Will this ADHD medication help my patient? Bridging the gap between efficacy and effectiveness
It has been over two years since I wrote a Mental Elf blog about conclusions drawn from the evidence in the treatment of attention deficit/hyperactivity disorder (ADHD) with my pediatrician colleague (Suetani S and Panagoda G, 2022). We thought ADHD was a hot topic then, but two and a half years later, it’s still very hot.
Since then, there have been several major Mental Elf blogs about ADHD (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 growing rapidly, many key questions remain unanswered (Chaulagain A et al., 2023), including how to evaluate the utility of interventions with low or no clinical evidence, the topic 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 Lancet Psychiatry by García-Argibay et al (2025) explore this question.
ADHD is a “hot topic” in mental health science right now, and rightly so, as there are many unanswered questions about where research can really improve people’s lives.
Methods
Using data from multiple Swedish national registries, the authors identified all people with a diagnosis of ADHD who had received ADHD medications. They divided the cohort into those who would be eligible for a typical randomized controlled trial (RCT) for ADHD and those who would not be eligible, 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 IQ, anxiety disorder, and autism spectrum disorder.
The study compared the two groups in terms of:
Primary results
- Treatment change
- Treatment interruption.
Secondary results
- The number of psychiatric hospitalizations
- The number of emergency department visits or hospitalizations related to accidental injuries or accidents.
- Specialty care visits for a diagnosis, depression or anxiety related to alcohol or drugs.
Results
Of 189,699 people included in this study, just over half (53%) were classified as ineligible for a typical RCT on ADHD medications. The proportion of ineligible persons was higher among adults aged 17 years or older (74%) compared to adolescents (35%) or children (21%).
Let me repeat this for emphasis: More than 70% of adults were not eligible for a typical RCT of ADHD medications.
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 results:
- The ineligible group had a higher risk of
- psychiatric hospitalizations (incidence rate [IRR] 9.68 with 95% CI: 9.57 to 9.78)
- emergency department visits or hospitalizations related to accidental injuries or accidents (IRR 1.31 with 95% CI: 1.27 to 1.35)
- specialty care visits 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 of the eligible group was 13 years (age range 10 to 16 years) compared to 26 (age range 17 to 37 years) of the ineligible group. For adults (ages 17 and older), the median age of the eligible group was 20 years (age range 17 to 29 years) compared to 30 years for the ineligible group (age range 23 to 40 years ).
This study found that more than 70% of adults were ineligible for a typical research drug trial (RCT) for ADHD. Can we trust the evidence we are producing if we exclude such a large proportion of people from our research?
Conclusions
The authors concluded:
[the] study showed that a substantial portion of people with ADHD, particularly adultsare not eligible for standard RCTand these individuals have higher rates of adverse clinical outcomes compared to their eligible counterparts.
As the authors state in the discussion section, we have a paradox, especially for adults with ADHD, of;
those patients who could benefit most from an evidence-based guideline are the least represented in clinical trials that are intended to inform guidance.
These ADHD researchers conclude that “those patients who could benefit most from evidence-based counseling are the least represented in clinical trials intended to inform counseling.”
Strengths and limitations
This is an exceptional study. The authors proposed a key question, collected a large amount of data, and analyzed it to arrive at relevant findings. The entire studio 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 detailed clinical data at the individual patient level. This meant that the study used more robust tools to estimate clinical parameters, as is most evident in the study’s secondary outcomes.
For example, the number of psychiatric hospitalizations was used as a proxy measure of overall psychiatric burden. At least in Australia, I have never seen anyone admitted to a public hospital for an ADHD relapse. The number of emergency department visits or hospitalizations related to accidental injuries or accidents was used as an objective measure of functional impairment, but this is an unusual way to assess a person’s daily functioning. Although comorbidity is a rule and not an exception among adults with ADHD and the clinical approach can be challenging (Katzman MA et al, 2017), I am not sure if many of them would require specialized care specific to their comorbidities.
Lastly, I know very little about Sweden, but I assume the legal framework for prescribing psychostimulant medications would be different than in Australia, where I practice. Sweden also has a much higher rate of ADHD medication prescription. compared to places like the UK or Australia. However, the rate is much lower than those observed in North America (Chan AYL et al., 2023). I also suspect that many cultural factors beyond the healthcare system, such as gross domestic product per capita and societal attitude toward the concept of ADHD, would play a role in how the condition is treated in different countries.
This research was carried out in Sweden. When considering the relevance of research, we must always ask whether patients and the environment are so different that we cannot apply this evidence to our own situation.
Implications for practice
As a doctor, I want to know the answer to the question; “Will this medication help my patient improve in these circumstances?“, instead of “How well does this medication work under ideal circumstances?“
As an adult psychiatrist, most of my patients present for an ADHD evaluation when they are in their 30s and 40s. How much faith would you invest in your evidence-based guidance if you knew that more than 70% of your patients would not be eligible 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. Since this is not a problem unique to ADHD, I would say that we should consider a similar approach for all psychiatric conditions. they suggest Combine findings from RCTs, pragmatic trials, observational studies and targeted trials in typically excluded populations to triangulate data. 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 detailed clinical information about a particular population in particular circumstances could be more valuable than a large amount of high-level data.
We must also agree on what to measure. How do we measure results at the individual level? What do we understand by functional impairment? Do we want our patients to feel less distracted or do we want them to be employed? How do we measure results at the population level? If we sufficiently treat ADHD in a population, would we see a reduction in lost productivity as a society? And is population-level productivity a legitimate reason and measurable outcome for treating the patient sitting in front of me?
This is an opportunity for us to leverage the findings of this exceptional study to advance the field. All that glitters is not gold; RCTs may no longer be the gold standard of clinical research in psychiatry. We urgently need to build the bridge that takes us from efficiency to effectiveness.
All that glitters is not gold. Should we trust RCTs less and be more open-minded about different types of evidence?
Declaration of interests
Shuichi is a member of the Royal Australian and New Zealand College of Psychiatrists ADHD Network and the Australasian Association of ADHD Professionals.
Golf course
primary job
García-Argibay M, Chang Z, Brikell I. et al (2025) Assessing the representativeness of ADHD medication trials: a Swedish population-based study comparing individuals hypothetically eligible and ineligible for the trial. Lancet Psychiatry (open access)
Other references
Badenoch D. ADHD is a substantial risk factor for poor academic performance, according to a new study conducted in Norway #CAMHScampfire. The mental elf, September 23, 2022.
Bhavsar V and Duggal J. What is the evidence that ADHD is a risk factor for intimate partner violence or sexual violence? The Mind Elf, November 6, 2023.
Chan AYL, Ma TT, Lau WCY, et al (2023). Medication use for attention-deficit/hyperactivity disorder in 64 countries and regions from 2015 to 2019: a longitudinal study. ECClinical Medicine. March 20, 2023; 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. European psychiatry. Nov 17, 2023;66(1):e90. doi: 10.1192/j.eurpsy.2023.2451. PMID: 37974470; PMCID: PMC10755583.
Fielding C. What is the link between mental or neurodevelopmental disorders and school absence or exclusion? The mental elf, November 10, 2022.
Karmakar S. Behavioral therapies can reduce inattention symptoms in adults with ADHD. The mental elf, January 24, 2022.
Katzman MA, Bilkey TS, Chokka PR. et al (2017) Adult ADHD and comorbid disorders: clinical implications of a dimensional approach. BMC Psychiatry. August 22, 2017; 17 (1): 302. doi: 10.1186/s12888-017-1463-3. PMID: 28830387; PMCID: PMC5567978.
Suetani S and Panagoda G. Critiquing the evidence behind “evidence-based conclusions” about ADHD. The mental elf, September 21, 2022.
