Acute Sleep Medications for Professional Athletes

CATEGORY 1 CME

Premiere Date: December 20, 2025

Expiration Date: June 20, 2027

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1. Physicians (CME)

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ACTIVITY GOAL

To inform readers how best to choose interventions, both pharmacologic and nonpharmacologic, when working with athlete patients.

LEARNING OBJECTIVES

1. Learn about acute sleep disruption among elite athletes.

2. Learn about the benefits and risks of pharmacologic interventions in this patient population, including their unique challenges.

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This accredited continuing education (CE) activity is intended for psychiatrists, psychologists, primary care physicians, physician assistants, nurse practitioners, and other health care professionals who seek to improve their care for patients with mental health disorders.

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Acute sleep disruption is common among elite athletes, with rates of sleep complaints and insomnia symptoms exceeding those of the general population; 13% to 70% of athletes report sleep disturbance complaints, with an average of 26% scoring significantly for insomnia on tools such as the Insomnia Severity Index or the Pittsburgh Sleep Quality Index.¹ Unique contributors include irregular competition schedules, frequent international travel with rapid time zone changes, precompetition anxiety, competitive stress, chronic pain and injuries, stimulant use and behavioral factors, and unfamiliar sleeping environments, all of which can precipitate acute sleep crises that are not amenable to standard sleep hygiene or cognitive behavior therapy for insomnia (CBTi) in the short-term.^2,3 Even a single night of poor sleep can result in measurable declines in reaction time, cognitive processing, and physical performance, which are critical in high-stakes athletic environments.^4,5

Nonpharmacologic Interventions

Nonpharmacologic approaches, including CBTi and sleep hygiene, are considered first-line treatments for chronic insomnia. However, their utility is limited in acute or emergency scenarios where immediate sleep restoration is required.² See Table 1 for a list of sleep hygiene tips.

Pharmacology

There is a glaring lack of randomized controlled trials addressing acute pharmacologic interventions for sleep crises among elite athletes. As per the European Insomnia Guidelines of 2023, the initial treatment for insomnia and sleep-related problems is CBTi, following a medical and psychiatric assessment for comorbid illnesses.⁶ Upon CBTi’s failure, patients are referred to a treating physician to evaluate the risks and benefits of using a medication to aid their sleep. For the purposes of this article, we will focus on the pharmacological options available to help manage sleep disturbances and disorders.

Benzodiazepine receptor agonists/GABA receptor agonists. Benzodiazepine receptor agonists, often referred to as Z-drugs, are agonists on the γ-aminobutyric acid type A (GABAA) receptor with different chemical structures but a similar mechanism of action to benzodiazepines.⁷ Benzodiazepines and Z-drugs increase the overall GABA activity, causing extensive inhibition of the central nervous system (CNS).⁸ Zolpidem, the most widely prescribed Z-drug, has selective α1, α2, α3, and α5 subunit agonism, with the α2 subunits in the amygdala causing its anxiolytic effect. Z-drugs typically have a shorter half-life and are thought to carry a lower risk of dependence than benzodiazepines. However, concerns remain regarding cognitive and motor adverse effects without the overall sleep architecture being affected; thus, Z-drugs are promoted as being less severe, with less risk of dependence, tolerance, and withdrawal.⁷

Research findings suggest that Z-drugs have their maximum positive sleep effects when taken for up to 4 weeks, with eszopiclone continuing to show positive signs for up to 6 months in specific cases. Although there are data ranging from 3 to 12 months for some Z-drugs, caution is advisable when considering use beyond 4 weeks, due to the long-term risks and adverse effects when compared with other effective treatments and research evidence.⁶

When assessing persistent risks, clinicians should give attention to tolerance, dependence, nocturnal confusion, memory impairment, negative cognitive functioning effects, hangover driving and motor function difficulties, and rebound insomnia with withdrawal.^6,8 Additionally, partial sleep activities, such as sleepwalking, -talking, and -eating, are also noted while individuals are semiconscious.⁷ Falls also appear to be dose dependent with Z-drugs compared with benzodiazepines. Although less likely, serious injuries such as fractures and intracranial hemorrhages, followed by self-injuries, fatal falls, accidental overdose, hypothermia, suicide attempts, fatal motor vehicle collisions, gunshot wounds, carbon monoxide poisoning, drowning or near drowning, burns, and homicide, have occurred. Given these events, which can occur as early as after 1 dose of the medication, patients with complex sleep behaviors are contraindicated for Z-drugs. Notably, zolpidem has the most reported adverse events compared with other Z-drugs. Following the initial ingestion of zolpidem, patients experienced psychomotor vigilance, poor working memory, delayed word recall, and subjective sleepiness, which decreased as use was continued.⁷

Regarding concerns of addiction, dependence, tolerance, and withdrawal, zolpidem has been shown to have the highest rates, with the potential for hallucinations, delirium, paradoxical stimulant effects, and drug-induced mania.⁷ The likelihood of stimulating, euphoric, and manic-like effects is associated with repeated intake and dose increases due to tolerance. The initial dose to cause these euphoric effects was as low as 10 mg, which occurred within the first month of use and as quickly as within the first 15 minutes, lasting up to 3 hours. Subjectively, patients rate their experience with the Z-drugs, on a scale of 1 to 10 (1 = very poor, 10 = very positive), as 7.3 compared with ramelteon (4.63) and suvorexant (3.65), although this was attributed to their higher addictive properties and not a direct reflection of efficacy.⁷ While there are several benefits to using Z-drugs to address sleep concerns and insomnia, they do not come without risks.

Melatonin receptor agonists (melatonin and ramelteon). Melatonin, a naturally occurring hormone from the pineal gland that regulates the sleep-wake cycle, and ramelteon, a synthetic melatonin receptor agonist, have also been studied and used for sleep disturbances and disorders. Due to melatonin’s minimal adverse effect profile and decreased concern for addiction, it is frequently utilized as an augmenting agent that increases sedative activity when coadministered with other hypnotic agents.⁷ As a singular agent, data from most studies show small to medium effects on sleep-related parameters when treating insomnia with melatonin, with occasional conflicting results and doses ranging from 0.15 mg to 12 mg, which is why many clinicians reserve it for circadian rhythm disorders rather than primary insomnia, but specifically when addressing circadian rhythm concerns, such as jet lag.^6,7

Although melatonin is not associated with clinically significant adverse events, some patients report fatigue, mood changes, dizziness, headache, and changes in psychomotor and neurocognitive performance, which are short-lived and mostly related to daytime dosing. There have been rare instances of endocrine disturbances (reproductive parameters and glucose metabolism) and cardiovascular changes (blood pressure and heart rate believed to be dependent on dose, timing, and drug interactions with antihypertensive medication), as well as hypothermia, agitation, nightmares, and skin irritation; however, they all appear to be self-limiting within a few days with no changes related to discontinuation or dose changes.⁷

One advancement with these medications has been the development of prolonged or continuous-release melatonin, which has been approved for insomnia management in Europe.⁶ An initial issue with melatonin use is the short half-life, due to the gastrointestinal (GI) acidity needed for absorption, whereas the continuous-release model allows the tablet to maintain its acidity well into the intestines for up to almost 7 hours of use.⁷ This did bring on a GI adverse effect profile of nausea, vomiting, and stomach cramping for some, but showed promise for more effective use, as previous subjective patient criticism suggests regular-release melatonin supplements are ineffective as hypnotics.⁷

The minimal risk of taking melatonin or ramelteon is balanced by their limited efficacy. European Insomnia Guidelines suggest it is safe to provide these medications well beyond the typical 4 week period, but continue to question their utility outside the potential for a continuous-release method.⁶ Another drawback against melatonin is that, as a supplement, its quality varies widely depending on the source of manufacturing, leading to inconsistent results. Melatonin-based treatments have their place for sleep disturbances and disorders but are far from being an effective first-line consideration.

Dual orexin receptor antagonists (DORAs; suvorexant, lemborexant, daridorexant). DORAs are relatively new medications, with suvorexant, lemborexant, and daridorexant gaining FDA approval for insomnia in 2014, 2019, and 2022, respectively. DORAs promote sleep by selectively inhibiting orexin-A and orexin-B from binding to their wake-promoting receptors, the G-protein–coupled OX1 and OX2 receptors, thereby decreasing a patient’s wake drive.8 The discovery of these neuropeptides dates back to 1998, when 2 separate research groups named them orexin-A and -B, as well as hypocretin-1 and -2, due to their connection with feeding and their production in the lateral/paraventricular hypothalamus, respectively. A year later, their connection between canine narcolepsy and a defective OX2R gene brought interest to their role in sleep, which was confirmed in humans in 2000, with a deficit of orexin neurons causing narcolepsy with cataplexy.⁸

After the undertaking of much more research, orexin has also been found to play a role in appetite regulation, heart rate, blood pressure, lipid profile, metabolic rate, physical activity, thermogenesis, and energy expenditure.⁹ Although orexin is only produced in the hypothalamus, the neurons have extensive projections to other brain areas, with orexin-A having a similar affinity to both receptors, and orexin-B having a strong affinity for OX2R.⁸ Orexin-A levels in the brain’s extracellular and cerebrospinal fluid follow a circadian rhythm by adapting to emotional states, light/dark cycles, sleep pressure, and energy balance, with higher levels correlating to more wakefulness and sleep avoidance by inhibiting the ventrolateral preoptic nucleus “sleep center.” There have also been studies whose data show that orexin neurons decrease with age, although they are more hyperexcitable, providing more context for why older patients have a decreased arousal threshold during sleep and sleep fragmentation.⁸

Among the available pharmacological sleep agents in Europe, the largest clinical trials were two controlled phase 3 studies of daridorexant, involving 1854 patients treated for insomnia with either daridorexant or placebo for 3 months.⁶ During this period, 50 mg of daridorexant had significant effects on polysomnography-defined sleep parameters, sleep latency, and wake after sleep onset, and increased subjective total sleep time, with reductions in daytime sleepiness/fatigue, with small to medium effect sizes; however, no subjective improvements in sleep-onset latency were reported. The study was also extended for up to 1 year in over 800 patients and continued to demonstrate efficacy with no next-morning sleepiness and no withdrawal-related symptoms or rebound observed after treatment discontinuation, indicating the role of DORAs as potential long-term sleep medications.⁶ Data from alternative studies have also shown improvements in daytime functioning using the Insomnia Daytime Symptoms and Impacts Questionnaire, a self-reporting instrument for insomnia.⁸

Pharmacologically, all 3 DORAs are lipophilic, metabolized hepatically by cytochrome P450 3A4 (CYP3A4), and mainly excreted into feces, with their main differences in their pharmacokinetic/pharmacodynamic (PK/PD) properties.⁸ It is important to note the CYP3A4 metabolization of DORAs because concomitant use with a CYP3A4 inhibitor, such as grapefruit juice, can cause higher plasma levels of DORAs and is contraindicated in Europe. However, there are no reports of increased intensity or prolonged duration of next-morning somnolence in patients or study participants.

There have been also trials assessing the safety and tolerability using supratherapeutic doses of lemborexant, 200 mg, compared with the highest approved dose of 10 mg for insomnia, in which participants complained of headaches and somnolence with daytime administration; this may not be as applicable to those taking it for insomnia at night before bed, although it has been mentioned in other insomnia studies and does appear to be dose dependent.⁸ Of note, the safety warnings and precautions on the DORAs’ prescribing information comment on CNS-depressant effects and daytime impairment with decreased motor coordination, specifically regarding driving, if taken with less than a full night of sleep. The FDA requires a 1-hour monotonous highway driving assessment for its safety evaluation of drugs with CNS effects to evaluate sustained vigilance and attention, through objective performance, of the individual’s staying in lane, and subjective judgment of their driving quality. Interestingly, participants were able to perceive their own driving challenges, which provides a safeguard against dangerous behaviors and is not seen in other CNS medications (eg, GABAergic drugs, such as benzodiazepines or Z-drugs).⁸

Unique adverse events for DORAs are nightmares, muscle weakness, and sleep paralysis, without any noted increased risk of cataplexy, although the drugs are contraindicated in patients with narcolepsy.^7,8 However, DORAs are devoid of any QT liability. Lastly, there is no current evidence of dependence, withdrawal, tolerance, or rebound insomnia with treatment discontinuation; data from rat studies showed no positive reinforcing effects with self-administrations, unlike benzodiazepines and Z-drugs, and in the human abuse potential studies, results from a self-rated visual analogue scale showed DORAs produced greater drug-liking—a measure of the subjective pleasurable effects of a drug—compared with placebo, leading to their classification as Schedule IV controlled substances.⁸

Given DORAs’ effectiveness in treating insomnia and sleep disturbances, there has been a shift in the theory of insomnia as a disease of hyperarousal with an overactive wake system, which is then dampened through the antagonism of orexin.⁸ This idea further highlights why stimulating the sleep-signaling system (eg, GABAergic drugs) may give incomplete help. In retrospect, it may make more sense why the American Geriatrics Society Beers Criteria recommended that Z-drugs should be avoided in older adults in 2019, due to adverse GABAergic events, whereas DORAs have remained a safe and tolerable alternative in geriatric patients.

Similarly, due to the overarching CNS and respiratory depression of benzodiazepines and Z-drugs, there is substantial concern about their use in individuals with compromised respiratory function. However, there have been direct studies of DORAs in patients with COPD and obstructive sleep apnea with insomnia, and there were no meaningful changes in nighttime respiratory function.⁸ When comparing brotizolam, a benzodiazepine analog, with suvorexant in physical and cognitive impairment following forced awakening 90 minutes post ingestion, with brotizolam’s impairment significant to that of placebo (total z score, 0.03 vs 0.61), suvorexant was not significantly different when compared with placebo and brotizolam (total z score, 0.25 vs 0.03 vs –0.61, respectively).⁷ Patients taking suvorexant and brotizolam performed more poorly than those taking placebo in all different function tests performed; the only statistically significant difference between the 2 agents was in patients’ body sway with open eyes (static balance), with brotizolam being worse, suggesting DORAs may have a lower fall risk than GABAergic medications. Data from another study showed that suvorexant and ramelteon significantly improved subjective sleep quality compared with zolpidem (difficulty staying asleep: 6.3% vs 34%, P < .001; daytime sleepiness: 33% vs 63%, P < .001) and ramelteon, with decreased delirium (7.0% vs 31%, P < .001) in patients with acute stroke.⁷ For all these reasons and more, evidence implies that DORAs may be superior sleep medications to Z-drugs and melatonin.

Tempting as it may be to immediately consider DORAs as “go-to” sleep medications in acute scenarios, data specific to acute or emergency use in athletes remain notably limited.10,11Further research is therefore imperative to establish optimal dosing, timing, and safety in this unique population.^2,10,12

Clinical Considerations

Using sleep medications with professional athletes calls for close attention to how the body processes these drugs. There is a paucity of research that specifically looks at elite athletes’ pharmacokinetics relative to competition schedules.¹³ Most of what we know comes from studies on the general population—and those findings might not fully apply to the unique physiology and metabolism of high-level athletes.² The pharmacokinetic profiles of appropriate sleep medications illustrate these critical timing considerations (Table 2). The timing of competitions plays a major role in determining which sleep medications are appropriate.¹⁴ Factors such as jet lag, unfamiliar sleep environments at away venues, and events scheduled outside an athlete’s usual sleep-wake cycle shape the need for and choice of pharmacological support.¹⁵ Morning events in particular present a challenge, as there is little time for the body to clear the drug before performance. In contrast, evening competitions may offer greater flexibility for dosing.

Choosing whether and what to prescribe requires a careful risk-benefit analysis—weighing the performance costs of inadequate sleep against the possible downsides of medication adverse effects.^5,16 Athletes vary widely in how they tolerate these medications, and the specific demands of the sport—such as the need for fast reflexes, precise movements, and sharp thinking—should guide decisions around the medication and its timing.¹⁷

The high cardiovascular load associated with training and competition and the potential for exercise-induced cardiac strain mean that any cardiac adverse effects of sleep agents must be evaluated carefully. Some medications can affect heart rate variability during restorative sleep, and for athletes with known arrhythmias, hypertrophic cardiomyopathy, or recent cardiac events, most sleep medications are considered off-limits.¹⁸

Respiratory concerns are also important, particularly for athletes at greater risk of sleep-disordered breathing. Although Z-drugs typically cause minimal respiratory depression at therapeutic doses, their effects can be amplified at altitude or in individuals with underlying respiratory vulnerabilities.¹⁹ Prescribers should resist the marketing influences to think these medications are safe enough to prescribe reflexively; they should always conduct a thorough prescreening that includes questions about snoring, observed apneas, and, where available, previous sleep study results.

Preserving next-day cognitive and motor function is paramount in high-performance sports environments.²⁰ Any medication that even mildly impairs reaction time, coordination, or mental clarity can compromise performance, especially in sports that demand precision, such as gymnastics, diving, or figure skating.^21,22 Even subtle effects on balance or decision-making must be evaluated in practice and real-world competition settings.

Screening Considerations

Psychiatric evaluation should be standard practice before prescribing sleep medications to athletes.^20,23 For DORAs, clinicians should screen for active psychosis, recent suicidal thoughts, a history of complex sleep behaviors, and any current mood disorders. Z-drugs, on the other hand, require careful consideration of past substance misuse, current treatment for depression, and any prior unusual or paradoxical responses.¹⁹ Even melatonin warrants caution in athletes with bipolar disorder, seasonal affective disorder, or autoimmune conditions, given its potential immune-modulating effects.

Age and sex can also influence how medications are metabolized and tolerated. Concerns include potential effects on growth and neurodevelopment in adolescent athletes. For female athletes, hormonal fluctuations and micronutrient deficiencies, especially iron, may complicate treatment. Older (masters-level) athletes often process medications more slowly, requiring dose adjustments and more frequent monitoring.²²

Antidoping Adherence

Any use of sleep medications in competitive athletes must adhere to current World Anti-Doping Agency (WADA) rules (Table 3).²⁴ The WADA prohibited substances list is updated annually, and team clinicians must confirm the adherence status of any medication before use. Clinicians must stay alert and aware of this ever-evolving landscape as usage patterns change and new evidence emerges.²⁵

The detection window for sleep medications in antidoping and in-competition testing is largely shaped by each drug’s pharmacokinetics and the sensitivity of available testing methods. Due to its endogenous nature and significant physiological variability, melatonin is generally not detectable through standard antidoping panels, and it is not currently a target of routine screening.²

Z-drugs such as zaleplon, which have a relatively short half-life of around 1 hour, can sometimes be detected in urine or blood for up to 24 hours post dose when sensitive analytic techniques are employed.^3,26 However, detection beyond this window is uncommon in most standard antidoping protocols.

DORAs, including lemborexant and daridorexant, have significantly longer half-lives—approximately 17 to 19 hours for lemborexant and around 8 hours for daridorexant. In forensic contexts, these agents can be detected in whole blood for 24 to 48 hours using advanced liquid chromatography–tandem mass spectrometry techniques. Still, DORAs are not part of current routine antidoping panels, and data on their detection in elite athletes remain limited.⁸

As the use of newer compounds grows, it is increasingly important to consider detection timing alongside competition schedules and sport-specific demands. Continued research is needed to refine our understanding of detection windows and to help shape future antidoping policy. Distinguishing between in-competition and out-of-competition use is essential. Although most sleep medications are allowed outside competition windows, timing becomes critical to avoid adverse test results during the in-competition period.²⁴ Physicians and performance teams must remain up to date on national and international policies, which can vary by jurisdiction.

Lastly, maintaining proper documentation is nonnegotiable, no matter how pressurized or fast-paced the sports environment. This includes detailed medical records, informed consent, and outcome tracking. As sleep pharmacotherapy becomes more widespread in sport, regulatory scrutiny will likely increase. Staying ahead of updates to WADA policy and clinical best practices will be key to ensuring adherence and protecting athlete health.²⁵

Clinical Decision-Making Algorithm

Acute sleep interventions in professional athletes should begin with an individualized, risk-based approach, prioritizing nonpharmacologic treatments as the foundation. Pharmacologic options are considered only when behavioral strategies prove insufficient or when immediate sleep is necessary due to travel or competition demands. Given the absence of athlete-specific randomized controlled trials for these medications, shared decision-making is critical, and clinicians should be transparent about the limitations in the evidence base.^2,3,12 Rather than relying on rigid thresholds, such as a specific number of hours of sleep deprivation or competition timelines, expert recommendations emphasize a more flexible, athlete-centered approach.⁵ The evaluation should account for the urgency of the situation, especially when sleep loss occurs near a high-stakes event, but should also weigh the athlete’s sleep history, current performance demands, and previous responses to sleep disruption.^5,12,20

Although some clinicians may consider interventions more urgently when the competition is due to start in less than 12 hours or when the athlete has experienced more than 24 hours without restorative sleep, these criteria are not formally codified in existing clinical guidelines. Instead, decisions should be guided by the broader context, including the athlete’s perception of impairment, level of competition, and psychological readiness.^5,27

Individualizing Treatment Planning

Risk stratification is an essential part of this process and includes screening for medical contraindications, as well as reviewing prior reactions to medications, the importance of the upcoming event, and the time available for postintervention recovery.²⁰ The American Medical Society for Sports Medicine underscores the importance of addressing mental health and monitoring for adverse effects from pharmacologic interventions, particularly in athletes with a history of anxiety, depression, or other psychiatric conditions.²

Ultimately, individualized treatment planning is considered best practice for optimizing both sleep outcomes and athletic performance. This flexible approach helps clinicians tailor interventions based not only on physiological risk but also on the realities of elite sport and the lived experience of the athlete.^5,12

A stepped hierarchy of pharmacologic options is consistent with current research findings, though specific clinical caveats apply:

• Melatonin (0.5-3 mg) is widely used for circadian rhythm–related sleep disruptions, such as jet lag or delayed sleep phase. It is generally considered safe for short-term use. Although study data show modest benefits in improving sleep onset latency, particularly in cases of circadian misalignment, its overall effect in primary insomnia remains limited.^3,11 The absence of next-day impairment makes it a sensible first-line option when athletes have more than 6 hours of recovery before competition.
• Zaleplon (5-10 mg), a short-acting nonbenzodiazepine hypnotic, promotes rapid sleep onset with minimal morning grogginess due to its very short half-life. Network meta-analyses support its moderate effectiveness and safety when used properly.^3,10,11 When athletes have only 4 to 6 hours before a performance, zaleplon may be appropriate, though clinicians should be mindful of rare neuropsychiatric adverse effects and the limited athlete-specific safety data.
• DORAs have demonstrated greater efficacy in sleep initiation and maintenance than Z-drugs and melatonin.²⁸ These agents have low abuse potential and are well tolerated in general populations. DORAs may be most suitable for athletes who experience persistent sleep maintenance issues, especially after first-line options have failed. However, due to DORAs’ longer half-lives, athletes must have at least 8 hours between dosing and competition to minimize residual sedation. Regulatory approval status should also be checked before prescribing.²⁹

Following the administration of a sleep aid, close observation for adverse effects such as excessive sedation, unusual behavioral responses, or impaired motor coordination is recommended. However, it is important to note that no standardized time points for postdose monitoring have been established specifically for elite athletes.^12,20 A morning assessment to evaluate competition readiness—focusing on cognitive alertness, balance, and psychomotor function—is considered good clinical judgment, particularly in the context of medications with known residual effects.^2,20 If an athlete experiences adverse reactions or if the intervention fails to achieve its intended sleep outcomes, timely adjustments or discontinuation of the treatment plan should follow. These decisions must be made collaboratively and documented thoroughly to guide future care.²

Athlete Supplement–Interaction

A comprehensive review of athlete supplements is a critical but often overlooked component of optimizing sleep in high-performance environments.³⁰ Stimulants such as caffeine and common preworkout blends can significantly disrupt sleep latency and quality, especially when consumed later in the day. These substances should be strategically timed to prevent interference with both natural sleep rhythms and any planned sleep interventions.^30,31

Even supplements that are not typically associated with stimulatory effects, such as protein powders or recovery shakes, should be evaluated for hidden additives such as caffeine, green tea extract, or melatonin. In contrast, creatine, though widely used in athletic circles, does not appear to influence sleep in any meaningful way based on current evidence.^32,33

On the supportive side, several nutritional compounds have demonstrated potential to improve sleep outcomes. Melatonin remains the most well established, but other naturally occurring substances such as magnesium and zinc, tart cherry juice (rich in phytomelatonin) and kiwifruit, and herbal supplements such as valerian root have also shown promise in enhancing sleep quality and duration.^34-36 These agents may provide additive benefits when used alongside behavioral or pharmacologic sleep interventions, though their timing, dosing, and interactions must be carefully considered.

Given the complex interplay between supplementation, sleep physiology, and performance recovery, a detailed evaluation of an athlete’s full supplement regimen and overall dietary habits should be a standard component of any high-performance sleep strategy.^30,31 Tailoring nutritional support to the athlete’s specific needs can reinforce circadian alignment and promote deeper, more restorative sleep.

Sleep maintenance difficulties in athletic populations often indicate underlying performance anxiety, environmental factors, or circadian misalignment that require a comprehensive evaluation beyond an acute pharmacological intervention.³⁷ Athletes with persistent sleep fragmentation despite appropriate medication selection should undergo a sports psychology evaluation and consideration of a broader sleep medicine consultation. Table 4 summarizes the appropriate medication selection based on specific sleep pattern presentations.

Inappropriate for Acute Athletic Use

Several commonly prescribed sleep medications are not appropriate for acute athletic interventions. Zolpidem (Ambien) presents unacceptable risks due to prolonged residual effects (8+ hours), documented complex sleep behaviors, and significant next-day psychomotor impairment that may persist into competition windows.^19,21 The dependency potential and narrow therapeutic window make zolpidem unsuitable for professional athletic populations when safer alternatives are available. Additional medications to avoid include eszopiclone (Lunesta), due to its long half-life and metallic taste affecting nutrition; doxepin, due to its anticholinergic effects and weight gain potential; and trazodone, due to orthostatic hypotension and cardiac considerations in athletic populations.¹⁸

Comparative Risk Profile:

• Half-life: zolpidem, 2.5 to 3 hours vs zaleplon, 1 hour
• Residual effects: zolpidem, 8+ hours vs zaleplon, 2 to 4 hours38
• Complex behaviors: zolpidem, higher incidence vs DORAs/zaleplon, minimal19

These significant safety differences strongly support the medication hierarchy outlined in this review, with zolpidem representing a relatively unacceptable risk-benefit profile for competitive athletes.

Concluding Thoughts

The current gold standard for insomnia and sleep disturbances is CBTi; however, it requires dedication and self-motivation, and is often without immediate results, prompting patients and prescribers to utilize sleep medications. As there is no general consensus regarding which pharmacological agent to use, the ideal hypnotic would be one with a fast absorption and short onset of action to shorten sleep latency, sustain restorative sleep through the night, and clear rapidly to minimize next-day effects to prevent next-day residual drug effects.

To better elucidate a potential hierarchy of these medications, more research needs to be undertaken in the general population, but also in athletes specifically, about the duration of these medications. It is imperative that research moves in the direction of athlete sleep studies, specifically utilizing DORAs. Maintaining the overall sleep architecture (improvements in sleep efficiency and total sleep time with proportional increase in time spent in all sleep stages, with no increase in abnormal REM-sleep behavior) is a unique element of DORAs, alongside minimal concerns for abuse or adverse events.

Sleep is vital to athletes, and effective treatment will only optimize their performance outcomes. Taking these steps can help ensure success for the elite performers we cheer for on the world stage.

Dr Suite is a psychiatrist and sports medicine expert in New York, New York. Dr Morales is an addiction psychiatry fellow at Harvard Medical School in Boston, Massachusetts.

References

1. Charest J, Grandner MA. Sleep and athletic performance: impacts on physical performance, mental performance, injury risk and recovery, and mental health. Sleep Med Clin. 2020;15(1):41-57.

2. Chang CJ, Putukian M, Aerni G, et al. Mental health issues and psychological factors in athletes: Detection, management, effect on performance, and prevention: American Medical Society for Sports Medicine position statement-executive summary. Br J Sports Med. 2020;54(4):216-220.

3. Morin CM, Buysse DJ. Management of insomnia. N Engl J Med. 2024;391(3):247-258.

4. Paryab N, Taheri M, H’Mida C, et al. Melatonin supplementation improves psychomotor and physical performance in collegiate student-athletes following a sleep deprivation night. Chronobiol Int. 2021;38(5):753-761.

5. Fullagar HHK, Vincent GE, McCullough M, et al. Sleep and sport performance. J Clin Neurophysiol. 2023;40(5):408-416.

6. Riemann D, Espie CA, Altena E, et al. The European Insomnia Guideline: an update on the diagnosis and treatment of insomnia 2023. J Sleep Res. 2023;32(6):e14035.

7. Haghparast P, Pondrom M, Ray SD. Sedatives and hypnotics. In: Ray SD, ed. Side Effects of Drugs Annual. Vol. 42. 1st ed. Elsevier; 2020:42:67-79.

8. Muehlan C, Roch C, Vaillant C, Dingemanse J. The orexin story and orexin receptor antagonists for the treatment of insomnia. J Sleep Res. 2023;32(6):e13902.

9. Messina G, Messina A, Monda V, et al. Evaluation of orexin-A serum levels in karate athletes cohort. J Hum Sport Exerc. 2020;15(supp 3):S781-S786.

10. Yue JL, Chang XW, Zheng JW, et al. Efficacy and tolerability of pharmacological treatments for insomnia in adults: a systematic review and network meta-analysis. Sleep Med Rev. 2023;68:101746.

11. De Crescenzo F, D’Alò GL, Ostinelli EG, et al. Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis. Lancet. 2022;400(10347):170-184.

12. Walsh NP, Halson SL, Sargent C, et al. Sleep and the athlete: narrative review and 2021 expert consensus recommendations. Br J Sports Med. 2021;55:356-368.

13. Preskorn SH. Comparative pharmacology of the 3 marketed dual orexin antagonists-Daridorexant, Lemborexant, and Suvorexant: part 1: pharmacokinetic profiles. J Psychiatr Pract. 2022;28(6):478-480.

14. Watson AM. Sleep and athletic performance. Curr Sports Med Rep. 2017;16(6):413-418.

15. Nobari H, Azarian S, Saedmocheshi S, et al. Narrative review: the role of circadian rhythm on sports performance, hormonal regulation, immune system function, and injury prevention in athletes. Heliyon. 2023;9(9):e19636.

16. Cunha LA, Costa JA, Marques EA, et al. The impact of sleep interventions on athletic performance: a systematic review. Sports Med Open. 2023;9(1):58.

17. Drust B, Waterhouse J, Atkinson G, et al. Circadian rhythms in sports performance - an update. Chronobiol Int. 2005;22(1):21-44.

18. Sateia MJ, Buysse DJ, Krystal AD, et al. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: An American Academy of Sleep Medicine Clinical Practice Guideline. J Clin Sleep Med. 2017;13(2):307-349.

19. Gunja N. The clinical and forensic toxicology of Z-drugs. J Med Toxicol. 2013;9(2):155-162.

20. Day C, Nishino N, Tsukahara Y. Sleep in the athlete. Clin Sports Med. 2024;43(1):93-106.

21. Otmani S, Pebayle T, Roge J, Muzet A. Effect of driving duration and partial sleep deprivation on subsequent alertness and performance of car drivers. Physiol Behav. 2005;84(5):715-724.

22. Kunz D, Dauvilliers Y, Benes H, et al. Long-term safety and tolerability of daridorexant in patients with insomnia disorder. CNS Drugs. 2022;37(1):93-106.

23. Kishi T, Koebis M, Sugawara M, et al. Orexin receptor antagonists in the treatment of insomnia associated with psychiatric disorders: a systematic review. Transl Psychiatry. 2024;14(1):374.

24. The Prohibited List. World Anti-Doping Agency. 2025. Accessed August 5, 2025. https://www.wada-ama.org/en/prohibited-list

25. Hueberger JAAC, Cohen AF. Review of WADA prohibited substances: limited evidence for performance-enhancing effects. Sports Med. 2018;49(4):525-539.

26. Atkin T, Comai S, Gobbi G. Drugs for insomnia beyond benzodiazepines: pharmacology, clinical applications, and discovery. Pharmacol Rev. 2018;70(2):197-245.

27. de Blasiis K, Joncheray H, Elefteriou J, et al. Sleep-wake behavior in elite athletes: a mixed-method approach. Front Psychol. 2021;12:658427.

28. Pan B, Ge L, Lai H, et al. The comparative effectiveness and safety of insomnia drugs: a systematic review and network meta-analysis of 153 randomized trials. Drugs. 2023;83(7):587-619.

29. Shaha DP. Insomnia management: a review and update. J Fam Pract. 2023;72(supp 6):S31-S36.

30. Barnard J, Roberts S, Lastella M, et al. The impact of dietary factors on the sleep of athletically trained populations: a systematic review. Nutrients. 2022;14(16):3271.

31. Gratwicke M, Miles KH, Pyne DB, et al. Nutritional interventions to improve sleep in team-sport athletes: a narrative review. Nutrients. 2021;13(5):1586.

32. Doherty R, Madigan S, Warrington G, Ellis J. Sleep and nutrition interactions: implications for athletes. Nutrients. 2019;11(4):822.

33. Doherty R, Madigan S, Warrington G, Ellis JG. Sleep and nutrition for athletes. The Nutrition Society, Scottish Section Conference 2024. Proc Nutr Soc. 2024;1-7.

34. Conti F. Dietary protocols to promote and improve restful sleep: a narrative review. Nutr Rev. 2025:nuaf062.

35. Langan-Evans C, Hearris MA, Gallagher C, et al. Nutritional modulation of sleep latency, duration, and efficiency: a randomized, repeated-measures, double-blind deception study. Med Sci Sports Exerc. 2023;55(2):289-300.

36. Chan V, Lo K. Efficacy of dietary supplements on improving sleep quality: a systematic review and meta-analysis. Postgrad Med J. 2022;98(1158):285-293.

37. Juliff LE, Halson SL, Peiffer JJ. Understanding sleep disturbance in athletes prior to important competitions. J Sci Med Sport. 2015;18(1):13-18.

38. Verster JC, Volkerts ER, Schreuder AHCM, et al. Residual effects of middle-of-the-night administration of zaleplon and zolpidem on driving ability, memory functions, and psychomotor performance. J Clin Psychopharmacol. 2002;22(6):576-583.