ADHD and Sleep: Why Non-Stimulants Might Be the Right Choice (Part 1)

For patients with ADHD who experience sleep disturbances, such as difficulty falling asleep or frequent nighttime awakenings, non-stimulant medications may help improve nighttime sleep quality.

Sleep disturbances, such as difficulty falling asleep and frequent nighttime awakenings, can cause significant hardship for individuals with ADHD. These nighttime issues may be more distressing to patients than the hallmark daytime ADHD symptoms of inattention and hyperactivity/impulsivity.¹ Furthermore, one study of 145,490 individuals with ADHD reported that 7.5% had a concrete diagnosis of a sleep disorder and 47.5% had a prescription for sleep medication, highlighting the prevalence of such symptoms.² 

Despite the high prevalence, sleep disorders in ADHD were largely overlooked in guidelines until recently. The 1980 DSM-III listed “restless sleep” among the criteria for a diagnosis of ADHD, but mentions of sleep disturbance were removed from subsequent DSM revisions until it finally reemerged as an important clinical factor in the DSM-5 and 2019 American Pediatric Association (APA) guidelines.¹ This reinvigorated interest has resulted in an uptick in research on sleep in ADHD,¹ both as a prominent comorbidity of ADHD itself and also as a potential byproduct of available ADHD therapies. 

Stimulant medications such as methylphenidate and amphetamines remain the mainstay first-line therapies for ADHD, and these are known to be effective at improving focus and decreasing hyperactivity during the daytime.¹ However, they can disrupt sleep when not carefully managed. Delayed sleep onset, shortened rapid-eye-movement (REM) sleep, reduced slow-wave sleep time, and insomnia are commonly reported adverse effects.³ Moreover, because sleep disturbances are known to exacerbate ADHD symptoms,¹ medications prescribed to treat those symptoms may instead contribute to ADHD symptoms by causing sleep disturbances. The resulting cycle in which loss of sleep worsens ADHD symptoms, but treatment can impair sleep, represents a significant clinical challenge. This bidirectional relationship necessitates treatment approaches that consider both daytime functioning and nighttime rest.⁴ 

For patients whose ADHD is complicated by poor sleep, non-stimulants may offer a more balanced solution.⁵ These agents include the alpha-2 agonists guanfacine and clonidine, the selective norepinephrine reuptake inhibitor (SNRI) atomoxetine, and most recently, the SNRI viloxazine. Each targets alternate pathways to address attention and reduce hyperactivity, but with less activation that can disrupt sleep in individuals who receive stimulants. Specifically, non-stimulants enhance noradrenergic neurotransmission, whereas stimulants inhibit reuptake of both dopamine and norepinephrine, enhancing neurotransmission of both. As a result, stimulants have a larger effect size for reducing core ADHD symptoms but are also more activating due to the increase in dopaminergic neurotransmission.⁵

Also, unlike stimulants, non-stimulants do not produce abrupt peaks and troughs in plasma concentration and are, therefore, less likely to cause late-day rebound of hyperactivity that might interfere with circadian rhythms.⁵ In fact, augmentation of stimulants with a non-stimulant can extend the duration of symptom control and allow for a lower stimulant dose, mitigating negative effects of stimulants on sleep.^5,6 Additionally, the absence of abuse potential may make non-stimulants a more attractive option for individuals with sleep disturbances, as substance abuse is often comorbid with ADHD and can further impair sleep architecture.^1,7

Nonetheless, while non-stimulants have a comparatively mild impact on sleep architecture, they are not without the potential for adverse effects on sleep.³ For example, guanfacine has been associated with increased awake time after sleep onset as well as reduced REM, non-REM, and slow-wave sleep time.³ Atomoxetine has not been associated with sleep disturbances,³ but guanfacine, clonidine, and atomoxetine have other untoward effects that may limit their utility, most notably cardiovascular effects such as increased blood pressure and heart rate.⁸ 

The latest entrant to the non-stimulant armamentarium is viloxazine. Although both viloxazine and atomoxetine are SNRIs, viloxazine shows weaker norepinephrine reuptake inhibition and minimal serotonin or dopamine reuptake effects compared to atomoxetine. Instead, viloxazine acts on serotonin receptors (5-HT_2B antagonist, 5-HT_2C partial agonist, 5-HT₇ antagonist) and increases serotonin, norepinephrine, and dopamine levels in the prefrontal cortex.⁶ With this broader mechanism of action, patients may show significantly greater improvement in ADHD symptoms with viloxazine. In a crossover study comparing viloxazine in 50 patients with ADHD (35 pediatric), discontinuation due to insomnia was infrequent with atomoxetine (n=1; 2%) but did not occur with viloxazine.⁶ 

Taken together, these findings highlight the growing importance of choosing ADHD treatments that support daytime symptom control while preserving or improving nighttime sleep quality. As sleep disturbances can both worsen ADHD symptoms and be worsened by first-line stimulants, non-stimulants represent an opportunity to reduce the risk of sleep disruption while improving core symptoms, helping to break the vicious cycle. In some cases, replacing stimulants or stimulant dose reductions may be possible.

REFERENCES

1. Cortese S, Veronesi GF, Gabellone A, et al. The management of sleep disturbances in children with attention-deficit/hyperactivity disorder (ADHD): an update of the literature. Expert Rev Neurother. 2024;24(6):585-596. doi:10.1080/14737175.2024.2353692
2. Ahlberg R, Garcia-Argibay M, Taylor M, et al. Prevalence of sleep disorder diagnoses and sleep medication prescriptions in individuals with ADHD across the lifespan: a Swedish nationwide register-based study. BMJ Ment Health. 2023;26(1):e300809. doi:10.1136/bmjment-2023-300809
3. Rocha NS, Correa RDESA, Dias ACM, Bueno CDF. Association between sleep pattern and pharmacological treatment in children with attention deficit disorder with hyperactivity: a systematic review. Rev Paul Pediatr. 2023:41:e2022065. doi:10.1590/1984-0462/2023/41/2022065
4. Hvolby A. Associations of sleep disturbance with ADHD: implications for treatment. Atten Defic Hyperact Disord. 2015;7(1):1-18. doi:10.1007/s12402-014-0151-0
5. Mechler K, Banaschewski T, Hohmann S, Häge A. Evidence-based pharmacological treatment options for ADHD in children and adolescents. Pharmacol Ther. 2022:230:107940. doi:10.1016/j.pharmthera.2021.107940
6. Price MZ, Price RL. Extended-Release viloxazine compared with atomoxetine for attention deficit hyperactivity disorder. CNS Drugs. 2023;37(7):655-660. doi:10.1007/s40263-023-01023-6
7. Dey A, Do TL, Almagor D, Khullar A. Managing comorbid sleep issues in patients with attention-deficit/hyperactivity disorder. CMAJ. 2025;197(12):E323-E324. doi:10.1503/cmaj.241262
8. Cutler AJ, Mattingly GW, Jain R, O'Neal W. Current and future nonstimulants in the treatment of pediatric ADHD: monoamine reuptake inhibitors, receptor modulators, and multimodal agents. CNS Spectr. 2022;27(2):199-207. doi:10.1017/S1092852920001984
9. Roehrs TA, Roth T. Sleep disturbance in substance use disorders. Psychiatr Clin North Am. 2015;38(4):793-803. doi:10.1016/j.psc.2015.07.008