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Stimulant medications have long been considered the default first-line treatment for attention-deficit/hyperactivity disorder (ADHD). Clinical guidelines, prescribing practices, and public narratives all reinforce the idea that stimulants should be tried first, with non-stimulants reserved for cases where stimulants fail or are poorly tolerated.
I recently partnered with leading ADHD researcher Jeffrey Newcorn for a Nature Mental Health commentary on the subject. We argue that this hierarchy deserves reexamination. It is important to note that our position is not anti-stimulant. Rather, we call into question whether the evidence truly supports treating non-stimulants as secondary options, and we propose that both classes should be considered equal first-line treatments.
Stimulants have earned their reputation as the go-to drug of choice for ADHD. They are among the most effective medications in psychiatry, reliably reducing core ADHD symptoms and improving daily functioning when properly titrated and monitored. However, when stimulant and non-stimulant medications are compared more closely, the gap between them appears smaller than commonly assumed.
Meta-analyses often report slightly higher average response rates for stimulants, but head-to-head trials where patients are directly randomized to one medication versus another frequently find no statistically significant differences in symptom improvement or tolerability. Network meta-analyses similarly show that while some stimulant formulations have modest advantages, these differences are small and inconsistent, particularly in adults.
When translated into clinical terms, the advantage of stimulants becomes even more modest. Based on existing data, approximately eight patients would need to be treated with a stimulant rather than a non-stimulant for one additional person to experience a meaningful benefit. This corresponds to only a 56% probability that a given patient will respond better to a stimulant than to a non-stimulant. This difference is not what we would refer to as “clinically significant.”
One reason non-stimulants may appear less effective is the way efficacy is typically reported. Most comparisons rely on standardized mean differences, a method of averages that may mask heterogeneity of treatment effects. In reality, ADHD medications do not work uniformly across patients.
For example, evidence suggests that response to some non-stimulants, such as atomoxetine, is bimodal: this means that many patients respond extremely well, while others respond poorly, with few in between. When this happens, average effect sizes can obscure the fact that a substantial subgroup benefits just as much as they would from a stimulant. In other words, non-stimulants are not necessarily less effective across the board, but that they are simply different in who they help.
In our commentary, we also highlight structural issues in ADHD research. Stimulant trials are particularly vulnerable to unblinding, as their immediate and observable physiological effects can reveal treatment assignment, potentially inflating perceived efficacy. Non-stimulants, with slower onset and subtler effects, are less prone to this bias.
Additionally, many randomized trials exclude patients with common psychiatric comorbidities such as anxiety, depression, or substance-use disorders. Using co-diagnoses as exclusion criteria for clinical trials on ADHD medications is nonviable when considering the large number of ADHD patients who also have other diagnoses. Real-world data suggest that a large proportion of individuals with ADHD would not qualify for typical trials, limiting how well results generalize to everyday clinical practice.
Standard evaluations of medication tolerability focus on side effects experienced by patients, but this narrow lens misses broader societal consequences. Stimulants are Schedule II controlled substances, which introduces logistical barriers, regulatory burdens, supply vulnerabilities, and administrative strain for both patients and clinicians.
When used as directed, stimulant medications do not increase risk of substance-use disorders (and, in fact, tend to reduce these rates); however, as ADHD awareness has spread and stimulants are more widely prescribed, non-medical use of prescription stimulants has become more widespread, particularly among adolescents and young adults. Non-stimulants do not carry these risks.
Non-stimulants are not without drawbacks themselves, however. They typically take longer to work and have higher non-response rates, making them less suitable in situations where rapid results are essential. These limitations, however, do not justify relegating them to second-line status across the board.
This is a call for abandoning a one-size-fits-all approach. Instead, future guidelines should present stimulant and non-stimulant medications as equally valid starting points, clearly outlining trade-offs related to onset, efficacy, misuse risk, and practical burden.
The evidence already supports this shift. The remaining challenge is aligning clinical practice and policy with what the data, and patient-centered care, are increasingly telling us.
Swedish researchers examined outcomes for adult women who sought treatment at the Stockholm Center for Eating Disorders over two years and nine months. Out of 1,517 women who came to the clinic, 1,143remained eligible for the study, after excluding women whose symptoms did not fulfill the DSM-IV criteria for eating disorders or had incomplete records.
Of these, seven hundred patients could not be reached or declined to participate, leaving 443 for follow-up. To guard against the possibility that the follow-up group might not be representative of the overall treatment group, researchers compared to age, body mass index, and scores on tests for depression, anxiety, compulsively, inattention, and hyperactivity. The only statistically significant differences were small ones. The median age of the group lost to follow-up was one year younger, they were less likely to be living alone, and on average scored a single point higher on the depression test. Otherwise, they were broadly similar.
The one-year follow-up on the study group found a substantial difference in the rate of recovery from eating disorders between those with and without comorbid ADHD. Almost three out of four patients (72%) who scored lower (between 0-17) on the World Health Organization adult ADHD self-report scale had recovered from their eating disorder. Among those scoring18 and higher, on the other hand, it was less than half (47%). This difference was extraordinarily unlikely (one chance in one thousand) to be due to chance(p=.001).
Another way of expressing this is through odds ratios. Those scoring 18 and up on the ADHD self-report scale were about two and a half times less likely to recover from their eating disorders following treatment. More specifically, thy were about three times less likely to recover from the loss of control and binging, and almost three and a half times less likely to recover from purging.
To improve outcomes, the researchers suggest "identifying concomitant ADHD symptoms and customizing treatment interventions based on this." They specifically propose controlled clinical trials to explore the effect of combining stimulant medications with standard treatment for eating disorders
A Dutch study compared the efficacy of mindfulness-based cognitive therapy (MBCT) combined with treatment as usual (TAU), with TAU-only as the control group. MBCT consisted of an eight-week group therapy consisting of meditation exercises (body scan, sitting meditation, mindful movement), psychoeducation about ADHD, and group exercises. TAU consisted of usual treatment in the Netherlands, including medications and other psychological treatments. Sixty individuals were randomly assigned to each group. MBCT was taught in subgroups of 8 to 12 individuals. Patients assigned to TAU were not brought together in small groups. Baseline demographic and clinical characteristics were closely matched for both groups.
Outcomes were evaluated at the start, immediately following treatment, and again after 3 and 6 months using well-validated rating scales. Following treatment, the MBCT + TAU group outperformed the TAU group by an average of 3.4points on the Conner's Adult Rating Scale, corresponding to a standardized mean difference of .41. Thirty-one percent of the MBCT + TAU group made significant gains, versus 5% of the TAU group. 27% of MBCT +TAU patients scored a symptom reduction of at least 30 percent, as opposed to only 4% of TAU patients. Three and six-month follow-up effects were stable, with an effect size of .43.
The authors concluded, "that MBCT has significant benefits to adults with ADHD up to 6 months after post-treatment, about both ADHD symptoms and positive outcomes." Yet in their section on limitations, they overlook a potentially important one. There was no active placebo control. Those who were undergoing TAU-only were aware that they were not doing anything different from what they had been doing before the study. Hence, no substantial placebo response would be expected from this group during the intervention period (post-treatment they were offered an opportunity to undergo MBCT). Moreover, MBCT + TAU participants were gathered into small groups, whereas TAU participants were not. We, therefore, have no way of knowing what effect group interaction had on the outcomes because it was not controlled for. So, although these results are intriguing and suggest that further research is worthwhile, the work is not sufficiently rigorous to definitively conclude that MBCT should be prescribed for adults with ADHD.
Though there have been numerous studies on the efficacy of cognitive-behavioral therapy (CBT) for ADHD symptoms in children, adolescents, and adults, few have examined efficacy among adults over 50. A new study begins to fill that void.
Psychiatric researchers from the New York University School of Medicine, Massachusetts General Hospital, and Pfizer randomly assigned 88 adults diagnosed with elevated levels of ADHD to one of two groups. The first group received 12 weeks of CBT targeting executive dysfunction - a deficiency in the ability to properly analyze, plan, organize, schedule, and complete tasks. The second group was assigned to a support group, intended to serve as a control for any effects arising from participating in group therapy. Each group was split into subgroups of six to eight participants. One of the CBT subgroups was run concurrently with one of the support-only subgroups and matched on the percent receiving ADHD medications.
Outcomes were obtained for 26 adults aged 50 or older (12 in CBT and 14 in support) and compared with 55 younger adults (29 in CBT and 26 in support). The mean age of the younger group was 35 and of the older group 56. Roughly half of the older group, and 3/5ths of the younger group, were on medication. Independent("blinded") clinicians rated symptoms of ADHD before and after treatment.
In the blind structured interview, both inattentive scores and executive function scores improved significantly and almost identically for both older and younger adults following CBT. When compared with the controls(support groups), however, there was a marked divergence. In younger adults, CBT groups significantly outperformed support groups, with mean relative score improvements of 3.7 for inattentive symptoms and 2.9 for executive functioning. In older adults, however, the relative score improvements were only 1.1 and0.9 and were not statistically significant.
Given the non-significant improvements over placebo, the authors' conclusion that "The results provide preliminary evidence that CBT is an effective intervention for older adults with ADHD" is premature. As they note, a similar large placebo effect was seen in adults over 50 in a meta-analysis of CBT for depression, rendering the outcomes non-significant. Perhaps structured human contact is the key ingredient in this age group. It may also be, as suggested by the positive relative gains on six of seven measures, that CBT has a small net benefit over placebo, which cannot be validated with such a small sample size. Awaiting results from studies with larger sample sizes, it is, for now, impossible to reach any definitive conclusions about the efficacy of CBT for treating adults over 50.

A two-year study examined the effect of digital media use on ADHD symptoms in over 2500 adolescents. An earlier meta-analysis found that traditional media use (TV and video console games) was modestly associated with ADHD-like behaviors (Nikkelen et al 2014). The current study extends the examination to a large sample, with modern digital media delivery of high-intensity stimuli, including mobile platforms.
The authors used the Current Symptom Self-Report Scale (Barkley R 1998) to establish ADHD symptoms at baseline and six-month assessments over 24 months. None of the subjects reported having ADHD, study entry. Subjects were considered to be ADHD symptom-positive (the primary binary outcome) if they had greater than or equal to six inattentive and/or hyperactive-impulsive symptoms rated on this frequency-based scale (0-3). Modern digital media use was surveyed on a frequency basis for 14 media activities(including checking social media sites, texting, browsing, downloading or streaming music, posting pictures, online chatting, playing games, online shopping, and video chatting). The most common media activity was the high-frequency checking of social media. Of note, high-frequency engagement in each of the digital media activities was significantly, but moderately, associated with having ADHD symptoms at each six-month follow-up (OR 1.10), even after adjusting for covariates. High-frequency media use at baseline seemed to be associated with the development of ADHD symptoms.
Among the 495 students who reported no high-frequency media use at baseline, 4.6% met ADHD symptom criteria at follow-up. Among 114 students scoring 7 for high-frequency media use at baseline, 9.5% met the symptoms criteria. For the 51 students with a score of 14 for high-frequency media use at baseline, the rate was 10.5% (both comparisons were statistically significant).
This study is important in that it notes that an association between high-frequency digital media use (in current platforms and modalities) may be associated with the development of ADHD-like symptoms. A significant limitation of the study, as noted by the authors, is that ADHD-like symptoms do not establish a diagnosis of ADHD and do not assess impairment; therefore, these results must be interpreted with some caution. It does highlight that even with the current level of understanding, it might be prudent for clinicians to recommend limiting high-frequency media use for adolescent patients.
An international group of twelve experts recently published a consensus report examining the state of the evidence and offering recommendations to guide the screening, diagnosis, and treatment of individuals with ADHD-SUD comorbidity.[1]
In a clear sign that we are still in the early stages of understanding this relationship, five of the thirteen recommendations received the lowest recommendation grade (D), eight received the next-lowest (C), and none received the highest (A and B). The lower grades reflected the absence of the highest level of evidence, obtained from meta-analyses or systematic reviews of relevant randomized controlled trials (RCTs).
Nevertheless, with these limitations in mind, the experts agreed on the following points:
Diagnosis
Treatmen
The grade C recommendations included considering adequate medical treatment of both ADHD and SUD; integrating ADHD treatment with SUD treatment as soon as possible;
To what extent are ADHD medications insufficiently used to address properly diagnosed ADHD? To what extent are they misused by persons who are either undiagnosed or improperly diagnosed? In search of answers, an international team of researchers from Brazil, the United Kingdom, and the United States conducted a systematic review of the peer-reviewed literature and a meta-analysis of studies from four continents - South America, North America, Europe, and Australia.
The benchmarks set for proper ADHD diagnosis were any of the following:
· Criteria established in the Diagnostic and Statistical Manual of Mental Disorders (DSM)or the International Statistical Classification of Diseases and Related Health Problems (ICD), confirmed by validated diagnostic instruments or clinical interviews.
· Use of validated ADHD symptom scales with pre-specified thresholds.
· Participants or caregivers affirming ADHD diagnosis by a physician.
Medications reviewed were those recommended by the majority of the international guidelines-both stimulant(methylphenidate, dexmethylphenidate, amphetamines), and non-stimulant (atomoxetine).
The team excluded studies relying on the insurance health system and third-party reimbursement datasets because the focus was on rates of ADHD medication use in the entire population rather than among individuals searching for treatment.
A meta-analysis of 18 studies with a total of 3,311 children and adolescents properly diagnosed with ADHD in seven countries on four continents (Canada, United States, Australia, Brazil, Netherlands, England, Venezuela) found an overall pharmacological treatment rate of only 19%. There was considerable variation, with the highest treatment rates in the United States (frequently over 40%) and the lowest treatment rates in Brazil, Venezuela, and Canada (under 10%). There was no sign of publication bias.
A second meta-analysis pooled 14 studies with a total of 29,559 children and adolescents without a proper diagnosis of ADHD in five countries on four continents (United States, Canada, Venezuela, Australia, Netherlands). Roughly 1% were using ADHD medications. Again, there was considerable variation, with the highest rates of medication misuse being reported in the United States and Venezuela (3-7%). Again, there was no sign of publication bias.
The authors cautioned, "it is important to note that even though the data collected constitute the most comprehensive evidence available in the literature and response/completion rates observed are acceptable, it does not constitute a world representative sample." Also, the predominance of samples from prosperous countries "most certainly inflates the treatment rates due to the exclusion of a large proportion of the world population with significant financial, cultural, and health access barriers to ADHD treatment."
They concluded, "Despite these limitations, our meta-analysis provides evidence for substantial under-treatment of children and adolescents affected by ADHD in different countries. This is a relevant public health issue worldwide since ADHD under treatment is associated with known negative outcomes in education, healthcare, and productivity systems. At the same time, we found evidence of overtreatment/misuse in individuals without a formal ADHD diagnosis. This practice might expose individuals to undesirable side effects of medications, increased risk of medication misuse, and unmeasured costs for the health care system."

It sounds like science fiction, but scientists have been testing computerized methods to train the brains of ADHD people to reduce both ADHD symptoms and cognitive deficits such as difficulties with memory or attention.
Two main approaches have been used: cognitive training and neurofeedback. Cognitive training methods ask patients to practice tasks aimed at teaching specific skills, such as retaining information in memory or inhibiting impulsive responses.
Currently, results from ADHD brain studies suggest that the ADHD brain is not very different from the non-ADHD brain, but that ADHD leads to small differences in the structure, organization, and functioning of the brain. The idea behind cognitive training is that the brain can be reorganized to accomplish tasks through a structured learning process. Cognitive retraining helps people who have suffered brain damage, so it was logical to think it might help the types of brain differences seen in ADHD people. Several software packages have been created to deliver cognitive training sessions to ADHD people.
Neurofeedback was applied to ADHD after it had been observed, in many studies, that people with ADHD have unusual brain waves as measured by the electroencephalogram (EEG). We believe that these unusual brain waves are caused by the different ways that the ADHD brain processes information. Because these differences lead to problems with memory, attention, inhibiting responses, and other areas of cognition and behavior, it was believed that normalizing the brain waves might reduce ADHD symptoms.
In a neurofeedback session, patients sit with a computer that reads their brain waves via wires connected to their heads. The patient is asked to do a task on the computer that is known to produce a specific type of brain wave. The computer gives feedback via sound or a visual on the computer screen that tells the patient how 'normal' their brainwaves are. By modifying their behavior, patients learn to change their brain waves. The method is called neurofeedback because it gives patients direct feedback about how their brains are processing information.
Both cognitive training and neurofeedback have been extensively studied. If you've been reading my blogs about ADHD, you know that I play by the rules of evidence-based medicine. My view is that the only way to be sure that a treatment works is to see what researchers have published in scientific journals. The highest level of evidence is a meta-analysis of randomized controlled clinical trials. This ensures that many rigorous studies have been conducted and summarized with a sophisticated mathematical method.
Although both cognitive training and neurofeedback are rational methods based on good science, meta-analyses suggest that they do not help reduce ADHD symptoms. They may be helpful for specific problems, such as problems with memory, but more work is needed to be certain if that is true. The future may bring better news about these methods if they are modified and become more effective. You can learn more about non-pharmacologic treatment for ADHD from a book I recently edited: Faraone, S. V. &Antshel, K. M. (2014). ADHD: Non-Pharmacologic Interventions. Child Adolesc Psychiatr Clin N Am 23, xiii-xiv.
Adults with ADHD are more likely to have accidents, drive unsafely, have unsafe sex, and abuse substances. These 'real world' impairments suggest that people with ADHD may be predisposed to making risky decisions. Many studies have attempted to address this, but it is only recently that their results have been aggregated into a systematic review and meta-analysis. This paper by Dekkers and colleagues reports 37 laboratory studies of risky decision-making that studied a total of 1175 ADHD patients and 1222 controls. In these laboratory tasks, research participants are given a task to complete which requires that they make choices that have varying degrees of risk and reward. Using the results of such experiments, researchers can score the degree to which participants make risky decisions. When Dekkers and colleagues analyzed the 37 studies together, they found substantial evidence that ADHD people are more likely to make risky decisions than people without ADHD. The tendency to make risky decisions was greatest for those who, in addition to having ADHD, also had conduct or oppositional disorders, which both have features that indicate antisocial behavior and aggressiveness. We can not tell from these studies why ADHD patients make risky decisions. One explanation is that it is simply the impulsivity of ADHD people that leads to rash, unwise decisions. Another theory postulates that risky decisions reflect deficits in one's sensitivity to rewards and punishments. If we are very motivated by reward and not aware of or affected by the possibility of punishment, then risky decisions will be common. The studies analyzed in the meta-analysis were not designed to demonstrate a link between risky decision-making in the lab and the real world, risky decisions that lead to accidents, and other outcomes. It is reasonable to hypothesize such a link, which is why clinicians should consider risky decision-making when planning treatments. If you suspect deficits in this area, it will not change your approach to pharmacologic treatment but, given the potential adverse consequences of risky decisions, you should consider referring such patients to cognitive behavior therapy for adult ADHD as this talk therapy may be able to teach ADHD adults how to cope with their decision-making deficits.
Professor Larry Seidman is world-renowned for his neuropsychology and neuroimaging research. In addition to all of his creative science, he has found the time to create what he calls "Neuropsychological Informed Strategic Psychotherapy (NISP)in Teenagers and Adults with ADHD."
Let's start with what NISP is not. NISP is not cognitive behavior therapy (CBT). CBT emphasizes teaching patients to identify thinking patterns that lead to problem behaviors. NISP describes how the interpersonal interaction we call psychotherapy can help patients increase self-regulation and self-control. NISP treatments vary in duration from brief psycho-educational interventions of one to five sessions to much longer-term therapies of indefinite duration. The duration of therapy is tailored to the needs and goals of the individual. The methods of NISP can be adaptively applied to well-known therapy modalities such as CBT and family therapy.
By creating a solid therapeutic alliance, NISP improves adherence to medications and addresses ADHD's psychiatric comorbidities and functional disabilities. NISP is "neuropsychological informed" because it follows a comprehensive neuropsychological assessment of strengths and weaknesses. This leaves the therapist with an understanding of the patient's personal experience of ADHD, the meaning of the disorder, how it affects self-esteem, and how cognitive deficits limit the ability to self-regulate and adapt to changing circumstances. Attending to the patient's strengths is a key feature of Prof. Seidman's method.
ADHD is a serious disorder and it usually has serious consequences. But ADHD people also have strong points in their character and their neuropsychological skills. These sometimes get lost in assessments of ADHD but, as Dr. Seidman indicates, by addressing strengths, patient outcomes can be improved. A NISP assessment also seeks to learn about the psychological themes that underlie each patient's story. He gives the all too common example of the patients who view themselves as failed children who have not tried hard enough to succeed.
A frank discussion of neuropsychological test results can be the first step to helping patients reconceptualize their past and move on to an adaptive path of self-understanding and self-regulation. Prof. Seidman's approach seems sensible and promising. As he recognizes, it has not yet, however, been subject to the rigorous tests of evidenced-based medicine. With this in mind, I would not recommend using it as a replacement for evidence-based treatment. That said, if you are a psychotherapist who treats ADHD people, read Prof. Seidman's paper. It will give you useful insights that will help your patients.

When my colleagues and I wrote our "Primer" about ADHD, the topic of brain mechanisms was a top priority. Because so much has been written about the ADHD brain, it is difficult to summarize. Yet we did it with the eight pictures reproduced here in one figure.
A quick overview of this figure shows you the complexity of ADHD's pathophysiology. There is no single brain region or neural circuit that is affected.
Figures (a) and (b) show you the main regions implicated by structural and functional neuroimaging studies.
As (c) shows, these regions are united by neural networks rich in noradrenalin (aka, norepinephrine) and dopamine, two neurotransmitters whose activity is regulated by medications that treat ADHD.
Figure (d) describes two functional networks.
The executive control network is, perhaps, the best-described network in ADHD. This network regulates behavior by linking the dorsal striatum with the dorsolateral prefrontal cortex. This network is essential for inhibitory control, self-regulation, working memory, and attention.
The Corticocerebellar network is a well-known regulator of complex motor skills. Data also suggest it plays a role in the regulation of cognitive functions.
Figure (d) describes the Reward Networks of the brain that link the ventral striatum with the prefrontal cortex. This network regulates how we experience and value rewards and punishments. In addition to its involvement in ADHD, this network has also been implicated in substance use disorders, for which ADHD persons are at high risk.
Figures (f)(g) and (h) complete the puzzle with additional regions implicated in ADHD whose role is less well understood. One role for these regions is in the regulation of the Default Mode Network, which controls what the brain does when it is not focused on any specific task (e.g., daydreaming, mind wandering).
People differ in the degree to which they shift between the default mode network and networks like Reward or Executive Control, which are active when we engage the world. Recent data suggest that the brains of ADHD people may be in 'default mode' when they ought to be engaged in the world.
