March 6, 2021

Are there adverse effects to long-term treatment of ADHD with methylphenidate?

Methylphenidate(MPH) is one of the most widely-prescribed medications for children. Given that ADHD frequently persists over a large part of an individual’s lifespan, any side effects of medication initiated during childhood may well be compounded over time. With funding from the European Union, a recently released review of the evidence looked for possible adverse neurological and psychiatric outcomes.

From the outset, the international team recognized a challenge: “ADHD severity may be an important potential confounder, as it may be associated with both the need for long-term MPH therapy and high levels of underlying neuropsychiatric comorbidity.” Their search found a higy heterogeneous evidence base, which made meta-analysis inadvisable. For example, only 25 of 39 groups studies reported the presence or absence of comorbid psychiatric conditions, and even among those, only one excluded participants with comorbidities. Moreover, in only 24 of 67 studies was the type of MPH used (immediate or extended-release)specified. The team, therefore, focused on laying out an “evidence map” to help determine priorities for further research.

The team found the following breakdown for specific types of adverse events:

·      Low mood/depression. All three non-comparative studies found MPH safe. Two large cohort studies, one with over 2,300 participants, and the other with 142,000, favored MPH over the non-stimulant atomoxetine . But many other studies, including a randomized controlled trial(RCT), had unclear results. Conclusion: “the evidence base regarding mood outcomes from long-term MPH treatment is relatively strong, includes two well-powered comparative studies, and tends to favor MPH.”

·      Anxiety. Here again, all three non-comparative studies found MPH safe. But only two of seven comparative studies favored MPH, with the other five having unclear results. Conclusion: “while the evidence about anxiety as an outcome of long-term MPH treatment tends to favor MPH, the evidence base is relatively weak.”

·      Irritability/emotional reactivity. A large cohort study with over 2,300 participants favored MPH over atomoxetine . Conclusion: “the evidence base … is limited, although it includes one well-powered study that found in favor of MPH over atomoxetine.”

·      Suicidal behavior/ideation. There were no non-comparative studies, but all five comparative studies favored MPH. That included three large cohort studies, with a combined total of over a hundred thousand participants, that favored MPH over atomoxetine. Conclusion: “the evidence base … is relatively strong, and tends to favor MPH.”

·      Bipolar disorder. A very large cohort study, with well over a quarter-million participants, favored MPH over atomoxetine. A much smaller cohort study comparing MPH with atomoxetine , with less than a tenth the number of participants, pointed toward caution. Conclusion: “the evidence base … is limited and unclear, although it includes two well-powered studies.”

·      Psychosis/psychotic-like symptoms. By far the largest study, with over 145,000 participants, compared MPH with no treatment, and pointed toward caution. A cohort study with over 2,300participants favored MPH over atomoxetine. Conclusion: “These findings indicate that more research is needed into the relationship between ADHD and psychosis, and into whether MPH moderates that risk, as well as research into individual risk factors for MPH-related psychosis in young people with ADHD.”

·      Substance use disorders. A cohort study with over 20,000 participants favored MPH over anti-depressants, anti-psychotics, and no medication. Other studies looking at dosages and durations of treatment, age at treatment initiation, or comparing with no treatment or “alternative” treatment, all favored MPH except a single study with unclear results. Conclusion: “the evidence base … is relatively strong, includes one well-powered study that compared MPH with antipsychotic and antidepressant treatment, and tends to favor MPH.”

·      Tics and other dyskinesias. Of four noncomparative studies, three favored MPH, the other, with the smallest sample size, urged caution. In studies comparing with dexamphetamine, pemoline, Adderall, or no active treatment, three had unclear results and two pointed towards caution. Conclusion: “more research is needed regarding the safety and management of long-term MPH in those with comorbid tics or a tic disorder.”

·      Seizures or EEG abnormalities. With one exception, the studies had small sample sizes. The largest, with over 2,300 participants, compared MPH with atomoxetine, with inconclusive results. Two small studies found MPH safe, one had unclear results, and two others pointed towards caution. Conclusion: “While the evidence is limited and unclear, the studies do not indicate evidence for seizures as an AE of MPH treatment in children with no prior history … more research is needed into the safety of long-term MPH in children and young people at risk of seizures.”

·      Sleep Disorders. All three noncomparative studies found MPH safe, but the largest cohort study, with over 2,300 participants, clearly favored atomoxetine. Conclusion: “more research is needed into the relationship between ADHD, sleep, and long-term MPH treatment.”

·      Other notable psychiatric outcomes. Two noncomparative studies, with 118 and 289 participants, found MPH safe. A cohort study with over 700 participants compared with atomoxetine, with inconclusive results. Conclusion: “there is limited evidence regarding long-term MPH treatment and other neuropsychiatric outcomes, and that further research may be needed into the relationship between long-term MPH treatment and aggression/hostility.”

Although this landmark review points to several gaps in the evidence base, it mainly supports prior conclusions of the US Food and Drug Administration (FDA) and other regulatory agencies (based on short-term randomized controlled trials) that MPH is safe for the treatment of ADHD in children and adults. Given that MPH has been used for ADHD for over fifty years and that the FDA monitors the emergence of rare adverse events, patients, parents and prescribers can feel confident that the medication is safe when used as prescribed.

Helga Krinzinger,Charlotte L Hall, Madeleine J Groom, Mohammed T Ansari, Tobias Banaschewski,Jan K Buitelaar, Sara Carucci, David Coghill, Marina Danckaerts, Ralf W Dittmann, Bruno Falissard, Peter Garas, Sarah K Inglis, Hanna Kovshoff, Puja Kochhar, Suzanne McCarthy, Peter Nagy, Antje Neubert, Samantha Roberts, Kapil Sayal, Edmund Sonuga-Barke , Ian C K Wong , Jun Xia, Alexander Zuddas, ChrisHollis, Kerstin Konrad,

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New Study Examines ADHD Stimulant Use and Substance Use Risks Among Adolescents

U.S. Study Finds No Increased Non-Medical Use Among Those Prescribed Stimulants as Adolescents, but Finds Other Links

A recent U.S. study challenges assumptions about the link between prescription stimulant use for ADHD and later substance abuse. Adolescents who used prescription stimulants under a physician’s supervision did not exhibit increased rates of non-medical stimulant use or cocaine use as they transitioned into young adulthood. However, other factors, like binge drinking and cannabis use, showed significant associations with later substance misuse, suggesting that the landscape of risk is more complex than previously understood.

Stimulants and ADHD: Understanding the Risks

Prescription stimulants are considered one of the most effective treatments for ADHD. While these medications can significantly improve focus and behavior, concerns have persisted that using stimulants during adolescence might predispose individuals to substance use disorder (SUD). Some theories suggest that early exposure to stimulants could increase the likelihood of cocaine use, as both substances affect the brain's dopamine pathways similarly.

Yet, previous research often lacked large, longitudinal studies focusing on adolescents with ADHD who had never been treated with stimulants. To fill this gap, a research team followed a nationally representative cohort of 11,905 high school seniors (12th graders, mostly aged 18) for six years, tracking their substance use behaviors.

Study Design: Following the Participants

At the start of the study, participants completed surveys regarding their ADHD treatment history—whether they had used stimulant therapy, non-stimulant therapy, or no medication at all. This formed three groups:

  • Adolescents treated with stimulant therapy for ADHD
  • Adolescents treated with non-stimulant therapy for ADHD (ADHD controls)
  • Adolescents with no history of ADHD treatment (non-ADHD controls)

Participants then completed follow-up surveys every two years, reporting on their use of substances like prescription stimulants and cocaine, as well as their engagement in behaviors like binge drinking and cannabis use.

Key Findings: No Direct Link to Non-medical Stimulant or Cocaine Use

The study found no significant differences in the rates of non-medical stimulant use or cocaine use among the three groups. Adolescents who had been prescribed stimulant medications were not more likely to misuse prescription stimulants or cocaine as young adults than those who had not received such medications.

However, other behaviors at age 18 showed strong associations with later substance use:

  • Binge drinking during late adolescence was linked to an 80% increase in the likelihood of subsequent nonmedical prescription stimulant use and cocaine use.
  • Nonmedical use of prescription opioids at age 18 increased the odds of later nonmedical stimulant use by 50% and of cocaine use by two-thirds.
  • Cannabis use by age 18 more than tripled the likelihood of later non-medical stimulant use and increased the odds of subsequent cocaine use sixfold.

Clinical Implications

The study’s findings have important implications for both clinicians and families managing ADHD. Although ADHD is associated with an increased risk of SUD, the researchers observed no higher risk of nonmedical stimulant use among adolescents who had taken stimulant therapy compared to those who hadn’t. Additionally, there was no evidence that stimulant medications posed a greater risk than non-stimulant medications for subsequent misuse.

The findings also highlight the need for more robust screening for alcohol and other drug use among adolescents. As the study notes, current guidelines do not recommend routine screening for substance misuse in adolescents due to limited evidence. However, given the associations found between binge drinking, cannabis use, and later substance misuse, such preventive measures could play a key role in reducing risks during this vulnerable period of development.

Ultimately, the study sheds light on the multifaceted nature of substance use risks in adolescents and young adults, suggesting that while prescription stimulant use for ADHD under medical supervision may not directly contribute to substance abuse, the broader context of an adolescent’s behaviors and environment is crucial in shaping future outcomes.

October 17, 2024

CDC: ADHD Diagnosis, Treatment, and Telehealth Use in Adults

The report "Attention-Deficit/Hyperactivity Disorder Diagnosis, Treatment, and Telehealth Use in Adults" published in the CDC's Morbidity and Mortality Weekly Report provides a detailed examination of the prevalence and treatment of ADHD among U.S. adults based on data collected by the National Center for Health Statistics Rapid Surveys System during October–November 2023. This data is crucial as it offers updated estimates on the prevalence of ADHD in adults, a condition often regarded as primarily affecting children, and highlights the ongoing challenges in accessing ADHD-related treatments, including telehealth services and medication availability.

Methods:

The methods used in this study involved the National Center for Health Statistics (NCHS) Rapid Surveys System (RSS), which gathers data to approximate the national representation of U.S. adults through two commercial survey panels: the AmeriSpeak Panel from NORC at the University of Chicago and Ipsos’s KnowledgePanel. The data were collected via online and telephone interviews from 7,046 adults. The responses were weighted to reflect the total U.S. adult population, ensuring that the results approximate national estimates. In identifying adults with current ADHD, respondents were asked if they had ever been diagnosed with ADHD and, if so, whether they currently had the condition. The study also collected data on treatment types (including stimulant and nonstimulant medications), telehealth use, and demographic variables such as age, education, race, and household income.

Results:

The results showed that approximately 6.0% of U.S. adults, or an estimated 15.5 million people, had a current ADHD diagnosis. Notably, more than half of the adults with ADHD reported receiving their diagnosis during adulthood (age ≥18 years), indicating that diagnosis can occur well beyond childhood. Analysis of demographics showed significant differences between adults with ADHD and those without; adults with ADHD were more likely to be younger, with 84.5% under the age of 50. Adults with ADHD were also less likely to have completed a bachelor's degree and more likely to have a household income below the federal poverty level compared to those without ADHD. Regarding treatment, the report found that approximately one-third of adults with ADHD were untreated, and around one-third received both medication and behavioral treatment. Among those receiving pharmacological treatment, 33.4% used stimulant medications, and 71.5% of these individuals reported difficulties in getting their prescriptions filled due to medication unavailability, reflecting recent stimulant shortages in the United States. Additionally, nearly half of adults with ADHD had used telehealth services for ADHD-related care, including obtaining prescriptions and receiving counseling or therapy.

The discussion emphasizes the public health implications of these findings. ADHD is often diagnosed late, with many individuals not receiving a diagnosis until adulthood, which underscores the need for improved awareness and early identification of ADHD symptoms across the life course. Moreover, the high prevalence of untreated ADHD and the barriers to accessing stimulant medications reveal significant gaps in the healthcare system's ability to support adults with ADHD. These gaps can contribute to poorer outcomes, such as increased risk of injury, substance use, and social impairment. The report also highlights the role of telehealth, which became more prominent during the COVID-19 pandemic. Telehealth appears to provide a viable solution for expanding access to ADHD diagnosis and treatment, though challenges remain regarding the quality of care and potential for misuse. The authors suggest that improved clinical care guidelines for adults with ADHD could help reduce delays in diagnosis and treatment access, thus improving long-term outcomes for affected individuals.

Conclusion:

In conclusion, the study provides a comprehensive view of the prevalence, treatment, and telehealth use for ADHD among adults in the U.S.  These data are crucial for guiding clinical care and shaping policies related to medication access and telehealth services. The findings underscore the importance of ensuring an adequate supply of stimulant medications and reducing barriers to ADHD care, ultimately enhancing the quality of life for adults with this condition.   The good news is that many adults with ADHD are being diagnosed and treated.  It is, however, concerning that many are not treated and that many of those treated with stimulants were impacted by the stimulant shortage.

For more details, see:   https://www.cdc.gov/mmwr/volumes/73/wr/mm7340a1.htm

October 14, 2024

News Tuesday Study! Understanding ADHD in Older Adults: An Overlooked Concern

60% to 90% of youth with ADHD continue to have symptoms as adults. In older adults, about 2.5% are believed to have ADHD, but it often goes unnoticed because research is limited and current diagnosis methods are based mostly on studies of young people.

Our commentary discusses key points about ADHD in older adults.  Although 2 to 3 percent of older adults have ADHD when using proper diagnostic tools, only 0.23% are diagnosed in medical records. This shows that ADHD is greatly underdiagnosed in older adults. Even worse, less than 40% of those who are diagnosed receive any treatment, which highlights the need for doctors to be better educated about ADHD in this age group. Current ways of diagnosing ADHD need to be improved for people over 50. Also, there isn’t much research on ADHD medications for people over 60, with most studies excluding them, which raises concerns about how safe and effective these treatments are for older adults, especially since stimulant medications can affect the heart.

There are also biases among doctors that make it harder to diagnose and treat ADHD in older adults. Many doctors aren’t trained to recognize ADHD in this age group and still see it as a condition that only affects young people. Some think that if a person hasn’t been treated for ADHD by this stage in life, they don’t need treatment now. But this ignores the fact that untreated ADHD can cause lifelong struggles and reduce the person’s quality of life. Some doctors are also worried about the risks of ADHD medications for older patients, even though research shows that these medications are usually safe when properly monitored.

Diagnosing ADHD in older adults can be tricky because its symptoms can look similar to other conditions, like mild cognitive impairment or dementia. This makes it important for doctors to do a thorough assessment that looks at medical, psychiatric, and psychological factors. Since older adults often have other health issues, it’s crucial for doctors to tell the difference between ADHD symptoms and those caused by other conditions.

In the end, we need more awareness, training, and research on ADHD in older adults. Doctors need to push past biases and consider the benefits of treating ADHD in this age group, carefully weighing the risks and rewards. As the population of older adults grows, so does the need for studies and guidelines to provide better care for older people with ADHD. Filling these gaps will ensure that older adults with ADHD get the attention and treatment they need.

October 8, 2024