September 22, 2023

Addressing the challenge of under-diagnosed adult ADHD

There is a well-documented gap between the known prevalence of adult ADHD and rates of diagnosis and treatment. In Germany, epidemiological studies of nationally representative community samples have found prevalence rates ranging from 3.1% to 4.7%. Yet, studies of publicly insured individuals aged 18 to 69 years old report rates of diagnosed ADHD between 0.04% and 0.4%. So, even in a country with universal health insurance, more than nine out of ten adults with ADHD go undiagnosed.

Many factors contribute to under-diagnosis: stigma, culturally influenced perceptions, and lack of motivation by those affected. Another crucial factor is the lack of recognition of ADHD symptoms by clinicians.

A research team surveyed 144 psychologists, 32 physicians, and two occupational therapists. Almost three in five participants were psychotherapists, a quarter were neuropsychologists, and one in seven were psychiatrists.

Four out of five clinicians stated they had received only a few hours of ADHD-specific training. One in four stated they had not examined guidelines for diagnosing ADHD. A lack of formal training among the vast majority, and unfamiliarity with current diagnostic guidelines in a significant minority, were surprising findings among clinicians who regularly work with adults with ADHD.

Many clinicians had difficulty identifying core features of adult ADHD as defined by the DSM-5 and International Classification of Diseases, Tenth Revision (ICD-10). Roughly one in five stated that hyperactivity had little relevance to adult ADHD. The only core feature correctly identified by more than half the respondents was having difficulties concentrating. Impairments in social behavior or aggression and memory impairment were not identified as being clearly relevant or irrelevant to adult ADHD.

The authors concluded that these findings appear to indicate some uncertainty or at least a lack of consensus among clinicians about what symptoms are relevant to ADHD in adulthood, and it is likely that this uncertainty contributes to diagnostic inaccuracy.

Most respondents reported using self-report scales of ADHD symptoms and using unstructured interviews. While slightly more than half agreed that collateral reports are important to diagnosis, only about a third reported regularly using them. This is a problem given the limited accuracy of self-reported childhood symptoms for documenting the childhood-onset of the disorder. Semi-structured interviews are also known to improve the accuracy of diagnosis, but are rarely used in clinical practice.

Over half of psychologists and a quarter of physicians reported using cognitive or neuropsychological testing, even though this is at variance with German (and other) guidelines, which specify that such testing is suitable for clarifying strengths and weaknesses, but not for ruling out or confirming a diagnosis of ADHD. The European Consensus Statement also states that cognitive/neuropsychological testing should only be used as a secondary or supplementary assessment tool.

While three out of four clinicians recommended stimulant drug treatment, psychologists tended to be more hesitant to do so. This is likely because German psychologists receive little training in pharmacotherapy, and do not have prescription privileges. Given the demonstrated efficacy of stimulant treatment, this points to a need to better educate psychologists in this regard.

Almost three in four respondents cited a lack of clinician knowledge and experience as a barrier to ADHD diagnosis. Most clinicians also stated they were either uncertain or only somewhat certain of their ability to diagnose ADHD. That suggests that more extensive ADHD-specific training is needed.

A limitation of the survey was the relatively low participation by physicians. It is also likely that the findings are not reflective of practices in ADHD specialty clinics.

The authors concluded, Further training is needed to improve clinicians' understanding of ADHD in adulthood and to align diagnostic practices with guideline recommendations. Whereas discrepancies between respondents regarding the relative importance of peripheral symptoms (e.g., memory problems) were most common, a lack of consensus was found even for core symptoms listed by diagnostic criteria. Particularly among psychologists improved awareness regarding the benefits of stimulant medications is needed to bring their treatment recommendations in line with evidence-based guidelines.

Brooke C. Schneider, Daniel Schöttle, BirgitHottenrott, Jürgen Gallinat, and Steffen Moritz, "Assessment of Adult ADHD in clinical Practice: Four Letters-40 Opinions," Journal of Attention Disorders(2019) DOI: 10.1177/1087054719879498.

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Population Study: Stimulants Shown to Reduce Hospitalization and Suicidality

Swedish Population Study Suggests Stimulants Reduce Hospitalization and Suicidality, Have No Significant Effect on Work Disability

A meta-analysis of short-term, placebo-controlled, randomized clinical trials (Cortese et al. 2018), looking at both efficacy and safety, supported prescribing stimulants – methylphenidate use in children and adolescents and amphetamine use in adults – as first-choice medications. 

However, these were short-term studies, and they focused on relieving ADHD symptoms. What about longer-term outcomes, especially looking more broadly at functional impairment and overall quality of life? 

Sweden has a single-payer health insurance system that encompasses virtually every resident and is linked to national registers that enable researchers to conduct nationwide population studies. 

A joint Finnish-Swedish research team used Sweden’s registers to study outcomes for all individuals of working age, 16 to 65 years old, living in Sweden who had received a diagnosis of ADHD from 2006 through 2021. The resulting study cohort encompassed 221,714 persons with ADHD. 

The team adjusted for the following confounding variables: Genetics, baseline severity of symptoms, baseline comorbidities, temporal order of treatments (which medication was used as first, second, third, and so forth, including also nonuse of ADHD medications), time since cohort entry, and time-varying use of psychotropic drugs, including antidepressants, anxiolytics, hypnotics, mood stabilizers (carbamazepine, valproic acid, and lamotrigine), lithium, antipsychotics, and drugs for addictive disorders. 

With these adjustments, they discovered that amphetamine treatment was associated with a roughly 25% reduction in psychiatric hospitalization relative to unmedicated ADHD. Lisdexamphetamine was associated with a roughly 20% reduction, dexamphetamine with a 12% reduction, and methylphenidate with a 7% reduction. All four medications are stimulants

None of the non-stimulant medications – atomoxetine, guanfacine, clonidine – had any significant effect on psychiatric hospitalization. Nor did modafinil a drug that is not FDA approved for ADHD but is sometimes used when other drugs fail. 

Amphetamine was also associated with the greatest reduction in suicide attempts or deaths, with a roughly 40% decline relative to unmedicated ADHD. Dexamphetamine was associated with a roughly 30% decline and lisdexamphetamine with a roughly 25% decline. The stimulant methylphenidate was only associated with an 8% reduction, and modafinil had no significant effect. 

Surprisingly, non-stimulant medications were associated with significant increases in suicide attempts or deaths: 20% for atomoxetine, 65% for guanfacine, and almost double for clonidine

Amphetamine and lisdexamphetamine also reduced the risk of nonpsychiatric hospitalization by more than a third compared to unmedicated ADHD. Dexamphetamine was associated with a risk reduction of more than 25%, methylphenidate with 20% lesser risk.  

The non-stimulant atomoxetine was associated with a roughly 15% reduction in risk of nonpsychiatric hospitalization. But neither guanfacine nor clonidine had any significant effect. 

Turning to work disability, atomoxetine was the only ADHD medication associated with a reduction – a roughly 10% improvement. All other medications had no significant effect

The team concluded, “In this cohort study of adolescents and adults with ADHD, the use of medications for ADHD, especially lisdexamphetamine and other stimulants, was associated with decreased risk of psychiatric hospitalizations, suicidal behavior, and nonpsychiatric hospitalizations during periods when they were used compared with periods when ADHD medication was not used. Non-stimulant atomoxetine use was associated with decreased risk of work disability.” 

September 13, 2024

Meta-analysis: Efficacy of Antioxidant Therapy for ADHD

Network Meta-analysis Finds No Significant Evidence for Efficacy of Antioxidant Therapy for Treating ADHD

Noting that “Oxidative stress disrupts the structure and function of neurons in the prefrontal lobe of the brain,” and “Structural and functional impairments in the prefrontal cortex have been shown to be highly correlated with behavioral and emotional problems of ADHD,” a Chinese team at Dalian University set out to systematically evaluate the safety and efficacy of antioxidant therapy in children and adolescents with ADHD. 

The team’s systematic search of the peer-reviewed medical literature identified a total of 48 randomized controlled trials (RCTs) or prospective studies involving 12 antioxidant agents (resveratrol, pycnogenol, omega-3, omega-6, quercetin, phosphatidylserine, almond, vitamin D, zinc, folic acid, ginkgo biloba, Acetyl-L-carnitine) that met criteria for inclusion: 

  • Ages 18 or younger. 
  • Clinical diagnoses of ADHD. 
  • Minimum treatment duration of two weeks. 
  • Experimental group received antioxidant treatment. 
  • Control group received either a placebo, the stimulant medication methylphenidate, or a different antioxidant or combination of antioxidants. 

Treatment efficacy was measured through ADHD symptom scores using Conners’ parent rating scale (CPRS), Conners’ teacher rating scale (CTRS), ADHD rating scale-parent (ADHD RS-Parent), and ADHD rating scale-teacher (ADHD RS-Teacher), as well as secondary outcome indicators such as the Clinical Global Impressions scale (CGI) and Continuous Performance Test (CPT), relative to controls. 

None of the antioxidant therapies were significantly better than placebo.

One limitation is that no effort was made to assess publication bias. 

These results indicate that antioxidants should not be used for treating ADHD.

September 12, 2024

No Association Found Between Acetominophen Use During Pregnancy, Subsequent ADHD

Swedish Nationwide Population Study Finds No Association Between Acetaminophen Use During Pregnancy and Offspring ADHD

A 2021 consensus statement by an international group of scientists and clinicians (Bauer et al.) recommended that pregnant individuals “forego [acetaminophen] unless its use is medically indicated,” due to the potential risk of developmental disorders such as autism and attention-deficit/hyperactivity disorder (ADHD). 

A mostly Swedish research team, collaborating with a U.S. researcher, nevertheless noted that previous studies have been limited by: 

  • Confounding by indication, because acetaminophen is taken for infection, fever, and pain (including pain from autoimmune disease), which are themselves risk factors for neurodevelopmental disorders such as ADHD. 
  • Confounding by parental health and genetics, because neurodevelopmental disorders are highly heritable. 
  • Small sample sizes. 

Sweden has a single-payer health insurance system that includes virtually its entire population, and national registers that enable tracking the health history of mothers and their children, including their children’s siblings. 

The team used the Swedish registers to identify the roughly two-and-a-half million children born in Sweden from mid-1995 through 2019. They were also able to identify all siblings to be able to control for otherwise unmeasured familial and genetic confounding. 

Almost 186,000 of these children were exposed to acetaminophen during pregnancy.  

After adjusting for available known confounders, including (but not limited to) child sex and birthdate, mother’s age and medical history, use of any other painkillers, use of any psychoactive medications, country of birth, residential region, smoking status, highest household education, and disposable income, children exposed to acetaminophen during pregnancy were 7% more likely to be diagnosed with ADHD subsequently than those who were not exposed. 

However, roughly the same results were found for other painkillers, including aspirin, non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and antimigraine medication.   High doses of acetaminophen did not produce any stronger association with subsequent ADHD than low dosage. 

Moreover, when confining results to siblings – 8,526 children who were exposed versus 87,679 who were unexposed – the association between acetaminophen use during pregnancy and subsequent offspring ADHD vanished altogether (and, again, at every dose level). The associations similarly vanished with every other painkiller medication.  

The Swedish team concluded, “Acetaminophen use during pregnancy was not associated with children’s risk of autism, ADHD, or intellectual disability in sibling control analyses. This suggests that associations observed in models without sibling control may have been attributable to confounding.” 

September 5, 2024