What's the best treatment for ADHD? Large new study offers clues

A new study has investigated how different medications and therapies compare with placebos in treating ADHD symptoms. (Kobus Louw/E+/Getty Images via CNN Newsource)

Attention deficit hyperactivity disorder, or ADHD, was long thought to be a disorder that only affected children. But now it’s well established that the symptoms can persist into adulthood — and a large new study has assessed which treatments may be most effective at alleviating them.

Stimulant medications, and atomoxetine (a type of antidepressant), were more effective than placebos at reducing core ADHD symptoms during a 12-week period, found the study published Tuesday in the journal Lancet Psychiatry. Core symptoms of the neurodevelopmental disorder are inattention, hyperactivity and impulsivity, said study author Dr. Samuele Cortese, professor of child and adolescent psychiatry at the University of Southampton in England, in a Tuesday press briefing hosted by the Science Media Centre.

Prior to conducting this study, Cortese and several other study authors had various types of affiliations — such as for consulting or research — with pharmaceutical companies, some of which manufacture ADHD medications. But the affiliations had no bearing on any aspect of the research, according to the study.

Cortese said about 5 per cent to 7 per cent of children and 2.5 per cent of adults worldwide have ADHD, which stems from underdeveloped or impaired executive function and self-regulation skills, according to Harvard University’s Center on the Developing Child. Those skills help people plan, focus attention, remember instructions, multitask and more. The symptoms of inattention, hyperactivity and impulsivity mean people with ADHD may have trouble staying organized, concentrating, managing time or controlling impulses, which can affect all areas of life.

A health care provider determines a diagnosis by assessing whether symptoms are persistent, pervasive and inappropriate according to one’s developmental stage, and whether they interfere with a patient’s daily life. The disorder can also be associated with various additional challenges, such as mental or physical conditions, social problems and a higher risk of premature death.

“It’s a serious condition. It’s not a trivial one,” Cortese, also chair of the European ADHD Guidelines Group, said.

“If you look at the current guidelines on the management of ADHD in the U.K.,” Cortese said, “they recommend medication as the first line. They also mention non-pharmacological treatment if medication is not effective or not well tolerated, but they don’t specify which kind of non-pharmacological treatment. They also mention the possible combination.”

There are still uncertainties about the best treatment for adults with ADHD, Cortese said — so he and the other authors aimed “to provide an updated synthesis of all the evidence available from trials on the pharmacological and nonpharmacological interventions.” The research was done in association with people with lived experience of ADHD, the authors said.

Assessing ADHD treatments

The study is a systematic review and meta-analysis of 113 published and unpublished randomized controlled trials that compared various types of interventions against placebos or other controls for the symptoms of, in total, nearly 14,900 adult participants formally diagnosed with ADHD.

In a short-term period of 12 weeks, in ratings of symptom improvement by both clinicians and patients, only stimulants, such as lisdexamfetamine and methylphenidate, and atomoxetine yielded better results than a placebo.

When it came to the effectiveness of nonpharmacological treatments versus a placebo, there was a mismatch between clinicians’ opinions versus those of the patients themselves. Cognitive behavioural therapy, cognitive remediation, mindfulness, psychoeducation and transcranial direct current stimulation were also more effective than a placebo at reducing patients’ symptoms, but this outcome was reported by clinicians only.

Transcranial direct current stimulation is a noninvasive, painless brain stimulation technique that uses low-intensity electrical currents to stimulate specific parts of the brain.

The authors found several other outcomes, including that medications were more likely than placebos to be discontinued due to adverse events. For emotional dysregulation, which Cortese said many people with ADHD experience, atomoxetine and stimulants were more helpful than a placebo. But for executive function and quality of life, none of the treatments performed differently than a placebo.

“There are several take home points from this study, which used a very clever approach to pool and contrast different types of ADHD treatments,” said Dr. Philip Shaw, professor in the Institute of Psychiatry, Psychology & Neuroscience at King’s College London, in a statement to the Science Media Centre.

“First, the study shows that there are effective interventions for adults living with ADHD who are looking for ways to reduce any unwanted impact from symptoms,” said Shaw, who wasn’t involved in the research. “The downside was that some medications had troublesome side effects, though this wasn’t the case for psychostimulants, which are the most widely used medication.”

The study also highlights “big gaps in our knowledge,” he said.

Advancing research on adult ADHD

The limitations of the study are due to shortcomings in the literature analyzed for the review, as well as the lack of research on some factors, said clinical psychologist Dr. Margaret Sibley, professor of psychiatry and behavioural sciences at the University of Washington School of Medicine. Sibley wasn’t involved in the study.

Since most of the treatment trials included in the review lasted less than three months, it’s hard to be sure about how long the benefits may last, Shaw said. The authors also looked at outcomes at 26 and 52 weeks, but these were limited due to an insufficient amount of data, said study author Dr. Edoardo G. Ostinelli, senior researcher and deputy lead at the University of Oxford’s Oxford Precision Psychiatry Lab, in the Science Media Centre briefing.

However, “non-pharmacological treatments like (cognitive behavioural therapy) are not designed to reduce core symptoms of ADHD, although they sometimes do indirectly,” Sibley said via email. “They are designed to teach coping skills to reduce the impact of symptoms on one’s life. So if the primary outcome in this review had been impairment or ADHD coping skills, or psychological variables like self-worth or self-efficacy or sense of autonomy — you might have seen different findings.”

It’s also likely that differences in effectiveness of treatments simply boil down to the fact that one size doesn’t fit all, Ostinelli said.

Some people with ADHD are apprehensive about taking medication or have experienced side effects they are uncomfortable with, said Dr. Alessio Bellato, a lecturer in child and adolescent mental health at the University of Southampton who wasn’t involved in the study.

“The review also points out a continual challenge when conducting ADHD research with adults,” Sibley added. “Self-perception of ADHD symptoms is fallible in all people. They are somewhat subjective symptoms. However, there are no ‘objective’ tests that can accurately measure ADHD symptoms. Best practice is actually to use informant reports (i.e., reports of loved ones) in combination with self-report when assessing adult ADHD.”

These reports are sometimes integrated with clinician reports to make a final determination of whether a symptom is present, but most treatment studies don’t use this strategy, which can lead to unclear findings in research studies, she added.

All considered, because people with ADHD usually seek treatment with the hope of improving more than just core symptoms, best practice in adult ADHD treatment typically includes both pharmacological and non-pharmacological care, Sibley said — a combination the study did not have data for, but one that can “help people take control of their ADHD and learn to write their own owner’s manual as they craft a life that works for them.”

The study reflects the need for more long-term studies on various types of treatments and combinations of them, especially among adults, experts said.