August 25, 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 searches found a highly heterogeneous evidence base, which made meta-analysis inadvisable. For example, only 25 of 39 group 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 2,300 participants 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 dyskinetic. Of four non-comparative 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 comorbidities or tic disorder.

·        Seizuresor 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 non-comparative 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 289participants, 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 another neuropsychiatric outcome, 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 sins in the evidence base, it mainly supports prior conclusions of the US Food antidrug 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 JGroom, Mohammed T Ansari, Tobias Banaschewski, Jan K Buitelaar, Sara CarucciDavid Coghill, Marina Danckaerts, Ralf W Dittmann, Bruno Falissard, PeterGaras, Sarah K Inglis, Hanna Kovshoff, Puja Kochhar, Suzanne McCarthy, PeterNagy, Antje Neubert, Samantha Roberts, Kapil Sayal, Edmund Sonuga-Barke , Ian CK Wong , Jun Xia, Alexander Zuddas, Chris Hollis, Kerstin Konrad, Elizabeth Biddle and the ADDUCE Consortium,Neurological and psychiatric adverse effects of long-term methylphenidate treatment in ADHD: A map of the current evidence, Neuroscience and Biobehavioral Reviews(2019)DOI:https://doi.org/10.1016/j.neubiorev.2019.09.023

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Updated Analysis of ADHD Prevalence in the United States: 2018-2021

Attention-Deficit/Hyperactivity Disorder (ADHD) remains a prevalent condition among children and adolescents in the United States. A recent analysis based on the National Health Interview Survey (NHIS), conducted by the National Center for Health Statistics at the CDC, provides an updated look at ADHD prevalence from 2018 to 2021. Here’s a closer look at what the data reveals.

How the Survey Works

The NHIS is an annual survey primarily conducted through face-to-face interviews in respondents’ homes. Telephone interviews are used as a substitute in cases where travel is impractical. For each family interviewed, one child aged 3-17 is randomly selected for the survey through a computer program. Over the four years studied (2018-2021), a total of 26,422 households with children or adolescents participated.

Overall ADHD Prevalence and Age-Related Trends

The analysis found that 9.5% of children and adolescents in the United States had been diagnosed with ADHD, based on reports from family members. However, the prevalence varied significantly with age:

  • Ages 3-5: 1.5%
  • Ages 6-11: 9.6%
  • Ages 12-17: 13.4%

The increase in ADHD diagnosis with age underscores the importance of monitoring children’s developmental needs as they progress through school and adolescence.

Gender Differences: Higher Rates Among Males

The survey revealed a notable difference in ADHD prevalence between genders, with 12.4% of males diagnosed compared to 6.6% of females—nearly a two-to-one gap. This aligns with previous research indicating that ADHD is more frequently diagnosed in boys than girls, though awareness of how ADHD presents differently across genders is growing.

Family Income and ADHD Rates

Family income played a significant role in ADHD prevalence, particularly among lower-income groups:

  • Below the poverty line: 12.7%
  • Above the poverty line but less than twice that level: 10.3%
  • Above twice the poverty level: 8.5%

This pattern suggests that socioeconomic factors might influence the diagnosis and management of ADHD, with lower-income families possibly experiencing greater barriers to early diagnosis or consistent treatment.

Regional Differences Across the U.S.

Geographic location also impacted ADHD rates. Prevalence was highest in the South (11.3%), followed by the Midwest (10%), the Northeast (9.1%), and significantly lower in the West (6.9%). These variations could reflect regional differences in healthcare access, diagnostic practices, or cultural attitudes towards ADHD.

Stability Over Time

Despite these variations in demographics, the overall prevalence of ADHD remained relatively stable across the study period from 2018 to 2021, showing no significant changes by year.

What This Means for Families and Healthcare Providers

The findings from this updated analysis provide a clearer picture of ADHD’s prevalence across different demographic groups in the United States. They highlight the need for tailored approaches to diagnosis and care, taking into account factors like age, gender, income, and geographic location. With ADHD being a common condition affecting nearly 1 in 10 children, ongoing research and support for families are crucial to ensure that those with ADHD receive the care and resources they need.

Conclusion: 

This study reinforces the importance of awareness and early intervention, especially for families in underserved regions or those facing economic challenges. As clinicians and educators continue to support children with ADHD, understanding these demographic trends can help in creating more equitable access to diagnosis and treatment.

October 29, 2024

Meta-Analysis Shows No Significant Impact of Caffeine on ADHD Symptoms

Stimulant medications like methylphenidate and amphetamines are well-established treatments for reducing ADHD symptoms, making a notable difference in focus and behavior. Given that caffeine is also a stimulant, researchers have wondered whether it might offer similar benefits for managing ADHD symptoms. A recent meta-analysis conducted by a Brazilian research team sought to explore this question.

The Search for Evidence: A Limited Pool of Studies

The researchers faced an immediate challenge: there is surprisingly little research directly investigating caffeine's effects on ADHD symptoms. After a thorough review of peer-reviewed literature, they identified only four randomized controlled trials (RCTs) suitable for their analysis, encompassing a combined total of just 152 participants.

The limited number of studies—and participants—meant that the meta-analysis was not as robust as the research team might have hoped. However, they proceeded to examine the available data to determine whether caffeine showed any measurable benefit over a placebo.

Findings: Minimal Impact, No Statistical Significance

The results of the meta-analysis showed a slight decrease in ADHD symptoms among those who consumed caffeine compared to those given a placebo. However, this reduction was not statistically significant. The small sample size likely played a role in this outcome, making the study underpowered. Even if future studies with larger groups of participants were to show statistical significance, the observed effect size would likely remain too small to be clinically meaningful.

Interestingly, the four trials included in the meta-analysis showed very little variation in their findings. Each study slightly favored caffeine over placebo, but none came close to achieving statistical significance.

Conclusion: Caffeine Is Not a Substitute for ADHD Medications

Ultimately, the researchers concluded that “overall, the totality of the evidence suggests no significant benefit of caffeine over placebo in the treatment of children with ADHD.” The findings indicate that while caffeine might produce a slight reduction in symptoms, it is not an effective alternative to established ADHD treatments like methylphenidate or amphetamines.

This study highlights the importance of relying on proven medications for ADHD management rather than seeking alternatives that lack substantial evidence. While caffeine might offer a slight stimulant effect, it falls short of delivering the therapeutic benefits needed for those with ADHD to manage their symptoms effectively. For clinicians, parents, and individuals with ADHD, these results underscore the value of evidence-based treatments in improving quality of life and daily functioning.

October 28, 2024

ADHD’s Impact on Criminal Convictions—and How Medication Reduces Risk

Swedish Study Reveals ADHD’s Impact on Criminal Convictions—and How Medication Reduces Risk

ADHD has long been associated with higher rates of criminal behavior, but most studies have relied heavily on self-reported data and small, non-representative samples. A new Swedish study addresses these limitations, providing a more comprehensive and reliable picture using data from nationwide registers. It sheds light on the role of ADHD medication in reducing the risk of criminal convictions, offering insights for clinicians, policymakers, and families.

Previous Research: The Denmark Comparison

Earlier research, such as a 2019 Danish study, found that ADHD diagnosed in children and adolescents ages 4 to 15 was associated with a 1.6-fold increased risk of future criminal conviction. However, these findings were limited by a smaller sample size and a focus on just one nation’s context. Like Denmark, Sweden’s single-payer universal healthcare system allows for the collection of extensive data on health and crime records, providing an ideal environment for large-scale, population-based research.

Swedish Study Design: A Robust Approach

To investigate ADHD’s connection to criminal behavior, the Swedish research team analyzed records from a cohort of 1,646,645 individuals born between 1986 and 1997. They excluded those who died or emigrated before age 15 (the age of criminal responsibility in Sweden) and those who immigrated to Sweden, resulting in a final study group of 1,235,939 individuals. Slightly more than half of the cohort was male.

ADHD diagnoses were based on clinical records and prescriptions for approved ADHD medications, while criminal convictions—both violent and nonviolent—were identified using Sweden’s National Crime Register, covering the years 2001 to 2013. The study adjusted for various potential confounding factors, including sex, birth year, parental education, and other psychiatric conditions. They also used the Swedish Multi-Generation Register to control for unmeasured familial factors to compare outcomes among full siblings.

Key Findings: ADHD and Criminality

The study found that ADHD is strongly associated with increased rates of criminal convictions. Compared to individuals without ADHD, those with an ADHD diagnosis were roughly:

  • Four times more likely to be convicted of a violent crime.
  • Twice as likely to be convicted of a nonviolent crime.

Interestingly, when comparing conviction rates among males and females with ADHD, the rates of nonviolent convictions were similar, but females with ADHD were about 25% more likely to be convicted of a violent crime than males with ADHD.

The Role of Medication: A Significant Moderating Factor

The research also highlighted the importance of ADHD medication in reducing criminal behavior. When individuals with ADHD who were taking medication were excluded from the analysis, the data showed significantly higher rates of criminal convictions:

  • Unmedicated males with ADHD had a 50% higher rate of violent convictions and more than double the rate of nonviolent convictions compared to their typically developing peers.
  • Unmedicated females with ADHD faced even greater risks, with nearly triple the rate of violent convictions and quadruple the rate of nonviolent convictions.

These findings suggest that ADHD medications can significantly reduce the risk of both violent and nonviolent criminal behavior in individuals with ADHD, emphasizing the value of pharmacological treatment for those with the condition.

Clinical Implications: Medication as a Risk-Reducing Strategy

The researchers concluded that “ADHD is a strong risk factor for both violent and non‐violent criminal convictions in males and females even after adjustments for psychiatric comorbidities and unmeasured familial factors.” The study also found that untreated ADHD poses a particularly high risk for criminal behavior, highlighting the protective role of medication.

These findings are clinically relevant for several reasons. First, they reinforce the importance of ensuring that individuals with ADHD have access to effective treatment options, especially during the transition from adolescence into adulthood, which is statistically a period of higher risk for criminal behavior. Additionally, the study provides critical data for shaping public policy and interventions aimed at supporting individuals with ADHD, with a focus on reducing criminality through proper management of the disorder.

Conclusion:

This study offers new insights into the complex relationship between ADHD, medication, and criminal behavior, emphasizing the crucial role of treatment in mitigating risks. It provides a compelling case for prioritizing access to ADHD medication as part of a broader strategy for supporting those with ADHD.