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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).
The Background:
Dementia is a rapidly growing public health problem affecting more than 50 million people worldwide. Nearly 10 million new cases are diagnosed each year, and that number is expected to almost triple by 2050. The most common form is Alzheimer’s disease, accounting for roughly 60–70% of cases, followed by vascular dementia at around 20%. Other types include dementia with Lewy bodies, Parkinson’s disease dementia, and frontotemporal dementia. While no cure exists, managing modifiable risk factors (such as high blood pressure, smoking, physical inactivity, and poorly controlled diabetes) can delay or slow both the onset and progression of the condition.
Several studies have reported an elevated dementia risk among people with ADHD, and a number of mechanisms may explain this association. These include shared genetic or neurobiological vulnerabilities, reduced cognitive reserve (leaving the brain less resilient to age-related damage), and greater lifetime exposure to other established dementia risk factors.
Earlier reviews explored the possible link between ADHD and dementia, but tended toward a broader scope (incorporating other neurodegenerative disorders or mixing study designs), which introduced substantial variability and precluded quantitative synthesis. The relevant research literature has also expanded considerably since those reviews appeared.
The Study:
This meta-analysis restricted inclusion to case-control and cohort studies, yielding five that met the criteria. One was a case-control study with 400 participants; the other four were cohort studies collectively covering 3.7 million individuals, two retrospective and two prospective.
The Results:
Pooling the four cohort studies, individuals with ADHD showed approximately two-and-a-half times the dementia risk of those without the diagnosis. There was no indication of publication bias.
The Take-Away:
The authors concluded that ADHD is associated with a significantly increased risk of all-cause dementia in later life, while noting that its relationship to specific dementia subtypes remains less clear and warrants attention in future research.
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The Background:
Women with polycystic ovary syndrome (PCOS) themselves show higher rates of ADHD. Because ADHD is partly heritable (meaning genes contribute to the condition), some of the increased ADHD seen in children of mothers with PCOS could come from shared genetic factors. In other words, a mother’s and her child’s increased risk might sometimes reflect common genes rather than an effect of the pregnancy itself.
Beyond genetics, growing evidence points to maternal metabolic problems during pregnancy as another important risk factor for neurodevelopmental outcomes. PCOS is one of these conditions and is considered both potentially modifiable (treatable or manageable) and biologically plausible as a contributor to risk. PCOS affects an estimated 5–10% of women of reproductive age worldwide and is characterized by signs such as hyperandrogenism (higher-than-normal levels of “male” hormones), insulin resistance (poorer ability to use the hormone insulin, which can affect blood sugar and metabolism), and chronic low-grade inflammation.
However, studies to date have not all reached the same conclusions. Some research suggests the association between maternal PCOS and offspring ADHD is stronger for girls, while other studies did not analyze results by child sex. Methodological differences make it harder to draw clear conclusions.
The Study:
It’s important to note that the studies included in this meta-analysis were observational (cohort studies and case-control studies). Observational studies can identify associations (that two things occur together) but cannot prove that one causes the other. A cohort study follows people over time, and a case-control study compares people with a condition to similar people without it.
The pooled results came from six studies that together included almost 1.4 million mother–child pairs and that adjusted for confounders (other factors that might influence the result, such as maternal age or socioeconomic status). After statistical adjustment, children of mothers with PCOS had about 40% greater odds of ADHD than children of mothers without PCOS. The analysis reported no evidence of publication bias (no clear sign that only positive studies were published) and zero heterogeneity (the results were consistent across the studies).
There was no meaningful difference in results between cohort and case-control studies, and the meta-analysis did not find a significant difference in the association when comparing male and female offspring.
The Take-Away:
The research team concluded that this large-scale synthesis found an association between maternal PCOS and higher odds of ADHD and other neuropsychiatric conditions in children. They suggested that children born to mothers with PCOS may benefit from developmental monitoring to identify and address problems early, while emphasizing that causal relationships have not been established. They called for further studies to confirm these findings and to investigate the biological and environmental mechanisms that might explain the association. Indeed, because women with PCOS show higher rates of ADHD than other women, we need genetically informed research designs to see if the reported association is confounded.
The Background:
Food insecurity is a widespread public‑health problem. Food insecurity refers to limited or uncertain access to enough safe, nutritious food. This term is used to describe households that sometimes or often can’t afford enough food or can only buy cheaper, less‑healthy options.
In the United States, almost eleven million children and teens (14%) lived in food‑insecure households in 2019. By 2023, the share of households with food‑insecure children and adolescents was estimated to have risen to about 18%.
Food insecurity is linked to worse physical health in children, including conditions like anemia (low red‑blood‑cell count), asthma, and delays in physical or mental development. It is also associated with problems in thinking and conduct (for example, aggressive behavior, anxiety, depression, and trouble concentrating or sitting still).
Those thinking and behavior problems can look a lot like ADHD (persistent patterns of inattention, hyperactivity, and impulsivity. This can make it hard for clinicians to tell whether symptoms come from ADHD itself, from the stress of poverty and food insecurity, or a mix of both. That overlap can complicate diagnosis and sometimes lead to misdiagnosis.
Smaller recent studies have looked at mental‑health links and found higher odds of ADHD and other mental‑health conditions among food‑insecure children aged 5–11 years. In one set of findings, moderate food insecurity was associated with 50% greater odds of an ADHD diagnosis and severe food insecurity with about 67% greater odds relative to food‑secure children.
The Study:
Because many past studies looked at single risk factors or only measured symptom severity, fewer investigations have focused specifically on household food insecurity as it relates to actual ADHD diagnoses and how that might matter for care. To address that gap, researchers used multiple years (2016–2022) of data from the U.S. National Survey of Children’s Health (NSCH). This survey is designed to be nationally representative and asks parents about their child’s health, including whether a doctor or other clinician has diagnosed ADHD.
The study included 232,571 children and adolescents (ages 3–17) and used statistical methods to adjust for other factors that could affect ADHD risk. Those factors included the child’s sex and race/ethnicity; the mother’s age; family income expressed as a percentage of the federal poverty level (a government measure used to classify income groups); the highest level of parent education; adverse childhood experiences (such as exposure to abuse, household substance use, or parental separation); birthweight (for example, low birthweight); and not getting enough sleep. Adjusting for these variables helps isolate the association between food insecurity and ADHD, though it cannot prove cause and effect.
The Results:
In this large, nationally representative sample, the researchers found a clear dose–response relationship: as the level of household food insecurity increased, so did the odds of a child having a clinician‑diagnosed ADHD (as reported by parents). In other words, greater food insecurity was linked to a higher likelihood of ADHD.
Compared with children in households that “could always afford to eat good, nutritious meals” (the reference group), the study found the following increases in odds of ADHD: children in households that “could always afford enough to eat but not always the kinds of food we should eat” had about 30% greater odds; children in households that sometimes “could not afford enough to eat” had about 55% greater odds; and children in households that often “could not afford enough to eat” had about 80% greater odds. (Saying “30% greater odds,” etc., means the odds were 1.30, 1.55, and 1.80 times those of the reference group, respectively — this describes a relative increase, not the absolute percentage of children with ADHD.)
The Take-Away:
The authors conclude that household food insecurity was associated with higher odds of parent‑reported clinician‑diagnosed ADHD in a dose‑response pattern. They suggest that reducing food insecurity (for example, ,by improving access to nutritious food and combining nutritional supports with mental‑health care) may help lower ADHD risk or reduce symptoms in some children. Reducing food insecurity should be a priority for society, but it is premature to conclude it will reduce the risk for ADHD. We know that parents with ADHD are more likely to lose their jobs and have lower incomes compared to parents with ADHD. That might create food insecurity for their children who we know are at high risk for ADHD from genetic studies.
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