Field notes · ADHD · New medications

New for ADHD, 2021–2026. What's genuinely new, how each one works, and how to read their labels for yourself.

A 15-minute read, with four explorable labels · Reid Robison, MD

Since 2021 the FDA has approved a steady stream of ADHD medicines. Most are new ways to take drugs we've had for decades. A few are genuinely new molecules, and the newest, Simtriyo, arrived this July. Here's the whole five years at a glance, a close look at the novel ones, and a tool to explore their package inserts the way a psychiatrist reads them.

TL;DR

First, why ADHD medicines work at all.

ADHD is common. About 11% of US children have been diagnosed at some point, and in 2023 about 6% of US adults reported a current diagnosis — half of them diagnosed as adults9,10. At its core it's a difference in how the brain regulates attention, effort and impulse, and much of that regulation runs through the prefrontal cortex.

The prefrontal cortex depends on two chemical messengers, norepinephrine and dopamine, in just the right amounts. Too little and its networks go quiet; too much, as under intense stress, and they go offline too. Nearly every ADHD medicine nudges these signals back toward the middle of that inverted U11.

A neat bit of neuroanatomy explains a lot. In the prefrontal cortex there are few dopamine transporters, so the norepinephrine transporter mops up dopamine too. Block it, and dopamine rises in the prefrontal cortex but not in the striatum, the brain's reward hub12. That's why norepinephrine-only drugs like atomoxetine and viloxazine have little abuse potential. It's also why a drug that touches the dopamine transporter, as centanafadine does, gets treated more cautiously.

Explore · the ADHD medicine cabinet, at the synapse
norepinephrinedopamineserotonin✕ = transporter blocked

Five years at a glance.

Every ADHD approval and major regulatory change since 2021. Filter by what kind of "new" it is, and tap any entry for details.

Where things stand, September 2026.

Approved · Jul 24, 2026Simtriyo (centanafadine)Otsuka. A new molecule and the first NDSRI. Adults and children 6+ (at least 20 kg). DEA scheduling was pending at approval, so check availability3.
Complete response · Jun 2, 2026CTx-1301 (dexmethylphenidate)Cingulate. A once-daily tablet designed to release medicine in three timed pulses. The FDA asked for manufacturing (CMC) information only; no clinical safety or efficacy concerns were identified. Resubmission is planned7.
In the pipelineSolriamfetol for ADHDAxsome. Already approved for daytime sleepiness. In a 6-week adult ADHD trial (516 people), 150 mg beat placebo (a 17.7- vs 14.3-point drop, p = 0.039) but 300 mg did not. A pediatric trial is next13.

Simtriyo: a new key, mostly for one lock.

Centanafadine blocks the reuptake of three messengers: norepinephrine, dopamine and serotonin. That's why Otsuka calls it the first "NDSRI." But the potency numbers tell a more specific story. It's strongest at the norepinephrine transporter (IC50 about 6 nM), about six times weaker at dopamine (38 nM) and fourteen times weaker at serotonin (83 nM)5. Unlike amphetamine, it only blocks transporters; it doesn't force messengers out of the neuron.

The dopamine piece matters for regulation. For years the drug was described as a nonstimulant. The approved label instead classifies it as a CNS stimulant, carries a boxed warning for abuse and misuse, and notes that controlled-substance scheduling is pending3.

What the trials showed

4positive six-week phase 3 trials — two in adults, one in children, one in adolescents3
2.7–5.6points better than placebo on 54-point symptom scales, depending on age and dose
0 of 2lower pediatric doses that beat placebo. Only the higher dose worked in kids and teens3.

In adolescents, 47.7% on the higher dose reached a clinically meaningful change (an 18-point drop) versus 31.7% on placebo14. Improvement showed up from the first week in the pediatric and adult studies, though in teens the early separation was clearer for inattention than for hyperactivity. The standout side effects were a rash in children (9% vs 0% on placebo) and decreased appetite in teens (15% vs 2%). In children 6–12 there's a boxed warning for suicidal thoughts and behaviors: two suicide attempts among 304 children on the drug versus none among 153 on placebo in the six-week trial3.

How big is the effect? Converting the label's results to standardized effect sizes gives roughly 0.24–0.41. For comparison, a large network meta-analysis put methylphenidate at 0.78 in children and 0.49 in adults, and amphetamines at 1.02 and 0.796. Different trials, so treat this as a yardstick:

Bars show the range across trial arms (new drugs) or the network meta-analysis estimate (older drugs). Separate trials, different eras and placebo responses, so it's a rough guide only.

What does a "modest" effect actually mean?Why smaller numbers don't make a medicine useless

An effect size of 0.3–0.4 means the average person on the drug did better than about 62–66% of people on placebo. That's modest, but it's in the same range as many treatments we rely on in psychiatry. Stimulants stand out because they're unusually strong, not because everything else is weak.

Averages also hide the spread. In any trial some people respond strongly, some partly and some not at all, and we can't yet predict who's who in advance. A drug with a modest average can still be the one that works for a particular person.

And size isn't the only reason to choose a medicine. People pick a nonstimulant because stimulants caused side effects or didn't help, because of a history of substance misuse, because of tics or anxiety, to avoid controlled-substance hassles, or for steadier coverage into the evening. The honest framing isn't "weak drug." It's "useful option, with realistic expectations."

My read · Simtriyo

A genuinely new molecule and a reasonable option for people who can't take or don't do well on first-line stimulants. But the benefit over placebo is modest: roughly a third to half of what stimulants deliver in comparable trials. The lower pediatric dose failed, and the label treats it as a stimulant with abuse and pediatric suicidality boxed warnings. Early marketing leaned on "non-stimulant" framing, but the approved label doesn't support it. There are no head-to-head trials yet. I'd want to see real-world data on insomnia, appetite and rash before calling it anyone's first choice.

The nonstimulant that came before: Qelbree.

Qelbree (viloxazine extended-release) is a once-daily nonstimulant approved in 2021 for children 6 and older and in 2022 for adults2. It's a new ADHD formulation of an older molecule rather than an entirely new compound: viloxazine was sold as an antidepressant in Europe from the 1970s15.

Mechanism. Viloxazine inhibits the norepinephrine transporter and also acts on serotonin receptors, as a 5-HT2C agonist and 5-HT2B antagonist16. The current label is careful about the distinction: its mechanism for improving ADHD is unclear, though norepinephrine reuptake inhibition is thought to contribute. The clinical contribution of the serotonin activity has not been established2.

What supported approval. Three randomized, placebo-controlled pediatric trials lasting 6–8 weeks and one 6-week adult trial, all using clinician-rated ADHD symptom scales. In children 6–11 it beat placebo by 5.8–6.9 points; in adolescents by 4.5–5.1; and in adults by 3.7 points (95% CI 1.2–6.2). In the adult trial, symptoms fell 15.5 points on viloxazine versus 11.7 on placebo, and the average dose at the end was 504 mg/day. Every dose group beat placebo, but the trials don't establish superiority to stimulants or atomoxetine2.

Prescribing considerations. The boxed warning is suicidal thoughts and behaviors: 0.9% versus 0.4% in children and 1.6% versus 0% in adults. The label also calls for blood pressure and pulse monitoring, screening for bipolar disorder, and attention to sleepiness, fatigue, appetite loss, insomnia and irritability. Viloxazine is a strong CYP1A2 inhibitor, which creates clinically important interactions — including with caffeine2.

Qelbree, CYP1A2 and caffeineWhat prescribers and patients should know

The mechanism. CYP1A2 is the liver enzyme that clears about 95% of the caffeine we drink. Viloxazine is a strong CYP1A2 inhibitor. In a formal interaction study, it raised caffeine exposure (AUC) about 4.4-fold without changing the peak17. In practice, caffeine doesn't hit harder so much as it lasts much longer. An afternoon coffee can still be in the system at bedtime. The same enzyme clears some medicines, so the label makes it a contraindication to combine Qelbree with sensitive or narrow-range CYP1A2 drugs, such as tizanidine, theophylline, duloxetine, ramelteon and tasimelteon. Melatonin also runs through CYP1A22,18.

What the real-world data show. About 85% of adults in the Qelbree trial used caffeine. Caffeine intake didn't raise most side effects, but it did make insomnia more likely19.

For prescribers
  • Ask about all caffeine: coffee, tea, energy drinks, pre-workout, soda, and caffeine pills.
  • Check the medication list for CYP1A2 substrates (contraindicated or dose-sensitive), including over-the-counter melatonin.
  • Suggest cutting caffeine roughly in half at the start, and none after late morning.
  • If insomnia, jitteriness or palpitations appear, look at caffeine before blaming the drug or changing the dose.
  • Viloxazine also weakly inhibits CYP2D6 and CYP3A4 (about 1.9× and 1.7× exposure in the same study)17.
For patients and families
  • Expect caffeine to last much longer than you're used to.
  • Try half your usual amount, and keep it to the morning.
  • Watch for trouble sleeping, a racing heart, shakiness or feeling on edge.
  • Tell your prescriber about every medicine and supplement, including melatonin and muscle relaxants.
  • Don't stop Qelbree to have coffee; adjust the coffee.

More on how caffeine works in the body: Caffeine — America's favorite psychotropic.

My read · Qelbree

A credible additional nonstimulant option, with replicated short-term efficacy in children and one positive adult pivotal trial. Its serotonergic pharmacology is interesting, but claims that 5-HT2C activity gives it a distinct clinical advantage go beyond what the approval trials demonstrate.

Azstarys: a new molecule, an old mechanism.

Azstarys (March 2021) pairs two forms of dexmethylphenidate, the more active half of ordinary methylphenidate. About 30% of the capsule (by molecules) is regular dexmethylphenidate, which starts working quickly. The other 70% is serdexmethylphenidate, a genuinely new molecule: a prodrug that does nothing until it's converted in the lower gut, which stretches the effect through the day1.

The chemistry has a second purpose. When the prodrug was taken by routes people use to misuse stimulants — snorted or injected — it produced much less active drug. The DEA put serdexmethylphenidate on its own in Schedule IV. But the capsule still contains immediate-release dexmethylphenidate, so Azstarys is Schedule II with the same boxed warning as every stimulant1.

The evidence base is narrow. Approval rested on a single laboratory classroom study of 150 children aged 6–12: after finding each child's dose, children were randomized to Azstarys or placebo and rated across a classroom day. Azstarys beat placebo by 5.4 points on the SKAMP-Combined scale (95% CI 3.7–7.1). Teens and adults were approved by bridging to existing dexmethylphenidate data. In a year-long open-label study, children's growth ran slightly below expected1.

My read · Azstarys

A clever delivery idea wrapped in a new molecule, but not a new mechanism: it's methylphenidate. It's a reasonable choice when someone needs a smooth, long day from one capsule and does well on methylphenidate. I wouldn't expect it to help people who haven't responded to methylphenidate before. The abuse-deterrent chemistry is real but partial.

Onyda XR: clonidine at bedtime.

Clonidine has been around since 1974, first for blood pressure. Extended-release clonidine tablets were approved for ADHD in 2010. Onyda XR (May 2024) is the same medicine as a once-daily liquid given at bedtime. It's the first liquid nonstimulant for ADHD and the only nonstimulant designed for nighttime dosing, for children and teens 6–17, alone or added to a stimulant4.

Clonidine works differently from everything else here. Instead of raising norepinephrine or dopamine, it activates alpha-2A receptors on prefrontal neurons, strengthening the signal the network already has11. Onyda XR didn't need new efficacy trials. It was approved by showing it delivers the same exposure as the tablets (96.1% relative bioavailability), whose trials showed clear benefits: 8.5–9.1 points over placebo on its own, and 4.5 points when added to a stimulant4.

The trade-off is sedation. On clonidine alone, about a third of children were sleepy (38% on 0.2 mg vs 4% on placebo), which is exactly why bedtime dosing makes sense. It can lower heart rate and blood pressure, and it must be tapered rather than stopped suddenly, to avoid rebound high blood pressure4.

My read · Onyda XR

Nothing new pharmacologically, but a genuinely useful new form. A bedtime liquid solves two real problems: kids who can't swallow pills, and daytime sleepiness. It's also a sensible add-on when a stimulant covers the school day but evenings, sleep or irritability are hard. Families need to know about the taper.

About those suicidality warnings.

This is one of the questions I'm asked most. Three of the drugs here carry a boxed warning for suicidal thoughts and behaviors — Qelbree, Simtriyo and the older nonstimulant atomoxetine (Strattera). The stimulants, including Azstarys, and the alpha-2 agonists like Onyda XR don't; the stimulants' boxed warning is about misuse and addiction.

MedicineWhat the trials foundWarning
Atomoxetine (2002)Suicidal thinking in 0.4% of children and teens (5 of 1,357) vs 0% on placebo (0 of 851), pooled across 12 trials; no suicides20Boxed, 2005
Qelbree (2021)Suicidal thoughts or behavior in 0.9% of children (9 of 1,019) vs 0.4% (2 of 463); adults 1.6% (3 of 189) vs 0% (0 of 183)2Boxed
Simtriyo (2026)In the 6-week trial in ages 6–12, suicide attempts in 0.7% (2 of 304) vs 0% (0 of 153)3Boxed, ages 6–12
Stimulants, alpha-2 agonistsNo suicidality signal requiring a warningNo suicidality box

Three things help put these numbers in context. First, the events are rare and mostly reports of suicidal thinking, picked up because trials ask about it carefully. Second, ADHD itself raises the risk of suicidal behavior, so the baseline matters. Third, in a 2025 Swedish study of almost 150,000 people newly diagnosed with ADHD, starting medication was linked to 17% less first-time suicidal behavior over two years21.

One important nuance: a very large US study found that suicidal behavior was most likely in the weeks just before someone started an ADHD medication — for stimulants, atomoxetine and alpha-2 agonists alike — and only slightly raised during treatment compared with time off treatment22. People often start treatment during their hardest stretch. That's why the first weeks, and any dose change, deserve closer check-ins no matter which medicine is chosen.

What to do. Before starting a nonstimulant, screen for bipolar disorder and past suicidal thinking. Check in early — weekly if you can — for the first month and after dose changes. Families should call right away about new or worsening sadness, agitation, sleeplessness or talk of death. A safety plan is worth making before it's needed. If you or someone you love is struggling, call or text 988. For the full story of where these warnings came from, what the science shows and how to handle the risk, read The warning in the box.

What they cost.

Price is part of the story, especially for newer brands. Below is what pharmacies actually pay, on average, for each medicine at a common dose, from the federal NADAC survey (updated weekly; these figures are as of September 30, 2026)8. It isn't what you'll pay at the counter. Insurance, coupons and pharmacy markups change that. But it's the most reliable public yardstick for comparing medicines to each other.

NADAC is the national average price retail pharmacies pay wholesalers, surveyed monthly by CMS and published weekly. It excludes pharmacy markup and dispensing fees and doesn't reflect insurance, rebates or manufacturer savings cards. Brand-name savings programs can lower out-of-pocket costs a lot. Simtriyo isn't priced yet (it hasn't launched). Strattera figures are as of July 15, 2026, its last listing.

New ways to take familiar drugs.

Most of the last five years has been reformulation, not new chemistry. That matters more than it sounds: the right form can make the difference between a medicine someone takes and one they don't.

Nov 2021 · amphetamineDyanavel XR tabletsA once-daily extended-release amphetamine tablet, joining the existing liquid23.
Mar 2022 · dextroamphetamineXelstrym patchThe first amphetamine skin patch, for ages 6 and up. Useful when swallowing is a problem or you want an adjustable "off switch"24.
Jun 2022 · methylphenidateRelexxiiAn osmotic extended-release tablet, similar to Concerta, including a 72 mg strength, for ages 6–6525.
Jun 2025 · lisdexamfetamineArynta (oral solution)Liquid Vyvanse, approved in 2025 and expected to launch in mid-202626.

Two non-approvals also changed practice. In May 2023 the FDA required every stimulant's boxed warning to spell out the risks of misuse, abuse, addiction and overdose, and to tell patients never to share their medication27. In August 2023 the first generic versions of Vyvanse were approved, making one of the most-prescribed ADHD medicines far cheaper for many people28.

How they got here.

New ADHD medicines rarely arrive quickly. Tap a drug to see its story.

Interactive reference · from the FDA label

The label, explorable.

Every new medicine ships with a package insert: dense, legal and full of real data. Here are four of them, rebuilt so you can explore them. Pick a drug, then look at dosing, the trials, side effects, warnings, interactions and what happens in the body — or compare them side by side.

Built from the FDA prescribing information and the trials behind it. Plain-English summaries are mine; the label is the authority. This is education, not medical advice. Interaction and dosing views cover label highlights only — always check with a prescriber or pharmacist.

How to read any new drug's label.

The explorer above works the same way for every new medication, and I'll add more as they're approved. Here are the five questions I ask of every package insert:

  1. How big is the benefit over placebo? Not "did it work," but by how much. Look at section 14 for the placebo-subtracted difference and its confidence interval.
  2. How much improved on placebo? In ADHD trials, placebo groups often improve 10–14 points. A drug's real contribution is what's left after that.
  3. Which doses failed? Failed arms are easy to miss and tell you where the effective dose actually starts.
  4. What's the number needed to harm? Compare side-effect rates to placebo in section 6. "Treat 8 teens with Simtriyo and one extra loses appetite" is more useful than "15%".
  5. What was not tested? Head-to-head comparisons, long-term outcomes, people with common co-occurring conditions. The label only covers what the trials studied.

For more on attention itself, see Your attention isn't broken. Everything on ADHD lives at doctorreid.com/adhd.

Label data sources:3,29,14,5,30,31,1,2,18,15,16,32,33,4,11

Sources

  1. Corium. AZSTARYS (serdexmethylphenidate and dexmethylphenidate) capsules, for oral use, CII. Full prescribing information. Initial U.S. approval: 2021; revised 2025 (NDA 212994). Silver Spring, MD: U.S. Food and Drug Administration.
  2. Supernus Pharmaceuticals. QELBREE (viloxazine extended-release capsules), for oral use. Full prescribing information. Initial U.S. approval: 2021; revised 2025 (NDA 211964/S-013). Silver Spring, MD: U.S. Food and Drug Administration.
  3. Otsuka America Pharmaceutical. SIMTRIYO (centanafadine) extended-release capsules, for oral use. Full prescribing information. Initial U.S. approval: 2026. NDA 218145. Silver Spring, MD: U.S. Food and Drug Administration; 2026.
  4. Tris Pharma. ONYDA XR (clonidine hydrochloride) extended-release oral suspension. Full prescribing information. Initial U.S. approval: 1974; revised 2025 (NDA 217645). Silver Spring, MD: U.S. Food and Drug Administration.
  5. Hu L. Centanafadine (Simtriyo®): a first-in-class triple reuptake inhibitor approved for attention-deficit/hyperactivity disorder (ADHD). Med Chem Res. 2026;35(9):1548–1552.
  6. Cortese S, Adamo N, Del Giovane C, et al. Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis. Lancet Psychiatry. 2018;5(9):727–738.
  7. Cingulate Inc. Cingulate receives complete response letter from FDA for CTx-1301. Press release, June 2, 2026.
  8. Centers for Medicare & Medicaid Services. National Average Drug Acquisition Cost (NADAC) weekly data, as of September 30, 2026 (effective September 23, 2026). data.medicaid.gov.
  9. Danielson ML, Claussen AH, Bitsko RH, et al. ADHD prevalence among U.S. children and adolescents in 2022: diagnosis, severity, co-occurring disorders, and treatment. J Clin Child Adolesc Psychol. 2024;53(3):343–360.
  10. Staley BS, Robinson LR, Claussen AH, et al. Attention-deficit/hyperactivity disorder diagnosis, treatment, and telehealth use in adults — National Center for Health Statistics Rapid Surveys System, United States, October–November 2023. MMWR Morb Mortal Wkly Rep. 2024;73(40):890–895.
  11. Arnsten AFT, Pliszka SR. Catecholamine influences on prefrontal cortical function: relevance to treatment of attention deficit/hyperactivity disorder and related disorders. Pharmacol Biochem Behav. 2011;99(2):211–216.
  12. Bymaster FP, Katner JS, Nelson DL, et al. Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/hyperactivity disorder. Neuropsychopharmacology. 2002;27(5):699–711.
  13. Axsome Therapeutics. FOCUS phase 3 trial of solriamfetol in adults with ADHD achieves primary endpoint. Press release, March 25, 2025.
  14. Ward CL, Childress AC, Wilens TE, et al. Centanafadine for attention-deficit/hyperactivity disorder in adolescents: a randomized clinical trial. J Am Acad Child Adolesc Psychiatry. 2026;65(6):805–817.
  15. Lamb YN. Viloxazine: pediatric first approval. Paediatr Drugs. 2021;23(4):403–409.
  16. Yu C, Garcia-Olivares J, Candler S, Schwabe S, Maletic V. New insights into the mechanism of action of viloxazine: serotonin and norepinephrine modulating properties. J Exp Pharmacol. 2020;12:285–300.
  17. Wang Z, et al. Impact of viloxazine extended-release capsules (Qelbree) on select cytochrome P450 enzyme activity and evaluation of CYP2D6 genetic polymorphisms on viloxazine pharmacokinetics. Clin Drug Investig. 2024;44(5):303–317.
  18. U.S. Food and Drug Administration. Drug development and drug interactions: table of substrates, inhibitors and inducers. Updated regularly.
  19. Nasser A, Gomeni R, Hull J, Maldonado-Cruz Z, Earnest J, Rubin J. Evaluating the impact of caffeine on the incidence of adverse events during treatment with viloxazine extended-release (Qelbree) in adults with ADHD. CNS Spectr. 2023;28(2):234–235.
  20. Eli Lilly and Company. STRATTERA (atomoxetine) capsules. Prescribing information, including the boxed warning on suicidal ideation added in 2005 (pooled pediatric trials: 0.4% vs 0%).
  21. Zhang L, Zhu N, et al. ADHD drug treatment and risk of suicidal behaviours, substance misuse, accidental injuries, transport accidents, and criminality: emulation of target trials. BMJ. Published August 13, 2025.
  22. Adams SM, Meraz R, O'Reilly LM, et al. Pharmacotherapies for attention-deficit/hyperactivity disorder and risk of suicidal behavior: a within-individual study of stimulants, atomoxetine, and alpha-2 agonists. Biol Psychiatry Glob Open Sci. 2026;6(3):100698.
  23. Tris Pharma. Tris Pharma announces FDA approval of DYANAVEL XR (amphetamine) once-daily extended-release oral tablets, CII, for ADHD. Press release, November 2021.
  24. CHADD. FDA approves Xelstrym to treat ADHD. March 2022.
  25. Vertical Pharmaceuticals. RELEXXII (methylphenidate hydrochloride) extended-release tablets. Prescribing information (NDA 216117); approved June 2022.
  26. Psychiatric Times. Lisdexamfetamine dimesylate oral solution (Arynta) for ADHD approved June 16, 2025; availability mid-2026.
  27. U.S. Food and Drug Administration. FDA updating warnings to improve safe use of prescription stimulants used to treat ADHD and other conditions. Drug Safety Communication, May 11, 2023.
  28. U.S. Food and Drug Administration. FDA approves first generics of Vyvanse (lisdexamfetamine dimesylate). August 2023.
  29. Adler LA, Adams J, Madera-McDonough J, et al. 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. J Clin Psychopharmacol. 2022;42(5):429–439.
  30. Otsuka Pharmaceutical. Otsuka Pharmaceutical to acquire Neurovance, Inc. News release, March 3, 2017.
  31. Otsuka. Otsuka announces FDA acceptance and priority review of New Drug Application for centanafadine (submitted November 25, 2025). Press release, January 27, 2026.
  32. Supernus Pharmaceuticals. Supernus announces FDA approval of Qelbree (SPN-812) for the treatment of ADHD. Press release, April 2, 2021.
  33. Supernus Pharmaceuticals. Supernus provides regulatory updates for SPN-812 and SPN-830. Press release, November 9, 2020.

Educational only — not medical advice. Don't start, stop or change a medication without talking to your prescriber. If you're having thoughts of suicide, call or text 988.