April 29, 2021
A recent paper by Margaret Sibley and colleagues addresses a key issue in the diagnosis of adult ADHD. Is it sufficient to only collect data from the patient being diagnosed or are informants useful or, perhaps, essential, for diagnosing ADHD in adults? Dr. Sibley presented a systematic review of twelve studies that prospectively followed ADHD children into adulthood. Each of these studies asked a simple question: What fraction of ADHD youth continued to have ADHD in adulthood. Surprisingly, the estimates of ADHD's persistence ranged from a low of4% to a high of 77%. They found two study features that accounted for much of this wide range. The first was the nature of the informant; did the study rely only on the patient's report, or were other informants consulted. The second was the use of a strict diagnostic threshold of six symptoms. When they limited the analysis to studies that used informants and eliminated the six symptom threshold, the range of estimates was much narrower, 40% to 77%. From studies that computed multiple measures of persistence using different criteria, the authors concluded: "(1) requiring impairment to be present for diagnosis reduced persistence rates; (2) a norm-based symptom threshold led to higher persistence than a strict six-symptom DSM-based symptom count criterion; and (3) informant reports tended to show a higher number of symptoms than self-reports." These data have clear implications for what clinicians can do to avoid false positive and false negative diagnoses when diagnosing adult ADHD. It is reassuring that the self-reports of ADHD patients tend to underestimate the number and severity of ADHD symptoms. This means that your patients are not typically exaggerating their symptoms. Put differently, self-reports will not lead you to over-diagnose adult ADHD. Instead, reliance on self-reports can lead to false-negative diagnoses, i.e., concluding that someone does not have ADHD when, in fact, they do. You can avoid false negatives by doing a thorough assessment, which is facilitated by some tools available at www. ADHD in adults. Command described in CME videos there. If you think a patient might have ADHD but are not certain, it would be helpful to collect data from an informant, i.e., someone who knows the patient well such as a spouse, partner, roommate, or parent. You can collect such data by sending home a rating scale or by having the patient bring an informant to a subsequent visit. Dr. Sibley's paper also shows that you can avoid false-negative diagnoses by using a lower symptom threshold than what is required in the diagnostic manual. The new DSM 5 lowered the symptom threshold for adults from six to five. Can you go lower? Yes, but it is essential to show that these symptoms lead to clear impairments in living. Importantly, this symptom threshold refers to the number of symptoms documented in adulthood, not to the number of symptoms retrospectively reported in childhood. To be diagnosed with ADHD in adulthood, one must document that the patient had at least six impairing symptoms of ADHD before the age of 12.
Sibley, M. H., Mitchell, J. T. & Becker, S. P. (2016). Method ofadult diagnosis influences estimated persistence of childhood ADHD: asystematic review of longitudinal studies. Lancet Psychiatry3,1157-1165.
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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