April 13, 2021
In the world of research, it is unusual for a single study to be definitive. A possible exception is a recent report in the highly esteemed Lancet, which concluded that people diagnosed with ADHD were about two times more likely to die early than people without ADHD. The data came from the medical registers of Denmark that include1.92 a million people, of which 32,061 have ADHD. The registers included the times and causes of deaths spanning 32 years.
It is a remarkable resource. We know that people with very severe ADHD are at high risk for substance use disorders and antisocial behaviors. In the Danish study, these disorders also increased the risk for premature death, but the risk was even higher if people with those disorders also had ADHD. ADHD also increased the risk for early death among people without these extra problems. This latter finding points to an ADHD-specific pathway to premature death. What is it? Well, we know that ADHD people are at risk for injuries, traffic accidents, and traumatic brain injury. We don't know for certain why, but two symptom clusters of ADHD, inattention, and impulsivity, would be expected to increase the risk for accidents and injuries. For example, adults who are distracted while driving are clearly at risk for accidents. Accidents accounted for most of the early deaths in the Danish study. But the study also found an increase in natural causes of death due to having ADHD. This may be due to the well-replicated association between ADHD and obesity, or the possibility that ADHD symptoms lead to poor health habits.
In the Danish study, the mean age at diagnosis was 12.3, which means that many of the ADHD people in the study were not treated for many years after the onset of symptoms. The risk for early death increased with the age at diagnosis. This suggests that failing to diagnose and treat ADHD early makes the disorder worse and increases the risk for the types of behaviors that lead to premature death. Will these data change public policy or clinician behavior? I hope so. Perhaps the media will stop trivializing ADHD and accept it as a bona fide disorder in need of early identification and treatment. Policymakers should allocate ADHD people their fair share of healthcare and research resources. For clinicians, early identification and treatment should become the rule rather than the exception.
Talk of premature death will worry parents and patients. That is understandable, but such worries can be alleviated by focusing on two facts: the absolute risk for premature death is low, and this risk can be greatly reduced by seeking and adhering to evidence-based treatments for the disorder.
Dalsgaard, S., Ostergaard, S. D., Leckman, J. F., Mortensen,P. B. & Pedersen, M. G. (2015). Mortality in children, adolescents, andadults with attention deficit hyperactivity disorder: a nationwide cohortstudy. Lancet.
Vaa T. ADHD and relative risk of accidents in road traffic:a meta-analysis. Accident; analysis and prevention.2014; 62: 415-25.
Adeyemo BO,Biederman J, Zafonte R, Kagan E, Spencer TJ, Uchida M, et al. MildTraumatic Brain Injury and ADHD: A Systematic Review of the Literature andMeta-Analysis. J AttenDisord. 2014; 18(7): 576-84.
Cortese S, Faraone SV, Bernardi S, Wang S, Blanco C. Adultattention-deficit hyperactivity disorder and obesity: epidemiological study. BrJ Psychiatry.2013; 203: 24-34.
Spencer TS, Faraone SV, Tarko L, McDermott K, Biederman J.ADHD and Adverse Health Outcomes in Adults: Results from a Large ControlledStudy. 2013.
Faraone SV. The scientific foundation for understandingattention-deficit/hyperactivity disorder as a valid psychiatric disorder.EurChild Adolesc Psychiatry.2005; 14: 1-10."
Prevalence of cannabis use among pregnant women is on the rise with the spread of legalization. The most frequently reported reasons for use are to relieve stress or anxiety, nausea or vomiting, pain, and for recreation.
Given that the primary psychoactive ingredient of cannabis, ∆9-tetrahydrocannabinol (THC) is a small fat-soluble molecule that can easily cross the placenta, an Israeli-U.S. research team conducted a systematic search of the peer-reviewed medical literature for studies exploring possible neuropsychiatric effects on offspring.
They included not only studies evaluating likelihood of ADHD, but also autism spectrum disorder, anxiety, depression, and psychotic symptoms. For each of these, adjustment was made for known confounding variables.
With that adjustment, meta-analysis of six studies with a total of over half a million (503,661) participants reported a 13% increase in the odds of ADHD in offspring of mothers using cannabis during pregnancy compared with offspring of mothers not using cannabis while pregnant.
That is generally considered a small effect size increase in risk. But there are multiple reasons to question even this minimal finding:
Meta-analysis of two studies with a total of 741 individuals reported a 20% increase in offspring use of cannabis among mothers who used cannabis during pregnancy, but once again this was subject to methodological shortcomings:
Some studies have suggested a link between cannabis and psychotic symptoms. But meta-analysis of four studies combining over nineteen thousand persons found no significant association between maternal cannabis use during pregnancy and offspring psychotic symptoms.
Many studies have pointed to commonalities in the etiology of ADHD and autism spectrum disorder (ASD). Yet meta-analysis of five studies encompassing over half a million participants found absolutely no association between maternal prenatal cannabis use and ASD.
The remaining meta-analyses also reported no association with depression or anxiety.
With the caution that absence of evidence is not the same as evidence of absence, it is by no means clear from what is presently known that prenatal cannabis exposure has any significant neuropsychiatric effects on offspring. And if further research finds any effects, they are likely to be minor.
Dasotraline is a serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI) that had been under development by Sunovion for treating ADHD and binge eating disorder.
An Indian research team conducted a systematic search of the peer-reviewed medical literature to perform meta-analyses of the quantitative outcomes of clinical trials.
Meta-analysis of five double-blinded randomized clinical trials (RCTs) with a combined total of 1,498 participants reported a small-to-medium effect size reduction in ADHD symptoms in patients given dasotraline as opposed to those given placebo.
There were, however, strong indications of publication bias. Using the trim-and-fill procedure to correct for that bias yielded a small effect size reduction in ADHD symptoms in patients given dasotraline compared with those given placebo.
Insomnia were more than four times more frequent among patients given dasotraline than among those given placebo. There was no evidence of the frequency of insomnia being dose-dependent.
Similarly, patients given dasotraline were more than four times more likely to report decreased appetite than those receiving placebo. In this case, however, the effect was clearly dose-dependent, rising from 3x for 2mg to 4x for 4mg to 5x for 6mg and almost 8x for 8mg.
The authors concluded, “dasotraline can reduce the core symptoms of ADHD, that is, hyperactivity/impulsivity and inattentiveness, leading to an overall improvement of ADHD compared to placebo. Dasotraline can also improve clinician-determined patients’ global functioning compared to the placebo. The most common adverse drug reactions related to dasotraline were insomnia and decreased appetite. However, to fill the knowledge gap, multicentric randomized active-controlled clinical trials are warranted in this domain for a successful translation into clinical practice.”
Weighing these less than impressive initial results against the cost of further RCTs, Sunovion withdrew its application for approval by the Food and Drug Administration, stating, “while Sunovion considers dasotraline to be a promising, novel treatment for binge eating disorder and ADHD, we believe that further clinical studies would be needed to support a regulatory approval for dasotraline in these indications.”
Children and adolescents with ADHD are known to have difficulties in relating to family members, peers, and teachers. Over the long run this can contribute to anxiety or even delinquency.
Several cognitive functions that allow individuals to process social information and interact with others contribute to shaping everyday social interactions. These include:
A European research team performed a systematic search of the peer-reviewed medical literature to conduct meta-analyses of ToM, Empathy, Facial and Non-Facial Emotion Recognition in children and adolescents with ADHD when compared to typical development. As a comparison measure, they also included Everyday Social Skills (using self, parent, teacher, or clinician questionnaires/interviews of social skills) as an outcome.
The search yielded 142 case-control studies (including dissertations) with a total of 16,283 participants.
Meta-analysis of 82 studies with a combined total of 10,770 participants found a very large effect size impairment in everyday social skills among children and adolescents with ADHD when compared with typically developing peers. Adjusting for covariates only strengthened the finding. There was no sign of publication bias.
This was mirrored in three out of five measures of social cognition:
The team concluded, “Our findings show that children and adolescents with ADHD have deficits in ToM, Facial Emotion Recognition, and Everyday Social Skills, three domains that warrant clinical attention.”
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