April 29, 2021

How to Avoid False Positives and False Negatives when Diagnosing Adult ADHD?

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.

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Inflammation and Childhood ADHD: Platelet-to-Lymphocyte Ratios

Dose-response Association Found Between Platelet-to-Lymphocyte Ratio (PLR) and Childhood ADHD

Recent research suggests that inflammation may play a role in ADHD. Inflammation, marked by elevated proteins and cytokines, affects brain development and structure. Evidence suggests it plays a role in the development of ADHD, making the study of inflammatory markers crucial. 

The platelet-to-lymphocyte ratio (PLR) is a cost-effective test for predicting outcomes of chronic inflammation and neuroimmune diseases. Studies show PLR may be an important inflammatory marker in the pathophysiology of ADHD in children. 

The Study:

A Chinese study team used the National Health and Nutrition Examination Survey (NHANES) database maintained by the National Center for Health Statistics of the United States to investigate the association between PLR and ADHD in children aged 6–14. 

The team identified ADHD through prescriptions of ADHD medications. 

After exclusions for missing information, the study encompassed 1,455 children. 

The authors adjusted for the following potential confounders: sex, age, race, poverty-to-income ratio, maternal age at childbirth, smoking during pregnancy, asthma, health insurance status, dietary inflammatory index, monocyte count, segmented neutrophil count, eosinophil count, and basophil count. 

They also split the PLR results into quartiles, with the first quartile having the lowest readings. 

Prescriptions of ADHD medications were twice as frequent among children in the second quartile as they were among children in the first quartile. They were four times as frequent among children in the third quartile than among children in the first quartile.  

Conclusion

The team concluded, “These findings further support the potential role of inflammation in the onset and development of ADHD, providing preliminary evidence for PLR as a potential biomarker for ADHD and suggesting its possible use in identifying high-risk populations. However, considering the limitations of this study, future research should be designed as larger-scale, prospective, multi-center randomized controlled trials to validate these findings and further explore the relationship between inflammatory mechanisms and ADHD.” 

In other words, this study suggests that while high PLR values may serve as a potential biomarker for ADHD, particularly in specific high-risk groups, further research is needed to confirm these findings and fully understand the role of inflammation in ADHD development. Larger, more robust studies will be crucial to validating PLR as a reliable tool for identifying at-risk populations.

April 15, 2025

Meta-analysis of Two Nationwide Population Studies Finds No Harm to Offspring from Taking ADHD Medications During Pregnancy

ADHD is the most prevalent neurodevelopmental disorder. Nearly 1% of pregnant women in the Nordic countries and more than 1% in the United States are prescribed ADHD medications, ranking these among the most commonly used medications during pregnancy. However, the safety of exposing a fetus to ADHD medications is still uncertain, prompting many expectant mothers to stop using them out of fear for their unborn child’s well-being. 

The Study:

A European research team conducted a comprehensive nationwide study on the safety of ADHD medications during pregnancy using populations from Sweden and Denmark. The Swedish population was studied first, followed by inclusion of a separate study of the Danish population. Results were then combined through meta-analysis. Nordic countries, with their single-payer national health insurance systems and national population registers, facilitate the tracking of residents’ health from birth to death, thus providing robust data for such studies. 

The team accounted for various potential confounders, including maternal age, year of delivery, whether the mother was a first-time parent, self-reported smoking during pregnancy, and any psychiatric history. They also considered psychiatric inpatient or outpatient treatment received within two years before pregnancy, as well as the dispensing of other psychotropic medications during pregnancy, including antidepressants, antipsychotics, antiseizure medications, and anti-anxiety medications. Additionally, they examined the highest level of maternal education and civil status at delivery (married or cohabiting compared to single, divorced, or widowed). 

Out of 861,650 Swedish children, 2,257 were exposed to ADHD medications during pregnancy. Another 3,917 were born to mothers who discontinued ADHD medications before pregnancy.  

Children exposed to ADHD medications had lower rates of ADHD, autism spectrum disorder, and overall neurodevelopmental disorders; however, none of these differences were significant. 

Limiting the analysis to siblings to control for family environmental influences and genetics likewise found no significant differences.  

A meta-analysis combining the Swedish results with a separately conducted nationwide population study in neighboring Denmark similarly found no significant differences between children exposed to ADHD medications during pregnancy and children born to mothers who discontinued ADHD medications before pregnancy. 

Conclusion:

The team concluded, “Overall, our study provides reassuring evidence that continuing ADHD medication during pregnancy does not increase the risk of long-term NDDs [neurodevelopmental disorders] in offspring." 

From Meds to Mindfulness: What Actually Works for Adult ADHD?

A new large-scale study has shed light on which treatments for attention-deficit/hyperactivity disorder (ADHD) in adults are most effective and best tolerated. 

Researchers analyzed 113 randomized controlled trials involving nearly 15,000 adults diagnosed with ADHD. These studies included medications (like stimulants and atomoxetine), psychological therapies (such as cognitive behavioral therapy), and newer approaches like neurostimulation.

The Findings

Stimulant medications (lisdexamfetamine and methylphenidate) as well as selective norepinephrine reuptake inhibitors (SNRI) (atomoxetine) were the only treatments that consistently reduced core ADHD symptoms—both from the perspective of patients and clinicians. It may be worth noting that atomoxetine, while effective, was less well tolerated, with more people dropping out due to side effects.

Psychological therapies such as CBT, mindfulness, and psychoeducation showed some benefits, but mainly according to clinician ratings—not necessarily from the patients themselves. Neurostimulation techniques like transcranial direct current stimulation also showed some improvements, but only in limited contexts and with small sample sizes. Interestingly, none of the treatments—medication or otherwise—made a clear impact on long-term quality of life or emotional regulation. 

Conclusion 

So, what does this mean for people navigating ADHD in adulthood? Stimulant medications remain the most effective treatment for managing ADHD symptoms day-to-day but nonstimulant medication are not far behind, which is good given the problems we’ve had with stimulant shortages. This study also supports structured psychotherapy as a viable treatment option, especially when used in conjunction with medication. 

The study emphasizes the importance of ongoing, long-term research and the need for treatment plans that are tailored to the individual ADHD patient– Managing adult ADHD effectively calls for flexible, patient-centered care.

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April 9, 2025