Attention-Deficit/Hyperactivity Disorder (ADHD) is a highly prevalent, chronic neurodevelopmental disorder characterized by persistent, impairing patterns of inattention and/or hyperactivity-impulsivity, affecting an estimated 7.2% of children globally^1,2. The disorder is formally recognized by three distinct clinical presentations (subtypes): Predominantly Inattentive Presentation (ADHD-PI), often associated with challenges in executive functions and organizational skills; Predominantly Hyperactive-Impulsive Presentation (ADHD-HI); and the Combined Presentation (ADHD-C), which represents the most common form^3,4. The etiology of ADHD is fundamentally multifactorial, underpinned by a highly polygenic architecture; recent large-scale genome-wide association studies (GWAS) have identified 27 independent risk loci, firmly establishing genetics as the primary risk factor^5,6. This genetic vulnerability impacts core brain regions, such as the prefrontal cortex, basal ganglia, and cerebellum, and is strongly linked to dopaminergic and noradrenergic system dysfunction, which supports the long-standing dopamine hypothesis^7,8.

Sleep disturbance is a pervasive comorbidity in Attention-Deficit/Hyperactivity Disorder (ADHD), often contributing to a more severe clinical presentation across the lifespan. Both children and adolescents with ADHD exhibit notable sleep discontinuity, characterized by increased sleep-onset latency and greater nocturnal movements compared to neurotypical peers^9,10. This association extends into adulthood, with numerous systematic reviews confirming that adults with ADHD report significantly poorer sleep quality and greater sleep-onset latency across both subjective and objective (actigraphic) measures^11,12. Crucially, these nocturnal deficits translate into impaired daytime functioning, manifesting as excessive daytime sleepiness (EDS) or a state of hypoarousal, which is considered by some to be a core physiological feature, particularly in children¹³. Among adults, this daytime sleepiness significantly mediates the relationship between ADHD symptom severity and deficits in cognitive performance, suggesting that sleep-related impairment acts as a key contributing factor to executive dysfunction and overall functional outcomes¹⁴.

The Karolinska Sleepiness Scale (KSS) is a widely utilized, single-item, nine-point ordinal rating scale designed to provide a rapid, subjective assessment of an individual’s immediate sleepiness level. Originally developed and introduced by Åkerstedt and Gillberg¹⁵, the scale ranges from 1 ("extremely alert") to 9 ("very sleepy, fighting sleep"). The KSS is particularly valued for its high temporal resolution, reflecting moment-to-moment fluctuations in alertness, making it highly effective for measuring sleepiness during sleep deprivation protocols and shift-work simulations¹⁵. Furthermore, the scale has undergone rigorous validation, demonstrating a robust correlation with objective measures of central nervous system alertness, including electroencephalography (EEG) indicators (e.g., theta/alpha power) and impaired performance on vigilance tasks¹⁶. Its validity, simplicity, and sensitivity to acute changes in wakefulness have cemented its status as a standard tool in both clinical sleep research and occupational health studies.

In our previous study, we investigated the "sleepiness curve" of young adult males (aged 18–30) with combined-type Attention-Deficit/Hyperactivity Disorder (ADHD-C) during 25 hours of continuous wakefulness, aiming to determine their vulnerability to fatigue compared to neurotypical controls¹⁷. Although objective baseline sleep measures via actigraphy did not reveal significant differences in total sleep time or efficiency between the groups, the hourly assessments using the Karolinska Sleepiness Scale (KSS) demonstrated a significantly elevated subjective sleepiness curve in the ADHD group throughout the sleep deprivation protocol. Crucially, this difference was most pronounced during the night and early morning hours, specifically between 1:00 a.m. and 9:00 a.m., the period associated with maximal homeostatic sleep drive and circadian misalignment. These findings suggest that young adults with ADHD-C exhibit a lower threshold for subjective fatigue when facing extended wakefulness, lending empirical support to the hypoarousal model by indicating a fundamental difference in central nervous system alertness regulation¹⁷.

Pharmacological treatments are a foundational component of ADHD management across childhood, adolescence, and adulthood, demonstrating both efficacy and tolerability. Stimulant medications, primarily methylphenidate and amphetamines, remain the most effective and commonly prescribed agents, showing robust symptom reduction across age groups^11,18. These medications often exert their benefits by enhancing dopaminergic and noradrenergic activity in the brain, mechanisms closely tied to increased wakefulness and alertness throughout the day. For individuals who are unresponsive to or cannot tolerate stimulants, non-stimulant medications such as atomoxetine and guanfacine provide alternative options, albeit with somewhat lower efficacy profiles^{11, 18}. In adolescents, pharmacotherapy has been shown to improve not only core symptoms but also broader quality-of-life domains when treatment adherence is maintained^19,20. Importantly, medication effects on quality of life appear to vary by age and subtype, with early and individualized intervention showing the greatest benefits. These findings underscore the importance of tailoring pharmacological strategies to developmental stage and patient-specific needs.

The present study aims to examine whether pharmacological treatment for ADHD modulates alertness levels across an extended period of wakefulness. Specifically, the research compares three groups: individuals with ADHD receiving medication, individuals with ADHD not receiving medication, and neurotypical controls without ADHD. Participants in all groups were monitored for 25 consecutive hours of wakefulness under controlled conditions, with repeated assessments of subjective alertness. We hypothesized that the medicated ADHD group would exhibit alertness levels comparable to the control group and significantly higher than the unmedicated ADHD group.

ADHD Rating Scale–IV²¹ is an 18-item questionnaire for the assessment of ADHD. The items are based on the symptoms listed in the DSM–IV for ADHD diagnosis, including 9 items assessing attentiveness and 9 items assessing hyperactivity and impulsivity. In the version used in the current study²⁴, participants were asked to choose whether each described symptom was correct or incorrect with respect to them. The internal consistency (Cronbach’s α) of the attentiveness section and the hyperactivity-impulsivity section of the scale in the current study were 0.82 and 0.87, respectively.

The Symptom Checklist–90–Revised (SCL-90-R²⁶): A 90-item self-report inventory assessing psychological symptoms across nine domains. Items were rated on a 0–4 Likert scale, with higher scores indicating greater distress. The internal consistency (Cronbach’s α) of the Hebrew translation of the SCL-90-R was found to be within the range of .71–.85²⁷. An expert clinical psychologist examined the responses of each participant on the SCL-90-R to rule out any psychological disorder.

Pittsburgh Sleep Quality Index (PSQI²⁸): A 18-item self-report questionnaire assessing seven components of sleep quality (Subjective Sleep Quality, Sleep Latency, Sleep Duration, Sleep Efficiency, Sleep Disturbance, Hypnotic Medication Use, Daytime Dysfunction) over the past month. The seven component scores are then totaled to provide a global PSQI score. The internal consistency (Cronbach’s α) of the Hebrew translation of the PSQI in the current study was .73.

Karolinska Sleepiness Scale (KSS¹⁵): A scale measuring subjective sleepiness at a given time. The participant is required to rate his level of sleepiness over the last 10 min on a 9-point Likert scale ranging from 1 (“extremely alert”) to 9 (“extremely sleepy, fighting sleep”).

Actigraphy: The actigraph (Mini Motionlogger, Ambulatory Monitoring Inc., New York) is a wrist-worn ambulatory, noninvasive device designed for studies in naturalistic settings with minimal distortions. The actigraph measures wrist movements utilizing a piezoelectric element and translates them into 1-minlong epochs of sleep and wake. To that end, wrist activity levels were sampled at 10-s intervals and summed across 1-min intervals. Actigraphic raw data were translated to sleep measures using the Actigraphic Scoring Analysis program for an IBM-compatible personal computer (W2 scoring algorithm) provided by the manufacturer. Four measures of sleep were obtained: total sleep time (minutes of sleep from intended bedtime to final wake time), sleep onset latency (minutes to fall asleep from bedtime), sleep efficiency (percentage of total sleep time between falling asleep and final awakening), and wake time after sleep onset (WASO; total number of wake minutes after sleep onset). The daily actigraphy data of each subject were averaged over the five days of actigraph use in order to obtain aggregated measures that reliably characterize individuals. The participants were instructed to press a button on the actigraph when they began trying to fall asleep and when they woke up the following morning. The first button-press was used to determine bedtime and the second was used to determine wake time. For the purpose of precise analysis of the actigraph data, over the course of actigraphic recording participants were instructed to complete the Consensus Sleep Diary that included intended bedtime, initial and final wake times, number of awakenings, and lengths of awakenings.

Eligible participants were provided with an actigraph device five days prior to the laboratory session and instructed to wear it continuously for five nights while completing daily evening/morning sleep diaries. They were asked to sleep at least seven hours per night to avoid prior sleep deprivation.

On the experimental day, participants were collected from their homes at 07:00 AM and transported to the laboratory, where the experiment began at 08:00 AM. Actigraphy data from the previous five nights were verified to ensure compliance with sleep requirements. Participants who had slept less than seven hours per night were excluded. After completing baseline questionnaires on demographics and sleep quality (PSQI), participants remained awake for approximately 25 consecutive hours under constant supervision to prevent unintended sleep. Among the ADHD group, 17 participants were medicated with their regular doses of methylphenidate (n = 13) or amphetamine (n = 4) at the start of the experiment (08:00 AM) and again at midnight (00:00), while 22 were unmedicated throughout the study. Subjective sleepiness was recorded hourly using the KSS. Food and non-caffeinated beverages were provided ad libitum. Upon completion of the 25-hour sleep deprivation protocol, participants were thanked, debriefed, and transported home.

The study groups did not differ in age or the proportion of tobacco smokers and alcohol users (Table 1). Group differences in sleep variables measured via the PSQI (global scores) and actigraphy were examined (Table 2). No significant differences were found among the three groups in the PSQI scores (subjective sleep quality). In relation to actigraphy-measures sleep variables, no significant differences were found between the groups in total sleep duration [χ²₍₂₎ = 0.39, p = .822,[ sleep onset latency [χ²₍₂₎ = 2.98, p = .224], or WASO [χ²₍₂₎ = 3.95, p = .138]. However, a significant difference was found in sleep efficiency [χ²₍₂₎ = 7.77, p = .020]. Post-hoc analyses revealed that the control group had significantly higher sleep efficiency (M = 0.95, SD = 0.01) compared to both the ADHD group without medication (M = 0.91, SD = 0.01; Z = 2.28, p = .044) and the ADHD group with medication (M = 0.90, SD = 0.01; Z = 2.69, p = .020). No significant difference was found between the two ADHD groups (Z = 0.43, p = .662).

Pearson correlations between the average sleep efficiency, as measured during the week preceding the experimental trial and the level of subjective sleepiness as measured by the KSS at the beginning of the trial (r = -0.05, p = .71) and at its end (e.g., following sleep deprivation; r = -0.05, p = .697) were not significant. Thus, sleep efficiency was not controlled for in subsequent sleepiness analyses.

Note: WASO: Wake After Sleep Onset; PSQI: Pittsburgh Sleep Quality Index (subjective sleep quality)

This study investigated the effects of sleep deprivation and stimulant medication (methylphenidate and amphetamine) on subjective sleepiness in young adults with ADHD, compared to individuals without ADHD. Subjective sleepiness was assessed hourly over a 25-hour experimental session using the Karolinska Sleepiness Scale (KSS). The findings support the study’s hypotheses: participants with ADHD exhibited significantly higher levels of sleepiness throughout the experiment, particularly following 25 hours of sleep deprivation. Notably, medicated ADHD participants and control participants did not differ significantly in their sleepiness levels.

The observation that unmedicated individuals with ADHD experienced elevated sleepiness during sustained wakefulness, especially overnight and into the following morning, replicates our previous findings¹⁷ and aligns with studies reporting excessive daytime sleepiness in both children and adults with ADHD^29–32. However, our studies are among the first to systematically compare sleepiness levels throughout the day between individuals with ADHD and the general population.

The sleepiness trajectory observed in the control group mirrored patterns reported in prior KSS-based studies^33,34, with relatively stable levels from morning to evening followed by a gradual increase along the night. In contrast, participants with ADHD showed a significantly steeper rise in sleepiness during the night and subsequent morning. This was further reflected in the proportion of participants scoring above 7 on the KSS the morning after sleep deprivation, 88.2% in the ADHD group versus 55% in the control group, indicating heightened vulnerability to sleep deprivation among individuals with ADHD.

The differences in sleepiness in the current study between the control participants and the non-medicated ADHD participants cannot be attributed to psychiatric comorbidities that are commonly associated with ADHD³⁵ as individuals suffering from such psychopathologies were excluded from the study. They also cannot be explained by the tendency of ADHD patients to exhibit lower sleep quantity and quality ^36–39. First, the study included only individuals without diagnosed sleep disorders and the participants were instructed to maintain a minimum of seven hours of sleep for nights prior to the experimental trial. Second, actigraphy data collected along these nights revealed that the study groups did not differ in total sleep duration or sleep onset latency. Although sleep efficiency was higher in the control group compared to the unmedicated ADHD group this difference likely did not account for the differences in subjective sleepiness as there were no significant correlation between sleep efficiency and the KSS scores at either the beginning of the experimental trial or its end. These findings are consistent with prior research suggesting that increased sleepiness in ADHD is not solely due to sleep disturbances^29,40. Taken together, these findings support the notion that sleep deprivation exacerbates sleepiness in individuals with ADHD, indicating increased vulnerability to fatigue in this population.

Stimulant medications, particularly methylphenidate and amphetamines, are the first-line treatment for ADHD⁴¹. The current findings demonstrate that these medications not only improve attention and reduce hyperactivity but also normalize subjective sleepiness levels in individuals with ADHD, making them comparable to those of non-ADHD participants. This is consistent with previous research indicating that stimulants can reduce daytime sleepiness^42,43.

The findings underscore the importance of considering sleep-related factors in both the theoretical understanding and clinical management of ADHD. From a theoretical perspective, these findings support to models that conceptualize ADHD as involving dysregulation in arousal and sleep systems, in addition to cognitive and behavioral symptoms. Pharmacologically, methylphenidate and amphetamine enhance central dopamine and norepinephrine activity by inhibiting their respective transporters⁴⁴. Given their dual efficacy in reducing ADHD symptoms^45,46 and sleepiness, it is plausible that dysregulation in these neurotransmitter systems underlies both domains³⁸. Although the impact of stimulants on sleepiness may be independent of their cognitive effects, prior research has shown a positive correlation between daytime sleepiness and inattentiveness in ADHD⁴⁷, suggesting that improvements in attention may be partially mediated by reductions in sleepiness. However, this intriguing hypothesis warrants further empirical investigation.

Clinically, the study highlights the dual role of stimulant medications - not only in improving attention and reducing hyperactivity but also in alleviating daytime sleepiness, particularly under conditions of sleep deprivation. However, it is important to note that the impact of stimulant medication on sleep is complex^48,49. Some studies report adverse effects when stimulants are taken late in the day, including increased sleep latency and reduced sleep efficiency^49–52. Therefore, clinicians should monitor sleep patterns and adjust medication timing and dosage to optimize therapeutic outcomes while minimizing sleep-related side effects.

Interpretation of the present findings should be viewed in light of a few limitations. First, due to constraints imposed by the experimental design, the study sample was limited to young adult males (ages 18–30) in order to minimize variability and enhance statistical power²³. Consequently, the generalizability of the findings to females and other age groups remains limited and warrants further investigation in future research. Second, since all ADHD participants in the current study were of the combined subtype (ADHD-C) and did not present with any psychiatric comorbidities, the applicability of these findings to individuals with other ADHD subtypes or those with co-occurring psychiatric conditions remains uncertain. Third, the experiment was conducted in a controlled laboratory setting, which may not reflect real-world conditions where environmental factors vary widely. Finally, the extreme sleep deprivation protocol (25 hours) represents an atypical scenario that may elicit exaggerated behavioral and cognitive responses.

This study provides empirical support for the heightened vulnerability of individuals with ADHD to the effects of sleep deprivation on sleepiness. The stimulant medications methylphenidate and amphetamine were shown to effectively attenuate sleepiness in ADHD participants, aligning their wakefulness levels with those of non-ADHD controls. These findings highlight the dual therapeutic role of stimulants in managing both attentional deficits and sleep-related vulnerabilities in ADHD.