Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric disorder diagnosed in children and adolescents. Marked by restlessness, inattentiveness, impulsivity, and other forms of hyperactivity, ADHD poses an obstacle for many youths, especially in the classroom. Because of this, many people look for treatment options available to children to help reduce these symptoms. The most prevalent of these options comes in the form of the stimulant drugs methylphenidate (MPH) and amphetamine (AMPH), commonly prescribed as Ritalin and Adderall, respectively. Unsurprisingly, many people have concerns about prescribing these drugs to children and worry about potential adverse effects these medications could have on their development. The most common concerns include increased risk of suppressed growth, substance use disorders, stunted cortical development, sleep pattern interference, long-term cardiovascular issues, and alterations on dopaminergic systems.
Despite these concerns, studies have shown little significant correlation between the prescribed use of stimulants in these ADHD children and deviance with what would be considered normal or expected development. There is however ample evidence supporting the many positive effects these medications can have for children with this disorder, including better classroom behavior, increased focus, and overall improved academic performance (Kortekaas-Rijlaarsdam et. al, 2018). Between this lack of evidence for adverse effects and the significant positive responses found by taking these medications, they appear to be a safe and effective ADHD medication to prescribe to children. As mentioned, one of the biggest fears people have when it comes to prescribing youths with stimulant medications is that it will lower their overall growth rate. With or without medication, it has been shown that ADHD itself can have a negative impact on skeletal maturation, and many believe that adding medications to the mix will only suppress growth further (Urban & Gao, 2017).
A study done at the University of Medical Sciences looked into this theory by evaluating dental age and cervical vertebral maturation in healthy controls, ADHD-individuals not taking medication, and ADHD-individuals who have been treated with MPH for 1-3 years. In their study, researchers used these two measures to compare skeletal development of each individual at controlled chronological ages and compared the different groups against each other. Upon analysis, they found no significant difference in skeletal age based on diagnosis or MPH treatment, though they did find differences based on sex and age, which they adjusted the data to accommodate. Overall, results showed that the presence of MPH was not having a large effect on skeletal development (Tehranchi et. al, 2018), indicating that growth rate”at least skeletal growth rate”is not significantly stunted by use of MPH. That being said, a common reported side effect of MPH and AMPH medications is a decrease in appetite, which can lead to weight loss or prevent appropriate weight gain. This could contribute to the fear of stunted growth, as studies have shown a significant relationship between ADHD-individuals taking MPH treatments and a lower BMI, as well as overall body weight when compared to healthy controls (McCarthy et. al, 2018). This, thankfully, is a much easier issue to address individually and on a case-by-case basis than impaired skeletal growth would be. Low BMI and body weight can be addressed by something as simple as altering diet and exercise regimes and controlling/monitoring caloric intake.
Children may have a diminished appetite, but the lower average BMI that results can be counteracted by more foods that can help maintain a healthy body weight. Skeletal growth deficiencies would be much harder than this to address and would increase the risks of taking MPH dramatically. Coinciding with that fear of growth deficiencies, many people have concerns regarding suppressed neural growth and believe that use of prescription stimulants can stunt cortical thickening and thinning. During normal neural development, the thickness of the cerebral cortex increases to a certain point before slowly starting to thin, usually around age 7 or 8, as an expected marker of typical aging (Shaw et. al, 2011). It has been found that ADHD itself can have a negative effect on cortical development, and that individuals with the disorder on average display increased rates of cortical thinning (Narr et. al, 2009). Many believe that MPH medications can affect that nuanced development even further. Studies conducted by the National Institution of Mental Health (NIMH) and the David Geffen School of Medicine at UCLA have shown that while it does appear that ADHD individuals have lower total brain volumes on average and lower volumes of gray matter, there is nothing that indicates detrimental effects of MPH administration on cortical mantle development.
When NIMH researchers compared data from a group of healthy individuals, nonmedicated ADHD individuals, and ADHD individuals on a psychostimulant medication, they found that the medicated ADHD individuals showed evidence of cortical thinning at a rate more consistent with the control, healthy individuals. Using neuroimaging to assess cortical thickness, they found slower cortical growth and thinning in non-medicated ADHD individuals compared to the control, further indicating that it may be a result of the disorder itself, and not the medication (Shaw et. al, 2009). In contrast to what people believe, their research shows that administration of stimulant medications may actually be beneficial in normalizing the otherwise increased rate of cortical thinning. Not only are there concerns about neural development, but also concerns regarding stimulant effects on neural functioning as a whole. One of the functional markers of ADHD is disordered frontostriatal and fontoparietal activity, which are neural pathways critical to executive function (Dickstein et. al, 2006).
This disordered hypoactivity is thought to be one of the causes of the behavioral symptoms exhibited by ADHD individuals: impulsivity, hyperactivity, and inability to concentrate, to name a few. One of the main functions of stimulant medications like methylphenidate and amphetamine is to try and increase the activity of these areas back up to normal levels. And, according to a study done by multiple institutions (Peking University, King’s College London, Hangzhou Normal University, and Beijing Normal University), MPH is able to do just that. By using fMRI scans to look at brain activity of individuals at a resting state, they found that acute doses of MPH were able to successfully normalize fronto-parietal-cerebellar activity in boys aged 9-15 who had been diagnosed with ADHD (An et. al, 2013). Along the same lines, many people in the scientific community have been looking into potential stimulant interference in the development of the dopaminergic system. In ADHD, there is a deficit in dopamine (DA) availability in the prefrontal cortex (PFC), the main cortical area involved in attention and decision making. This DA deficiency is believed to be another aspect of what contributes to the symptomatic hyperactivity, inattentiveness, and impulsivity seen in ADHD patients, and can potentially be considered the cause of the dysregulation of frontoparietal cortical areas mentioned above.
Amphetamine and methylphenidate have slightly nuanced reactions in the dopaminergic systems of the brain, but both influence catecholamine (DA and norepinephrine (NE)) levels and abundance in a way that promotes activity in the PFC, and even the temporal lobe. These stimulants have been known to interact with dopaminergic systems to block DA reuptake channels and transporters (DAT) in the PFC, inhibiting reuptake and allowing for greater synaptic DA accumulation (Urban & Gao, 2017). The danger in this, many people believe, is that long-term use of these medications can start to have neurotoxic effects on the brain, especially on the DA systems that they directly interact with. However, studies have shown that MPH has far fewer neurotoxic properties than other types of stimulants, which not only block DA reuptake, but often stimulate increased rates of DA release, as well (Gerlach, 2013). These dopaminergic systems are involved in another concern many people have in regard to prescribing stimulant medications to children: an increased risk of developing a substance use disorder, or SUD. Stimulants, in general, act upon the central nervous system (CNS) in a way that increases activity, and that stimulation can become addictive by nature because it triggers activity in these DA pathways.
Dopamine is heavily involved in the reward systems of the body and the brain, often paving the way for feelings of pleasure and euphoria, which are common effects triggered by stimulant drugs like MDMA and cocaine. This is a large contributor to the addictive qualities that these drugs have been shown to have, and a large contributor to the fear that prescription medications like MPH and AMPH will lead to higher risk of developing a substance-related problem, since it exposes children to these effects at an early age (Quinn et. al, 2017). That being said, it has been shown that these prescription stimulants (MPH and AMPH) taken orally do not trigger these same psychoactive experiences, simply due to their chemical nature and the way they interact with the DA system (Urban & Gao, 2017). They have relatively low-intensity responses in the DA system than other, non-prescription stimulants taken recreationally. Using animal models researchers have found evidence of sensitization when it comes to MPH treatment, which is commonly believed to increase the likelihood of developing long-term SUDs. When applied to humans, however, no such association has been found.
In fact, when comparing data gathered from non-ADHD individuals, ADHD individuals receiving medication, and ADHD individuals with no medication, it has been shown that the ADHD individuals receiving medication are on average less likely to experience substance-related events both concurrently with the medication regime, as well as long term, measured by frequency two years later (Quinn et. al, 2017). This association was particularly strong in male patients, but was also indicated in female patients, though the non-ADHD control group was found to be the cohort least likely to experience substance-related events overall. In summation, these studies indicate that because there is no significant increase in SUDs between non-medicated ADHD individuals and medicated ADHD individuals, the increased frequency of substance-related events is less likely due to the medications, and more likely a result of the disorder, itself, which is known to increase impulsivity and have altered activity in the brain region associated with decision-making. Another adverse effect that make people believe MPH is an unsafe treatment to give to children is an increased risk of cardiovascular issues later in life. MPH has been shown to lead to an increase in blood pressure and heart rate, and over time, many worry that this can be problematic and lead to harmful cardiovascular events.
Strain on the heart ad nauseum is not good for it, and many believe continuous administration of a drug that interacts with the cardiac system and increases that strain over a prolonged period of time is unsafe. Researchers have looked into this concern and have found proof of stage 1 hypertension in ADHD individuals who have been taking MPH for twelve months or more, based on increases in average systolic and diastolic blood pressures, which at length could be considered harmful to an individual (McCarthy et. al, 2018). Another study conducted longitudinal assessments and found that there was no significant increase in diagnoses of cardiovascular ailments or incidence of harmful cardiovascular events between people taking MPH long-term for ADHD and healthy controls (Olfson et. al, 2012). So while the information currently available indicates there is no need to be concerned about cardiovascular ailments, further research is needed in the area to get a better idea of how exactly these stimulant medications affect the cardiovascular system, and what danger they might pose in the long-run.
Moving away from the cardiovascular system, there are also many concerns about how prescription stimulants can interfere with sleep patterns in children and young adults. These concerns do, in fact, have scientific evidence to support them, as there have been many studies conducted in the area of youth and adolescent sleep on a broader spectrum, as well as in more concentrated areas. Researchers who have looked into MPH’s effects on sleeping patterns have found significant negative interference effects between sleep quality and use of medication, specifically significant impairment of sleep duration, latency, and efficiency [(Kidwell et. al, 2015), (Morash-Conway, Gendron & Corkum, 2017)]. These effects can actually have a hand in some of the other concerns people have (low body weight, for example) (McCarthy et. al, 2018), as disrupted sleep patterns can have a negative effect on growth. Since sleep is such a vital aspect of development, the fact that stimulant medications can have such a negative impact on both quality and length of sleep is a very crucial aspect to consider when judging the safety of the medication.
These effects can be minimized by closely monitoring the administration of the medication, or restricting the regiment so that children are only on the medications during school hours, where they are more crucially needed. While disrupted sleeping patterns have a foothold from empirical data, most of the concerns people have surrounding the use of stimulants as medications for ADHD are unfounded by scientific evidence. With the information and studies currently available, there is little to indicate that the potential adverse effects of medications like methylphenidate and amphetamine have lasting, harmful consequences when administered to children and young adults. If anything, researchers have proved more often than once that treatments like MPH and AMPH have more results beneficial to the patient than harmful. While more research is undoubtedly needed to further the confidence and reliability of these studies, given this body of knowledge, prescription stimulants seem to be not only the most effective treatment options available, but also relatively safe to be administered to children and young adults diagnosed with ADHD.
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