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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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

Meta-analysis Finds Strong Link Between Parental and Offspring ADHD

A large international research team has just released a detailed analysis of studies looking at the connection between parents' mental health conditions and their children's mental health, particularly focusing on ADHD (Attention Deficit Hyperactivity Disorder). This analysis, called a meta-analysis, involved carefully examining previous studies on the subject. By September 2022, they had found 211 studies, involving more than 23 million people, that could be combined for their analysis.

Most of the studies focused on mental disorders other than ADHD. However, when they specifically looked at ADHD, they found five studies with over 6.7 million participants. These studies showed that children of parents with ADHD were more than eight times as likely to have ADHD compared to children whose parents did not have ADHD. The likelihood of this result happening by chance was extremely low, meaning the connection between parental ADHD and child ADHD is strong.

Understanding the Numbers: How Likely Is It for a Child to Have ADHD?

The researchers wanted to figure out how common ADHD is among children of parents both with and without ADHD. To do this, they first analyzed 65 studies with about 2.9 million participants, focusing on children whose parents did not have ADHD. They found that around 3% of these children had ADHD.

Next, they analyzed five studies with over 44,000 cases where the parents did have ADHD. In this group, they found that 32% of the children also had ADHD, meaning about one in three. This is a significant difference—children of parents with ADHD are about ten times more likely to have the condition than children whose parents who do not have ADHD.

How Does This Compare to Other Mental Disorders in Parents?

The researchers also wanted to see if other mental health issues in parents, besides ADHD, were linked to ADHD in their children. They analyzed four studies involving 1.5 million participants and found that if a parent had any mental health disorder (like anxiety, depression, or substance use issues), the child’s chances of having ADHD increased by 80%. However, this is far less than the 840% increase seen in children whose parents specifically had ADHD. In other words, ADHD is much more likely to be passed down in families compared to other mental disorders.

Strengths and Weaknesses of the Research

The study had a lot of strengths, mainly due to the large number of participants involved, which helps make the findings more reliable. However, there were also some limitations:

  • The researchers did not look into "publication bias," which means they didn’t check whether only certain types of studies were included (those showing stronger results, for example), which could make the findings seem more extreme.
  • The team reported that differences between the studies were measured, but they didn’t explain clearly how these differences affected the results.
  • Most concerning, the researchers admitted that 96% of the studies they included had a "high risk of bias," meaning that many of the studies might not have been entirely reliable.

Conclusion

Despite these limitations, the research team concluded that their analysis provides strong evidence that children of parents with ADHD or other serious mental health disorders are at a higher risk of developing mental disorders themselves. While more research is needed to fill in the gaps, the findings suggest that it would be wise to carefully monitor the mental health of children whose parents have these conditions to provide support and early intervention if needed

Meta-analysis Finds Vocal Emotion Recognition Accuracy is Significantly Lower in ADHD

Meta-analysis finds vocal emotion recognition accuracy is significantly lower in ADHD

Emotion dysregulation (ED) refers to the difficulty someone has in managing their emotions. People with ED might experience strong reactions like anger, irritability, emotional outbursts, or even excessive happiness. This issue affects 25% to 45% of children with ADHD and 30% to 70% of adults with ADHD. ED may come from challenges in recognizing emotions—like anger, sadness, fear, or happiness—based on facial expressions or tone of voice. People with ADHD struggle to control their emotions in a similar way that they have trouble controlling their attention and behavior.

Emotion Recognition in ADHD

One way researchers study ED in people with ADHD is by testing how well they recognize emotions. In these studies, participants are shown faces or hear voices expressing different emotions, and they are asked to identify which emotion is being shown. This helps measure how accurately people with ADHD recognize emotions compared to people without ADHD (referred to as typically developing, or TD, individuals).

Research Findings

A group of psychologists from the UK reviewed many studies that compared how well people with ADHD and TD individuals performed on emotion recognition tasks. They focused on studies that looked specifically at how well participants could recognize emotions through vocal expressions (such as changes in tone of voice).

They combined the results of 20 different studies, which together included 1,651 participants, and found that people with ADHD had more difficulty recognizing emotions than those without ADHD. The overall difference between the two groups was moderate, meaning the ADHD group consistently had more trouble, but the differences weren’t extreme. Only two of the 20 studies showed slightly different results, and there was no sign that the studies were biased. Whether or not participants were taking medication for ADHD didn’t change the outcomes.

Recognizing Positive and Negative Emotions

The study found that people with ADHD had more trouble recognizing both positive and negative emotions compared to the TD group:

  • Anger and sadness: People with ADHD showed a moderate level of difficulty in recognizing these emotions.
  • Happiness: There was a small-to-moderate level of difficulty in recognizing happiness.
  • Overall: There was no clear pattern showing that ADHD participants struggled more with certain types of emotions; instead, their errors seemed random. This suggests that their difficulties in recognizing emotions may be linked to their general attention problems.
Age Differences

The study found that emotion recognition difficulties were more pronounced in children with ADHD than in adults. Among children, the deficit was large, while among adults, the difference was moderate.

Conclusion

The psychologists concluded that their analysis provides strong evidence that people with ADHD struggle with recognizing emotions, particularly through vocal expressions. They also found that these difficulties aren’t specific to certain emotions (like only anger or sadness), but rather seem to affect emotion recognition in general. This supports the idea that ED in ADHD is partly due to the same attention problems that make it difficult for people with ADHD to focus or control their behavior. The findings highlight that emotion dysregulation in ADHD may be a secondary problem caused by these underlying attention issues.

October 4, 2024