Cookie Preferences
By clicking, you agree to store cookies on your device to enhance navigation, analyze usage, and support marketing. More Info
Thank you! Your submission has been received!
Oops! Something went wrong while submitting the form.
August 5, 2025
Centanafadine, which is currently under investigation as a treatment for ADHD, will be the first triple reuptake inhibitor for the disorder if it is approved by the FDA. It improves norepinephrine, dopamine and serotonin levels. This new medication is not a stimulant, but due to the dopamine component, it has a stimulant-like effect in patients. In adults, two phase 3 trials and a year-long extension have shown sustained benefits and a tolerable safety profile, laying the groundwork for pediatric research.
Based on this study, improvement was already noticeable after the first week and held steady through week 6. The lower dose (164.4 mg) didn’t separate from placebo, reminding us that getting the dose right will be critical. The effect size was smaller than what is seen for stimulants but 50% of patients had excellent outcomes as indicated by reductions in the ADHD-RS of 50% or more.
Side effect patterns look familiar to anyone who prescribes ADHD medications; loss of appetite, nausea and headaches topped the list. About half of teens on the higher dose reported at least one treatment-emergent adverse event, compared with a quarter of those on placebo. Severe reactions were rare but did include isolated liver enzyme spikes, rash, and a few reports of aggression or somnolence. For everyday practice, that translates to routine growth checks, a look at baseline liver function, and clear guidance to families about reporting rashes or mood changes promptly.
The researchers noted that the study had certain limitations, including limited generalizability to adolescents beyond North America, the exclusion of teacher ratings on the ADHD-RS-5 scale and the study’s short duration. They added that future studies should explore long-term treatment outcomes and efficacy compared with other ADHD treatments, as well as its effect on treating ADHD with comorbid conditions.
First, speed. Centanafadine separated from placebo within a week. In this regard, it might be closer to stimulants than to the multi-week ramp-up we expect from current non-stimulants. Second, it offers another option when stimulants are contraindicated or poorly tolerated, or when they raise diversion concerns. Its mechanism also makes it intriguing for patients who need both norepinephrine and dopamine coverage but prefer to avoid schedule II drugs. Because it also improves serotonergic transmission, it may be useful for some of ADHD’s comorbidities (see our new article for evidence about serotonin’s role in these disorders).
Keep in mind that centanafadine for ADHD is still investigational, so participation in clinical trials remains the only access route.
Adler, Lenard A. MD1; Adams, Julie MD2; Madera-McDonough, Jessica MD2; Kohegyi, Eva MD2; Hobart, Mary PhD2; Chang, Denise PhD2; Angelicola, Mark MS2; McQuade, Robert PhD2; Liebowitz, Michael MD3. Efficacy, Safety, and Tolerability of Centanafadine Sustained-Release Tablets in Adults With Attention-Deficit/Hyperactivity Disorder: Results of 2 Phase 3, Randomized, Double-blind, Multicenter, Placebo-Controlled Trials. Journal of Clinical Psychopharmacology 42(5):p 429-439, 9/10 2022. | DOI: 10.1097/JCP.0000000000001575
Raising children is not easy. I should know.
As a clinical psychologist, I've helped parents learn the skills they need to be better parents. And my experience raising three children confirmed my clinical experience.
Parenting is a tough job under the best of circumstances, but it is even harder if the parent has ADHD.
For example, an effective parent establishes rules and enforces them systematically. This requires attention to detail, self-control, and good organizational skills. Given these requirements, it is easy to see how ADHD symptoms interfere with parenting. These observations have led some of my colleagues to test the theory that treating ADHD adults with medication would improve their parenting skills. I know about two studies that tested this idea.
In 2008, Dr. Chronis-Toscano and colleagues published a study using a sustained-release form of methylphenidate for mothers with ADHD. As expected, the medication decreased their symptoms of inattention and hyperactivity/impulsivity. The medication also reduced the mother's use of inconsistent discipline and corporal punishment and improved their monitoring and supervision of their children.
In a 2014 study, Waxmonsky and colleagues observed ADHD adults and their children in a laboratory setting once when the adults were off medication and once when they were on medication. They used the same sustained-release form of amphetamine for all the patients. As expected, the medications reduced ADHD symptoms in the parents. This laboratory study is especially informative because the researchers made objective ratings of parent-child interactions, rather than relying on the parents' reports of those interactions. Twenty parents completed the study. The medication led to less negative talk and commands and more praise by parents. It also reduced negative and inappropriate behaviors in their children.
Both studies suggest that treating ADHD adults with medication will improve their parenting skills. That is good news. But they also found that not all parenting behaviors improved. That makes sense. Parenting is a skill that must be learned. Because ADHD interferes with learning, parents with the disorder need time to learn these skills. Medication can eliminate some of the worst behaviors, but doctors should also provide adjunct behavioral or cognitive-behavioral therapies that could help ADHD parents learn parenting skills and achieve their full potential as parents.
Few studies have examined the safety and tolerability of ADHD medications (stimulants and atomoxetine) extending beyond six months, and none beyond a few years. A pair of Swedish neuroscientists at Uppsala University Hospital set out to explore longer-term outcomes. They conducted a six-year prospective study of 112 adults diagnosed with ADHD who were being treated with ADHD medications (primarily MPH, but also dexamphetamine and atomoxetine).
They found that at the end of that period, roughly half were still on medication, and half had discontinued treatment. There were no significant differences between the two groups in age, sex, ADHD severity, or comorbidity. The average ADHD score for the entire cohort declined to vary significantly, from a mean of 37 to a mean of 26, with less than one in a thousand odds of that being due to chance. There was also no sign of drug tolerance or a need to increase the dosage over time.
All 55 adults who discontinued treatment had taken MPH for at least part of the time. Eleven had also been treated with dexamphetamine(DEX) and 15 with atomoxetine (ATX). The average time on treatment was just under two years. Almost a third quit MPH because they perceived no beneficial effect. Since they were on average taking higher doses at discontinuation than initiation, that is unlikely to have been due to suboptimal dosage. Almost another third was discontinued for various adverse mental effects, including hyperactivity, elation, depressive moods, aggression, insomnia, fatigue, and lethargy. Another one in eleven quit when they lost contact with the prescribing physician. In the case of ATX, almost half quit because of what they perceived as adverse mental effects.
Among the 57 adults who remained on medication, four out of five reported a strong beneficial effect. Only two reported minimal or no effect. Compared with the group that discontinued, the group that remained on medication was far more likely to agree with the statements, "My quality of life has improved," and "My level of functioning has improved." Yet, as the authors caution, it is possible "that the subjects' subjective ratings contained a placebo-related mechanism in those who are compliant with the medication and pursue treatment over time." The authors reported that there were no significant differences in ADHD scores or ADHD severity between the group that quit and the group that remained on medication, even though, on average, the group that quit had been off medication for four years at follow-up.
We cannot explain why the patients who quit treatment showed similar levels of ADHD symptoms to those who continued treatment. It is possible that some patients remit symptoms over time and do not require sustained treatment. But we must keep in mind that there was a wide range of outcomes in both groups. Future work needs to find predictors of those who will do well after treatment withdrawal and those who do not.
Any decision on whether to maintain a course of medication should always weigh expected gains against adverse side effects. Short of hard evidence of continuing efficacy beyond two years, adverse events gain in relative importance. With that in mind, it is worth noting that this study reports that among those who remained on MPH, many reported side effects. More than a quarter complained of decreased appetite, one in four of dry mouth, one in five of anxiousness and increased heart rate, one in six of decreased sexual desire, one in nine of depressed mood, and one in eleven of insomnia.
This study breaks important ground in looking at the long-term effects of medication. It reaffirms findings elsewhere of the efficacy of ADHD medications. But contrary to the authors' conclusion, the data they present suggests the possibility that permanently medicating ADHD patients may not be more efficacious than discontinuation beyond a certain point, especially when balanced against adverse side effects.
But this is just one study with a relatively small sample size. This suggests a need for additional studies with larger sample sizes to pursue these questions with greater statistical reliability.
.png)
Attention-Deficit/Hyperactivity Disorder (ADHD) in adults is commonly treated with stimulant medications such as methylphenidate and amphetamines. However, not all patients respond well to these stimulants or tolerate them effectively. For such cases, non-stimulant medications provide an alternative treatment approach.
Recent research by Brancati et al. reviews the efficacy and safety of non-stimulant medications for adult ADHD. Atomoxetine, a well-studied non-stimulant, has shown significant effectiveness in treating ADHD symptoms in adults. The review highlights the importance of considering dosage, treatment duration, safety, and the presence of psychiatric comorbidities when prescribing atomoxetine.
Additionally, certain antidepressants, including tricyclic compounds, bupropion, and viloxazine, which possess noradrenergic or dopaminergic properties, have demonstrated efficacy in managing adult ADHD. Antihypertensive medications, especially guanfacine, have also been found effective. Other medications like memantine, metadoxine, and mood stabilizers show promise, whereas treatments like galantamine, antipsychotics, and cannabinoids have not yielded positive results.
The expert opinion section of the review emphasizes that while clinical guidelines primarily recommend atomoxetine as a second-line treatment, several other non-stimulant options can be utilized to tailor treatments based on individual patient needs and comorbid conditions. Despite these advancements, the authors call for further research to develop and refine more personalized treatment strategies for adults with ADHD.
This review underscores the growing landscape of non-stimulant treatment options, offering hope for more personalized and effective management of ADHD in adults.
What do we mean by expert? In simple terms, an expert possesses in-depth knowledge and specialized training in a particular field. In order to be considered an expert in any field, a person must have both deep knowledge of and competence in their specific area of expertise. Experts have a background that includes education, research, and experience. In the world of mental health and psychology, this typically means formal credentials (a PhD, MD, etc) in addition to years of study, peer-reviewed publications, and/or extensive clinical experience.
Experts are recognized by their peers (and often by the public) as reliable authorities on a specific topic. Experts usually don’t make big claims without evidence; instead, they cite studies and speak cautiously about what the evidence shows.
Tip: Those looking for likes and clicks will often speak in absolutes (e.g., “refined sugar makes your ADHD worse, but the Keto Diet will eliminate ADHD symptoms”) while experts will use language that emphasizes evidence (e.g., “research has proven that there is no ‘ADHD Diet’, but some evidence has suggested that certain individuals with ADHD may benefit from such dietary interventions as limiting food coloring or increasing omega fatty acids.”)
Social media has created an incredible opportunity for those with ADHD to gain access to invaluable resources, including the creation of communities by and for those with ADHD. Many people with ADHD report feeling empowered and less alone by connecting with others online. These online social platforms provide a space for those with ADHD to share their own perspectives and their lived experience with the disorder. Both inside and outside of mental health-related communities, social media is a powerful tool for sharing information, reducing stigma, and helping people find community. When someone posts about their own ADHD challenges or tips, it can reassure others that they’re not the only ones facing these issues. This kind of peer support is valuable and affirming.
It is vital for those consuming this media, however, to remember that user-generated content on social media is not vetted or regulated. Short TikTok or Instagram videos are designed to grab attention, not to teach nuance or cite scientific studies. As it turns out, most popular ADHD posts are misleading or overly simplistic, at best. One analysis of ADHD TikTok videos found that over half were found to be “misleading” by professionals. Because social feeds reinforce what we already believe (the “echo chamber” effect, or confirmation bias), we can easily see only content that seems to confirm our own experiences, beliefs, or fears.
Stories aren’t a substitute for expert guidance.
It’s important to recognize the difference between personal experience and general expertise. Having ADHD makes you an expert on your ADHD, but it does not make you an expert on ADHD for everyone. Personal stories are not scientific facts. Even if someone’s personal journey is true, the same advice or experience may not apply to others. For instance, a strategy that helps one person focus might have no effect– or possibly even a negative effect– on someone else.
Researchers have found that most ADHD content on social media is based on creators’ own experiences, not on systematic research. In one study, almost every TikTok ADHD creator who listed credentials actually just cited their personal story. Worse, about 95% of those videos never noted that their tips might not apply to everyone (journals.plos.org.) In other words, they sound absolute even though they really only reflect one person’s situation. It’s easy to misunderstand the condition if we take those singular experiences as universal facts.
So how can you tell when someone is speaking from expertise rather than personal experience or hearsay? Experienced professionals usually speak cautiously, rather than in absolutes. They tend to say things like “research suggests,” “some studies show,” or “evidence indicates,” rather than claiming something always or never happens. As one health-communication guide puts it, a sign of a trustworthy source is that they do not speak in absolutes; instead, they use qualifiers like “may,” “might,” or refer to specific studies. For example, an expert might say, “Some people with ADHD may have difficulty with organization,” instead of “ADHD people always lose things.”
Real experts also cite evidence. In science and psychology, experts usually share knowledge through peer-reviewed articles, textbooks, or professional conferences – not just social media posts. Reliable health information is typically backed by references to studies published in reputable journals.
If someone makes a claim online, ask: Do they point to research, or is it just their own testimony? This is why it’s wise to prefer content where the author is a recognized authority (like a doctor or researcher) and where references to scientific studies or official guidelines are provided. In fact, advice from sites ending in “.gov”, “.edu”, or “.org” (government, university, or professional organizations) tends to be more reliable than random blogs. When in doubt, look up who wrote the material and whether it cites peer-reviewed research.
When navigating mental health information online, remember these key points:
If you see sweeping statements like “This one habit will predict if you have ADHD” or “Eliminating this one food will cure your ADHD symptoms”--- that’s a red flag. Instead, the hallmark of expert advice is a tone of humility (“evidence suggests,” “it appears that,” etc.), clear references to studies or consensus statements, and an acknowledgment that individual differences exist.
At the same time, we need to acknowledge that community voices are incredibly valuable – they help us feel understood and less alone. The goal is not to dismiss personal stories, but to balance them with facts and evidence-based information. Let lived experience spark questions, but verify important advice with credible sources. Follow trusted organizations (for example, the National Institutes of Health, CDC, or ADHD specialist groups) and mental health professionals who communicate carefully. Use the online ADHD community for support and sharing tips, but remember it’s just one piece of the puzzle.
By being a savvy reader (checking credentials, looking for cited evidence, and spotting overgeneralizations), you can make the most of online ADHD content. In doing so, you give yourself both the empathy of community and the accuracy of real expertise. That way, you’ll be well-equipped to separate helpful insights from hype and to keep learning from both personal stories and science-based experts.
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.
Today, most treatment guidelines recommend starting ADHD treatment with stimulant medications. These medicines often work quickly and can be very effective, but they do not help every child, and they can have bothersome side effects, such as appetite loss, sleep problems, or mood changes. Families also worry about long-term effects, the possibility of misuse or abuse, as well as the recent nationwide stimulant shortages. Non-stimulant medications are available, but they are usually used only after stimulants have not been effective.
This stimulant-first approach means that many patients who would respond well to a non-stimulant will end up on a stimulant medication anyway. This study addresses this issue by testing two different ways of starting medication treatment for school-age children with attention-deficit/hyperactivity disorder (ADHD). We want to know whether beginning with a non-stimulant medicine can work as well as the “stimulant-first” approach, which is currently used by most prescribers.
From this study, we hope to learn:
Our goal is to give families and clinicians clear, practical evidence to support a truly shared decision: “Given this specific child, should we start with a stimulant or a non-stimulant?”
Who will be in the study?
We will enroll about 1,000 children and adolescents, ages 6 to 16, who:
We will include children with common co-occurring conditions (such as anxiety, depression, learning or developmental disorders) so that the results reflect the “real-world” children seen in clinics, not just highly selected research volunteers.
How will the treatments be assigned?
This is a randomized comparative effectiveness trial, which means:
Parents and clinicians will know which type of medicine the child is taking, as in usual care. However, the experts who rate how much each child has improved using our main outcome measure will not be told which treatment strategy the child received. This helps keep their ratings unbiased.
What will participants be asked to do?
Each family will be followed for 12 months. We will collect information at:
At these times:
We will also track:
Data will be entered into a secure, HIPAA-compliant research database. Study staff at each site will work closely with families to make participation as convenient as possible, including offering flexible visit schedules and electronic options for completing forms when feasible.
How will we analyze the results?
Using standard statistical methods, we will:
All analyses will follow the “intention-to-treat” principle, meaning we compare children based on the strategy they were originally assigned to, even if their medication is later changed. This mirrors real-world decision-making: once you choose a starting strategy, what tends to happen over time?
Why is this study necessary now?
This study addresses a critical, timely gap in ADHD care:
In short, this study is needed now to move ADHD medication decisions beyond “one-size-fits-all.” By rigorously comparing stimulant-first and non-stimulant-first strategies in real-world settings, and by focusing on what matters most to children and families overall functioning, side effects, and long-term well-being, we aim to give patients, parents, and clinicians the information they need to choose the best starting treatment for each child.
This project was conceived by Professor Stephen V. Faraone, PhD (SUNY Upstate Medical University, Department of Psychiatry, Syracuse, NY) and Professor Jeffrey H. Newcorn, MD (Icahn School of Medicine at Mount Sinai, Department of Psychiatry, New York, NY). It will be conducted at nine sites across the USA.
_logo%201.svg)
