Youths with ADHD are at higher risk of suicide, burn injuries, road injuries, and more generally all-cause mortality than normally developing children. Methylphenidate (MPH) is known to be effective in reducing ADHD symptoms. Can it also reduce the risk of all-cause mortality? A team of Taiwanese researchers, collaborating with two British researchers, explored that question by looking at a nationwide population cohort.
Taiwan has a single-payer national health insurance system that includes the entire population (99.6 percent coverage). Using the National Health Insurance Research Database (NHIRD), the team identified over 183,000 youths under 18 with an ADHD diagnosis. Of these, just over 68,000 had been prescribed to MPH. The team matched them with an equal number of ADHD youths who were not prescribed MPH. All records were anonymized and checked against the National Mortality Register.
All-cause mortality was split into two subcategories. Unnatural-cause mortality consisted of homicide, suicide, and motor vehicle fatalities. Natural-cause mortality encompassed all other premature deaths. In the raw data, ADHD youths on MPH had half the all-cause mortality of those not on MPH. Natural-cause mortality was down about 40 percent and unnatural-cause mortality was by almost two-thirds. In the non-MPH group, 32 committed suicide in the follow-up year, versus only a single individual in the MPH group. There were seven homicide victims in the non-MPH group, versus none at all in the MPH group.
These staggering reductions, however, were almost exclusively among males. The team then adjusted for potential confounding variables - gender, age, residence, insurance premium, out-patient visits, and pre-existing diagnoses. In the adjusted model, the risk for all-cause mortality was still reduced - by about 20 percent - for those on MPH and remained statistically significant. Virtually identical reductions were found for males and for children first diagnosed with ADHD between 4 and 7 years old. But all other risk estimates became statistically non-significant, due in large measure to the rarity of mortality events.
The authors concluded, "This is the first study reporting that a longer interval between first ADHD diagnosis and first prescription of MPH is associated with a higher risk of all-cause mortality. In addition, we also found that participants receiving longer-duration MPH treatment had a lower risk of all-cause mortality. ... an implication is that receiving a diagnosis earlier and receiving medication earlier may reduce the risk of later adverse consequences."
They nevertheless cautioned, "although we adjusted for multiple covariant, information lacking in the database precluded the measurement of other possible confounders, such as family history, psychosocial stressors, the effect of behavioral therapy or severity of comorbidities. Therefore, as with all observational data, it is not possible to be conclusive about whether the association with lower mortality is related to an effect of MPH treatment itself or whether other characteristics of the children receiving MPH may account for the lower risk (i.e. confounding by indication).
Finally, although the cohort sizes were large, the number of deaths was small, and this limited statistical power, particularly for the investigation of cause-specific mortality and of subgroup differences. Because of the relatively low number of deaths and limited follow-up duration, longer-term studies with larger samples are warranted ..."
Vincent Chin-HungChen, Hsiang-Lin Chan, Shu-I Wu, Mong-Liang Lu, Michael E. Dewey, Robert Stewart, and Charles Tzu-Chi Lee, "Methylphenidate and mortality in children with the attention-deficit hyperactivity disorder: a population-based cohort study," British Journal of psychiatry (2020), https://doi.org/10.1192/bjp.2020.129.
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