July 8, 2021

High Dropout Rate in Six-Year Cohort Study of Medication Treatment for ADHD

Few studies have examined the safety and tolerability of ADHD medications (stimulants and atomoxetine) extending beyond six months, and none beyond a few years. A pair of Swedish neuroscientists at Uppsala University Hospital set out to explore longer-term outcomes. They conducted a six-year prospective study of 112 adults diagnosed with ADHD who were being treated with ADHD medications (primarily MPH, but also dexamphetamine and atomoxetine).


They found that at the end of that period, roughly half were still on medication, and half had discontinued treatment. There were no significant differences between the two groups in age, sex, ADHD severity, or comorbidity. The average ADHD score for the entire cohort declined to vary significantly, from a mean of 37 to a mean of 26, with less than one in a thousand odds of that being due to chance. There was also no sign of drug tolerance or a need to increase the dosage over time.
All 55 adults who discontinued treatment had taken MPH for at least part of the time. Eleven had also been treated with dexamphetamine(DEX) and 15 with atomoxetine (ATX). The average time on treatment was just under two years. Almost a third quit MPH because they perceived no beneficial effect. Since they were on average taking higher doses at discontinuation than initiation, that is unlikely to have been due to suboptimal dosage. Almost another third was discontinued for various adverse mental effects, including hyperactivity, elation, depressive moods, aggression, insomnia, fatigue, and lethargy. Another one in eleven quit when they lost contact with the prescribing physician. In the case of ATX, almost half quit because of what they perceived as adverse mental effects.


Among the 57 adults who remained on medication, four out of five reported a strong beneficial effect. Only two reported minimal or no effect. Compared with the group that discontinued, the group that remained on medication was far more likely to agree with the statements, "My quality of life has improved," and "My level of functioning has improved." Yet, as the authors caution, it is possible "that the subjects' subjective ratings contained a placebo-related mechanism in those who are compliant with the medication and pursue treatment over time." The authors reported that there were no significant differences in ADHD scores or ADHD severity between the group that quit and the group that remained on medication, even though, on average, the group that quit had been off medication for four years at follow-up.


We cannot explain why the patients who quit treatment showed similar levels of ADHD symptoms to those who continued treatment.  It is possible that some patients remit symptoms over time and do not require sustained treatment.  But we must keep in mind that there was a wide range of outcomes in both groups. Future work needs to find predictors of those who will do well after treatment withdrawal and those who do not.


Any decision on whether to maintain a course of medication should always weigh expected gains against adverse side effects. Short of hard evidence of continuing efficacy beyond two years, adverse events gain in relative importance. With that in mind, it is worth noting that this study reports that among those who remained on MPH, many reported side effects. More than a quarter complained of decreased appetite, one in four of dry mouth, one in five of anxiousness and increased heart rate, one in six of decreased sexual desire, one in nine of depressed mood, and one in eleven of insomnia.


This study breaks important ground in looking at the long-term effects of medication. It reaffirms findings elsewhere of the efficacy of ADHD medications. But contrary to the authors' conclusion, the data they present suggests the possibility that permanently medicating ADHD patients may not be more efficacious than discontinuation beyond a certain point, especially when balanced against adverse side effects.
But this is just one study with a relatively small sample size. This suggests a need for additional studies with larger sample sizes to pursue these questions with greater statistical reliability.

Dan Edvinsson and Lisa Ekselius, "Long-Term Tolerability and safety of Pharmacological Treatment of Adult Attention-Deficit/hyperactivity disorder," Journal of clinical psychopharmacology, vol. 38, no. 4(2018).

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Network Meta-analysis Explores Long-term Efficacy of Nonpharmacological Treatments for Improving Inhibitory Control in Children and Adolescents with ADHD

Background Info:

Executive functions include inhibitory control, working memory, and cognitive flexibility. Inhibitory control is the ability to suppress distractions and focus on goals, which is the main deficit in ADHD. 

Children and adolescents with ADHD often have off-task, unrelated thoughts and are easily distracted, limiting their sustained attention. This makes it difficult for them to focus on tasks and leads to impulsive behaviors that affect their daily life, academics, and social interactions. Improving inhibitory control in ADHD children and adolescents is essential. 

Stimulant medications are commonly used to treat ADHD. However, side effects like insomnia, loss of appetite, and headaches may make parents hesitant to use these medications for their children. 

Non-pharmacological treatments like cognitive training, behavior therapy, and physical exercise have gained attention for their lack of side effects. Research shows that some non-pharmacological methods can improve cognitive outcomes significantly, underscoring their potential in treating ADHD. 

Study:

A Chinese research team identified four key gaps in current research on non-pharmacological treatments for inhibitory control in children with ADHD: 

  • Existing meta-analyses seldom differentiate between short-term and long-term interventions.  
  • Most studies focus primarily on short-term effects and neglect evaluation of maintenance effects through follow-up assessments.  
  • New treatment methods, such as meditation and board games, have not been systematically assessed in meta-analyses for their impact on inhibitory control in children and adolescents with ADHD, leaving their effectiveness uncertain.  
  • Traditional meta-analysis does not tell us which intervention is most effective. Without this comparative analysis, it is difficult to rank efficacy. 

The team therefore performed a network meta-analysis of long-term randomized controlled trials (RCTs) to assess and rank the effectiveness of various non-pharmacological treatments on inhibitory control in children and adolescents with ADHD. 

The team included only RCTs relying on professional diagnoses of ADHD, excluding those based only on parent and teacher rating scales.  

The included studies measured inhibitory control using objective neurocognitive tasks, such as the Stroop test and the Go/No-Go test, to reduce potential subjective bias. Studies relying on parent- or teacher-reported questionnaires were excluded. 

Controls either received no intervention or placebo, such as watching running videos and attending history classes. 

Meta-analysis of 16 studies combining 546 participants found large short-term effect size improvements in inhibitory control from physical exercise. But the two studies with a total of 110 participants that performed a follow-up test reported only a small-to-medium effect size improvement. 

For cognitive training, a meta-analysis of fifteen studies totaling 674 participants reported a medium effect size of short-term improvement in inhibitory control. The ten studies with 563 participants that performed a follow-up test found only a small effect size improvement since treatment initiation. 

For behavioral therapy, meta-analysis of six studies encompassing 244 individuals likewise found a medium effect size short-term improvement in inhibitory control. In this case, however two studies combining 91 participants that performed a follow-up test reported that the medium effect size improvement was maintained. 

For neurofeedback, meta-analysis of seven studies encompassing 186 individuals found a small-to-medium effect size short-term improvement in inhibitory control. The only study that performed a follow-up test reported a small effect size improvement since treatment initiation. 

The two studies with a combined 44 individuals exploring board games found no significant improvement in inhibitory control. Likewise, the two studies combining 32 participants that explored meditation found no significant improvement in inhibitory control. 

There was no indication of publication bias. 

Conclusion:

The team concluded, “Existing evidence shows that physical exercise, behavior therapy, cognitive training, and neurofeedback can effectively improve the inhibitory control of children and adolescents with ADHD. However, meditation, EMG feedback, and board games did not significantly affect inhibitory control. Physical exercise has the best effect among all non-pharmacological treatments, but its impact will be weakened after intervention. Behavior therapy and cognitive training had a slightly lower effect, but they have a better maintenance effect.” 

Ultimately, the study results suggest that non-drug treatments can help children and teens with ADHD improve their ability to control their actions and stay focused. Some methods, like physical exercise, work well at first but may fade once the activity stops. Other methods, like behavioral therapy and cognitive training, may take a little longer to show results but can last longer and make a bigger difference over time. Ultimately, and most importantly, because this work did not study the symptoms of ADHD or its real-world impairments, it provides no reason to change current treatment practices for ADHD.

July 16, 2025

The Role of Serotonin in ADHD and Its Many Comorbidities

Serotonin is a key chemical in the body that helps regulate mood, behavior, and also many physical functions such as sleep and digestion. It has also been linked to how ADHD (attention-deficit/hyperactivity disorder) develops in the brain. This study looks at how serotonin may be involved in both the mental health and physical health conditions that often occur alongside ADHD.

It is well-established that ADHD is more than just trouble focusing or staying still. For many, it brings along a host of other physical and mental health challenges. It is very common for those with ADHD to also have other diagnosed disorders. For example, those with ADHD are often also diagnosed with depression, anxiety, or sleep disorders. When these issues overlap, they are called comorbidities. 

A new comprehensive review, led by Dr. Stephen V. Faraone and colleagues, delves into how serotonin (5-HT), a major brain chemical, may be at the heart of many of these common comorbidities.

Wait! I thought ADHD had to do with Dopamine–Why are we looking at Serotonin?

Serotonin is a neurotransmitter most often linked to mood, but its role in regulating the body has much broader implications. It regulates sleep, digestion, metabolism, hormonal balance, and even immune responses. Although ADHD has long been associated with dopamine and norepinephrine dysregulation, this review suggests that serotonin also plays a central role, especially when it comes to comorbid conditions.

The Study:

  • Objective: To systematically review which conditions commonly co-occur with ADHD and determine whether serotonin dysfunction might be a common thread linking them.

  • Method: The authors combed through existing literature up to March 2024, analyzing evidence for serotonin involvement in each comorbidity associated with ADHD.

  • Scope: 182 psychiatric and somatic conditions were found to frequently occur in people with ADHD.

Key Findings

  • 74% of Comorbidities Linked to Serotonin: Of the 182 comorbidities identified, 135 showed evidence of serotonergic involvement—91 psychiatric and 44 somatic (physical) conditions.

  • Psychiatric Comorbidities: These include anxiety disorders, depression, bipolar disorder, and obsessive-compulsive disorder—all of which have long-standing associations with serotoninergic dysfunction.

  • Somatic Comorbidities: Conditions like irritable bowel syndrome (IBS), migraines, and certain sleep disorders also showed a significant serotonergic link.

This research suggests that serotonin dysregulation could explain the diverse and sometimes puzzling range of symptoms seen in ADHD patients. It supports a more integrative model of ADHD—one that goes beyond the brain’s attention, reward and executive control circuits and considers broader physiological and psychological health.

future research into the role of serotonin could help develop more tailored interventions, especially for patients who don't respond well to stimulant medications. Future studies may focus on serotonin’s role in early ADHD development and how it interacts with environmental and genetic factors.

The Take-Away: 

This study is a strong reminder that ADHD is a complex, multifaceted condition. Differential diagnosis is crucial to properly diagnosing and treating ADHD. Clinicians' understanding of the underlying link between ADHD and its common comorbidities may help future ADHD patients receive the individualized care they need. By shedding light on serotonin’s wide-reaching influence, this study may provide a valuable roadmap for improving how we diagnose and treat those with complex comorbidities in the future. 

July 14, 2025

Undiagnosed ADHD May Be Undermining Diabetes Control in Adults with Type 1 Diabetes

Our recent study, published in the Journal of Clinical Medicine, aims to shed light on an under-recognized challenge faced by many adults with Type 1 diabetes (T1D): attention-deficit/hyperactivity disorder (ADHD) symptoms.

We surveyed over 2,000 adults with T1D using the Adult Self-Report Scale (ASRS) for ADHD and analyzed their medical records. Of those who responded, nearly one-third met the criteria for ADHD symptoms—far higher than the general population average. Notably, only about 15% had a formal diagnosis or were receiving treatment.

The findings are striking: individuals with higher ADHD symptom scores had significantly worse blood sugar control, as indicated by higher HbA1c levels. Those flagged as "ASRS positive" were more than twice as likely to have poor glycemic control (HbA1c ≥ 8.0%). They also reported higher levels of depressive symptoms.

As expected, ADHD symptoms decreased with age but remained more common than in the general public. No strong links were found between ADHD symptoms and other cardiometabolic issues.

This study highlights a previously overlooked yet highly significant factor in diabetes management. ADHD-related difficulties—such as forgetfulness, inattention, or impulsivity—can make managing a complex condition like T1D more difficult. The researchers call for more screening and awareness of ADHD in adults with diabetes, which could lead to better mental health and improved blood sugar outcomes.

Takeaway: If you or a loved one with T1D struggles with focus, organization, or consistent self-care, it may be worth exploring whether ADHD could be part of the picture. Early identification and support are crucial to managing this common comorbidity. 

July 10, 2025