You might be interested in…ADHD

Attention-deficit hyperactivity disorder (ADHD) is the most prevalent neurodevelopmental condition. In the US, the prevalence of ADHD is uncertain, but is estimated to be 9.8 per cent among children and adolescents, and 4.4 per cent among adults. The disorder is associated with a broad range of psychiatric and physical comorbidities, as well as adverse functional outcomes. Furthermore, individuals with ADHD have a twofold increased risk of premature death compared with those without it, mainly due to unnatural causes.

Dr Ray O’Connor

Pharmacological treatment, including stimulant and nonstimulant medications, is recommended for both children and adults diagnosed with ADHD, alongside nonpharmacological treatment. The objectives of this nationwide observational cohort study in Sweden1 was to investigate whether initiation of ADHD pharmacotherapy was associated with reduced all-cause mortality risk in individuals with ADHD.

The authors identified individuals aged six through 64 years with an incident diagnosis of ADHD from 2007 through 2018 and no ADHD medication dispensation prior to diagnosis. Follow-up started from ADHD diagnosis until death, emigration, two years after ADHD diagnosis, or December 31, 2020. The results were that 148,578 individuals with ADHD (41.3 per cent females and 56.7 per cent males) initiated ADHD medication. The median age at diagnosis was 17.4 years.

The two-year mortality risk was lower in the initiation treatment strategy group (39.1 per 10 000 individuals) than in the non-initiation treatment strategy group (48.1 per 10 000 individuals), particularly for death due to unnatural causes.

What is the true global prevalence of ADHD? The estimates across various studies are significantly variable. Previous systematic reviews and meta-analyses have attributed this variability primarily to the methodological characteristics of the studies, including the diagnostic criteria, source of information, and impairment requirement for the diagnosis.

The authors of this systematic review and meta-analysis2 identified studies reporting ADHD prevalence in representative samples of children and adults in Europe and worldwide. In total, 117 studies were subjected to full evaluation. In the meta-analysis, the overall prevalence of ADHD depended on the type of study.

In register studies the prevalence was 1.6 per cent, in survey studies 5.0 per cent, in one-stage clinical studies 4.2 per cent, and in two-stage clinical studies 4.8 per cent. The authors concluded that exact comparisons among studies with different diagnostic criteria and types of sampling can impact prevalence estimates. When comparing data from methodologically different studies, these factors need to be considered.

What brings about ADHD? Could it be related to family dynamics? Parenting and family environment have a significant impact on child development, including development of executive function, attention, and self-regulation, and may affect the risk of developmental disorders including ADHD.

This paper3 was a systematic review and meta‑analysis of parenting and family environment as risk factors for ADHD in children. The findings were that factors with sufficient information for analysis were parenting interaction quality (sensitivity/warmth, intrusiveness/reactivity, and negativity/harsh discipline), maltreatment (general maltreatment and physical abuse), parental relationship status (divorce, single parenting), parental incarceration, and child media exposure.

All factors showed a significant direct association with ADHD outcomes, except sensitivity/warmth which had an inverse association. The authors conclude that their findings support the possibility that parenting and family environment influence ADHD symptoms and may affect a child’s likelihood of being diagnosed with ADHD. They recommend that prevention strategies that support parents, such as decreasing parenting challenges and increasing access to parent training in behaviour management, may improve children’s long-term developmental health.

There are concerns around the safety of currently available ADHD medications, including their possible cardiovascular effects and limited abuse potential. Therefore, there is a need for additional efficacious and safer medications for adults with ADHD. The authors of this review article4 which searched the clinical trials register found 90 eligible randomised controlled trials (RCTs).

Of these, 24 reported results with statistical analysis for primary efficacy endpoints. While several pharmacological and non-pharmacological interventions had evidence of superiority compared to the control condition from a single RCT, centanafadine (norepinephrine, dopamine, and serotonin re-uptake inhibitor) was the only treatment with evidence of efficacy on ADHD core symptoms replicated in at least one additional RCT, alongside reasonable tolerability. Overall, the authors concluded that the body of ongoing RCTs in adults with ADHD is insufficient. They recommend that additional effective and well-tolerated treatments for adults with ADHD require development and testing.

Could there be a blood test available any time soon to help us diagnose ADHD? Metabolomics presents an objective approach, seeking biomarkers for precise diagnosis and targeted interventions. This systematic review paper5 synthesizes existing metabolomic insights into ADHD, aiming to reveal biological mechanisms and diagnostic potentials. Unfortunately, there was no clear simple blood test that emerged as usable by practicing clinicians currently.

The authors found intricate links between ADHD and altered amino acid metabolism, neurotransmitter dysregulation (especially dopamine and serotonin), oxidative stress, and the kynurenine pathway impacting neurotransmitter homeostasis. Sleep disturbance markers, notably in melatonin metabolism, and stress-induced kynurenine pathway activation emerged. Distinct metabolic signatures, notably in the kynurenine pathway, show promise as potential diagnostic markers for the future.

References:

1. Li L et al. ADHD Pharmacotherapy and Mortality in Individuals With ADHD. JAMA 2024 Mar 12;331(10):850–860. doi: 10.1001/jama.2024.0851
2. Popit S et al. Prevalence of attention-deficit hyperactivity disorder (ADHD): systematic review and meta-analysis. European Psychiatry 2024, 67(1), e68, 1–23 https://doi.org/10.1192/j.eurpsy.2024.1786
3. Claussen A et al. All in the Family? A Systematic Review and Meta‑analysis of Parenting and Family Environment as Risk Factors for Attention‑Deficit/Hyperactivity Disorder (ADHD) in Children. Prevention Science 2022 https://doi.org/10.1007/s11121-022-01358-4
4. Veronesi G et al. Treatments in the pipeline for attention-deficit/hyperactivity disorder (ADHD) in adults. Neurosci Biobehav Rev 2024 Aug:163:105774. doi: 10.1016/j.neubiorev.2024.105774 Epub 2024 Jun 22.
5. Predescu E et al. Metabolomic Markers in Attention-Deficit/Hyperactivity Disorder (ADHD) among Children and Adolescents—A Systematic Review. Int. J. Mol. Sci. 2024, 25, 4385. https://doi.org/10.3390/ijms25084385