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ADHD Medication

By Anna Witkin |
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Recent trends in ADHD diagnosis make it abundantly clear that diagnostic procedures are inconsistent at best and systematically flawed at worst. Prevalence of ADHD in children and adolescents has shot up an alarming 41% in the past decade, and by high school it is estimated that one in five boys have been diagnosed (Hinshaw, 2018, p. 294). Given the improbability that this represents a true increase in prevalence and considering that ADHD could hardly be considered a disorder if it affected 20% of boys, we are left with the inevitable conclusion that rampant overdiagnosis is occurring.

Recent Trends in ADHD Diagnosis Make it Abundantly Clear That Diagnostic Procedures are Inconsistent at Best and Systematically Flawed at Worst

Further suggestive of error-prone diagnostic practices are consistent findings that the youngest children in each grade are considerably more likely to be diagnosed with ADHD than their older peers (Kazda et al., 2021, p. 4). This finding suggests that many children are being diagnosed with ADHD who are simply being asked to perform beyond their neurocognitive maturity, and that this may be a driving force in the apparent rise in prevalence.

CDC surveys have found that the percentage of children under 17 who have ever received an ADHD diagnosis varies dramatically by region of the country. Some southern states reach rates as high as 16.6%, which is roughly three times that in most western states. It is illogical to assume that these differences are due to massive variation in prevalence of ADHD by state, so these findings must represent highly inconsistent practices in diagnosis. Similar inconsistencies have been found in stimulant dispensing practices for the treatment of ADHD: rates reached 13.6 per 100 in Alabama, and only 1.0 per 100 in Hawaii (Board et al., 2020, p. 5).

CDC Surveys Have Found That the Percentage of Children Under 17 who Have Ever Received an ADHD Diagnosis Varies Dramatically by Region of the Country

The astronomical rise in the rates of ADHD diagnoses, psychostimulant prescription, and non-medical stimulant abuse on both the national and global scale demands a critical examination of diagnostic criteria and indications for medical treatment. As of 2007, worldwide prevalence of ADHD has been estimated at 5.29% in children and 4.4% in adults (Carolan, 2022, p. 315). A 2020 study found that roughly 13% of adults between 18 and 29 years of age used prescription stimulants within the past year, and estimated that 16 million US adults and 2.8 million US children took prescription stimulants (Board et al., 2020, p2). Recent estimates have placed the rate of nonmedical prescription stimulant use among US college students at an alarming 25% (Carolan, 2022, p. 315), while approximately half of all 10–18-year-olds in the US have participated in prescription stimulant diversion either by receiving diverted medications or diverting their own prescription (Board et al., 2020, p. 3).

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Faced with such staggering numbers, physicians and mental health professionals must now make a concerted, unified effort to understand the complex landscape within which psychostimulants are used and abused. Toward this end, the following will address some of the key facets of the most commonly prescribed stimulants for ADHD: amphetamines, methylphenidate, and lisdexamphetamine. We must consider not only the evidence amassed over the 70-plus year history of these compounds, but also the weight of the still significant unknowns and the caution necessitated by the unanswered questions that remain.

Non-Stimulant ADHD Meds

Stimulants are definitively first-line in the medical management of ADHD due to their significantly higher efficacy than non-stimulants, which are generally used only in individuals who don’t tolerate stimulants (Zalsman and Shilton, 2016, p. 72). Atomoxetine is the most commonly used non-stimulant and may be of benefit to individuals with ADHD and comorbid anxiety disorders as it has been shown to be therapeutic for both (Kooij et al., 2019, p. 23). Clonidine and guanfacine are rarely used as they produce only modest improvements in symptoms when used in isolation.

Is ADHD Medication Safe?

There is a substantial volume of data suggesting that stimulants taken as prescribed for ADHD are safe in the short term (i.e. under 2 years) with very few exceptions. Significant adverse events are extremely rare, and the most commonly reported side effects are generally mild to moderate.  However, precaution should always be applied when taking stimulants, as studies by no means rule out 2nd and 3rd order potential negative side effects. Stimulants may cause slight increases in heart rate and blood pressure, but there is currently no evidence to suggest that this increases risk of cardiovascular events (Alpert, 2019).

Precaution should always be applied when taking stimulants, as studies by no means rule out 2nd and 3rd order potential negative side effects

The most common side effects should hardly be considered side effects. Considering that amphetamines have been used to treat narcolepsy since 1935, and that both amphetamine and methylphenidate can be prescribed today to treat hypersomnia, fatigue, and binge eating, it is no surprise that their use is associated with decreased appetite and insomnia. Sleep disturbances are common in untreated ADHD, and often there is no reported decrease in sleep quantity or quality on stimulants.

Depressed appetite may be more problematic as it seems to negatively impact children’s growth in the short term. Growth slowing in the first 6 months of treatment is relatively common, but normalizes in the long term (Zachor et al., 2006, p. 172). There is a strong body of evidence providing reassurance that even with long-term stimulant use there is no statistically significant decrease in adult height.   

Despite persistent concerns over potential for addiction and overdose with prescription stimulants, the evidence suggests that these risks are minimal. While psychological dependence (i.e. feeling reliant on a substance) is certainly possible, there is little evidence for actual physiological addiction, which requires the presence of tolerance and withdrawal. At therapeutic doses, tolerance to these stimulants does not occur, and individuals can remain on the same dose for years with no decrease in effectiveness.

Similarly, apart from a rebound effect consisting of lethargy and increased appetite when the medication is stopped, there appears to be very little risk of true withdrawal even after prolonged use (Krinzinger et al., 2019, p. 963). It is in fact very common for children to only take medications on weekdays or to take a drug holiday over summer breaks with no adverse effects.

Does ADHD Medication Work?

Studies investigating the effect of a single dose of methylphenidate on individuals with ADHD have found marked improvements in neuropsychological functioning in relation to their unmedicated ADHD peers. Methylphenidate has been shown to acutely increase activation and connectivity in regions of the brain involved in planning, attention, and inhibitory control (Berberat et al., 2021, p. 2). A single dose of methylphenidate produces moderate improvements in the ability to stop and start tasks, switch between tasks on demand, and inhibit motor responses. Furthermore, these improvements have been found to correlate with individuals’ self-reported decrease in ADHD symptoms (Vertessen et al., 2022, p. 642).

Comprehensive meta-analyses of the literature provide strong evidence for protective effects of stimulant treatment of ADHD across several categories. Perhaps the strongest body of evidence is for the decreased risk of substance misuse with stimulant treatment. In a study of 40,000 individuals with ADHD followed over 4 years, there was a statistically significant decrease in substance misuse in the treated population vs. the medication-naïve population (Chang et al., 2014, p. 6). Of note, there was a positive correlation between longer duration of stimulant treatment and decreased rate of substance misuse (Chang et al., 2014, p. 6).

Children with ADHD often perform poorly in academic settings relative to their IQ-controlled peers, but meta-analyses have shown an improvement in academic performance with stimulant treatment (Arnold et al., 2020, p. 76). Furthermore, stimulants have been shown to reduce the rates of criminality, mood disorders (depression and bipolar disorder), suicide attempts, traumatic brain injuries, motor vehicle accidents, and fractures (Boland et al., 2020, p. 23). These effects were found not only in comparing treated individuals with untreated individuals, but also in comparing periods when a given individual was adherent or non-adherent to their medication (Boland et al., 2020, p. 23).

While these findings are encouraging, it is important to remember that effect sizes are variable and there are potential confounding factors at play. Individuals with access to treatment and medication may be more likely to come from higher-resource families able to provide additional advantages contributing to favorable outcomes.

Neuroimaging advances have provided us with a window into what may be different in the brains of individuals with ADHD and how stimulants may attenuate those differences. Regions of the brain heavily involved in dopamine signaling (primarily in the basal ganglia and prefrontal cortex) have been found to be smaller in volume in children with ADHD than in healthy controls (Tripp and Wickens, 2009, p. 580). Recent studies indicate that the volumes in these regions normalize with stimulant treatment, ultimately resembling the control population more than the unmedicated ADHD group (Pretus et al., 2017, p, 1239).

How do you Treat ADHD Without Medication?

Stimulant medications are effective treatment options for ADHD, but there are other interventions that should be considered either in place of or in addition to pharmaceuticals. Academic accommodations, increased physical exercise, parental education, limiting sugar / processed food, and good sleep hygiene all benefit children with ADHD and may be sufficient in those with milder presentations. While newer treatment options such as meditation and biofeedback have not yet been proven to be effective, they show some promise for the future. Research has shown that medication has an overall greater effect size than any other intervention when used in isolation, but studies have shown that a combination of behavioral interventions and medication produces the most significant improvement in functioning and reduction in symptomatology (Hinshaw, 2018, p. 307).

The Medicalization of Childhood

It is also patently unethical to medicate children for the convenience of parents and teachers, or at the behest of parents determined to give their child a competitive advantage academically that the child themself likely has no interest in. A critical prerequisite for writing a stimulant prescription for a child must be that it is for their own benefit, not the benefit of their school or family.

The challenge for providers, parents, and teachers is thus to accurately assess to what extent a child is struggling due to ADHD, what adverse outcomes the child is at risk for, and what interventions may mitigate those risks. Given that we often cannot modify their environment, our aim should be to help each individual function their best within the constraints of an environment to which they may be poorly suited, while acknowledging that they are different not defective.

Conclusion

Every medication or drug of abuse has a unique profile of risks and benefits that can vary considerably depending on the individual to whom it is administered; a debilitating adverse effect in one patient could be the primary intended benefit in another. Thus, it is irrational to either demonize a chemical compound or deem it universally safe and effective. To avoid such reductive thinking, we must approach the compendium of information available to us with a balance of skepticism and open-mindedness.

There is strong short-term evidence that stimulants are safe both cardiovascularly and neuropsychiatrically, and a growing body of long-term evidence suggesting the same. However, more longitudinal data is needed to feel confident that stimulant use in childhood does not have adverse effects later in life, particularly as there are still so many unknowns about neurodevelopment.

The evidence does suggest that stimulant use decreases ADHD symptomatology in the short-term and improves long-term outcomes in several key categories. However, the possibility of confounding factors detracts from these findings. There is promising evidence suggesting that stimulants attenuate the structural abnormalities found in the brains of children with ADHD, but these findings are currently more correlative than causative and sometimes lack statistical power.

The current scientific and medical knowledge suggests that psychostimulants are generally safe, and effective at mitigating ADHD symptoms. However, there are still questions and unknowns, and prescribing pharmaceuticals to children should always be preceded by a thorough analysis of risks and benefits. While stimulants may be a useful component of treatment, particularly in severe cases, they should not be administered reflexively to everyone with an ADHD diagnosis.

Ideally, reasonable behavioral, lifestyle, and academic interventions should all be in place before resorting to pharmaceuticals; however, environmental factors often prevent this from being feasible. This is a crucial source of tension surrounding stimulant prescription, and one that must be addressed on an individual basis.

Non-pharmaceutical interventions are particularly important in children who meet diagnostic criteria for “mild ADHD” who are likely perfectly healthy and are being saddled with a label that should not apply to them.

We ask elementary school children to sit quietly and focus on school for ten hours per day only to label them disruptive or disabled for failing to do so. Expecting children to behave in ways that are challenging for many adults and subsequently diagnosing them with a disorder when they cannot amounts to the medicalization of childhood.

For children who are further along the normal spectrum of childhood traits including restlessness and distractibility, the gulf between how their brain is expected to work and how it actually functions is even wider. This incompatibility does not mean the brains of children with ADHD are broken or inferior, it simply means they are even less suited to perform in a system unsuited to children’s brains to begin with.

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Anna Witkin

Anna Witkin is a contributing writer for Polygon. Anna holds a BA from UC Berkeley, a Masters in Biomedical Science from Tufts, and researched ADHD and other learning differences during her time at Dartmouth School of Medicine studying for her MD.