It has been over two years since I wrote a Mental Elf blog about conclusions drawn from evidence in the treatment of attention deficit/hyperactivity disorder (ADHD) with my paediatrician colleague (Suetani S and Panagoda G, 2022). We thought ADHD was a hot topic then, but two and half years later, it remains very hot.

There have been several important Mental Elf blogs on ADHD since then (e.g. ADHD and intimate partner violence (Bhavsar V and Duggal J, 2023), ADHD and school absence/exclusion (Fielding C, 2022), ADHD and academic performance (Badenoch D, 2022)). Although the evidence base for ADHD is rapidly growing, many key questions remain unanswered (Chaulagain A et al., 2023), including how to assess the utility of interventions with low/no clinical evidence – the subject of another Mental Elf blog (Karmakar S, 2022).

An emerging priority in ADHD is: how relevant is the research evidence we have, to the patient sitting in front of me?

A new study published today in the Lancet Psychiatry by Garcia-Argibay et al (2025) explores this question.

Methods

Using the data from multiple Swedish national registries, the authors identified everyone with a diagnosis of ADHD who had received ADHD medication. They divided the cohort into those who would be eligible for a typical ADHD randomised controlled trial (RCT) and those who would be ineligible, based on an analysis of 164 RCTs of ADHD medications.

The most common exclusion criteria included: antidepressant use, psychosis, bipolar disorder, substance use disorder, cardiovascular disorder, learning disability/low intelligence quotient, anxiety disorder, and autism spectrum disorder.

The study compared the two groups in terms of:

Primary outcomes

• Treatment switching
• Treatment discontinuation.

Secondary outcomes

• The number of inpatient psychiatric hospitalisations
• The number of emergency department visits or hospitalisations related to accidental injuries or accidents
• Specialist care encounters for an alcohol or drug related diagnosis, depression, or anxiety.

Results

Of 189,699 individuals included in this study, just over half (53%) were classified as being ineligible for a typical ADHD medication RCT. The proportion of ineligible individuals was higher for adults aged 17 and over (74%) compared to adolescents (35%) or children (21%).

Let me repeat this for emphasis: over 70% of adults were ineligible for a typical ADHD medication RCT.

In terms of the primary outcomes;

• The ineligible group had a higher risk of treatment switching compared to the eligible group (Hazard ratio [HR] 1.14 with 95% confidence interval [CI] 1.12 to 1.16)
• The ineligible group had a slightly lower risk of medication discontinuation (HR 0.96 with 95% CI 0.94 to 0.98)

In terms of the secondary outcomes:

• The ineligible group had a higher risk of
  • inpatient psychiatric hospitalisations (incidence rate ratio [IRR] 9.68 with 95% CI 9.57 to 9.78)
  • emergency department visits or hospitalisations related to accidental injuries or accidents (IRR 1.31 with 95% CI 1.27 to 1.35)
  • specialist care encounters for an alcohol or drug related diagnosis (IRR 14.78 with 95% CI 14.64 to 14.91), depression (IRR 6.00 with 95% CI 5.94 to 6.06), or anxiety (IRR 11.63 with 95% CI 11.56 to 11.69)

Of note, the mean age for the eligible group was 13 (age range 10 to 16) compared to 26 (age range 17 to 37) for the ineligible group. For adults (those aged 17 and over), the mean age for the eligible group was 20 (age range 17 to 29) compared to 30 for the ineligible group (age range 23 to 40).

Conclusions

The authors concluded:

[the] study showed that a substantial portion of individuals with ADHD, in particular adults, are ineligible for standard RCTs, and these individuals have higher rates of adverse clinical outcomes compared with their eligible counterparts.

As the authors state in the discussion section, we have a paradox, especially for adults with ADHD, of;

those patients who might benefit most from evidence-based guidance are the least represented in clinical trials that are meant to inform guidance.

Strengths and limitations

This is an exceptional study. The authors proposed a key question, grabbed a whole lot of data, and analysed them to come up with relevant findings. The entire study was elegant in its design and graceful in its delivery.

As the authors acknowledge, the study has the usual limitations associated with cohort studies. In particular, there is a lack of fine-grained clinical data at the individual patient level. This meant the study used more blunt tools to estimate clinical parameters, as is most evident in the secondary outcomes of the study.

For instance, the number of inpatient psychiatric hospitalisations was used as a proxy measure for overall psychiatric burden. At least in Australia, I have never seen anyone being admitted to a public hospital for a relapse of ADHD. The number of emergency department visits or hospitalisations related to accidental injuries or accidents was used as an objective measure for functional impairment, but this is an unusual way of assessing someone’s day-to-day function. Although comorbidity is a rule rather than an exception among adults with ADHD and the clinical approach can be challenging (Katzman MA et al, 2017), I’m not sure if many of them would require specific specialist care for their comorbidities.

Finally, I know very little about Sweden, but I assume that the legal framework for prescribing psychostimulant medication would be different to Australia, where I practice. Sweden also has a much higher rate of ADHD medication prescription compared to places like the United Kingdom or Australia. Yet, the rate is much lower than those seen in North America (Chan AYL et al., 2023). I also suspect that many cultural factors beyond the health system, such as gross domestic product per capita and the societal attitude towards the concept of ADHD, would play a large role in how you treat the condition in different countries.

Implications for practice

As a clinician, I want to know the answer to the question; “Will this medication help my patient get better under these circumstances?”, rather than “How well does this medication work in an ideal circumstance?”

As an adult psychiatrist, most of my patients present for ADHD assessment in their 30’s and 40’s. How much faith would you invest in your evidence-based guidance if you knew that over 70% of your patients would be ineligible to participate in a typical RCT? To misquote Winston Churchill, is RCT the worst form of evidence (except for all those other forms that have been tried from time to time)?

The authors propose a more comprehensive approach to clinical research in ADHD. Given that this is not a problem unique to ADHD, I would argue that we need to consider a similar approach for all psychiatric conditions. They suggest combining the findings from RCTs, pragmatic trials, observational studies, and targeted trials in typically excluded populations to triangulate the data to provide clinicians with a better understanding of the effectiveness of each intervention in different cohorts. I would also add the local service level data to the mix. A small amount of fine-grained clinical information about a particular population under particular circumstances might be more valuable than a large amount of high-level data.

We also need to agree on what to measure. How do we measure outcomes at the individual level? What do we mean by functional impairment? Do we want our patients to feel less distracted, or do we want them to be employed? How do we measure outcomes at the population level? If we treat ADHD sufficiently in a population, would we see a reduction in lost productivity as a society? And is productivity at a population level, a legitimate reason and measurable outcome for which to treat the patient sitting in front of me?

Here is an opportunity for us to take the findings from this exceptional study to move the field forward. All that glitters is not gold; RCTs may no longer be the gold standard of clinical research in psychiatry. We need to urgently build the bridge to take us from efficacy to effectiveness.

Statement of interests

Shuichi is a member of the Royal Australian and New Zealand College of Psychiatrists ADHD Network, and Australasian ADHD Professionals Association.

Links

Primary paper

Garcia-Argibay M, Chang Z, Brikell I. et al (2025) Evaluating ADHD medication trial representativeness: a Swedish population-based study comparing hypothetically trial-eligible and trial-ineligible individuals. Lancet Psychiatry (open access)

Other references

Badenoch D. ADHD is a substantial risk factor for poor academic performance, according to a new study from Norway #CAMHScampfire. The Mental Elf, 23 Sep 2022.

Bhavsar V and Duggal J. What is the evidence for ADHD as a risk factor for intimate partner violence or sexual violence? The Mental Elf, 6 Nov 2023.

Chan AYL, Ma TT, Lau WCY, et al (2023). Attention-deficit/hyperactivity disorder medication consumption in 64 countries and regions from 2015 to 2019: a longitudinal study. EClinicalMedicine. 2023 Mar 20;58:101780. doi: 10.1016/j.eclinm.2022.101780. PMID: 37181411; PMCID: PMC10166776.

Chaulagain A, Lyhmann I, Halmøy A. et al (2023) A systematic meta-review of systematic reviews on attention deficit hyperactivity disorder. Eur Psychiatry. 2023 Nov 17;66(1):e90. doi: 10.1192/j.eurpsy.2023.2451. PMID: 37974470; PMCID: PMC10755583.

Fielding C. What’s the link between neurodevelopmental or mental disorders and school absence or exclusion? The Mental Elf, 10 Nov 2022.

Karmakar S. Behavioural therapies may reduce inattention symptoms in adults with ADHD. The Mental Elf, 24 Jan 2022.

Katzman MA, Bilkey TS, Chokka PR. Et al (2017) Adult ADHD and comorbid disorders: clinical implications of a dimensional approach. BMC Psychiatry. 2017 Aug 22;17(1):302. doi: 10.1186/s12888-017-1463-3. PMID: 28830387; PMCID: PMC5567978.

Suetani S and Panagoda G. Critiquing the evidence behind the “evidence-based conclusions” about ADHD. The Mental Elf, 21 Sep 2022.

Photo credits

• Clément Philippe on unsplash.com
• Lawrence Chismorie on unsplash.com
• MUILLU on unsplash.com