EXPERT REACTION: ADHD meds work short-term, major study finds

The most telling findings from this study are that for adults diagnosed with ADHD, the medications usually used (stimulants and atomoxetine):

• have somewhere between very low to moderate impact on symptoms in the short term
• have no positive impact on outcomes at one year follow up
• are not shown to improve quality of life, a more important measure than symptomatic improvement.

The authors rightly point out the quality of evidence is poor; there are harms from medication; and more research is needed about meaningful benefits beyond symptomatic improvement of questionable significance.

The study reinforces the need for clinicians to go beyond over simplified symptomatic diagnosis to seek understanding of why each individual is experiencing some combination of inattentiveness, overactivity and impulsivity, since merely diagnosing and treating ADHD will have dubious benefit.

The findings highlight that stimulant mediation, the most acceptable pharmacological treatment, decreases ADHD symptoms but does not take all ADHD-related challenges away. Adults with ADHD also require multimodal care that fosters the traits people with the condition report are important for living well with the condition. These being an in-depth understanding of ADHD, self-acceptance, acceptance of disability, self-compassion, and skills and compensatory strategies that support self-mastery. These traits align with the tenants of mental health recovery (i.e., hope; an understanding of personal strengths and limitations; self-determination; personalised skill development; and empowered self-management). Accessing such treatment, however, remains difficult - as reflected in the failure of current treatment interventions to improve quality of life in adults with ADHD. Research and treatment intervention development involving people with ADHD is desperately required to address this issue.

The study by Ostinelli and colleagues reviewed randomised controlled trials on treatments for adult ADHD (≥18 years). While stimulants are the only intervention consistently reducing self-reported and clinician-reported ADHD symptoms in the short term, they fail to improve broader outcomes like quality of life. Adults with ADHD face challenges that extend beyond core symptoms, highlighting the need for treatments and trials that address functional and emotional well-being.

Non-stimulant options, such as atomoxetine, showed some symptom reduction but were less tolerable due to side effects and slower onset of efficacy. Non-pharmacological treatments demonstrated inconsistent effects, likely due to variability in intervention types, frequency, and duration, as well as limited high-quality trials. Notably, of the included trials only 38 examined non-pharmacological approaches vs 113 of pharmacological treatments.

Ultimately a tailored multimodal treatment approach that considers functional and emotional well-being as well as core symptom reduction should be adopted (an approach supported by the Australian ADHD Guideline). Finally the study also highlights a significant gap in evidence for the long-term effects of ADHD treatments. Given that ADHD is a lifelong condition for many individuals, it is essential that sustained, effective interventions are available to adults with ADHD. As such research needs to move beyond short-term symptom control and focus on long-term outcomes that truly improve daily life for those with ADHD.

ADHD is a very prevalent psychiatric disorder in adults, affecting about 2.5-6% of adults. It is frequently undiagnosed and untreated. Less is known about adult ADHD than childhood ADHD, and whether both conditions respond to treatment with the same types of treatment. This massive work surveys all clinical trial evidence to conclude that psychostimulants (methylphenidate- and dexamfetamine-based drugs) stand out as the only clear winner in treating Adult ADHD, although their use comes at the price of side effects.

This study could not endorse an improvement in the quality of life associated with treatment with these drugs. The meaning of this, and whether this is a technical issue in patient self-reports, could explain that puzzling finding. The non-stimulant drugs for Adult ADHD were unimpressive - guanfacine was not effective for treating core symptoms and atomoxetine caused more side effects than placebo, although it did help the core symptoms.

Non-drug interventions (e.g. psychological treatments, neurostimulation) were also unimpressive in helping the core symptoms and emotional dysregulation of ADHD. But it is important to note that, in clinical practice, we treat more than the core symptoms - ADHD is complicated by several psychiatric disorders such as anxiety and depression. It makes sense that these complications would not respond to psychostimulants as robustly. These findings reinforce the importance of treatment with psychostimulants for ADHD, with impact within 12 weeks. It does not rule out non-pharmacological interventions as being of value to the complications of this prevalent disorder.

This study systematically reviewed and meta-analysed over a hundred clinical trials of attention-deficit/hyperactivity disorder (ADHD) treatments, which collectively involved almost 15,000 adult participants (all over the age of 18 years; studies in children were excluded). The study identifies specific treatments for ADHD which were effective in reducing core symptoms of this complex and heterogeneous brain disorder.

Some treatments were found to be effective (in the combined ‘network meta-analysis’) on both clinician-reported and self-reported measures, whereas others were only effective on self-reported measures. However, even those treatments that were effective for core symptoms did not show significant benefits in ‘quality of life’ measures.

As David Coghill noted in his associated Lancet Psychiatry commentary article, it is extremely challenging for clinicians to know ‘how best to balance the merits of pharmacological and non-pharmacological approaches’ and that different types of clinical trials differ in ways that make them very difficult to compare directly (in such a meta-analysis).

So the key message for mental health clinicians and researchers is that some existing treatments are effective, but we could do much better in making them more effective, with fewer side effects. The ideal we are striving for in ongoing research is ‘precision psychiatry’ (as part of ‘precision medicine’) where treatment is tailored to the individual based not only on their symptoms but also biological ‘markers’. This requires much more research to understand the causes of ADHD and identify new approaches for novel therapies.

With the growing number of people seeking a diagnosis of ADHD in adulthood in Aotearoa, and potentially 5% of the adult population struggling with ADHD, it is important to conduct regular reviews and meta-analysis on the current state of treatment choices.

Not surprisingly, this review focused primarily on medications, but also reviewed some nonpharmacological interventions such as psychological therapies, neurofeedback, and nonstimulatory therapies. Stimulants and atomoxetine were identified as the most efficacious treatment in the short-term for ADHD symptoms. This is not surprising as this has been the common theme over the last 30 years in the child literature. It was also highlighted that stimulants are not as effective with adults as they are with children, again a well-known observation reconfirmed with this report. However, there was acknowledgement that there is a paucity of studies that investigate effectiveness of these interventions long-term. Given that people with ADHD typically take these medications long-term, it is a crucial aspect of treatment that is overlooked by studies and makes it more challenging for prescribers to make decisions about extending scripts past 12 weeks.

This review highlighted that medications and cognitive training have no effect on executive function. This is consistent with observations of children showing stimulants, despite improving focus, do not necessarily improve academic outcomes. Is the same true for the workplace? Are these medications having a positive effect long-term on work performance? We simply don’t know. We clearly need research into novel interventions that might significantly support these essential capabilities.

I was surprised that lifestyle interventions, such as physical exercise, diet and nutrients, were not identified in the search and completely excluded from the analyses. There is no reason stated in the main text for these exclusions.

The acknowledgment that treatment of just ADHD symptoms is not sufficient to improve quality of life was appreciated. People with ADHD are more than just ADHD symptoms – they can often struggle in other aspects of life, like challenges with regulating emotions, and sometimes those symptoms are more impairing. ADHD in adulthood can be chronic and so dedicating research funds to investigate treatments that also can improve the co-occurring challenges and improve quality of life is essential.

Finally, the inclusion of people with lived experience was original and refreshing. Clinicians and researchers can so often think that they know best on what measures are most effective at capturing change and I appreciated the value that this angle added to the discussion. Those with lived experience highlighted the strong pull of the “Hawthorne effect” that can plague so many clinical trials – that is, when you know you are being observed, your responses of benefit are different than when you are not being observed. This is an impossible dilemma to address in clinical trials; however, it does encourage cautious interpretation of efficacy obtained from clinical trials as they are very likely to be overinflated.