Atomoxetine and viloxazine
Atomoxetine reduced ADHD symptoms more than placebo in children and adults, with a medium effect in children and a smaller one in adults, less than amphetamines achieved. Viloxazine raised response in children about 1.6 times. Nausea, low appetite and sleepiness were very common, heart rate and blood pressure rose, and both labels carry suicidal-thoughts warnings.
- Status
- Prescription drugs in the US, FDA-approved for ADHD in adults and children aged 6 and older. Neither is a controlled substance. Both labels carry a boxed warning for suicidal thoughts and behaviors, in children for atomoxetine and in all patients for viloxazine. Neither is approved for focus or concentration in people without ADHD.
- Also called
- atomoxetine, Strattera, viloxazine, viloxazine extended-release, Qelbree, SPN-812, non-stimulant ADHD medication, selective norepinephrine reuptake inhibitor
- Taken for
- ADHD, attention, focus, concentration, impulsivity, ADHD without a stimulant, ADHD with substance use concerns
Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on
Shown to help5
- StrongShown to reduce ADHD symptoms in children and adolescents more than placebo, a medium effect size of about 0.6.
- StrongShown to reduce ADHD symptoms in adults more than placebo, a small to moderate effect of about 0.4, with more people stopping for side effects.
- StrongShown to raise response in children and adolescents with ADHD about 1.6 times over placebo, about 5.5 points on a symptom scale, with benefit leveling off above 400 mg.
- LimitedOne trial found viloxazine lowered adult ADHD symptoms 3.7 points more than placebo over 6 weeks.
- LimitedSmall trials found a single dose of atomoxetine improved stopping a started action in healthy volunteers, mostly in those who did worst on placebo, with no effect on learning.
Reported risks10
- ModerateShown to raise nausea in adults to 26% on atomoxetine against 6%, and low appetite in children to 16% against 4%.Very common
- ModerateShown to cause sleepiness in 16% of children on viloxazine against 4%, and 11% on atomoxetine against 4%. Adults more often reported insomnia.Very common
- ModerateShown to raise heart rate 20 beats a minute or more in 29% of adults on viloxazine against 13%, and diastolic pressure 15 mmHg in 25% of teenagers against 13%.Very common
- ModerateShown to raise urinary hesitation to 5.6% against 0.5% and urinary retention to 1.7% against none in adults, and erectile dysfunction to 8% of men against 1%.Common
- ModerateFDA states atomoxetine raised suicidal thoughts in children and teenagers in short-term trials, 0.4% against none on placebo. No suicides occurred.Uncommon
- LimitedFDA states viloxazine raised suicidal thoughts and behaviors, 0.9% of children against 0.4% on placebo, and 1.6% of adults against none.Uncommon
- LimitedCase reports: the label describes rare severe liver injury after approval, including liver failure and one transplant. None was found in trials of about 6,000 patients.How often is not known
- LimitedThe label reports that weight and height gain in children on atomoxetine lagged behind population norms in long-term open-label studies.How often is not known
- LimitedThe labels warn that atomoxetine can cause psychotic or manic symptoms in people without such history, and that both drugs can trigger mania in people at risk.How often is not known
- LimitedThe labels contraindicate both drugs with MAO inhibitors. Fluoxetine and paroxetine raise atomoxetine levels 3 to 8 times, and viloxazine raises duloxetine, ramelteon, tizanidine and theophylline levels.How often is not known
What people take it for, and what was found
Shown to help5
ADHD in children, atomoxetine
Shown to reduce ADHD symptoms in children and adolescents more than placebo, a medium effect size of about 0.6.
The numbers and sources
- Effect
- In a network meta-analysis, atomoxetine lowered clinician-rated core ADHD symptoms in children and adolescents at about 12 weeks (SMD -0.56, 95% CI -0.66 to -0.45). For teacher ratings, only methylphenidate and modafinil separated from placebo among the drugs with data [1]. Across 25 trials, atomoxetine outperformed placebo on overall ADHD symptoms (effect size -0.64, 95% CI -0.56 to -0.71), and the authors noted about 40% kept significant symptoms [2].
- Population
- 10,068 children and adolescents in the efficacy analysis of 81 trials [1]; 3,928 children and adolescents in 25 trials [2].
- Sources
- [1], [2]
- Caveats
- Short-term trials. There were too few data at 26 and 52 weeks [1].
ADHD in adults, atomoxetine
Shown to reduce ADHD symptoms in adults more than placebo, a small to moderate effect of about 0.4, with more people stopping for side effects.
The numbers and sources
- Effect
- Atomoxetine lowered clinician-rated ADHD symptoms in adults (SMD -0.45, 95% CI -0.58 to -0.32) and was less well tolerated than placebo (OR 2.33) [1]. Across 12 trials, symptoms fell on clinician (SMD -0.40) and self ratings (SMD -0.33). Stopping for any reason (OR 1.39) and for adverse events (OR 2.57) was more frequent than on placebo [3].
- Population
- 8,131 adults in the efficacy analysis of 51 adult trials [1]; 3,375 adults in 12 trials [3].
- Sources
- [1], [3]
- Caveats
- The authors of [3] described the balance of benefit and risk in adults as poor.
ADHD in children, viloxazine
Shown to raise response in children and adolescents with ADHD about 1.6 times over placebo, about 5.5 points on a symptom scale, with benefit leveling off above 400 mg.
The numbers and sources
- Effect
- Viloxazine raised the share with a 50% drop on the ADHD Rating Scale (RR 1.62, 95% CI 1.36 to 1.93), and raised adverse events and sleepiness [4]. In fixed-dose trials, symptoms improved 5.47 points more than placebo (95% CI 4.03 to 6.91). The dose curve was bell-shaped, with no added benefit above about 400 mg, and effects leveled off at 4 to 6 weeks [5].
- Population
- 1,605 patients in 5 trials [4]; 1,560 children and adolescents, mean age 10.6, in 5 trials [5].
- Sources
- [4], [5]
- Caveats
- The two reviews share the same five trials.
ADHD in adults, viloxazine
One trial found viloxazine lowered adult ADHD symptoms 3.7 points more than placebo over 6 weeks.
Compared with placebo [6]
Focus and self-control in healthy adults
Small trials found a single dose of atomoxetine improved stopping a started action in healthy volunteers, mostly in those who did worst on placebo, with no effect on learning.
Compared with placebo, in crossover designs [7][8]
The numbers and sources
- Effect
- In healthy volunteers, atomoxetine improved response inhibition on a stop-signal task but had no effect on probabilistic learning [7]. In a later crossover trial, a single 40 mg dose sped responses and improved stopping efficiency only in proportion to how poorly a person stopped on placebo [8].
- Population
- Healthy volunteers [7]; 28 control volunteers and 26 people with cocaine use disorder [8].
- Sources
- [7], [8]
- Caveats
- Single doses on lab tasks. No trial tested daily use for focus at work or study in people without ADHD.
Mixed results1
Atomoxetine against stimulants
Mixed results: in head-to-head comparisons, amphetamines reduced clinician-rated ADHD symptoms more than atomoxetine in both children and adults.
Compared with amphetamines and methylphenidate [1]
The numbers and sources
- Effect
- In head-to-head comparisons, the only efficacy differences favored amphetamines over atomoxetine, methylphenidate and modafinil, with SMDs of -0.46 to -0.24 in children and -0.94 to -0.29 in adults [1].
- Population
- 133 trials in children, adolescents and adults [1].
- Sources
- [1]
- Caveats
- Most comparisons were indirect and rated low or very low confidence [1].
Doses studied
The atomoxetine label starts children under 70 kg at 0.5 mg/kg a day and targets 1.2 mg/kg a day, up to 1.4 mg/kg or 100 mg. Heavier children and adults start at 40 mg and target 80 mg a day, up to 100 mg. It states no added benefit was shown above 1.2 mg/kg a day or 100 mg a day [9]. The healthy-volunteer trial gave a single 40 mg dose [8]. The viloxazine label starts children aged 6 to 11 at 100 mg, adolescents at 200 mg, both up to 400 mg once daily, and adults at 200 mg up to 600 mg [6]. The viloxazine pediatric trials used 100 to 400 mg [5], and the adult trial averaged 504 mg a day [6].
Risks
Reported risks10
Nausea, low appetite and stomach pain
Shown to raise nausea in adults to 26% on atomoxetine against 6%, and low appetite in children to 16% against 4%.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- In children on atomoxetine, decreased appetite occurred in 16% against 4% on placebo, abdominal pain 18% against 10%, vomiting 11% against 6% and nausea 10% against 5%. In adults, nausea occurred in 26% against 6%, dry mouth 20% against 5%, decreased appetite 16% against 3% and constipation 8% against 3% [9]. On viloxazine, decreased appetite occurred in 7% of children against 0.4%, and nausea in 12% of adults against 3% [6].
- Population
- 1,597 children on atomoxetine and 934 on placebo; 1,697 adults on atomoxetine and 1,560 on placebo [9]; viloxazine label trials [6].
- Sources
- [9], [6]
- Caveats
- Trials of up to 18 weeks in children and 25 weeks in adults [9].
Sleepiness, tiredness and insomnia
Shown to cause sleepiness in 16% of children on viloxazine against 4%, and 11% on atomoxetine against 4%. Adults more often reported insomnia.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- In children, sleepiness occurred in 16% on viloxazine against 4% on placebo [6] and 11% on atomoxetine against 4%, with fatigue in 8% against 3% [9]. In adults, insomnia occurred in 15% on atomoxetine against 8% [9] and 23% on viloxazine against 7%, with fatigue in 12% against 3% [6]. A meta-analysis of viloxazine found sleepiness significantly more frequent than placebo [4].
- Population
- Label trials in children and adults [9][6]; 1,605 patients in 5 viloxazine trials [4].
- Sources
- [6], [9], [4]
- Caveats
- Sleepiness may lessen with time, which short trials do not show.
Heart rate and blood pressure
Shown to raise heart rate 20 beats a minute or more in 29% of adults on viloxazine against 13%, and diastolic pressure 15 mmHg in 25% of teenagers against 13%.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- On viloxazine, a heart rate rise of 20 bpm or more occurred in 22% to 34% of children and teenagers against 9% to 23% on placebo, and in 29% of adults against 13%. Diastolic pressure rose 15 mmHg or more in 25% of teenagers on 400 mg against 13%, and 13% of adults against 9% [6]. On atomoxetine, about 5% to 10% of children had clinically important changes in heart rate or blood pressure. Mean heart rate rose about 5 bpm in children, and 9.4 to 11 bpm in poor CYP2D6 metabolizers. Tachycardia was reported in 1.5% of adults against 0.5%. The label reports sudden death in children with heart abnormalities, and sudden death, stroke and heart attack in adults, of unknown relation to the drug [9].
- Population
- Viloxazine label trials in children, teenagers and adults [6]; atomoxetine label trials [9].
- Sources
- [6], [9]
- Caveats
- The band above is from the viloxazine trials. Rates are any rise at any visit, not sustained hypertension.
Urinary hesitation and erectile problems in adults, atomoxetine
Shown to raise urinary hesitation to 5.6% against 0.5% and urinary retention to 1.7% against none in adults, and erectile dysfunction to 8% of men against 1%.
The numbers and sources
- How common
- Common: between 1 in 100 and 1 in 10 people.
- Effect
- In adult trials, urinary hesitation occurred in 5.6% (30 of 540) against 0.5%, and urinary retention in 1.7% (9 of 540) against 0%. Erectile dysfunction occurred in 8% of men against 1%. Rare cases of priapism, an erection lasting over 4 hours, were reported after approval in children and adults [9].
- Population
- 540 adults on atomoxetine and 402 on placebo, and 943 men on atomoxetine against 869 on placebo [9].
- Sources
- [9]
- Caveats
- Priapism reports have no denominator.
FDA boxed warning: suicidal thoughts in children, atomoxetine
FDA states atomoxetine raised suicidal thoughts in children and teenagers in short-term trials, 0.4% against none on placebo. No suicides occurred.
The numbers and sources
- How common
- Uncommon: between 1 in 1,000 and 1 in 100 people.
- Effect
- In 12 placebo-controlled studies of 6 to 18 weeks, suicidal ideation occurred in 0.4% (5 of 1,357) of children on atomoxetine, including one suicide attempt, against 0% (0 of 851) on placebo, all aged 6 to 12 and all in the first month. A similar analysis in adults found no increase [9]. A meta-analysis found suicidal behavior or ideation in 0.37% of children against 0.07% on placebo, not statistically significant (MHRR 1.57), and 0.11% against 0.12% in adults [10]. In 279,315 young people in Medicaid, suicidal events did not differ between atomoxetine and stimulants (HR 0.95, 95% CI 0.47 to 1.92) [11].
- Population
- Over 2,200 children in 12 trials [9]; 3,883 children and 3,365 adults in trials [10]; young people aged 5 to 18 in 26 Medicaid programs [11].
- Sources
- [9], [10], [11]
- Caveats
- Few events, so intervals are wide [11]. The trials were short, and the label states it is unknown whether the risk extends to longer use [9].
FDA boxed warning: suicidal thoughts, viloxazine
FDA states viloxazine raised suicidal thoughts and behaviors, 0.9% of children against 0.4% on placebo, and 1.6% of adults against none.
The numbers and sources
- How common
- Uncommon: between 1 in 1,000 and 1 in 100 people.
- Effect
- In short-term trials, 9 of 1,019 children (0.9%) on viloxazine reported suicidal ideation or behavior against 2 of 463 (0.4%) on placebo. In adults, 3 of 189 (1.6%) reported suicidal ideation against 0 of 183. No suicides occurred [6].
- Population
- 1,019 children on viloxazine and 463 on placebo; 189 adults on viloxazine and 183 on placebo [6].
- Sources
- [6]
- Caveats
- Small numbers of events.
Liver injury, atomoxetine
Case reports: the label describes rare severe liver injury after approval, including liver failure and one transplant. None was found in trials of about 6,000 patients.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- No liver injury was detected in trials of about 6,000 patients. After approval, rare cases of clinically significant liver injury were reported, mostly within 120 days of starting, some with liver enzymes over 20 times normal and jaundice. In one patient, injury recurred on restarting, which the label calls evidence the drug likely caused it [9].
- Population
- About 6,000 trial patients and postmarketing reports [9].
- Sources
- [9]
- Caveats
- Reports have no denominator.
Growth in children
The label reports that weight and height gain in children on atomoxetine lagged behind population norms in long-term open-label studies.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- In long-term open-label studies, weight and height gain in children treated with atomoxetine lagged behind that predicted from population data. Weight decreased in 7% of poor CYP2D6 metabolizers against 4% of others [9].
- Population
- Children in long-term open-label studies [9].
- Sources
- [9]
- Caveats
- Compared with population norms, not a randomized control group.
Mania, psychosis and aggression
The labels warn that atomoxetine can cause psychotic or manic symptoms in people without such history, and that both drugs can trigger mania in people at risk.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- The atomoxetine label states hallucinations, delusional thinking or mania can be caused by the drug at labeled doses, and that there is evidence it may cause or worsen aggression or hostility [9]. The viloxazine label warns of activation of mania or hypomania [6].
- Population
- Labeling statements [9][6].
- Sources
- [9], [6]
- Caveats
- No rates are given.
Drug interactions
The labels contraindicate both drugs with MAO inhibitors. Fluoxetine and paroxetine raise atomoxetine levels 3 to 8 times, and viloxazine raises duloxetine, ramelteon, tizanidine and theophylline levels.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- Atomoxetine is contraindicated with MAO inhibitors, including linezolid and intravenous methylene blue, or within 14 days, after reports of serious, sometimes fatal reactions. Fluoxetine raised atomoxetine exposure 6 to 8 times, and paroxetine or fluoxetine raised peak levels 3 to 4 times. The label advises caution with blood pressure drugs and pressor drugs, and notes oral albuterol's effects on heart rate and blood pressure can be increased [9]. Viloxazine is contraindicated with MAO inhibitors because of hypertensive crisis risk, and with alosetron, duloxetine, ramelteon, tasimelteon, tizanidine or theophylline, whose levels it raises by blocking CYP1A2 [6].
- Population
- Labeling statements and interaction studies [9][6].
- Sources
- [9], [6]
- Caveats
- Changes in drug levels, not measured harm.
Possible, not studied in people1
Pregnancy
Not studied in people. Animal studies found fewer live rabbit fetuses on atomoxetine and fetal toxicity in rats on viloxazine. Human data are insufficient.
No study in people. This rests on animal studies.
The numbers and sources
- Effect
- The atomoxetine label states published human data are insufficient, and one of three rabbit studies found fewer live fetuses and more early resorptions [9]. The viloxazine label states case series are insufficient, and animal studies found fetal toxicity and delayed development in rats and maternal toxicity in rabbits at doses near the maximum labeled dose [6].
- Population
- Pregnant rabbits, rats and mice (animal) [9][6].
- Sources
- [9], [6]
- Caveats
- Animal data do not show what happens in human pregnancy.
Claims tested and not found
- That atomoxetine reduces ADHD symptoms as much as stimulants. In head-to-head comparisons, amphetamines reduced clinician-rated symptoms more than atomoxetine in children and adults [1].
- That more viloxazine gives more benefit. The dose curve in children was bell-shaped, with no added benefit above about 400 mg [5].
- That atomoxetine improves every kind of thinking in healthy people. It improved stopping a response but had no effect on probabilistic learning [7].
Related
Sources
- 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. The Lancet Psychiatry. 2018. https://doi.org/10.1016/S2215-0366(18)30269-4
- Schwartz S, Correll CU. Efficacy and Safety of Atomoxetine in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder: Results From a Comprehensive Meta-Analysis and Metaregression. Journal of the American Academy of Child & Adolescent Psychiatry. 2014. https://doi.org/10.1016/j.jaac.2013.11.005
- Cunill R, Castells X, Tobias A, et al. Atomoxetine for attention deficit hyperactivity disorder in the adulthood: a meta-analysis and meta-regression. Pharmacoepidemiology and Drug Safety. 2013. https://doi.org/10.1002/pds.3473
- Singh A, Balasundaram MK, Singh A. Viloxazine for Attention-Deficit Hyperactivity Disorder: A Systematic Review and Meta-analysis of Randomized Clinical Trials. Journal of Central Nervous System Disease. 2022. https://doi.org/10.1177/11795735221092522
- Yu CL, Kao YC, Thompson T, et al. Response Trajectories and Temporal Trends of Viloxazine Treatment for Young People With ADHD: A Meta-Analysis. JAMA Network Open. 2024. https://doi.org/10.1001/jamanetworkopen.2024.45885
- U.S. Food and Drug Administration. QELBREE (viloxazine extended-release capsules), prescribing information. 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aedf408d-0f84-418d-9416-7c39ddb0d29a
- Chamberlain SR, Müller U, Blackwell AD, et al. Neurochemical Modulation of Response Inhibition and Probabilistic Learning in Humans. Science. 2006. https://doi.org/10.1126/science.1121218
- Zhukovsky P, Morein-Zamir S, Ziauddeen H, et al. Prefrontal Cortex Activation and Stopping Performance Underlie the Beneficial Effects of Atomoxetine on Response Inhibition in Healthy Volunteers and Those With Cocaine Use Disorder. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. 2022. https://doi.org/10.1016/j.bpsc.2021.08.010
- U.S. Food and Drug Administration. STRATTERA (atomoxetine) capsules, prescribing information. 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=309de576-c318-404a-bc15-660c2b1876fb
- Bangs ME, Wietecha LA, Wang S, et al. Meta-Analysis of Suicide-Related Behavior or Ideation in Child, Adolescent, and Adult Patients Treated with Atomoxetine. Journal of Child and Adolescent Psychopharmacology. 2014. https://doi.org/10.1089/cap.2014.0005
- Linden S, Bussing R, Kubilis P, et al. Risk of Suicidal Events With Atomoxetine Compared to Stimulant Treatment: A Cohort Study. Pediatrics. 2016. https://doi.org/10.1542/peds.2015-3199