Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by a persistent pattern of inattention, hyperactivity-impulsivity, or both. It is estimated to affect around 5% of school-aged children, with impairing symptoms persisting into adulthood in up to 75% of people. ADHD often co-occurs with other disorders, including:
Challenges in the Treatment of ADHD
Living with ADHD as an adult can bring daily challenges related to inattention, hyperactivity, and impulsivity. Managing these core symptoms often involves weighing the options between medications, psychological therapies, and other non-drug interventions.
While medications are often helpful, some patients may find that they are ineffective and/or not well tolerated, or some individuals may find it difficult to adhere to medication requirements.
In addition, concerns about the safety of some medications, including their possible cardiovascular effects, have contributed to an increased interest in non-pharmacological treatments. Therefore, gaining insight into the efficacy and safety of both non-pharmacological and pharmacological interventions for ADHD in adults remains crucial.
In a recent study, researchers conducted a systematic review and component network analysis to compare the short-term efficacy and acceptability of all available treatment types. This approach allowed researchers to directly compare treatments that were never tested head-to-head in a single trial, providing the most robust evidence base to date.
Overview of the Study
Researchers searched multiple databases for published and unpublished randomised controlled trials (RCTs) investigating pharmacological and non-pharmacological interventions for ADHD in adults from database inception to 26 September 2023. Data from RCTs comparing interventions against controls or any other eligible active intervention were included in the review.
The review included eligible RCTs which:
- Had at least a 1-week duration for medications;
- At least four sessions for psychological therapies;
- Any length deemed appropriate for neurostimulation.
For RCTs of medications, cognitive training, or neurostimulation alone, the researchers included only double-blind RCTs.
Primary outcomes of the review were:
- Efficacy: Change in ADHD core symptom severity on self-rated and clinician-rated scales at timepoints closest to 12 weeks.
- Acceptability: All-cause discontinuation of treatment.
Secondary outcomes were:
- Severity of ADHD core symptoms according to self-rated and clinician-rated scales at timepoints closest to 26 weeks and 52 weeks.
- Tolerability: Proportion of participants discontinuing treatment due to adverse events.
- Severity of emotional dysregulation.
- Severity of executive function.
- Quality of life.
Key Findings of the Study
A total of 113 unique RCTs involving nearly 15,000 adults were eligible for analysis. The RCTs encompassed pharmacological therapies (n = 63; 6,875 participants), psychological therapies (n = 28; 1,116 participants), neurostimulatory therapy and neurofeedback (n = 10; 194 participants), and control conditions (n = 97; 5,770 participants).
Short-Term Efficacy: Reducing Core ADHD Symptoms
When examining the impact of interventions on reducing core ADHD symptoms in the short term (approximately 12 weeks), researchers tracked results reported by both the patient (self-rated) and the clinician (clinician-rated).
- Stimulants and Atomoxetine: These were the only two interventions that showed a beneficial effect, performing better than placebo on both self-reported and clinician-reported rating scales.
- Psychological and Neurostimulatory Therapies: Several non-pharmacological components, including cognitive behavioural therapy (CBT), cognitive remediation, mindfulness, psychoeducation, and transcranial direct current stimulation (tDCS), performed better than placebo. However, this evidence was supported only by clinician-reported scales. Their beneficial effects were not supported by the patients’ own self-reported symptom ratings.
- All Other Interventions: For the remaining active therapeutic components tested, the study did not find evidence of a statistically significant difference compared with placebo for either clinician-reported or self-reported rating scales.
Short-Term Acceptability and Side Effects
Acceptability was measured by all-cause discontinuation, defined as the rate at which participants stopped treatment for any reason:
- Stimulants and Non-Drug Therapies: Most therapeutic components, including stimulants and the various psychological and neurostimulatory interventions, were found to have an acceptability profile similar to that of placebo.
- Less Acceptable Treatments: The exceptions were atomoxetine and guanfacine, both of which were found to be less acceptable than placebo (meaning participants were more likely to discontinue them).
- Discontinuation due to Adverse Events: Atomoxetine, guanfacine, modafinil, and stimulants were all associated with higher rates of discontinuation compared with placebo.
Longer-Term Effects and Quality of Life
The study found a major gap in the available evidence regarding the long-term effects of all treatments:
- Longer-Term Efficacy: Very few studies were available for timepoints closer to 26 weeks and even fewer for 52 weeks. Some non-drug therapies (CBT, neurofeedback, and relaxation therapy) did show beneficial effects on self-reported symptoms at 52 weeks, but this was based on a very small body of evidence.
- Quality of Life: None of the available interventions, pharmacological or otherwise, showed evidence of significantly improving quality of life in the short term (12 weeks). This is an outcome that is highly important to people with ADHD, suggesting a need for a broader focus in future research.
Interpreting the Findings
This extensive review provides the current best evidence to inform treatment discussions for ADHD in adults.
- For the short-term reduction of core ADHD symptoms, stimulants and atomoxetine are the only interventions supported by both patient and clinician ratings.
- However, considering both effectiveness and acceptability, stimulants had a more favourable profile than atomoxetine, which was associated with higher discontinuation rates.
- The discrepancy between patient and clinician ratings for non-drug therapies suggests that these treatments may be having beneficial effects that are easier for an objective observer to notice, but they may not be translating immediately into a patient’s perception of their core symptoms.
- Crucially, the lack of long-term data on efficacy, tolerability, and improvement in broader outcomes like quality of life means that clinical decisions must be made by carefully weighing the short-term benefits and harms in a shared decision-making process.
This study underscores the urgent need for more long-term research on all available treatment options, including alternative medications and combinations of therapies, to better inform the long-term care of adults with ADHD.
