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July 8, 2021
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).
Background:
There are currently few long-term treatment options for adult ADHD. Psychostimulants can help reduce symptoms, but their benefits rely on availability, continued use, and are not easily tolerated by some. Cognitive-behavioral therapies have also proven to be helpful, but access is limited because they must be provided by trained specialists. These challenges highlight the need to explore alternative interventions that could provide cognitive and behavioral improvements with fewer side effects.
Exercise has shown potential as a nonclinical intervention for ADHD. Previous research indicates that physical activity can increase cortical volume, enhance brain activation, and boost connectivity in cognitive regions, as well as raise dopamine and norepinephrine levels – effects similar to psychostimulants. Research in children and teens with ADHD has found that both regular exercise programs and even single workout sessions can improve executive functions (mental skills like planning and self-control) and reduce core ADHD symptoms. But whether exercise helps adults with ADHD has remained an open question.
Study:
A Chinese sports medicine research team set out to answer this by reviewing all available peer-reviewed studies on exercise and adult ADHD. They found so few studies on regular exercise programs – only four total, and three of those were small pilot studies just testing whether the approach was feasible – that they couldn’t draw firm conclusions about long-term exercise interventions.
However, they were able to analyze four moderate-to-high-quality studies involving 152 adults with ADHD that tested single exercise sessions. The combined results showed moderate improvements in inhibitory control (the ability to resist impulses and stay focused). Adults not taking medication showed large improvements.
When they looked at four studies involving 170 adults, they found small but consistent improvements in core ADHD symptoms after single exercise sessions. There was little to no variation (heterogeneity) in individual study outcomes, and no sign of publication bias.
Results:
The team concluded, “Overall, these findings offer preliminary evidence on the potential role of exercise as a helpful strategy in the management of adult ADHD,” but cautioned that more well-designed randomized controlled trials are needed to determine the efficacy of both acute and chronic exercise interventions for adult ADHD, with particular emphasis placed on determining the best “prescription” for exercise – what type, how intense, and how often.
They also noted that most existing research has focused narrowly on attention and impulse control, while other important mental abilities like working memory and mental flexibility remain largely unexplored.
Take-Away:
The takeaway here is practical and accessible: you don't need a long-term fitness program to get a cognitive bump from exercise if you have ADHD. Even a single session appears to help — particularly with impulse control. While the research base is still thin and we don't yet know the ideal exercise "prescription," the risk-benefit calculation is hard to argue with. For adults with ADHD who can't access medication or therapy, or who simply want an additional tool, breaking a sweat may be worth building into the routine.
Background:
Non-suicidal self-injury (NSSI) means intentionally hurting yourself without trying to end your life. Common examples include cutting, scratching, or burning yourself. This behavior is most common in teenagers, affecting 13-20% of adolescents. It’s also called self-harm or deliberate self-injury.
Young people who struggle with managing emotions, act impulsively, or have mental health conditions like depression are more likely to self-harm.
Because ADHD involves impulsivity and often occurs alongside emotional difficulties, researchers have suspected a link between ADHD and self-injury. However, previous studies have tended to be small, unrepresentative, and inconsistent, making it hard to draw clear conclusions.
The Study:
Researchers combined results from 14 different studies involving nearly 30,000 people to get a clearer picture. They looked at children, teenagers, and adults with ADHD from various settings—including hospitals, community programs, and general population studies.
To be included, studies had to confirm ADHD diagnosis through professional evaluation or validated testing methods.
Key findings
Conclusion:
The researchers concluded that roughly one in four people with ADHD have engaged in non-suicidal self-harm. The findings suggest that ADHD and self-harm share overlapping vulnerabilities.
Overall, this meta-analysis strengthens evidence that people with ADHD face a significantly elevated risk of non-suicidal self-injury, likely reflecting overlapping challenges with impulsivity, emotional regulation, and co-occurring mental health conditions. Importantly, this does not mean self-harm is inevitable in ADHD. It does, however, highlight the need for early screening, supportive environments, and targeted mental-health care to help reduce risk and support healthier coping strategies.
Background:
While ADHD is generally linked to negative childhood outcomes, individual variability exists. Researchers have found that factors like cognition, emotion, parenting, and social interactions can help some adversity-exposed children develop better than expected. This variability has driven extensive resilience research, which now views resilience not as a single trait, but as a combination of biological, psychological, social, and ecological processes supporting adaptation.
The Study:
This meta-analysis sought to address several key research gaps. First, while many potential resilience factors have been identified, no previous meta-analysis has quantitatively synthesized evidence focused specifically on children with ADHD. Second, relatively little research has clarified how particular resilience factors relate to specific developmental outcomes. Third, there is currently no integrated conceptual model of resilience processes tailored to children and adolescents with ADHD.
To keep the analysis focused and clinically relevant, the authors examined psychosocial and ecological resilience factors only. Biological factors (such as genetics or cardiovascular health) and non-modifiable demographic characteristics (such as age and sex) were excluded, as they do not readily inform interventions. The analysis also focused strictly on outcomes for children and adolescents with ADHD, excluding adult outcomes and those reported for parents or teachers. Only studies based on clinical ADHD diagnoses were included.
In total, 28 studies involving more than 11,600 participants met the inclusion criteria. Fifteen studies were rated as high quality and 13 as fair quality; none were rated low quality. However, the evidence base was relatively thin for many analyses. Of the 50 components examined, only one included five studies, six included four studies, ten included three studies, and most (33) were based on just two studies. While some components involved large samples, most did not, meaning the findings should be viewed as suggestive rather than definitive.
Results:
Unsurprisingly, academic skills and cognitive functioning – specifically including working memory and intelligence – were strongly associated with better educational outcomes for children and adolescents with ADHD. In contrast, social skills and proactive attitudes or behaviors showed no significant link to educational attainment.
Well-being outcomes showed a different pattern. Proactive attitudes and behaviors, cognitive functioning, and parental resources were associated with small-to-moderate improvements in well-being. Emotional regulation and positive parenting or attachment, however, were not significantly related to well-being in this analysis.
For relationship outcomes, peer relationships – especially close friendships – stood out as particularly important, showing strong associations with better relational functioning. Social skills and positive parenting or attachment were linked to moderate improvements, although positive parenting alone had no significant effect. This suggests that the observed benefit likely stemmed from parental warmth and secure parent–child attachment rather than parenting practices in isolation. Parental resources (such as parental social support) and school-based support (including student–teacher relationships) showed no significant association with relationship outcomes.
The study also examined behavioral symptoms. Externalizing symptoms refer to outward-directed behaviors that affect others or the environment, such as aggression, defiance, impulsivity, hyperactivity, and rule-breaking. Peer relationships were linked to a modest reduction in these behaviors, while positive relationships with adults were associated with a strong reduction. In contrast, disciplinary parenting – particularly harsh punishment – was strongly associated with increased externalizing symptoms.
Internalizing symptoms involve inward-directed distress, such as anxiety, depression, withdrawal, excessive worry, and unexplained physical complaints. Here again, positive relationships with adults were important, showing a moderate association with fewer internalizing symptoms. Emotional regulation was also linked to small-to-moderate improvements.
Conclusion:
Overall, the findings highlight that resilience factors tend to be closely tied to specific outcomes rather than broadly protective across domains. For example, emotional regulation was associated with lower levels of both internalizing and externalizing symptoms but showed no significant link to well-being, educational achievement, or relationship quality. This suggests that emotional regulation may play a particularly important role in protecting mental health in children with ADHD, rather than driving broader developmental gains – consistent with evidence that emotional dysregulation is a core difficulty in ADHD.
Similarly, academic skills, social competence, and prosocial behaviors were linked mainly to their most closely related outcomes. Cognitive functioning was associated with both educational and well-being outcomes, but its impact was much stronger in education and more modest for well-being. Together, these context-specific patterns underscore the importance of designing interventions that target particular resilience factors with strategies tailored to specific developmental goals, rather than assuming that any single factor will promote resilience across all areas of life.
Key takeaway: resilience is individual and resilience isn’t one trait; different types of support help different individuals, in different areas.
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