Are adult ADHD clinical trials testing the right patients? A new study raises doubts

More than half of major clinical trials testing treatments for adult ADHD did not adequately verify that participants actually had the condition, raising serious concerns about the reliability of the evidence underpinning current care. This new study was published in European Psychiatry.

Attention-deficit/hyperactivity disorder (ADHD) was originally described as a childhood condition, defined by observable behaviors that parents and teachers could report, such as excessive running, an inability to sit still, or constant interruption. However, in recent decades, ADHD diagnoses in adults have risen sharply. This surge has prompted growing concern among researchers and clinicians about whether the diagnostic criteria—originally tailored for children—are fit for purpose when applied to adults.

The challenge is significant. To be diagnosed, adults must reflect on and self-report their own internal experiences (such as feeling distracted or restless) and recall childhood behaviors that occurred decades earlier. Many symptoms of adult ADHD can also be caused by depression, trauma, anxiety, and other mental health conditions. Without carefully ruling out these alternatives through a thorough, differential psychiatric assessment, misdiagnosis can easily occur.

A research team led by Igor Studart systematically reviewed 292 randomized controlled trials (RCTs) involving adult patients diagnosed with ADHD. RCTs are widely considered the “gold standard” of clinical research used to determine if a treatment works. The researchers examined how ADHD had been diagnosed in each trial, who conducted the assessment, whether psychiatric comorbidities were included, and whether general mental health was evaluated to rule out mimicking conditions.

The findings were striking. Overall, there was massive variation in the diagnostic methods used across the trials. Approximately half (49.7%) of the studies diagnosed ADHD without any formal assessment of broader general psychopathology. This means the researchers had no systematic way to rule out that participants’ attention or hyperactivity difficulties might actually be symptoms of depression, schizophrenia spectrum disorders, substance use, or another condition altogether.

In 65% of the studies, it was either unclear who had conducted the diagnostic assessment, or the assessment had not been done by a psychiatrist or psychologist. Instead, many trials relied on “trained raters,” self-rating scales, or computer assessments—methods that elevate the risk of diagnostic errors.

Furthermore, over half (53.8%) of the studies included participants with other psychiatric comorbidities. This is highly problematic because clinical guidelines stipulate that ADHD should not be diagnosed if the symptoms are better explained by another condition. While over 87% of the studies claimed to adhere to this diagnostic hierarchy (which prioritizes ruling out organic or severe psychiatric disorders first), the reviewers noted that this was practically impossible for most to verify, as they had skipped the general mental health assessment required to do so.

The authors concluded that these findings represent “a worrying shift in the common understanding of how a psychiatric diagnosis should be allocated in research studies.”

They added: “If neither clinicians nor researchers can rely on the basic fact that patients in scientific studies diagnostically resemble the patients they are facing, scientific studies risk losing their clinical relevance.”

An important limitation of this review is that it searched only one database (PubMed) and focused solely on the diagnostic methodology of the trials, rather than analyzing their actual outcomes. Additionally, because many RCTs poorly described their diagnostic procedures, the categorization of those approaches required some degree of subjective judgment by the reviewers.

The study, “Diagnosing ADHD in adults in randomized controlled studies: a scoping review,” was authored by Igor Studart, Mads Gram Henriksen, and Julie Nordgaard.