 31. “This is where programs like MARP have been helpful.”

Between July 2022 and August 2024, MARP medically qualified more than 9,900 applicants, 57% of whom ultimately enlisted. According to the DOD, about 60% of those recruits had a history of ADHD.

“ADHD is probably more prevalent in the military than you realize,” said Brandi Walker, Ph.D., in the ADDitude webinar “Can You Join the Military with ADHD? What Hopeful Service Members Need to Know.” In 2018, more than 41,000 active service members had an ADHD diagnosis, according to a study that looked at medical data among service members in a five-year period.¹

Individuals with ADHD should consider several factors before enlisting. “You’ll have to be honest with yourself about your strengths, challenges, and how well you cope with ADHD, especially without medication,” Walker said. “The first step is to conduct lots of research, including learning as much as you can about the military, its enlistment procedures, the service branches and roles within them that appeal to you, and the pros and cons of military life. Even if you’re set on joining, it’s a great idea to set the foundations for success well before applying.”

The pilot program will continue testing the feasibility of permanently changing military accession regulations to make enlistment easier for people with previously disqualifying medical conditions.

“Initial results from the program have been positive,” Helland said.

Source

¹Sayers, D., Hu, Z., & Clark, L. L. (2021). The Prevalence of Attention-Deficit/Hyperactivity Disorder (ADHD) and ADHD Medication Treatment in Active Component Service Members, U.S. Armed Forces, 2014-2018. MSMR, 28, (1), 9–14. https://health.mil/News/Articles/2021/01/01/Prevalence-of-Att-MSMR-Jan-2021

ADHD is not a static condition with fixed symptoms, but rather a dynamic disorder with symptoms that wax and wane over the lifespan, sometimes disappearing for years at a time. This was the finding of a new study published in the Journal of Clinical Psychiatry ¹ that made another unexpected discovery: periods of higher environmental demands were associated with times of remission or reduced ADHD symptoms.

Led by Margaret Sibley, Ph.D., professor of psychiatry and behavioral sciences at the University of Washington School of Medicine, the research used data from the longitudinal Multimodal Treatment of ADHD (MTA) study, which followed 483 participants, diagnosed with ADHD at 7-10 years of age, for 16 years.² Follow-up assessments, which were administered every two years, asked participants and parents about the severity and frequency of ADHD symptoms and impairments, as well as about environmental demands, including responsibilities in education, work, and finances.

The researchers found that longitudinal patterns revealed four groups:

• Fluctuating ADHD: 64%

Alternating periods of remission and recurrence

• Stable Partial Remission: 16%

A significant reduction in symptoms was experienced, typically beginning in late adolescence or early adulthood, that remained stable afterward

• Stable Persistence: 11%

High symptoms that met diagnostic thresholds with minimal or no improvement over time

• Recovery: 9%

Sustained full remission of symptoms

Among the group that experienced fluctuating ADHD, the following trends were uncovered:

• There were typically three to four transitions between remission and recurrence over the 16-year period.
• The first remission period often began in early adolescence, around age 12, with symptoms returning within a few years.
• Compared to other groups, symptom severity was moderate.

ADHD symptoms improved to a point of remission at some point over the 16 years for most study participants, Sibley explains in an article titled “ADHD’s Vanishing Act” that appears in ADDitude’s forthcoming spring 2025 issue. In most cases, faded symptoms returned three to four years later, Sibley says.

“In other words, most individuals with ADHD can expect to go through years when their symptoms do not cause meaningful problems,” Sibley writes. “The neurocognitive risks are always present, but the clinical problems may only emerge sometimes. This is comparable to a person who may struggle with weight gain biologically, but who may fluctuate in and out of the obesity range over the course of their lifetime.”

A Busy Schedule Linked to Reduced ADHD Symptoms

The MTA study gathered information about environmental demands, such as an increase in significant responsibilities at work, school, or home, in order to explore whether these demands impacted ADHD symptoms. It turns out they did — but not in the way researchers hypothesized.

“We speculated that increased stresses would be associated with higher levels of ADHD in participants,” Sibley explains. “We were surprised to find quite the opposite, [that] higher levels of demands were associated with remission of ADHD. In other words, people with ADHD were rising to the challenge when demands were high.”

Sibley notes that the nature of the relationship between higher demands and reduced symptoms remains unclear; the study revealed a link, but not how the link works.  “One explanation is that ADHD symptoms fade when consequences in the environment create an urgent need to stay on track,” she speculates. “It is also possible that, when people have lower ADHD symptom levels, they are able to take on greater responsibilities.” Likely, it’s a combination of the two, Sibley says.

Childhood Factors Predict Long-Term Outcomes

The study found that certain childhood factors served as predictors for long-term outcomes. Individuals in the stable persistent group tended to be at higher risk for mood disorders, substance use problems in adolescence, low medication utilization, and poorer response to treatment in childhood. Those in the partial remission group tended to have higher rates of comorbid anxiety. By contrast, individuals in the recovery group were less likely to have mood disorders and parents with psychopathology.

The study helps the scientific community more fully understand the complex landscape of ADHD, and Sibley sees great potential benefit if clinicians pass along this nuanced understanding to patients.

“For some people with ADHD, this may mean staying busy and keeping an active schedule,” Sibley ventures. “It may also mean working with practitioners to leverage a nuanced understanding of ADHD fluctuations when designing a treatment plan that boosts wellbeing.”

Sources

¹Sibley MH, Kennedy TM, Swanson JM, Arnold LE, Jensen PS, Hechtman LT, Molina BSG, Howard A, Greenhill L, Chronis-Tuscano A, Mitchell JT, Newcorn JH, Rohde LA, Hinshaw SP. Characteristics and Predictors of Fluctuating Attention-Deficit/Hyperactivity Disorder in the Multimodal Treatment of ADHD (MTA) Study. J Clin Psychiatry. 2024 Oct 16;85(4):24m15395. doi: 10.4088/JCP.24m15395. PMID: 39431909.

²The MTA Cooperative Group: A 14-Month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder (ADHD) . Arch Gen Psychiatry 1999;56:1073-1086.

Children with ADHD are more likely to be obese, despite lower-than-average birth weights, according to a new study that found a correlation between elevated ADHD symptoms and higher body mass index (BMI) scores for both females and males. ¹The study, published in the Journal of the American Academy of Child & Adolescent Psychiatry, complements additional research tying ADHD impulsivity to unhealthy food consumption and overeating.

In analyzing data from the Millennium Cohort Study (MCS) of more than 19,000 families with children born between 2000 and 2002, researchers found that children with ADHD had significantly lower birth weights than did children in the control group. Both groups maintained similar obesity rates until age 5, when the ADHD group experienced a rise in obesity that continued throughout adolescence.

“As children with ADHD are typically lighter in weight at birth than children without ADHD, the results suggest there may be a sensitive time period between the ages of 3 and 5 years during which this association reverses, and higher ADHD symptoms become associated with obesity,” the researchers wrote.

Researchers collected data when the 442 ADHD cohort members reached 9 months and 3, 5, 7, 11, 14, and 17 years. (The study excluded cohort members taking ADHD medications.) They found that weight gain began earlier for girls with ADHD (age 7) compared to boys with ADHD (age 11). “The weight changes in girls additionally seemed to be more long-lasting, whereas the observed changes in boys seemed to be transitory,” the researchers wrote. It is unclear whether these associations continue into adulthood.

Further analysis revealed that elevated ADHD symptoms in females at ages 7, 11, and 14 predicted higher body mass index (BMI) scores at ages 11, 14, and 17, respectively. The same association occurred in males at ages 11 and 14. These results suggest that ADHD symptoms are not entirely responsible for the uptick in weight children experience between the ages of 3 and 5 years.

Genetics, Prenatal Factors Impact BMI

Hormones and puberty contribute to weight gain. “Sometimes pre-teens can gain weight as the body prepares for a growth spurt in height,” says Roberto Olivardia, Ph.D., clinical psychologist at Harvard Medical School. “Therefore, BMI normalizes as they gain height.”

Prenatal factors, including the mother’s pre-pregnancy BMI, prenatal blood pressure, smoking during pregnancy, and poor nutrition, predicted a higher BMI at 5 years. Genetics may also increase the risk of obesity.

“It is possible that there is a common genetic background to both ADHD and [being] overweight or, as parents with ADHD are more likely to have children with ADHD, this may have an impact on executive function skills involved in parenting, such as planning healthy meals, which in turn may influence weight status,” the researchers wrote. “Parents with an increased genetic risk may be influencing their child’s home environment in ways that compound inherited risk.” ², ³

Impulsivity Linked to Poor Dietary Decisions

Another recent observational study found a strong link between impulsivity, a common ADHD trait, and unhealthy food consumption and overeating, specifically in the form of snacking. ⁴

The study, published in the Journal of Attention Disorders, analyzed data from the KOALA Birth Cohort Study of 810 adolescents aged 16 to 20 years. The researchers identified five dietary patterns

• Snack — high intakes of regular (non-diet) soft drinks, fruit juice/drinks, fried snacks, chips, nuts or snacks, and energy drinks
• Healthy — high intakes of lettuce, raw vegetables, fruit, eggs, and tea
• Animal-based — high intakes of animal dairy products, meat and chicken, and fish
• Sweet — high intakes of pastry, chocolate bars, candy bars, cake or biscuits, and sweets
• Beverage — high intakes of diet soft drinks, light fruit juice/drinks, sports drinks, and energy drinks

Among the five dietary patterns, adolescents with an ADHD diagnosis scored higher on the Snacking dietary pattern than did those without ADHD. Higher Snack scores were associated with difficulties with cognition, inattention, and impulsiveness. Impulsivity was inversely related to Sweet dietary patterns and positively related to Beverage dietary patterns.

Interestingly, adolescents with ADHD appeared no less likely than their neurotypical peers to engage in Healthy dietary patterns. “The lack of a reverse association between ADHD symptoms, especially impulsivity, and the healthy pattern is unexpected and raises questions,” the researchers wrote.

Though the study does not prove causality, the findings suggest that eating habits may differ based on the specific ADHD symptoms each individual experiences.

“When studying how ADHD impacts an adolescent’s diet, looking beyond a simple diagnosis and considering the specific dimensions of their ADHD symptoms, like inattention, hyperactivity, and impulsivity, provides a more nuanced understanding of their dietary behaviors, as these individual dimensions can differentially influence food choices and eating patterns, even among individuals with the same ADHD diagnosis,” the researchers wrote.

Both ADHD and high BMI are associated with poor health outcomes, including asthma, diabetes, and cardiovascular disorders, so it’s vital that children understand the potential consequences of their dietary decisions. ⁵,⁶

Adolescents have more independent access to food, which can also result in unhealthy choices when impulsivity collides with puberty. “Parents have less control over what teenagers eat since they are not always with them,” Olivardia says, “and this most likely plays a bigger role in weight gain.”

Preventing Childhood Obesity

Educating children about their food choices can help curb unhealthy food cravings. For example, instead of banishing carbs from your kitchen, Olivardia says, explain them in a way children can understand. “Say, ‘Simple carbs, like potato chips, taste good, but basically break down in the body as sugar. There is no nutritional value in simple carbs, and they get in the way of healthy weight, high energy, and other things that matter, like your complexion.’”

Caregivers can help children and adolescents make better dietary decisions by incorporating the following strategies:

• Set up a “food environment” that promotes healthy eating. Children with ADHD may not notice they’re hungry until they’re starving. To fend off unhealthy pantry raids, stock up on nutritious, easy-to-grab meals and snacks that require little preparation, such as peanut butter crackers, yogurt, or string cheese. Display healthy snacks and fruits in plain view in the refrigerator or pantry.
• Practice good sleep hygiene. In addition to regulating hormone levels, a good night’s sleep makes it less likely that children will turn to food for comfort in fragile moments.
• Set healthy eating rules. Create family eating rules that encourage children to eat attentively — for example, no eating while watching T.V. or eating straight out of the bag. Consider requiring children to eat only in the kitchen or dining area.
• Teach children mindful eating skills. Children are less likely to overeat when they practice mindful eating. Teach children to put down their fork in between bites. Or ask them to describe what they’re eating as though the person listening has never tasted that food.
• Set a good example. Children learn by watching others, especially their parents. Set a good example by making smart food choices, dishing appropriate portions, and not distractedly eating while engaging in another activity (like using your phone).
• Treat ADHD. Make sure children adhere to their ADHD treatment plan. ADHD stimulant medications help children better observe and regulate their behaviors and avoid impulsive eating. They also make it easier to follow through with healthy eating and exercise plans.

Sources

¹ Reed, C., Cortese, S., Golm, D., Brandt, V., et al. (2024). Longitudinal Associations Between Physical Health Conditions in Childhood and Attention-Deficit/Hyperactivity Disorder Symptoms at Age 17 Years. Journal of the American Academy of Child & Adolescent Psychiatry https://doi.org/10.1016/j.jaac.2024.09.009
² Barker, E.D., Ing, A., Biondo, F., Jia, T., et al. (2021). Do ADHD-Impulsivity and BMI Have Shared Polygenic and Neural Correlates? Mol Psychiatry;26(3):1019-1028. https://doi.org/10.1038/s41380-019-0444-y
³ Faraone, S.V., Larsson, H. (2019). Genetics of Attention Deficit Hyperactivity Disorder. Mol Psychiatry; 24(4):562-575. https://doi.org/10.1038/s41380-018-0070-0
⁴ Dalnoki, L., Hurks, P. P. M., Gubbels, J. S., Eussen, S. J. P. M., Mommers, M., & Thijs, C. (2024). Exploring the Relationship of Dietary Intake With Inattention, Hyperactivity, and Impulsivity, Beyond ADHD. Journal of Attention Disorders https://doi.org/10.1177/10870547241293946/a>
⁵ Arrondo, G., Solmi, M., Dragioti, E., et al. (2022).Associations Between Mental and Physical Conditions in Children and Adolescents: An Umbrella Review. Neurosci Biobehav Rev. https://doi.org/10.1016/j.neubiorev.2022.104662
⁶ Horesh, A., Tsur, A.M., Bardugo, A., et al. (2021). Adolescent and Childhood Obesity and Excess Morbidity and Mortality in Young Adulthood—a Systematic Review. Curr Obes Rep; 10, 301–310. https://doi.org/10.1007/s13679-021-00439-9

Brain volume, and the genetic variants that influence it, is tied to ADHD and Parkinson’s disease risks, suggests one of the most extensive international studies to date on DNA and brain structure.¹

The new study, published in Nature Genetics, examined how brain size and genetic differences influence key subcortical or ‘deep brain’ regions crucial for memory, emotional regulation, proprioception, sensory processing, and responses to rewards and punishments.

A team of 189 researchers from 45 countries analyzed data from genome-wide association studies (GWAS) and magnetic resonance imaging (MRI) brain scans of 74,898 participants across 19 countries. They identified 254 genetic variants that impact brain volume and the likelihood of developing ADHD and Parkinson’s disease.

“Genetic variants associated with larger brain volumes in key brain regions also increase the risk of Parkinson’s disease, while variants linked to smaller brain volumes in key regions are associated with an increased risk of ADHD,” said Miguel Rentería, Ph.D., study principal and associate professor at the Queensland Institute of Medical Research (QIMR Berghofer) in Australia, in a statement. “These findings suggest that genetic influences that underpin individual differences in brain structure may be fundamental to understanding the underlying causes of brain-related disorders.”

However, more studies are needed on the causal relationship between genes and brain-based diseases. “It’s worth noting that these are correlations, not causal relationships, and so interpretation must be approached with caution,” Rentería said.

“My theory is that the underlying mechanisms involve genes crucial to brain development, growth, and aging processes,” Rentería told Medical News Today. “We plan to further investigate to identify the exact biological pathways involved. Understanding these mechanisms could illuminate how brain structure impacts susceptibility to both neurodegenerative and psychiatric conditions, potentially guiding future therapeutic strategies.”

The researchers used data from the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) consortium, an international effort led by Keck School of Medicine of USC; the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) at Baylor College of Medicine; the UK Biobank; and the Adolescent Brain Cognitive Development (ABCD) study.

ADHD and Parkinson’s Disease

According to the World Health Organization and the Centers for Disease Control and Prevention, rates of Parkinson’s disease and ADHD continue to rise.

In 2018, researchers from the University of Utah Health found that the risk of early-onset Parkinson’s disease and similar disorders is 2.4 times greater among patients with ADHD than it is among individuals of the same gender and age without ADHD. The study, published in Neuropsychopharmacology, examined medical records from the Utah Population Database (UPDB) of 31,769 patients with ADHD and 158,790 individuals without the condition.²

Sources

¹ García-Marín, L. M., Campos, A. I., Diaz-Torres, S., Rabinowitz, J. A., Ceja, Z., Mitchell, B. L., Grasby, K. L., Thorp, J. G., Agartz, I., Alhusaini, S., Ames, D., Amouyel, P., Andreassen, O. A., Arfanakis, K., Arias-Vasquez, A., Armstrong, N. J., Athanasiu, L., Bastin, M. E., Beiser, A. S., … Rentería, M. E. (2024). Genomic Analysis of Intracranial and Subcortical Brain Volumes Yields Polygenic Scores Accounting for Variation Across Ancestries. Nature Genetics. https://doi.org/10.1038/s41588-024-01951-z

² Curtin, K., Fleckenstein, A.E., Keeshin, B.R., et al. (2018). Increased Risk of Diseases of the Basal Ganglia and Cerebellum in Patients with a History of Attention-Deficit/Hyperactivity Disorder. Neuropsychopharmacology. https://doi.org/10.1038/s41386-018-0207-5

Sleep problems are highly prevalent among adults with ADHD. Individuals who have ADHD and one or more psychiatric comorbidities face an increased risk for disordered sleep, according to a study published in the Journal of Attention Disorders.¹

The study followed a large sample of adults with ADHD in the Netherlands after they were referred to an outpatient mental health clinic. Nearly two-thirds of these patients screened positive for a sleep problem. Most screened positive for delayed sleep phase syndrome (35.8%), followed by insomnia (30.6%) and restless leg syndrome (28.8%).

Women with ADHD were more likely to report more types of sleep problems compared to men with ADHD. Women more often reported insomnia, hypersomnia, and parasomnia, while men more often reported sleep-related breathing disorders (SBD).

Adults with ADHD and mental health conditions faced a higher likelihood of having any type of sleep problem and of having more than one sleep problem than did those with ADHD alone. The risk of sleep problems was highest in adults with PTSD (OR=3.21), followed by:

• Substance use disorder (OR=1.76)
• Depression (OR=1.73)
• Anxiety (OR=1.51)
• Personality disorders (OR=1.54)

Why Do Adults with ADHD Struggle with Sleep?

Sleep disorders impact around 50 million Americans or 15% of the U.S. population.² This percentage is significantly higher in ADHD populations, as shown in the current study. According to data cited by the authors, disordered sleep affects an estimated 40% to 80% of adults with ADHD.^{3, 4} The most common sleep disorders are similar for both groups and include insomnia, restless legs syndrome (RLS), narcolepsy, and sleep apnea.^{5, 6}

ADHD and sleep go hand in hand, and the impact of one disorder can worsen the symptoms of the other. For example, the American Academy of Neurology found that people with ADHD and RLS experience more severe RLS symptoms than do those without ADHD.⁷

Many sleep problems are biological, but they can also be behaviorally motivated. A study cited by the authors shows that cognitive behavioral symptoms such as bedtime procrastination can delay sleep onset and potentially disrupt melatonin production.⁸

“Symptoms of ADHD exacerbate the things that make sleep hard for all of us,” said Joel Nigg, Ph.D., in his 2018 webinar with ADDitude, “Sleep and the ADHD Brain: Why It’s Critical and How to Get More.”

“Your body reacts more strongly to stimulation,” Nigg said. “You’re more hyper-aroused by things that happen during the day. It’s harder to turn your brain off. It’s a natural side effect of what ADHD is. Sleep requires the opposite of the energy that ADHD provokes, [making sleep] naturally difficult. That’s why it takes the kind of deliberate attention, behavioral strategy, or kind of tackling of this so often for those with ADHD.”

What Are the Consequences of Untreated Sleep Problems?

The impact of misdiagnosing symptoms of disordered sleep can have long-term consequences, leading to “poor treatment, and persistence and aggravation of symptoms,” the authors wrote.

Symptoms of poor sleep can look like ADHD and vice versa, making them somewhat difficult to differentiate. Left untreated, disordered sleep can worsen with age and cause a ripple effect from caregivers to their children.⁹

“Sung did a study [in 2008], which found that moderate or severe sleep problems in children with ADHD were strongly associated with the mental health of their primary caregivers and with those caregivers’ work attendance and overall family functioning,” said Roberto Olivardia, Ph.D., during his 2019 webinar with ADDitude, “Time for Bed! Sleep Solutions for the ADHD Brain.”

The good news is that “treatments for specific sleep problems are available, relatively accessible to implement in ADHD patients, and can improve ADHD treatment results substantially,” the authors wrote. Cognitive behavioral therapy (CBT) and lifestyle changes are first-line treatments for many sleep disorders and can be more effective than sleep medicine.¹⁰

Limitations, Strengths, and Future Research

The study followed 3,691 adults diagnosed with ADHD from 2018 to 2020. Data was assessed via electronic patient files and included an even male-to-female ratio. Adults with ADHD were referred to one of 46 specialized outpatient clinics in the Netherlands by their general practitioner or mental health counselor. The Holland Sleep Disorder Questionnaire (HSDQ) was used to assess sleep disorders, though it was used as a screening tool and not to diagnose. The DIVA-5 was used to test for ADHD, and the M.I.N.I was used to screen for psychiatric comorbidities.

Limitations of the study include a lack of control group. And although some patients had been diagnosed with a sleep disorder before being referred to an outpatient clinic, the HSDQ was only able to screen for sleep problems. Some data, such as BMI and treatment status, was not accounted for as it was not systematically recorded in patient files. Given each patient received a clinical referral, the severity of symptoms experienced by patients should be considered when interpreting results.

Future studies would benefit by measuring causal factors contributing to sleep problems in adults with ADHD. These studies should also include subjective sleep parameters, such as actigraphy and polysomnography, which were not included here. Insomnia has been widely studied in sleep research; more research is needed on other sleep disorders, including periodic limb movement disorder (PLMD), RLS, DSPS, and SBD.

Sources

¹ van der Ham, M., Bijlenga, D., Böhmer, M., Beekman, A.T.F., & Kooij, S. (2024). Sleep problems in adults With ADHD: prevalences and their relationship with psychiatric comorbidity. Journal of Attention Disorders, 28(13), 1642-1652. https://doi.org/10.1177/10870547241284477

² American Psychiatric Association. (2024). What are Sleep Disorders? https://www.psychiatry.org/patients-families/sleep-disorders/what-are-sleep-disorders

³Wynchank, D., Bijlenga, D., Beekman, A.T. et al. (2017). Adult attention-deficit/hyperactivity disorder (ADHD) and insomnia: an update of the literature. Curr Psychiatry Rep 19, 98. https://doi.org/10.1007/s11920-017-0860-0

⁴Batten, L. (2022, August 17). How ADHD Impacts Your Sleep And What You Can Do About It. Frida. https://www.talkwithfrida.com/learn/how-adhd-impacts-your-sleep/

⁵ U.S. Centers for Disease Control & Prevention. (2024, May 15). About Sleep. https://www.cdc.gov/sleep/about/index.html

⁶ Cleveland Clinic. (2023, June 19). Sleep Disorders. https://my.clevelandclinic.org/health/diseases/11429-sleep-disorders

⁷ American Academy Of Neurology. (2001, May 8). Adults With Restless Legs Syndrome More Likely To Have ADHD. ScienceDaily. www.sciencedaily.com/releases/2001/05/010508082849.htm

⁸ Li, X., Buxton, O. M., Kim, Y., Haneuse, S., & Kawachi, I. (2020). Do procrastinators get worse sleep? Cross-sectional study of U.S. adolescents and young adults. SSM – Population Health, 10, 100518. https://doi.org/10.1016/j.ssmph.2019.100518

⁹ Sung, V., Hiscock, H., Sciberras, E., Efron, D. (2008). Sleep problems in children with attention-deficit/hyperactivity disorder: prevalence and the effect on the child and family. Arch Pediatr Adolesc Med, 162(4):336–342. https://doi.org/10.1001/archpedi.162.4.336

¹⁰ Mitchell, M.D., Gehrman, P., Perlis, M. et al. (2012). Comparative effectiveness of cognitive behavioral therapy for insomnia: a systematic review. BMC Fam Pract, 13, 40. https://doi.org/10.1186/1471-2296-13-40

In this final installment of ADDitude magazine’s two-part series, “The Future of ADHD” (the first part appeared in the Winter 2023 issue), I’ll explain each of the developments poised to revolutionize ADHD understanding and treatment.

New Pharmacologic Interventions for ADHD

Development of pharmacologic interventions for ADHD has mushroomed over the last two decades. Though researchers have made progress in developing non-stimulant treatment options (i.e., long-acting forms of clonidine and guanfacine, as well as atomoxetine and viloxazine), most of the FDA-approved agents are simply tweaks of methylphenidate and amphetamine compounds.

There are now more choices available to prescribers and patients, offering stimulant preparations of varying durations, delivery formats (patch, liquid, tablet, capsule), and pharmacokinetic profiles. It should be noted that both older and newer preparations are exceptionally effective for most patients and, when comparing them to non-stimulants in head-to-head trials and in clinical practice, the psychostimulants generally win hands-down. However, the various forms of psychostimulants differ in their rate of onset, duration of coverage, convenience (once daily vs. multiple doses daily), and cost.

Psychostimulants, however, are not effective for everyone; about 30% of patients may not have a satisfactory response.¹ As a result, researchers are increasingly exploring the benefits of combining psychostimulant treatment with other compounds (e.g., methylphenidate paired with atomoxetine, or a dextroamphetamine compound plus guanfacine).

[Get This Free Download: 2024 Scorecard of ADHD Treatments]

The robust effectiveness of psychostimulants in treating ADHD has somewhat slowed the development of alternatives. However, researchers are exploring newer agents that target different neurotransmitter systems, including:

• Solriamfetol (used to treat excessive daytime drowsiness)
• Tipepidine (used as a cough suppressant)
• Amantadine (used to treat Parkinson’s disease)
• Dasotraline (used to treat depression and other disorders)

Not yet FDA-approved for ADHD, these compounds face two main challenges: matching the effectiveness of psychostimulants and effectively targeting symptoms not currently treated by psychostimulants.

ADHD and the Gut-Brain Axis

Emerging research suggests a significant, but underappreciated, relationship between the gut biome — a diverse community of microorganisms living in the digestive tract — and behavior and emotions. The gut and the brain communicate through the gut-brain axis, allowing gut microbiota to influence brain function and vice versa.

Multiple studies have now shown that abnormalities in the gut microbiome can affect mood, anxiety, and stress levels.² Certain gut bacteria can even produce neurotransmitters like serotonin and gamma-aminobutyric acid (GABA), which play a crucial role in regulating emotions.³ Other gut bacteria can produce toxins, inflammatory molecules, and other metabolites that can cross the blood-brain barrier to adversely impact brain health and cognitive function.⁴

[Get This Free Download: Lifestyle Changes for Adults with ADHD]

Imbalances in the gut microbiome can be caused by diet, stress, and even antibiotic use during the prenatal period or during infancy.^{5 6} Longitudinal studies have shown that these gut factors can be linked to mental health disorders, including ADHD, in later childhood.⁷ Multiple studies also suggest that restoring a healthy gut balance through probiotics, prebiotics, or dietary changes might improve emotional wellbeing.⁸ Research involving the microbiome’s impact on human behavior and emotions is still emerging.

ADHD and Gene-Environment Interactions

ADHD is highly heritable; however, environmental influences are exceptionally important in determining whether, when, and how a set of genes will manifest in ADHD symptoms. Environments determine whether a particular illness or disease manifests. This area of research — how certain genes are differentially expressed due to differences in environments — is in its infancy.

A major challenge: Because there are so many genes and possible environmental factors unfolding over time, there are literally trillions of possible gene-environment interactions that could affect the timing, severity, and persistence of ADHD. Due to the likely number and complexity of these interactions, multiple replications across independent studies will be essential.

Several studies have already shown that the severity and persistence of ADHD can be a function of parent-child interactions and supervision across different settings.⁹ This is not a “blame the parents” finding, but, instead, suggests that certain interventions from caregivers (and possibly teachers, coaches, and other adults) may mitigate a child’s symptom severity and persistence. For example, teaching parents how to remain neutral, or even express warmth in the face of difficult behaviors, is likely an important area of intervention. Related findings indicate that parental rejection¹⁰ can affect a child’s outcomes, as can the level of household disorganization¹¹, overall life stress¹², and other factors. Attention to such challenges offers an opportunity for targeted interventions.

Many different factors contribute to ADHD’s etiology, timing of onset, and severity, as well as possibilities for prevention and person-specific treatment. Our research to date, and our research programs unfolding over the next decades, will continue to lead to advances in the way we diagnose and treat ADHD in childhood and in adults.

ADHD Research: Next Steps

• Read: The Evolution of ADHD — Examining the Last 25 Years and the Future
• Read: Prenatal and Early Life Risk Factors of ADHD
• Watch: Epigenetics — Understanding Its Role in ADHD and Future Applications
• Hub: ADHD News & Research

Peter S. Jensen, M.D., is the founder of The REACH Institute, which trains providers in interventions for children’s mental health care.

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Sources

¹ Spencer, T., Biederman, J., & Wilens, T. (2004). Nonstimulant treatment of adult attention-deficit/hyperactivity disorder. The Psychiatric clinics of North America, 27(2), 373–383. https://doi.org/10.1016/j.psc.2003.12.001

² Xiong, R. G., Li, J., Cheng, J., Zhou, D. D., Wu, S. X., Huang, S. Y., Saimaiti, A., Yang, Z. J., Gan, R. Y., & Li, H. B. (2023). The Role of Gut Microbiota in Anxiety, Depression, and Other Mental Disorders as Well as the Protective Effects of Dietary Components. Nutrients, 15(14), 3258. https://doi.org/10.3390/nu15143258

³ Chen, Y., Xu, J., & Chen, Y. (2021). Regulation of Neurotransmitters by the Gut Microbiota and Effects on Cognition in Neurological Disorders. Nutrients, 13(6), 2099. https://doi.org/10.3390/nu13062099

⁴ Parker, A., Fonseca, S., & Carding, S. R. (2020). Gut microbes and metabolites as modulators of blood-brain barrier integrity and brain health. Gut microbes, 11(2), 135–157. https://doi.org/10.1080/19490976.2019.1638722

⁵ Madison, A., & Kiecolt-Glaser, J. K. (2019). Stress, depression, diet, and the gut microbiota: human-bacteria interactions at the core of psychoneuroimmunology and nutrition. Current opinion in behavioral sciences, 28, 105–110. https://doi.org/10.1016/j.cobeha.2019.01.011

⁶ Fish-Williamson, A., Hahn-Holbrook, J., Hobbs, M., Wallander, J., & Morton, S. M. B. (2022). Prenatal antibiotic exposure in pregnancy and early childhood socioemotional development. JCPP advances, 2(2), e12066. https://doi.org/10.1002/jcv2.12066

⁷ Cassidy-Bushrow, A. E., Sitarik, A. R., Johnson, C. C., Johnson-Hooper, T. M., Kassem, Z., Levin, A. M., Lynch, S. V., Ownby, D. R., Phillips, J. M., Yong, G. J. M., Wegienka, G., & Straughen, J. K. (2023). Early-life gut microbiota and attention deficit hyperactivity disorder in preadolescents. Pediatric research, 93(7), 2051–2060. https://doi.org/10.1038/s41390-022-02051-6

⁸ Bistas, K. G., & Tabet, J. P. (2023). The Benefits of Prebiotics and Probiotics on Mental Health. Cureus, 15(8), e43217. https://doi.org/10.7759/cureus.43217

⁹Haack, L. M., Villodas, M. T., McBurnett, K., Hinshaw, S., & Pfiffner, L. J. (2016). Parenting Mediates Symptoms and Impairment in Children With ADHD-Inattentive Type. Journal of clinical child and adolescent psychology : the official journal for the Society of Clinical Child and Adolescent Psychology, American Psychological Association, Division 53, 45(2), 155–166. https://doi.org/10.1080/15374416.2014.958840

¹⁰ Brinksma, D. M., Hoekstra, P. J., de Bildt, A., Buitelaar, J. K., van den Hoofdakker, B. J., Hartman, C. A., & Dietrich, A. (2023). Parental rejection in early adolescence predicts a persistent ADHD symptom trajectory across adolescence. European child & adolescent psychiatry, 32(1), 139–153. https://doi.org/10.1007/s00787-021-01844-0

¹¹ Agnew-Blais, J. C., Wertz, J., Arseneault, L., Belsky, D. W., Danese, A., Pingault, J. B., Polanczyk, G. V., Sugden, K., Williams, B., & Moffitt, T. E. (2022). Mother’s and children’s ADHD genetic risk, household chaos and children’s ADHD symptoms: A gene-environment correlation study. Journal of child psychology and psychiatry, and allied disciplines, 63(10), 1153–1163. https://doi.org/10.1111/jcpp.13659

¹² Hartman, C. A., Rommelse, N., van der Klugt, C. L., Wanders, R. B. K., & Timmerman, M. E. (2019). Stress Exposure and the Course of ADHD from Childhood to Young Adulthood: Comorbid Severe Emotion Dysregulation or Mood and Anxiety Problems. Journal of clinical medicine, 8(11), 1824. https://doi.org/10.3390/jcm8111824

October 24, 2024

Finding a clinician who takes your insurance has become a daunting task, largely because providers have abandoned insurance networks in droves. As a result, patients with ADHD and other conditions are forced to navigate a shrinking pool of in-network providers or pay out-of-pocket for care.

According to an August ProPublica report, more than 500 psychiatrists, psychologists, and therapists said they left insurance networks in recent years because insurers made it too difficult to properly care for patients and maintain a viable practice. The providers said it was often the insurers that determined who is eligible for treatment coverage, what kind, and for how long — not the professionals providing care. Some added that insurers pressed them to reduce care when patients were on the verge of harm. ¹

Many of the clinicians interviewed said they struggled to stay in business as insurers denied claims, withheld reimbursements for months, or otherwise made it nearly impossible to provide care and maintain financial viability.

A shortage of mental healthcare providers has severely limited patient access to affordable, high-quality care.

Source

¹ Why I Left the Network. (2024, August 25). ProPublica. Retrieved October 25, 2024, from
https://projects.propublica.org/why-i-left-the-network/

Boredom causes a heightened stress response in impulsive people, as evidenced by the elevated cortisol levels documented in new research published in Physiology & Behavior.¹ The research deepens the scientific community’s understanding of the interplay between impulsivity and boredom, suggesting that this relationship may be mediated by the hypothalamic-pituitary-adrenal (HPA) axis.

“This research suggests that the lived experience of boredom feels more intense and aversive for people who are highly impulsive, transforming into an overwhelming need to escape that boredom,” explained Matt Parker, Ph.D., the study’s senior author and a neuroscientist at the University of Surrey.

The research comprised two studies. ​​The first, in which participants completed a dull task and self-reported levels of boredom, confirmed previous findings that individuals who identify as impulsive are more prone to boredom than are others. ^{2, 3,4,5}

In the second study, researchers tested the levels of salivary cortisol in a portion of these participants, both before and after they completed the boring task. They found that cortisol levels were higher in those who had trait impulsivity, indicating activation of the HPA axis.

These studies help researchers more fully understand the feedback loop that can occur between impulsivity, stress, and boredom. Not only are highly impulsive people more prone to boredom, but boredom often leads to impulsivity ⁶ and to a stress response.⁷ Stress, in turn, increases impulsivity, keeping the cycle in motion.

“These findings offer promise for personalized interventions, designed for high-impulsivity individuals, to alleviate the negative impacts of boredom and potentially break the identified feedback loop,” explained the study’s authors.

Risks of Chronic Stress Response

The study’s authors write that boredom remains understudied in psychiatric research despite having “significant implications for mental health, and cognitive functioning.” In highly impulsive people, Parker explains, the intense drive to avoid boredom leads to maladaptive coping strategies including risk-taking behaviors and substance use, which sometimes alleviate boredom and reduce stress in the short term, but rarely in the long term.

This, combined with the evidence of a heightened stress response associated with boredom in impulsive people, underlines the importance of discovering effective interventions. “If people undergo chronic stress over a long period of time, and there is prolonged activation of that HPA axis, there is increased risk for cardiovascular disease, weakened immune function, and mental health problems, such as anxiety and depression,” Parker said. “The best interventions may focus on stress-management techniques, things that are designed to reduce stress axis response.”

The new studies offer insight into an experience described by ADDitude readers who call ADHD boredom intensely aversive and acutely stressful.

“I experience boredom as a profound inner restlessness,” said Jenn, an ADDitude reader in Missouri. “It isn’t just like I want to do something else; it’s like I must do something else. It’s like the restlessness is crawling under my skin.”

“Boredom feels like there is this engine running inside of me telling me to push on the gas pedal but the brakes are on, so there is smoke coming from my car,” said another ADDitude reader, Marta, from the United Kingdom.

Natalie, a reader in Pennsylvania, said: “Boredom translates to agitation, physical discomfort in my own skin, anxiety, and feeling lost — panicked, trapped-in-a-horror-movie-and-can’t-find-the-exit lost.”

Sources

¹J.M.Clay,  J.I. Badariotti, N. Kozhushko, M.O. Parker, HPA activity mediates the link between trait impulsivity and boredom, Physiology & Behavior, 284 (2024), 114637, ISSN 0031-9384, https://doi.org/10.1016/j.physbeh.2024.114637.

²C.J. Gerritsen, M.E. Toplak, J. Sciaraffa, J. Eastwood. I can’t get no satisfaction: Potential causes of boredom. Conscious Cogn, 27 (2014), pp. 27-41, 10.1016/j.concog.2013.10.001

³J. Isacescu, A.A. Struk, J. Danckert. Cognitive and affective predictors of boredom proneness. Cogn Emot, 31 (2017), pp. 1741-1748, 10.1080/02699931.2016.1259995

⁴A.A. Struk, A.A. Scholer, J. Danckert. A self-regulatory approach to understanding boredom proneness. Cogn Emot, 30 (2016), pp. 1388-1401, 10.1080/02699931.2015.1064363

⁵J.D. Watt, S.J. Vodanovich.Relationship between boredom proneness and impulsivity. Psychol Rep, 70 (1992), pp. 688-690, 10.2466/pr0.1992.70.3.688

⁶A.B. Moynihan, E.R. Igou, W.A.P. van Tilburg. Boredom increases impulsiveness: A meaning-regulation perspective. Soc Psychol, 48 (2017), pp. 293-309, 10.1027/1864-9335/a000317

⁷A.A. Moustafa, R. Tindle, D. Frydecka, B. Misiak. Impulsivity and its relationship with anxiety, depression and stress. Compr Psychiatry, 74 (2017), pp. 173-179, 10.1016/j.comppsych.2017.01.013

Sleep problems in children are associated with restless behavior and iron deficiency, two problems more common in patients with ADHD, according to a small study published in the journal Nutrients.¹

The study followed 199 patients referred to a Sleep/Wake Behavior Clinic between 2021 and 2023. It found that patients with ADHD were nearly twice as likely as their neurotypical counterparts to have restless leg syndrome (RLS). The most common psychiatric comorbidities among patients with sleep disorders included ADHD (46%), autism (45%), and anxiety disorder (41%).

Most patients in the study had an iron deficiency (94%), and 41% knew someone in their family who did. When comparing ADHD patients only, a family history of iron deficiency increased the patient’s risk of having RLS and insomnia.

“Recently, iron has received increasing attention due to its role in sleep disorders, as well as wake behaviors associated with mental health and/or neurodevelopmental disorders such as ADHD, autism spectrum disorder, and prenatal alcohol exposure/fetal alcohol spectrum disorder,” the research authors wrote.

RLS was the most common sleep disorder (74%) in the study, followed by:

• Chronic insomnia: 61%
• Signs of sleep-disordered breathing: 50%
• Restless sleep or PLMS: 30%
• Circadian rhythm sleep disorder (CRSD): 16%
• Probable painful RLS: 11%

Sleep and ADHD

Nearly three-quarters of children with ADHD experience a sleep problem or disorder.² For many children, sleep problems last into adolescence and can aggravate ADHD symptoms during the day.

“By the time they get into adolescence, we know that teens with ADHD are more likely than their peers without ADHD to get insufficient sleep on school nights,” said Stephen Becker, Ph.D., in his 2021 webinar with ADDitude, “Why Am I Always So Tired? The Latest Science on Improving Sleep in Children and Teens with ADHD.”

“We’ve also shown that poor sleep impacts academics, including academic performance, organization, and lower grades based on report cards that we’ve acquired from schools and college institutions,” Becker said. “In some of our work with young teens, even after we account for a teen’s initial levels of depressive symptoms or oppositional behaviors, those teens who had sleep problems went on to experience an increase in depressive symptoms and oppositional behaviors over time.”

Restlessness, defined as the “urge to move,” was a strong risk factor for sleep problems in children with and without ADHD in the present study. Hypermotor restlessness and hyper-arousal are central to ADHD and RLS but are often missed in pediatric patients, according to the authors. Symptoms of restlessness are based on adult criteria and do not account for physical differences that may be present in children.

“Characterizing hyper-motor restlessness during sleep as a new diagnostic entity supports our understanding that disorders presenting with hypermotor restlessness and/or hyper-arousability need an in-depth phenotyping approach from a pediatric sleep medicine perspective,” the authors wrote.

Limitations & Future Research

Standard diagnostic evaluations for sleep disorders typically do not assess for iron levels, according to the authors. Testing iron levels using blood tests could help improve treatment outcomes, as many patients in the present study were shown to be deficient. The authors noted that iron supplementation is often an effective treatment approach.

Evening activities, screen time, stimulant medication, homework stress, and inconsistent sleep/wake times may also make it difficult for children with ADHD to wind down at night.

Patients ages 3 months to 23 years and/or their family members answered questions upon intake about bedtime habits, excessive daytime sleepiness, nighttime awakenings, routines, sleep-disordered breathing, quality of sleep, and other non-specific concerns. The Sleep Disturbance Scale for Children (SDSC) and ADHD Rating Scale-IV were also administered.

The study has several limitations, including the absence of a control group and a small sample size. Additionally, medication use was not controlled, and there was no distinction made between anemic and non-anemic individuals with iron deficiency, nor between maternal and paternal family histories. Future research should explore the causes of iron deficiency. Inadequate nutrition, inflammation, and malabsorption were listed as potential contributors to iron deficiency.

Findings associated with other psychiatric disorders, including autism, were also shared in the study and can be found here.

Sources

¹ Ipsiroglu, O.S., Pandher, P.K., Hill, O., McWilliams, S., Braschel, M., Edwards, K., Friedlander, R., Keys, E., Kuo, C., Lewis, M.S., et al. (2024). Iron deficiency and restless sleep/wake behaviors in neurodevelopmental disorders and mental health conditions. Nutrients, 16(18):3064. https://doi.org/10.3390/nu16183064

² Sung, V., Hiscock, H., Sciberras, E., Efron, D. (2008). Sleep problems in children with attention-deficit/hyperactivity disorder: prevalence and the effect on the child and family. Arch Pediatr Adolesc Med, 162(4):336–342. https://doi.org/10.1001/archpedi.162.4.336

Onyda XR (clonidine hydrochloride), the first and only liquid non-stimulant ADHD medication approved in the U.S., and the only such medication with nighttime dosing, became available nationwide for the treatment of attention deficit hyperactivity disorder (ADHD) on October 1. ¹

The U.S. Food and Drug Administration (FDA) approved Onyda XR on May 24 as a monotherapy ADHD treatment or as an adjunctive therapy to approved central nervous system (CNS) stimulant medications in pediatric patients six years and older.

Tris Pharma developed Onyda XR with its proprietary LiquiXR® technology, which converts immediate-release drugs into extended-release formulations for once-daily dosing. Onyda XR is considered a centrally acting alpha2-adrenergic agonist medication that belongs to the same class of drugs as Guanfacine (Intuniv) and clonidine (Kapvay).

Patients with ADHD who experience adverse side effects from stimulants or who respond poorly to stimulant medications may find symptom relief in a non-stimulant medication. A systematic review and meta-analysis published in May by Neuroscience & Biobehavioral Reviews reported that non-stimulant medication is nearly as effective as stimulant medication at improving executive function in children, adolescents, and adults with ADHD. ²

Combination Therapy for ADHD

In addition, clinicians may prescribe Onyda XR along with a stimulant to treat ADHD symptoms. Combination therapy is becoming an increasingly popular option for patients who need longer durations of drug coverage than a stimulant dose can provide on its own or who hope to avoid common stimulant side effects.

“Most of the medicines we use for ADHD are safe in combination with other medications,” said Timothy E. Wilens, M.D., chief of child and adolescent psychiatry and co-director of the Center for Addiction Medicine at Massachusetts General Hospital, during the ADDitude webinar “Combination Therapy: Medication Strategies for Hard-to-Treat Complex ADHD.” “Certain combinations, such as stimulants plus clonidine or guanfacine, are FDA approved, and they wouldn’t be unless they were deemed effective and safe.”

Guanfacine ER (Intuniv) and clonidine ER (Kapvay), received FDA approval for the treatment of ADHD in patients 6 to 17 years old as monotherapy and as adjunctive therapy to stimulant medications in 2009 and 2010, respectively.

If a stimulant does not address symptoms at standard dosages, “it usually makes more sense to treat remaining symptoms with a second medication,” said Oren Mason, M.D., a physician at Attention MD in Grand Rapids, Michigan.

“Most adult patients in my practice who take extended-release stimulants need average to high dosages to achieve optimal symptom reduction,” Mason said. “They typically report 8 to 10 hours of medication benefit, and most require short-acting supplements to treat their evening symptoms. In contrast, most patients on combination therapy take low- to moderate stimulant dosages and report a duration of benefits of more than 12 hours.”

Mason said he finds that many adult patients using combination therapy decrease their stimulant dosages and experience fewer side effects than do patients taking only stimulants. “Waking up was less torturous, and getting ready for school was smoother,” he said. “Family life was better, without the meltdowns that many families accept as ‘normal’ as stimulants wear off.”

Anthony Rostain, M.D., M.A., professor of psychiatry and pediatrics at the Perelman School of Medicine at the University of Pennsylvania, recommends that clinicians consider several factors before prescribing combination therapy.

“The important thing to keep in mind if you’re combining agents,” he said, “is to be sure that the patient understands how to use each one and how to dose each one. They need to understand the inherent challenges they’re going to face, and make sure you’re paying attention to the side effects that might emerge from the combination of stimulant and non-stimulant.”

The FDA based its approval for Onyda XR on studies of clonidine hydrochloride extended-release tablets, including two 8-week, placebo-controlled trials evaluating 256 patients, as well as a 40-week, placebo-controlled, randomized-withdrawal study evaluating the drug in 135 pediatric patients aged 6 to 17 years. ³, ⁴

According to Onyda XR prescribing information, the most common adverse reactions with the medication’s use as monotherapy include somnolence, fatigue, irritability, nightmares, insomnia, constipation, and dry mouth. The most common adverse reactions with its use as an adjunct therapy include somnolence, fatigue, decreased appetite, and dizziness. ⁵

Sources

¹Tris Pharma’s Once-Daily ADHD Medication, ONYDA XR (clonidine hydrochloride) Extended-Release Oral Suspension, Now Available in the United States. News Release. Tris Pharma. October 1, 2024. Accessed October 2, 2024. https://www.businesswire.com/news/home/20241001522635/en/Tris-Pharma–Once-Daily-ADHD-Medication-ONYDA-XR-clonidine-hydrochloride-Extended-Release-Oral-Suspension-Now-Available-in-the-United-States

²Isfandnia, F., Masri, S.E., Radua, J., & Rubia, K. (2024) The Effects of Chronic Administration of Stimulant and Non-Stimulant Medications on Executive Functions in ADHD: A Systematic Review and Meta-Analysis. Neuroscience & Biobehavioral Reviews; 162. https://doi.org/10.1016/j.neubiorev.2024.105703

³Jain, R., Segal, S., Kollins, S.H., Khayrallah, M. (2011). Clonidine Extended-Release Tablets for Pediatric Patients with Attention-Deficit/Hyperactivity Disorder. J Am Acad Child Adolesc Psychiatry. https://doi.org/10.1016/j.jaac.2010.11.005

⁴Kollins, S.H., Jain, R., Brams, M., Segal, S., Findling, R.L., Wigal, S.B., Khayrallah, M. (2011). Clonidine Extended-Release Tablets as Add-On Therapy to Psychostimulants in Children and Adolescents with ADHD. Pediatrics. https://doi.org/10.1542/peds.2010-1260

⁵ Highlights of Prescribing Information. Onyda XR. FDA. Accessed May 29, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/217645s000lbl.pdf