Non-stimulant ADHD medicines are an option for adults who can't take stimulants, don't get on with them, or haven't been helped by them. There are three main ones. Atomoxetine is licensed for adults in Ireland, the UK and the US. Guanfacine is licensed only for children and teenagers in Ireland and the UK, so adult use is off-label. NICE says it should only be offered to adults with advice from a specialist (tertiary) ADHD service. Viloxazine (Qelbree) is approved for adults in the US. We found no authorisation for it in Ireland or the EU. In adult trials, atomoxetine reduced symptoms more than placebo, by about as much as methylphenidate and less than amphetamines. Non-stimulants take weeks to reach their full effect. Each carries its own warnings, including about suicidal thoughts. In Ireland, atomoxetine capsules were on the national shortage list when we checked on 1 November 2026.
If you are struggling right now: in Ireland and the UK, call Samaritans free on 116 123, any time. In Ireland you can also text 50808. In the US, call or text 988. If you or someone else is in immediate danger, call 112 or 999 in Ireland, or 999 in the UK.
Atomoxetine blocks the noradrenaline transporter, the protein that clears noradrenaline from the gap between nerve cells. Its product information says it does not directly affect the serotonin or dopamine transporters. It is not a stimulant. In a placebo-controlled study in adults, it did not produce a stimulant-like or euphoric response.
Guanfacine stimulates alpha-2A adrenergic receptors. Its product information says its mode of action in ADHD is "not fully established". It is also a blood pressure medicine, and it lowers blood pressure and heart rate.
Viloxazine is thought to work mainly by blocking noradrenaline reuptake, although the US label calls its mechanism in ADHD "unclear". It also binds to a serotonin receptor (5-HT2C).
For how stimulants compare, see what ADHD stimulants actually do.
NICE's adult ADHD guideline (NG87) is written for England. Its order for adults is:
NG87 doesn't mention viloxazine. It was last updated in 2019.
So for most adults, a non-stimulant is a second step, not a first one. In NICE's terms, the usual reasons are side effects you can't tolerate, or stimulants not working well enough.
A widely cited comparison is a 2018 network meta-analysis in The Lancet Psychiatry by Cortese and colleagues. It pooled 133 double-blind trials, including 8,131 adults in the efficacy analysis. Clinician-rated results in adults at around 12 weeks, versus placebo:
More negative numbers mean a bigger reduction in symptoms. Atomoxetine's effect is a little under half a standard deviation. In head-to-head estimates, amphetamines beat atomoxetine in adults (−0.34, −0.58 to −0.10). Atomoxetine and methylphenidate were not significantly different (0.04, −0.14 to 0.23).
Side effects are part of the picture too. More adults on atomoxetine than on placebo stopped because of side effects (odds ratio 2.33). That was also true of methylphenidate (2.39) and amphetamines (3.26). The authors rated confidence in most indirect comparisons as low or very low. They found too few studies to judge results at 26 or 52 weeks.
A 2025 network meta-analysis by Ostinelli and colleagues covered 113 adult trials. Stimulants and atomoxetine were the only treatments that beat placebo on both self-rated and clinician-rated symptoms. Atomoxetine scored −0.38 self-rated and −0.51 clinician-rated. Stimulants, pooled together, scored −0.39 and −0.61. More people stopped atomoxetine (odds ratio 1.43) and guanfacine (3.70) than placebo, for any reason. Medicines showed no benefit on quality of life, and longer-term evidence was thin.
Guanfacine in adults rests mainly on one Japanese trial of 201 adults. At week 10, symptoms fell more than on placebo (effect size 0.52). But 19.8% stopped because of side effects, against 3.0% on placebo.
Viloxazine in adults rests on one 6-week trial of 374 people, the study behind its FDA approval. Scores on a clinician-rated symptom scale (AISRS) fell 15.5 points on viloxazine and 11.7 on placebo. The difference was 3.7 points (95% CI 1.2 to 6.2). Most responder-rate comparisons were not significant. 107 of the 374 people did not complete the study.
The honest summary: atomoxetine has consistent evidence of benefit over placebo in adults. On average it does less than amphetamines. The adult evidence for guanfacine and viloxazine is much thinner.
Non-stimulants build up gradually:
So it can take a while to know whether one is working. Agree a review point with your prescriber before you start.
Atomoxetine. In adult trials, the most common side effects were nausea (26.7%), dry mouth (18.4%), headache (16.3%), reduced appetite (14.9%) and insomnia (11.3%). Trouble passing urine can be linked to it. NICE advises monitoring for erectile and ejaculatory problems. Some antidepressants, such as fluoxetine and paroxetine, can raise atomoxetine levels six- to eight-fold. It must not be combined with MAOI antidepressants. It is also not used in narrow-angle glaucoma or severe heart or blood-vessel disease.
Guanfacine. In the children and teenagers it was tested in, sleepiness affected 40.6%, headache 27.4% and tiredness 18.1%. It can cause low blood pressure, a slow heart rate and fainting. It must not be stopped suddenly. Stopping abruptly can cause a rebound rise in blood pressure and, very rarely, a serious complication called hypertensive encephalopathy. Any reduction should be planned with your prescriber.
Viloxazine. In adults, common side effects included insomnia, headache, sleepiness, fatigue, nausea, reduced appetite, dry mouth and constipation. In the adult trial, 29% had a heart rate rise of 20 beats per minute or more at some point, against 13% on placebo. It must not be combined with MAOIs or certain other medicines. Prescribers are told to screen for bipolar disorder first.
Blood pressure and pulse. A non-stimulant is not automatically gentler on the heart. A 2025 analysis found stimulants raised blood pressure and pulse no more than atomoxetine or viloxazine. Guanfacine lowered them. NICE advises checking heart rate and blood pressure before and after every dose change, and every 6 months.
Routine blood tests and ECGs aren't needed unless there's a clinical reason, NICE says. Sleep changes are worth tracking. ADHD and sleep problems often overlap anyway. Tell your prescriber and pharmacist about everything you take, including caffeine and supplements. We looked at caffeine alongside ADHD medication separately.
All three medicines carry warnings, but they differ.
Tell your prescriber promptly about low mood, agitation, unusual irritability or thoughts of self-harm. This matters most in the first months and after dose changes. Don't stop guanfacine suddenly on your own. If you feel unsafe, use the numbers at the top of this page.
Severe liver injury on atomoxetine is very rare, but it has happened. This has included acute liver failure, and one case led to a liver transplant. In the US label, most cases began within 120 days of starting.
Warning signs include itching, dark urine, yellowing skin or eyes, and tenderness on the upper right of the abdomen. Unexplained flu-like symptoms are another. Contact your doctor straight away if you notice them. If tests show liver injury, atomoxetine is stopped and not restarted. Routine liver tests are not needed otherwise, according to NICE.
We checked the HPRA's shortages list on 1 November 2026. All seven strengths of Atomoxetine Accord capsules were listed as in shortage. The reasons given were a quality issue (three strengths, listed since 2024) and manufacturing delays (four strengths, listed since July 2026). No expected return date was given. The HPRA noted that an appropriate alternative medicine is authorised.
This matters because Accord's are the only atomoxetine capsules the HPRA lists as marketed in Ireland. Other authorised atomoxetine products were listed as not marketed. No shortage was listed for guanfacine (Intuniv or Paxneury) on the same date.
If you take atomoxetine in Ireland:
We checked Irish supply only. In England, NICE says prescribing should move to your GP under shared care once your dose is stable. Your pharmacist will know the local position.
Is a non-stimulant weaker than a stimulant?
On average, yes, compared with amphetamines. In the 2018 meta-analysis, atomoxetine performed about as well as methylphenidate in adults, but less well than amphetamines. These are averages across trials, not predictions for any one person. The right choice depends on your history, side effects and other conditions.
How long does atomoxetine take to work?
It is increased gradually, and its leaflet says full improvement may take a few weeks. Adult trials measured results over 10 to 16 weeks. Agree with your prescriber when you'll review it.
Can adults take guanfacine?
Sometimes, but off-label. In Ireland and the UK it is licensed only for ages 6 to 17. NICE says adults should only be offered it with advice from a tertiary ADHD service. Published adult trials are few, and the main one was in Japanese adults.
Is viloxazine (Qelbree) available in Ireland or the UK?
We found no authorised viloxazine product in Ireland or the EU. It isn't listed in the UK medicines compendium either. It is approved for adults and children in the US.
Proco is preparing a clinician-led adult ADHD assessment service. It is not open yet; you can read about our assessments.
This article is general information, not medical advice. It does not replace a conversation with your GP, psychiatrist or pharmacist. Do not start, stop or change any medication without talking to your prescriber.
Reviewed by: Proco Team
Last updated: November 2026