In a comprehensive analysis of more than 100 clinical trials involving nearly 15,000 adults, researcher have found that there's one clear path to improving symptoms of attention-deficit/hyperactivity disorder (ADHD) – but even then it's not all good news.
A network meta-analysis (NMA) by the University of Oxford's Department of Psychiatry at Warneford Hospital, co-designed by a panel of people with lived experience of ADHD, has found that only stimulants, and to a lesser degree the norepinephrine reuptake inhibitor atomoxetine, are effective in treating core symptoms in the short-term.
"To our knowledge, this is the first component NMA on ADHD in adults that jointly synthesises comparative effects for pharmacological, psychological, and neurostimulatory interventions within a single network," the researchers wrote. "Our study is also, to our knowledge, the first study to provide comparative meta-analytic evidence showing that stimulants and atomoxetine, among all available pharmacological and nonpharmacological interventions for ADHD, are the only ones to be rated as efficacious in terms of ADHD core symptoms according to both self-reported and clinician-reported scales."
In the first 12 weeks, or in the short term, non-pharmacological treatments – cognitive behavioral therapy, relaxation therapy and dialectical behavioral therapy – had little benefit.
A NMA, which differs from a meta-analysis in that it compares multiple treatments at once, is considered a more robust method of determining a specific outcome – in this case, what ADHD treatment shows the most benefit, considering both clinician assessment and self-reported data. And stimulants had a significant impact on reducing core symptoms on both self-reported and clinician-reported scales after 12 weeks.
Only stimulants demonstrated efficacy for emotional dysregulation, a complex but common ADHD symptom, over short and long terms. Emotional dysregulation has traditionally been overlooked as one of the most debilitating aspects of ADHD and has resulted in people being misdiagnosed with conditions like depression and anxiety. However, the data also suggests that even these drugs didn't help people with ADHD better manage other challenges such as poor executive function – even though this is closely related to emotional dysregulation.
"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," noted Dr Hannah Kirk from Monash University. "Adults with ADHD face challenges that extend beyond core symptoms, highlighting the need for treatments and trials that address functional and emotional well-being."
This was echoed by Julia Rucklidge, a professor of clinical psychology at the University of Canterbury, who highlighted the fact that executive function – which impacts an individual's ability to stay organized, be on time, remember appointments and instructions, meet deadlines and finish tasks – is not improved by any existing ADHD treatments.
"This is consistent with observations of children showing stimulants, despite improving focus, do not necessarily improve academic outcomes," she said. "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.
"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," she added. "ADHD in adulthood can be chronic, so dedicating research funds to investigate treatments that also can improve the co-occurring challenges and improve quality of life is essential."
While non-pharmacological therapies were shown to have some benefits on the clinician-reported scale, not on the self-reported scale, these therapies also lack robust evidence, so we don't yet have a clear picture of what their long-term usefulness might be.
"The findings highlight that stimulant mediation, the most acceptable pharmacological treatment, decreases ADHD symptoms but does not take all ADHD-related challenges away," said Louise Brown, also from Monash University. "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 (ie, hope; an understanding of personal strengths and limitations; self-determination; personalized 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."
Despite this study being the most comprehensive of its kind to date, it highlights some massive gaps in research into adult ADHD. It also groups stimulants into one category, which doesn't factor in varying tolerability and the differences in short- and long-acting drugs.
"Less is known about adult ADHD than childhood ADHD, and whether both conditions respond to treatment with the same types of treatment," said Ashley Bush a professor at The University of Melbourne. "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."
So what does this study tell us? Well, much more research is needed, and that while treating core symptoms is a priority for clinicians, adult ADHD most likely requires a more holistic approach to address broader challenges that impact an individual's quality of life.
"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," said Anthony Hannan, a professor at the Florey Institute of Neuroscience and Mental Health. "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."
Despite its noted failings, this study highlights the need to improve research and treatment for adults with ADHD. A recent report found that people in the UK were waiting up to 10 years to get a clinical diagnosis and treatment. And the findings of an Australian senate inquiry into adult ADHD found that a lack of services, support, the high cost of diagnosis and stigma surrounding stimulants continued to fail the estimated one million Australians living with the condition.
"Our study provides the most comprehensive comparative evidence on the effects of pharmacological and nonpharmacological therapies for ADHD in adults to date," the researchers noted. "Clinical decision making should be based on a careful weighing of benefits and harms, considering the findings from this NMA and other sources of evidence. Overall, further longer-term studies on alternative medications, non-pharmacological strategies, and their combinations available to date are needed to better inform the care of ADHD in adults."
The study was published in the journal The Lancet.
Source: University of Oxford via Scimex
