Clinical manifestations

Presentation and course

The clinical effects of alcohol on sleep symptomology are complex. Most individuals note little consequence following the occasional use of small amounts of alcohol timed away from the sleep period. Alcohol has a greater impact on sleep as the amount increases, the timing of intake gets closer to bedtime, and the chronicity of use continues. In the acute setting, small amounts of alcohol (one drink) have been shown to decrease sleep latency and may increase total sleep time in healthy individuals. Studies have shown that alcohol ingestion consolidates sleep in the first part of the night compared to the latter half, with more time spent in slow-wave sleep in the first part and lighter stages in the second (30; 84; 82).

The overall blood level of alcohol may influence sleep. Acute alcohol use leads to sleepiness and promotes sleep onset, particularly in lower doses (no more than one to two drinks per day), but with chronic use at moderate (three to seven drinks per day) or greater doses, patients report increasing difficulty in falling asleep and staying asleep. Similarly, high alcohol consumption (BrAC of 0.11 ± 0.01 g%) at bedtime has also been shown to result in sleep disruption and appears to be more significant in women than in men (05). Moderate alcohol ingestion (eg, two or three standard drinks) leading to a blood alcohol level of 0.05% may also disrupt sleep, and this is worsened by the length of time the individual has gone without sleep and by the time of day the alcohol is ingested (97). In one study with a single night of either a low blood alcohol level (0.03% blood alcohol level) or a high blood alcohol level (0.1% blood alcohol level), high blood alcohol level was associated with increased N1 sleep in the second half of the night (32).

These effects can result in daytime sleep symptoms. An interaction between decreased sleep duration and increased heavy drinking frequency was found to predict increased daytime sleepiness (16). Alcohol also appears to have a biphasic effect on alertness, such that it increases alertness and prolongs sleep latency on the ascending limb of the breath alcohol concentration and decreases alertness and sleep latency on the descending limb (74). This effect persists irrespective of the circadian phase at which the alcohol is consumed (96). Thus, individuals may note both improved sleep as well as difficulty with sleep or inappropriate excessive daytime sleepiness related to the acute effect of alcohol.

Chronic alcohol use is associated with the development of poorer sleep over time. Patients with chronic heavy use are more likely to complain of disrupted sleep and insomnia. A study of nearly 12,000 individuals demonstrated a dose-response association between higher alcohol intake and higher prevalence of poorer subjective sleep quality and higher odds of snoring six years later (106). A separate study also found that higher amounts of alcohol consumption have been shown to be significantly correlated with the development of self-reported insomnia in females, even after controlling for potential confounding factors (41). In a 2-wave study of nearly 10,000 Norwegian adults, alcohol and sleepiness had a bidirectional relationship, but only among men (85). Women, however, may note more insomnia (51). Alcohol can also exacerbate symptoms of other existing sleep disorders, most notably, obstructive sleep apnea and sleep-related movements at night (17; 57). One confounding issue is that individuals may self-medicate to treat underlying sleep or mood issues, finding initially beneficial but ultimately worsening symptoms with chronic use. Therefore, more frequent alcohol use may produce more sleep disruption and exacerbation of underlying sleep issues.

Psychiatric disorders are associated with sleep disturbances but are also associated with alcohol use. Many patients use alcohol to self-treat mood and sleep issues, resulting in nightly use and, at times, escalating doses. This is hypothesized by many to produce a cycle of alcohol that initially improves symptoms but leads to worsening symptoms and ever-increasing doses of alcohol. Similarly, sleep disturbances may also contribute to prolonged alcohol use and abuse, making it difficult to know whether poor sleep contributes to alcohol abuse or dependence. The presence of comorbid psychiatric disorders, like depression, as well as the physical symptoms of withdrawal have also been found to be associated with insomnia during early recovery from alcohol dependence (58).

Although sleep disturbance and alcohol use and abuse may have a bidirectional relationship, long-term heavy drinking may indicate other underlying issues (45; 46; 47). Heavy drinking at baseline has been reported to increase the risk of future insomnia, and, likewise, insomnia symptoms increase the risk of heavy drinking (47). This hypothesis is challenged by some. In a sample of nearly a thousand European college students, estimation of high sleep quality represented a significant protective factor for problematic drug use, with an odds ratio of 0.8 (95% CI: 0.76-0.99) as measured by two alcohol screening tests (70). Therefore, the risk of escalation of alcohol use may be greater in those with sleep issues and those who are more vulnerable to sleep issues.

Alcohol dependence raises further issues with regard to sleep. Alcoholism usually starts in adolescence or early adulthood and is a major cause of hospital admissions of adults in the third and fourth decade of life. Sleep disturbances can develop almost immediately with alcohol abuse and become progressively worse with continued alcohol abuse. Estimates of the prevalence of complaints of sleep disturbance range from 36% to 91% (17; 38). In particular, insomnia is associated with alcohol use disorder in that insomnia appears to increase relapse rates, psychological and psychosocial impairment, suicidal ideation, and lower quality of life (83). The sleep disruption associated with alcohol use disorder appears to persist even into abstinence.

Alcohol use and withdrawal along with comorbid psychiatric symptoms are associated with insomnia. In one study, sleep disturbances were associated with anxiety and depression symptoms, as well as a craving for alcohol and the amount and frequency of alcohol consumption (58). During acute alcohol withdrawal, sleep latency is usually increased, and total sleep time is typically decreased, along with complaints of insomnia. Subjective sleep ratings using the Pittsburgh Sleep Quality Index (PSQI) improve in early abstinence. This was supported in a sample of alcoholics in a 1-month residential treatment program (p < 0.001), which showed older individuals as having greater improvement (59). However, there appeared to be no difference in gender, use of hypnotics, hazardous alcohol use, or comorbid psychiatric diagnosis. Using a novel measure called the Sleep Regularity Index to assess sleep timing and duration, Brooks and colleagues showed that those with less nap time and improved regularity of sleep had a better chance of improved sleep quality between weeks 1 and 3 of treatment (09). Typically, insomnia is frequently noted in the first 10 days of abstinence, but one study suggests the peak incidence of insomnia may be approximately 160 to 169 days of abstinence (101). The prevalence of insomnia does improve with a longer period of abstinence. Yet, even after achieving long-term abstinence, some patients may note insomnia, and this is a leading cause of relapse of alcohol abuse (82).

Alcohol use can exacerbate other existing sleep disorders. Patients may note an increase in snoring when taking alcohol. This increase in snoring raises the question of worsening sleep apnea. Obstructive sleep apnea can be worsened by any alcohol use before bed, though men may be more vulnerable to this effect than women. In an epidemiological study, increasing daily alcohol use was associated with an increased risk of obstructive sleep apnea, even in nonalcoholics. In some cases, there may be little or no apnea without the prior use of alcohol. Increased snoring, particularly in those with habitual snoring, and restlessness during sleep after alcohol use suggest this condition. The apneas occur more frequently in older alcohol abusers, suggesting an age interaction for the effects of alcohol on sleep apnea. In patients with obstructive sleep apnea, however, moderate alcohol ingestion does not appear to increase the required therapeutic setting of nasal continuous positive airway pressure. For some individuals, the presence of alcohol may cause more upper airway relaxation, but alcohol is also associated with increased reflux. Thus, patients may have other features of nighttime reflux and apnea (57). Sleep-related movements are also noted to increase with alcohol, and, thus, symptoms of increased movement during sleep or perceived fragmentation due to movement may be exacerbated by alcohol (17).

Acute alcohol use is well-known to impair one’s ability to perform cognitive tasks, including driving. Impairment is worse in sleep-deprived individuals. The sedating effects of alcohol are particularly a problem for persons who are already sleepy, either because of a preexisting sleep disorder or because of behaviorally induced sleep deprivation. These factors combine to produce significant sleepiness that can further impair cognitive and driving performance. Alcohol also contributes to impaired judgment about the degree of sleepiness (62). Women may be more aware of this impairment than men, possibly contributing to the lower incidence of alcohol or sleep-related crashes in women compared to men. Next day hangover effects continue to affect performance; notably, worse performance is noted on tests requiring both sustained attention and speed (86).

Prognosis and complications

Recovery of sleep and daytime alertness is dependent on the amount and length of time the individual has used alcohol. Sleep returns to normal within a few days to weeks after abstinence in most occasional-to-moderate consumers who otherwise have no other underlying medical or psychiatric issues. However, for individuals with long-time heavy use or a history of alcohol use disorder, insomnia during withdrawal and abstinence is common, especially in the first six months. Insomnia is a common complaint in individuals with alcohol use disorder, with a 36% to 91% prevalence (17). For many of those who can maintain abstinence, sleep gradually improves. However, for some, the sleep changes may last for more than two years, and the insomnia is a risk factor for relapse of alcohol abuse (82). Thus, the long-lasting sleep disorders of abstinent alcoholics appear to contribute to instability of abstinence. In one study of individuals completing in-patient treatment for alcohol use disorder, an inconsistent sleep pattern increased the risk of relapse (07). Therefore, consistent sleep appears to predict better outcomes.

The long-term presence of underlying poor sleep quality in patients’ alcohol use disorder does impact the patients’ quality of life. However, those individuals who remain abstinent are not associated with poorer cognitive performance (77).

Clinical vignette

A 35-year-old man presented to his primary care doctor complaining of fragmented, nonrestorative sleep. The patient requested a sleep aid to help him maintain sleep throughout the night. The patient noted that the insomnia began around the time he started having marital issues three years ago. He noted that this was the same time he felt that a “nightcap” helped him get to sleep. After his divorce, the patient noted his alcohol use had increased to several glasses of wine and the nightcap each night to sleep. He noted that he could drink a bottle of wine and feel no effect. He had increased his nightcap to four shots of vodka, but even with this, he would fall asleep quickly only to awaken four hours later with a dry mouth, slight headache, and inability to return to sleep. He noted feeling more anxious and depressed and was having difficulties at work. He tried not drinking for a week but became much more anxious and developed tremors.

His physical exam demonstrated a mild tachycardia and elevated blood pressure. The patient appeared mildly anxious. His general exam showed no abnormalities except for a fine rapid tremor in his hands.

The clinician had a frank conversation with the patient about his alcohol use disorder and discussed the long-term consequences of high alcohol use. The patient, although initially reticent, eventually entered an alcohol detox program, joined a local Alcoholics Anonymous group, and noted persistent insomnia. As part of his psychiatric care, the patient began cognitive behavioral therapy for insomnia as well as therapy for his underlying depression and anxiety. Although he had occasional relapses over the first two years of treatment, the patient noted gradual improvement of the insomnia and was eventually able to maintain abstinence. He continued to feel that his sleep was lighter than before but noted no daytime sequelae.

Comment. Persistently disturbed sleep is common in abstinent alcoholics and may contribute to relapse.

Biological basis

Etiology and pathogenesis

Alcohol influences sleep regulation in a dynamic manner. Initially, alcohol use will shorten sleep latency, and it can increase slow-wave sleep and reduce REM sleep. Acute alcohol intake suppresses REM sleep during the first part of sleep, thereby increasing slow-wave sleep, and reduces sleep latency. Later in sleep, when blood levels of alcohol are falling, REM times and wakefulness are both increased, rebounding from the suppression in the first part of the night. This effect of alcohol on REM sleep appears to be dose related, with significant reductions in REM sleep in the first part of the night. Some studies have shown increases in slow-wave sleep in the first half of the night (30), whereas others have not (80; 81). A 2012 study utilizing actigraphy to assess sleep time in college students revealed that participants who drank less alcohol than the mean alcohol consumption of the group (85 mL of alcohol/night) had reduction in sleep time associated with increased wakefulness in the second half of the night and a truncated sleeping period (38). Those who drank more alcohol than the mean of the group had fatigue the following day but no rebound wakefulness (36). For those with alcohol use disorder, the majority (67%) of individuals in early abstinence report insomnia. For alcoholics and chronic alcohol abusers, early abstinence brings decreased deep sleep, sleep fragmentation, shorter sleep times, and, sometimes but not always, increased REM sleep (53). Sleep architecture is further disturbed in patients with alcohol use disorder-related Korsakoff syndrome. Laniepce and colleagues demonstrated a relationship between the degree of reduction in REM sleep correlating to increased severity of episodic memory loss (61). This study raises the link between sleep changes and daytime cognitive functioning.

Polysomnography studies suggest that it may require up to two years before normal levels of slow-wave sleep are seen in recovering alcoholics, and this may not occur for all subjects. However, the duration of sobriety, ranging from approximately 1 month to 2 years, does not necessarily predict the level of improvement in EEG spectral power measures over time. Studies have shown some changes in the electrophysiological components of sleep (eg, amplitude of K complexes, a characteristic of stage 2 sleep) over time in abstinent alcoholics. Whether these changes reflect the improvement of sleep over time is still unclear. Other physiological differences have been detected in the sleep of recently recovering alcoholics. For example, reduced heart rate variability, a sign of poor autonomic nervous system functioning, was found in the first part of the night compared to age- and sex-matched healthy controls (27). These lingering effects of alcohol on sleep undoubtedly reflect one of the major toxic effects of alcohol on the central nervous system.

On a neuronal level, alcohol has complex effects on the nervous system, including effects on the regulation of sleep. Examining cellular physiology, alcohol has effects on three major systems in the brain: gamma-aminobutyric acid (GABA), glutamate, and calcium influx (63). Alcohol appears to enhance the GABA neurotransmitter system, which is the major inhibitory substance of the brain. Alcohol’s effect is specifically on the GABA-A receptor, which causes inhibition of the neurons for which the receptor resides. Acutely, alcohol causes widespread inhibition of many functions, including neuronal processing. Over time, with the long-term presence of alcohol and repeated activation of the GABA-A receptors, the GABA receptors become less sensitive to the effect of alcohol. This lessening effect appears to be related to downregulation in one of the alpha-1 subunits. Thakkar and colleagues suggest that the sleep-promoting effects of ethanol are the result of a decrease in the number of basal forebrain wake-promoting neurons with c-Fos via a possible GABA mechanism (94).

This GABA alteration may also be compounded by the effect of alcohol on interleukins. Alcohol may suppress interleukin-10 (IL-10), an antiinflammatory cytokine. Studies show that it is upregulated during withdrawal from chronic ethanol exposure. In a study, IL-10 was increased after one hour following a single intoxicating dose of alcohol (5 g/kg, intragastric) in Sprague Dawley rats (91). IL-10 also regulated GABAergic transmission in the dentate gyrus neurons in the brain, suggesting that IL-10 might be involved in sleep issues related to altered GABAergic functioning. Yet, an opposite correlation was found in an exploratory study comparing sleep and inflammatory markers in subjects with and without alcohol use disorder. Those individuals with elevated proinflammatory cytokines (IL-8 and monocyte chemoattractant protein-1) had poorer subjective sleep (54).

Long-term alcohol use also causes downregulation of glutamate receptors. Glutamate is the most common excitatory neurotransmitter in the brain, and the N-methyl-D-aspartate (NMDA) receptor appears to be inhibited by alcohol. Over time, the neurons’ response to this is upregulation of expression of NMDA receptors. This upregulation of NMDA receptors persists long after the alcohol is removed and may be responsible for some of the features of withdrawal. Alcohol also appears to diminish the flow of calcium through voltage-operated calcium channels in addition to the calcium channels associated with NMDA receptors. This calcium influx is important for several neuronal activities, including DNA transcription, receptor production, and signaling of neurotransmitter release.

Each of these systems has a unique role in sleep-wake regulation. GABA, the major inhibitory neurotransmitter, is responsible for turning off many of the mechanisms involved in promoting alertness. Thus, initial excessive sleepiness and suppression of REM sleep may be affected. GABA is also one of the major outputs of the circadian master clock, the suprachiasmatic nucleus. Therefore, the circadian rhythm may be influenced. Similarly, sleep spindles, a marker of NREM sleep and a marker of inhibition of sensory signals through the thalamus to the cortex, are initially enhanced with alcohol but later diminish in amplitude with chronic use. Glutamate, as an excitatory amino acid, is associated with alertness, neuronal activity, and learning. As long-term alcohol use enhances NMDA receptors, increased alertness, even during times for sleep, would be expected. Glutamate is also the neurotransmitter involved in transmitting information about light from the retina to the suprachiasmatic nucleus. Voltage-operated calcium channels are also involved in neuronal regulation and may play a role in the depth of NREM sleep. Both NMDA receptors and voltage-operated calcium channels are typically suppressed by alcohol and, thus, upregulated during its chronic use. Therefore, the downregulation of GABA-A receptors and upregulation of the NMDA and voltage-operated calcium channel systems lead to a greater push toward wakefulness during periods of sleep.

Studies exploring underlying neuronal functioning reveal that acute ethanol appears to increase adenosine, and this system plays a role in photic glutamatergic and nonphotic input to the circadian clock. This has also been shown in a circadian rhythm study of breath alcohol level concentrations (88). Chronic ethanol consumption leads to downregulated adenosine signaling, which underlies insomnia, a major predictor of relapse (87).

Preclinical studies in mice and rats exposed to ethanol have shown mixed results. Some studies show that chronic ethanol exposure disrupted circadian rhythms. In particular, chronic forced ethanol exposure disrupted the timing of locomotor activity and impaired the ability of the circadian clock to phase reset (40). Another study in which mice were exposed to a single day of ethanol exposure on postnatal day 7 did not modify circadian cycles. Instead, slow wave sleep was disrupted, and the mice exposed to ethanol had more memory impairments (103).

Alcohol also has effects on circadian markers in humans. Circadian genes have been found to be related to drinking behaviors. For example, the “Per 2” gene has been found to regulate alcohol intake in adults and the “Per3” gene is associated with both impaired sleep drive and heavy drinking in adolescents (22). Mouse models of Per 3 suggest that this period homolog is linked to circadian rhythms, stress response, and alcoholism. When treated with alcohol, there was increased expression of Per 3 in the mouse hippocampus and this interacted with stress response (99), suggesting that expression of Per 3 may be involved in response to alcohol.

Moderate amounts of alcohol reduce nocturnal melatonin levels in healthy adults. In substance abusing teens, the time interval between dim light melatonin onset and wake time was significantly and positively related to the Substance Problem Index (SPI), a scale of the severity of substance use. In adult male abstinent alcoholics, a lower level of melatonin during the early part of the night and a delay in the nocturnal rise of melatonin was found. This finding was supported in a separate study that included male and female subjects (23). The alcoholics also demonstrated a slower rate of rise of melatonin secretion in the early part of the night. This lower plasma melatonin level in alcohol-dependent patients has also been inversely correlated with intestinal permeability, which may promote endotoxemia, a common consequence of chronic heavy alcohol use (92). Moreover, tendency to go to bed late, or being a “late chronotype,” has been found to be moderated by alcohol drinking and smoking. A relationship between late chronotype and alcohol and tobacco use was also found by using the Morningness-Eveningness-Stability-Scale in a large sample of young adults in Mexico (06). These findings suggest that alcohol may play a role in circadian dysregulation. However, this may be associated with the amount and timing of alcohol ingestion. A sophisticated study on the effect of a single dose of alcohol was tested to determine if alcohol would alter the circadian phase advances or phase delays to light in humans. Alcohol did increase or decrease the phase shifts to light, but the effect of alcohol versus placebo on phase shifts to light was smaller than 30 minutes (13).

Research has been accumulating to suggest that acute alcohol also affects the homeostatic sleep drive. Sleep EEGs during protracted abstinence show lighter sleep, sleep fragmentation, increased arousal during sleep, and a profound decrease in slow wave sleep, with a gradual recovery occurring at least for some subjects. One study related the decrease in slow-wave sleep and the degree of recovery to the amount of atrophy shown on CT scans during abstinence. Even when undergoing a sleep “challenge,” ie, staying awake three hours later than their typical bedtime, alcoholic men showed a blunted response to the challenge as measured by deep slow-wave activity in the EEG (12). Slow-wave activity dissipation across the night in alcohol-dependent men and women showed a blunted SWA response to sleep delay with significantly lower slow-wave activity than the control group (04). In an animal model, mice underwent experimentally induced acute (1 day) and chronic sleep deprivation for (3 days). Acute sleep deprivation resulted in reduced SWA and adenosine tone for at least two weeks. Mice that were chronically sleep deprived for three days and then tested 24 hours later were less sensitive to the effects of alcohol (21). These studies suggest a possible interaction between sleep restriction, alcohol intake, and sleep compensatory mechanisms.

The ubiquitous use of alcohol in the evening occurs largely for social reasons. Nocturnal use of alcohol sets the stage for subsequent sleep disruption and exacerbation of existing sleep disorders. The sleepiness associated with alcohol-related sleep disorders occurs both because of the direct sedating effects of the alcohol and because of the arousals occurring during sleep, limiting the restoration of wakefulness. Individuals with disorders such as sleep apnea may note an exacerbation of their underlying symptoms. Additionally, the effects of alcohol on the upper airway appear to further enhance the relaxation occurring during sleep, thereby exacerbating obstructive sleep apnea. Alcohol may also exacerbate sleep apnea by blunting chemoreceptor response to blood gases or by raising the arousal threshold, although this is somewhat debated. Several studies have shown mixed results for alcohol’s influence on responsiveness to changes in blood oxygen and carbon dioxide levels (57). These changes may not be clinically significant for those treated with CPAP as the CPAP pressure required for effective treatment is unchanged by alcohol (57). The effects of alcohol on periodic limb movements in sleep are not well established, nor is there any known pathogenesis or pathophysiology for this relationship.

Epidemiology

Most casual users of alcohol have limited or no clear sleep issues. However, individuals with alcohol use disorder have a high prevalence of sleep issues (36% to 91%) (17). Similarly, obstructive sleep apnea may increase the risk of alcohol use, due to the sleep disturbance (50). Alcohol use disorder is the most common substance abuse disorder in the United States, with a 1-year prevalence of roughly 14% and a lifetime prevalence of a little over 29% (82). Alcohol use or abuse is estimated to be the cause in 6% to 9% of all deaths (94). Unfortunately, less than 20% of patients will receive treatment. Sleep complaints are common in patients with alcohol use and abuse. The cost of sleep disturbances related to alcohol has been estimated at roughly $18 billion.

Prevention

Sleep problems are associated with an increased risk for alcohol use and vice versa. Several studies have shown that sleep disturbance early in life is associated with increased substance use and abuse. In one such study, children as young as 3 to 5 years old who were noted by their mothers to have sleep problems were more likely to use substances in their early teens and more likely to have substance-related problems in their early adulthoods (104). A European study of 9300 teens aged 16 to 19 showed that insufficient sleep, insomnia, and variable bedtimes were associated with a higher risk for substance use (90).

Data from the Longitudinal Study of Australian Children (LSAC) also show that children with heavy prenatal alcohol exposure have 1.13 more sleep problems across childhood (2 to 9 years) relative to children whose mothers are abstainers (19). Children of alcoholics tend to get less sleep, and this decreased sleep time has been associated with decreased ability for these children to regulate their behaviors and emotional state (43).

A number of studies have now shown a bidirectional connection between sleep and future alcohol use during the teenage years. Sleep problems during adolescence are associated with more alcohol use along with internalizing and externalizing problems (78). The etiology of these findings may be related, in part, to the stronger preference for adolescents to be awake in the evening, or for “eveningness” (44). Two large population studies support a sleep-substance use connection. A sample of approximately 14,000 teens who participated in the National Longitudinal Study of Adolescent Health, binge drinking was positively and significantly associated with sleep disturbance, independent of psychiatric condition (79). Another population-based study of approximately 9300 teenagers (16-19 years of age) living in Norway revealed that not getting enough sleep, differences in bedtimes, and insomnia were all associated with greater risk of alcohol and drug use (90).

Another large longitudinal study also revealed that sleep plays an important role in substance use (45; 46). The study followed 696 adolescents in Pittsburgh (12 to 19 years of age) with alcohol use disorder and sleep disturbances showed that greater insomnia complaints predicted an increase in alcohol symptoms at one year and variability in sleep duration predicted an increase in alcohol symptoms at 3- and 5-year follow-up. Additional longitudinal data from the same research group showed that lower duration and quality of sleep in boys at age 11 was associated with substance use at age 20 to 22 years (66). Similarly, a cross-sectional study of 127 low-income ethnic minority teens (mean age=13) showed that difficulty falling asleep and daytime sleepiness were associated with frequency of alcohol use, even when parental monitoring and psychopathology were adjusted (64).

Identification of sleep problems early in life may help to reduce self-medication by drinking alcohol. A longitudinal study showed that sleep problems observed by mothers in children were associated with early-onset substance use between the ages of 12 and 14 as well as substance-related problems between the ages of 18 and 20.

An online survey of college students who drank alcohol (n=1878) revealed that students who reported poor sleep and who were motivated to drink alcohol to cope or to fit in also reported having more alcohol-related consequences, even controlling the drinking amount (55). The relationship between sleep and alcohol does not appear to be related to sociodemographic or mental health status (95).

In college students, other factors like impulsive personality traits or perception of not getting “adequate sleep” may also contribute to drinking (68). Moreover, university students who reported having more sleep problems and emotional dysregulation in their first year of college were more likely to have higher depressive symptoms and alcohol use by graduation time four years later (89).

Mood disorders are also associated with alcohol use and sleep disruption. Several studies of adults show that mood disorders play a role in the relationship between alcoholism and sleep. A longitudinal study found that among 364 alcohol-dependent individuals, depression and drinking quantity separately predicted insomnia severity even when controlling for age, time, and gender (105). Independently, depression and anxiety are noted to cause sleep disruption. One study showed that the amount of alcohol consumed and the presence of depression predicted the severity of insomnia (105). Patients with a prior history of trauma are also more likely to have sleep issues and to misuse alcohol (60).

One feature linking sleep, mood, and alcohol use appears to be the circadian rhythm. Individuals who are more “night owls” or have social delay in the sleep-wake pattern are more likely to develop mood issues in their adolescences and young adult years. This delay in sleep is also linked to greater likelihood of alcohol use and as mentioned above lead to great alcohol abuse (71). Identification of a pattern of delay in sleep may be an important clue for early intervention.

Prevention should be focused on early intervention of sleep issues as well as substance use. In addition, there should be a focus on treating conditions that may lead to sleep disturbance and alcohol misuse, such as mood disorders. Patients should be educated about the perils of self-medicating with alcohol and counseled to avoid alcohol within close proximity to bedtime. Public education is specifically needed to discourage the added influence of alcohol when a person is tired or having difficulty sleeping and to avoid alcohol within 2 to 4 hours of bedtime.

Differential diagnosis

Sleep disturbances may be related to primary sleep disorders or to other substances. Sleep disruption should have a temporal relationship to the use of alcohol as well as the amount. Hypersomnia or insomnia due to primary sleep disorders generally show a more persistent pattern and vary less in severity in relation to the history of alcohol use. Alcohol can also increase the risk of obstructive sleep apnea; thus, patients should be questioned regarding symptoms of snoring and treated for the sleep apnea once identified (56).

The patient should also be questioned for possible depression or other mood disorders. Disrupted sleep is common in depression and anxiety and may be concomitant with alcohol use as a treatment for those symptoms. In the setting of acute withdrawal any sleep symptoms are present, including severe sleepiness. Patients may also manifest acute REM sleep behavior disorder as a result of the alcohol withdrawal (14). This feature can be treated with a short course of benzodiazepines during the acute withdrawal period.

Diagnostic workup

A careful history of alcohol use and sleep problems helps to determine their temporal relationship and is the foundation to understanding and identifying this diagnosis. The interview should also contain a detailed sleep history. This consists of a number of items. The sleep schedule of the patient should be ascertained, namely bedtimes and wake times, as well as any daytime napping. In addition, the quality of sleep should be assessed. The patient should be asked about the time to fall asleep, any nighttime awakenings, and the time to fall back to sleep if awakened. Abnormal activities during sleep should also be queried, notably snoring, witnessed apneas, movements, and parasomnias, including nightmares. The patient should be asked about other substances that can interfere with sleep besides alcohol, namely caffeine. The patient should be asked about sleep disturbances and alcohol use in detail and delineate their relationship. For many patients, the sleep disturbances should have a temporal relationship to the timing and amount of alcohol used, but some of the features of insomnia and disrupted sleep may be at times away from alcohol use. A sleep diary with the inclusion data regarding alcohol intake may also help in demonstrating a relationship between alcohol and sleep issues.

There are several clinical questionnaires that can be used to assess a patient’s sleep complaints. The Pittsburgh Sleep Quality Index has been validated in a study assessing sleep complaints in the alcoholic population (76). Additional history about mental health problems can also be beneficial in examining this relationship. A number of sleep questionnaires have been used to characterize sleep complaints in the alcoholic population. One study validated the four sleep items from the Hamilton Anxiety and Depression Scale (the Short Sleep Index [SSI]) against the Pittsburgh Sleep Quality Index (PSQI) and found the two questionnaires correlate well with discriminant and convergent validity (76). Daily alcohol consumption has been shown to improve sleep latency in those with minimal to mild levels of anxiety, but it may decrease sleep quality in those with severe anxiety (20).

Excessive alcohol use is associated with several laboratory test abnormalities, particularly liver function tests. In particular, an elevated serum GGT commonly occurs with recent heavy alcohol use and when present in patients with a sleep disorder serves as a useful indication to inquire further about alcohol use. Determination of GGT levels is useful when there is an index of suspicion of an alcohol-related sleep disorder, but elevated levels do not prove excessive alcohol use. The test is not needed when the history is clear.

For individuals who continue to use alcohol and in whom the clinician suspects sleep-disordered breathing, polysomnography performed with the patient having their usual alcohol intake may more accurately demonstrate the array of sleep issues. Alcohol is known to cause greater upper airway muscle relaxation, and studies show mixed results that it influences responsiveness to oxygen and carbon dioxide. A few clinical studies suggest that alcohol worsens underlying obstructive sleep apnea; however, the CPAP pressure required for effective treatment does not appear to change (57). Alcohol has been associated with increased snoring, worsening of sleep-related breathing, and increased movements; therefore, documentation of these issues may help in planning a therapeutic regimen.

Management

The majority of sleep disturbances remit with the cessation of alcohol or reduction to a less problematic level (08). For disturbances that occur from the consumption of alcohol, cessation is usually all that is needed to improve these issues. Benzodiazepines are often used to alleviate neuroexcitability and to defend against delirium tremens for withdrawal from high, chronic alcohol use. The use of benzodiazepines may also be helpful for insomnia symptoms during acute withdrawal. However, the use of benzodiazepines for insomnia in the context of substance use disorders is controversial (29), and this author does not recommend benzodiazepines for this use. Recognizing and treating persistent insomnia in alcohol use disorder is important as persistent insomnia may contribute to individuals being less likely to complete an intensive outpatient substance use disorder treatment program (102). Treatment and, therefore, recognition of sleep disturbances, particularly insomnia, may result in a higher likelihood of participation in a treatment program (35). Offering a wide variety of treatments may improve the chance of participation in therapy to resolve the alcohol use disorder.

Nonpharmacological interventions

Abstinence or decreased alcohol use may improve some sleep symptoms. However, to improve sleep, education on sleep hygiene may provide a cornerstone for further cognitive behavioral therapies. In addition, improving the consistency of the sleep schedule may decrease the chance of relapse (07). Nonpharmacologic therapies have been associated with improvement in sleep disturbances, particularly cognitive behavioral therapy for insomnia (CBTi) in patients with alcohol dependence. CBTi is currently the recommended first-line treatment per guidelines for the treatment of chronic insomnia in nonalcoholics (35). Several randomized controlled trials have shown improvement in the reduction of insomnia symptoms, sleep latency, and sleep efficiency with the use of CBTi in this group (10; 18; 67). Even digital asynchronous CBTi delivered through an application has shown benefit in reducing symptoms of insomnia for this at risk group (98). In addition, smaller studies using sleep restriction, stimulus control, and cognitive restructuring suggest improved sleep quality in alcoholic patients during abstinence. Similarly, studies suggest that short-term mindfulness stress reduction program and progressive relaxation therapy may produce improvement in sleep (35; 100).

Pharmacological interventions

Pharmacological interventions can be used to decrease sleep-related symptoms, specifically insomnia, in those with alcohol use disorder. A variety of medications, such as sedating antidepressants, anticonvulsants, and antipsychotics, have been tried with varying success (73). Each of these have limitations in effectiveness as well as possible side effects. Thus, therapy should be tailored to the patient.

Gabapentinoids. There have been several studies on the efficacy of gabapentin in alcohol cessation in patients with alcohol dependence. Doses ranging from 300 to 1800 mg have been used and have been proven to be safe (49). Studies using higher doses, above 1200 mg, have been shown to have greater efficacy. In a review by Mason and colleagues, six of eight studies showed significant improvement in sleep disturbances with use of gabapentin (65). In the studies showing greater efficacy, the patients also received counseling as well as other supportive behavioral therapies, suggesting that improvement may not be an effect of the medication alone.

One study suggests that gabapentin may not help. A combination of gabapentin and naltrexone for 16 weeks prolonged the time to first heavy drinking period in comparison with those who took naltrexone alone (03). Sleep disturbance was associated with more drinking in the naltrexone only group.

A large multisite study tested the safety and efficacy of gabapentin enacarbil extended-release 600 mg twice a day in individuals with alcohol use disorder. This medication group was compared to a placebo and a computerized behavioral intervention. The study did not show reduction in alcohol use or improvement in sleep problems after six months of daily GE-XR use compared to the other groups (31). Moreover, Modesto-Lowe and colleagues warned of the potential for gabapentin abuse (69) and on December 19, 2019, the U.S. Food and Drug Administration warned that serious breathing difficulties may occur in patients using gabapentin (Neurontin, Gralise, Horizant) or pregabalin (Lyrica, Lyrica CR) who have respiratory risk factors (FDA Drug Safety Communication 12/19/19). Gabapentin should only be considered if first-line drugs such as naltrexone and acamprosate cannot be used (02).

Mirtazapine. Mirtazapine may improve sleep in those with underlying depression and alcohol use disorder. In an 8-week open-label study, individuals given 15 mg for 2 weeks, then 30 mg for six weeks, had subjective improvement in insomnia symptoms and lower drinking levels (35). A later study by the same group and a subsequent randomized controlled trial found that mirtazapine improved the depressive symptoms but not the alcohol intake (24). Sedation was noted to be equal in both the placebo and active treatment group.

Trazodone. Trazodone is commonly prescribed for insomnia but has little clinical data to support its use. A 3-month study of alcoholic patients showed improved sleep outcomes with the use of trazodone; however, heavy drinking was higher in the group receiving trazodone (34).

Quetiapine. Quetiapine XR at bedtime may help sleep. One small study using doses titrated from 50 to 400 mg over eight weeks showed a reduction in wake after sleep onset on polysomnogram and improvement in subjective ratings of insomnia (15). However, the effect was not sustained across the 9-week assessment period, and the risk of tardive dyskinesia and associated metabolic abnormalities suggest that it should be used cautiously, if at all, for insomnia.

Melatonin. Melatonin supplements have been tried to treat the sleep disruption in patients with alcohol use disorder. Yet, systematic review of this therapy shows no improvement in subjective sleep quality (26). The melatonin receptor agonist ramelteon is an option for treating insomnia in recovering alcoholics, though controlled trials are lacking. Ramelteon is not a controlled substance and has essentially no abuse liability. It is approved for the treatment of insomnia characterized by difficulty with sleep onset. The standard dose is 8 mg, taken within 30 minutes of going to bed. It is metabolized by cytochrome p450 enzyme 1A2 but does not appear to inhibit or induce this enzyme. It should not be used in combination with fluvoxamine, a strong 1A2 inhibitor. One study to date has tested ramelteon in recovering alcoholics. Four weeks of 8 mg nightly in five recovering alcoholic patients resulted in a reduction of scores on an insomnia questionnaire, a reduction in latency to sleep, and one additional hour of total sleep time (11).

Another therapeutic option may be agomelatine, which is a melatonin-agonist that has been used for the treatment of depression (25) and has been shown to improve sleep. A small study of nine alcohol-dependent patients with sleep problems who took between 25 to 50 mg of agomelatine nightly had improved subjective sleep quality after six weeks. Mean Pittsburgh Sleep Quality Index scores dropped from 13.1 (+/- 1.7) to 7.8 (+/-1.7) post treatment (39). Hepatoxicity, a common concern with agomelatine, was not evident in these doses.

Alcohol-dependence medications. In the United States, there are only three medications approved for the treatment of alcohol dependence: disulfiram, naltrexone, and acamprosate. These medications reduce the cravings for alcohol and the rate of relapse. However, disulfiram was shown to reduce REM sleep in a meta-analysis (73). This same study showed that naltrexone was associated with increased insomnia and daytime sleepiness. Acamprosate showed objective improvement in sleep on polysomnography, with increased sleep continuity and architecture; however, there was no improvement in subjective sleep measures.

For individuals with underlying sleep-related breathing disorders or restless legs and alcohol use disorder, treatment of the primary sleep disorder should follow standard therapy. Current guidelines advise against the use of alcohol in patients with obstructive sleep apnea. Studies show that alcohol can increase snoring and may worsen the severity of sleep apnea (57). However, alcohol did not appear to change the required pressure for effective CPAP. For restless legs syndrome in patients with alcohol use disorder, the restless legs may be an underlying driver for continued alcohol use (28). Consideration for therapy should include strategies to improve the discomfort and restlessness utilizing therapies that would not increase substance abuse. Although no studies show the effect of treatment of these sleep disorders on relapse rates of alcohol use disorder, improvement of drivers such as sleep disruption may play an important role for individual patients.

Special considerations

Alcohol appears to have differentiated effects on men and women. Acute alcohol consumption may have similar effects on women as men, with decreased sleep latency, increased slow-wave sleep, and reduced REM sleep in the first part of the night and increased N1 and wakefulness in the second half of the night. However, in one study, women reported higher levels of sleepiness than men when they reached an equivalent alcohol concentration, and sleep continuity was more disrupted. In patients with alcohol use disorder who are abstinent, it has been shown that women had better sleep efficiency, less waking after sleep onset, and more slow-wave activity than men. These measures were still decreased compared to women without alcohol use disorder. Moderate alcohol use is associated with fewer insomnia symptoms in men, and in a large European study, the bidirectional relationship between sleep disturbance and alcohol consumption was not shown for women (51).

Pregnancy

Alcohol use should be avoided during pregnancy. The potential adverse physical and neurocognitive effects, including fetal alcohol syndrome, of maternal alcohol consumption on the developing fetus have been extensively reviewed. Research has clarified the effects of prenatal alcohol consumption on a child’s postnatal sleep. Maternal prenatal consumption of alcohol results in infant postnatal sleep fragmentation as well as the suppression of spontaneous movements during sleep at 6 to 8 weeks of age. In a sample of 40 children with fetal alcohol spectrum disorder (1.8 to 17.5 years, median age 9.4 years), 100% had insomnia, 93% had circadian rhythm disorder, and 85% had restless sleep (52). In utero alcohol exposure results in altered neonatal autonomic control during sleep, possibly increasing the risk of sudden infant death syndrome.