Insomnia, alcoholism and relapse

SleepMedicineReviews,Vol. 7, No. 6, pp 523-539,2003

SLEEP

doi:l 0.1053/smrv.2002.0248

~IEDtCINE ! reviews t .......................

CLINICAL REVIEW

Insomnia, alcoholism and relapse Kirk J. Brower University of Michigan Addiction Research Center and Chelsea Arbor Addiction Treatment Center, MI, USA

KE~ORDS alcohol dependence, alcoholism, epidemiology, insomnia, neurotoxicity, polysomnography, sleep disorders, treatment guidelines

Summary Insomnia and alcoholism are significantly associated in community surveys and patient samples. Insomnia occurs in 36-72% of alcoholic patients and may last for weeks to months after initiating abstinence from alcohol. Some correlates of insomnia in alcoholic patients are identical to those observed in non-alcoholic insomniacs, including anxiety and depression, tobacco smoking, and the use of alcohol to aid sleep. Other studies suggest that as the severity of alcoholism increases, so does the likelihood of insomnia in alcoholic patients. In the sleep laboratory, alcoholic patients who complain of insomnia have disrupted sleep continuity when compared to alcoholic patients without insomnia complaints. Recently sober alcoholics are also more likely than non-alcoholics to have sleep-disordered breathing and increased periodic leg movements, which might contribute to insomnia in some alcoholic patients. The co-occurrence of insomnia and alcoholism is clinically significant because alcoholism can exacerbate the adverse consequences of insomnia (e.g. mood changes and performance decrements) and because insomnia among patients entering treatment for alcoholism has been significantly associated with subsequent alcoholic relapse. Baseline polysomnographic correlates of subsequent relapse include prolonged sleep latency, decreased sleep efficiency and total sleep time, increased rapid eye movement sleep pressure, and decreased slow wave sleep. Whether treatment of insomnia in alcoholic patients reduces relapse rates is unknown, but preliminary treatment guidelines that accommodate the special characteristics of alcoholic patients are provided, with a goal to reduce daytime impairment and psychological distress. © 2003 Elsevier Science Company. All rights reserved.

INTRODUCTION Insomnia is a frequent symptom in the general population that has been associated with impaired daytime performance, increased risk for depression and, in some studies, premature mortality. Insomnia is especially frequent among individuals with alcoholism [I]. Correspondence should be addressed to: Kirk J. Brower, University of Michigan Addiction Research Center, 400 East Eisenhower Parkway, Suite 2A, Ann Arbor, MI 48108, USA. Tel: 734-930-0201; Fax: 734-930-0727; E-mail: [email protected]

When the two disorders co-occur, alcoholism can exacerbate the adverse consequences of insomnia (e.g. impaired performance). Moreover, a number of clinical studies have demonstrated a relationship between baseline sleep problems when patients enter alcoholism treatment and subsequent return to drinking [I]. Thus, insomnia has special clinical significance when it occurs in alcoholic patients. For the purposes of this review, insomnia refers to a patient's subjective complaint of difficulty falling asleep, staying asleep, or nonrestorative sleep (i.e. not feeling rested in the morning). Insomnia is not defined in terms of its polysomnographic correlates,

1087-0792/03/$ - see front matter © 2003 ElsevierScience Company. All rights reserved.

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K. ~ BROWER

although these will be discussed. Alcoholism refers to a chronic disorder characterized by impaired control over the use of alcohol, compulsive use of alcohol despite adverse consequences from its use, and sometimes, tolerance and withdrawal. As defined here, alcoholism is generally equivalent to the DSM-IV diagnosis of alcohol dependence [2]. For reviewed studies that define insomnia or alcoholism differently, the alternative definitions as used in each such study will be described. This review is divided into four major sections. The first section reviews the co-occurrence of insomnia and alcoholism as well as the correlates of insomnia in alcoholic patients. The second section reviews the evidence that insomnia is associated with alcoholic relapse. The third section introduces a theoretical model to explain the causal relationships between insomnia and alcoholism, with a focus on neurobiological mechanisms. Finally, treatment implications of insomnia in alcoholic patients will be discussed.

C O - O C C U R R E N C E OF INSOMNIA AND ALCOHOLISM Community

samples

At least five studies have examined the association between insomnia and a diagnosis of alcoholism in the general population [3-7]. An early study published in 1979 failed to find an association between "alcohol problems" and insomnia [3], but the study's interpretation was limited by its measure of alcohol problems. Respondents were scored positive for alcohol problems if "they felt the need for help in the last year for such difficulties" (p. 1258), but many individuals with alcohol problems do not recognize that they need help. The other four studies found a positive relationship between insomnia and alcoholism in the general populations [4-7]. Ford and Kamerow [4], for example, investigated the 6-month prevalence of alcoholism in a community survey of individuals with and without insomnia. They defined alcoholism to include both alcohol abuse and alcohol dependence according to DSM-III criteria (which preceded DSM-IV [2]) and used a face-to-face structured diagnostic interview to determine the diagnosis of alcoholism. Insomnia was defined by a "yes" response to the question, "Have you ever had a period of 2 weeks or more when you had trouble falling asleep, staying asleep, or with waking up too early?" Insomnia was counted only if it occurred in the

previous 6 months and was not always the result of physical illness, medication, or substance use. Ford and Kamerow [4] found that the 6-month prevalence of alcoholism was significantly higher in individuals with insomnia (7.0%) than in those without insomnia (3.8%). Using a sample derived from the same epidemiological survey, Brower et al. [5] found that insomnia affected 18% of alcoholic individuals vs 10% of non-alcoholic individuals in the previous 6 months. Furthermore, alcoholism significantly predicted insomnia after controlling for age, gender, and other drug use and mental disorders. Two studies found an association between insomnia and a four-item screening questionnaire for alcoholism known as the CAGE. The CAGE screens for a lifetime history of alcoholism, and yields a score ranging from 0 to 4; scores _~2 indicate a positive screen for alcoholism [8]. The first study found a significant association between insomnia and raw CAGE scores in a random sample of 1000 Brazilian inhabitants [6]. The second study [7] randomly selected a sample of 2602 men and found that alcoholism was more frequent in individuals with insomnia than those without ( 18.9 vs 8.6%, P< 0.00 I). Alcoholism remained an independent predictor of recent insomnia (odds ratio --- 1.75) after adjusting for age, body mass index, smoking, a history of insomnia 10 years earlier, and medical and psychiatric disorders. In summary, alcoholism and insomnia are significantly associated in community surveys. Stoller [9] estimated that about 10% of alcohol-related costs could be attributed to insomnia. Given that alcohol problems cost the United States an estimated $184.6 billion in 1998 dollars, alcohol-related insomnia may cost the country around $18.5 billion each year [ I ].

Patient samples A study of primary care patients found a significant association between severe insomnia and a physician's diagnosis of alcohol or drug abuse (4.6% of patients with insomnia had substance abuse vs 1.3% of patients without insomnia) [10]. Among patients admitted for alcoholism treatment, rates of insomnia range from 36-72% [I, I I - I 3]. The range is wide, most likely because different insomnia measures and time frames were employed, and because samples differed in demographics, drinking severity, time since last drink, presence of alcohol withdrawal, and diagnostic comorbidity. Studies of the duration of insomnia following alcohol withdrawal suggest that symptoms persist for

INSOMNIA AND ALCOHOLISM 4-8 weeks [14], although polysomnographic studies suggest that sleep disturbances may persist for months to years during sobriety [I], To the author's knowledge, rates of insomnia among adolescents with alcohol dependence have not been published. Nevertheless, a recent study reported that adolescents with alcohol dependence scored higher on a 5-item scale for sleep problems than did adolescents from the community without alcohol dependence [I 5]. Importantly, the difference in sleep scores remained after controlling for negative emotional states and tobacco involvement. In summary, insomnia is a common symptom in alcoholic patients that may persist for weeks to months after initiating abstinence from alcohol. The persistence of insomnia and other symptoms - such as mood instability and c r a v i n g - beyond the acute withdrawal period of I-2 weeks has at times been labeled, subacute or protracted withdrawal [14, 16]. However, persistent insomnia in abstinent alcoholics may also reflect sleep problems that preceded the development of alcoholism (to be discussed).

Correlates and predictors o f co-occurring insomnia and alcoholism Correlates of insomnia among alcoholic individuals include measures of alcohol consumption [13, IT], severity of alcohol dependence [ I I ], depressive symptoms [I I, 13, 18], anxiety symptoms [13], hostility [I 9], and possibly female gender. Tobacco smoking is both a correlate of insomnia and alcoholism and, thus, might explain in part the co-occurrence of insomnia and alcoholism. In two recent studies, however, alcoholism remained a significant predictor of insomnia even after controlling for smoking [7, 15]. Another correlate of insomnia in alcoholic patients is the use of alcohol to self-medicate sleep problems. In one study [I I], about twice as many alcoholic patients with insomnia reported frequent use of alcohol as a sleep aid than did alcoholic patients without insomnia (55 vs 28%, P<0.01).

Polysomnographic findings A number of studies investigated the sleep of alcoholic patients with polysomnography during periods of intoxication, withdrawal, and sustained abstinence. Several published reviews provide details of these studies [I, 20-22]. In general, sleep latency (SL) is

525 increased and total sleep time (TST) is decreased in alcoholic patients during periods of drinking, acute alcohol withdrawal (weeks I and 2 of abstinence), and post-acute withdrawal (weeks 2 through 8 of abstinence). During post-acute withdrawal, sleep efficiency (SE) is also decreased, whereas stage I% sleep is increased as compared to control subjects [22, 23]. The percentage of slow wave sleep (SWS%) increases during nights of drinking and decreases during acute alcohol withdrawal, and may remain decreased after 3-14 months of sobriety. Rapid eye movement (REM) sleep is generally suppressed during drinking and tends to rebound during acute alcohol withdrawal. After acute withdrawal (during weeks 2 through 8), some studies reported that alcoholics had more REM sleep and shorter REM latency times than healthy controls, whereas other studies did not find these differences [I]. These inconsistent findings may reflect differences in alcoholic subtypes, with persistent REM sleep abnormalities most evident in depressed alcoholics and those who subsequently relapse [24, 25]. Further studies are required to confirm this hypothesis. Only one published study to date analyzed correlations between subjective and objective measures of sleep for a single sample of alcoholic patients. In that study, retrospectively self-reported insomnia (for the 6 months prior to treatment) was significantly associated with increased SL and decreased SE on polysomnography after 2 weeks of abstinence [ I I ]. Polysomnographic studies suggest that alcohol can increase inspiratory resistance in healthy controls and cause apnea in asymptomatic snorers. Other studies show that abstinent alcoholics are more likely to have sleep-disordered breathing than control subjects [2 I, 22, 26]. Aldrich et al. [26] reported that alcoholic patients with sleep-disordered breathing (apneahypopnea index~10) had significantly greater SL times (60 vs 34rain), less total sleep (269min vs 314min), and less efficient sleep (70 vs 81%) than alcoholics without sleep-disordered breathing (apneahypopnea index < I 0). Thus, sleep-disordered breathing may contribute to insomnia in some alcoholic patients. Brower [I] reviewed three studies of periodic leg movements (PLMs) in alcoholic patients. Two found that recently abstinent alcoholic patients had significantly more PLMs than non-alcoholic controls, whereas one study found an absence of PLMs in both alcoholic (abstinent for 3-6 weeks) and non-alcoholic subjects. Therefore, PLMs may also contribute to insomnia in some alcoholic patients.

s26

K. L- BROWER

In summary, some correlates of insomnia in alcoholic patients are identical to correlates of insomnia observed in non-alcoholic individuals, such as depression, anxiety, alcohol consumption, smoking, and the use of sleep aids such as alcohol. One unique correlate of insomnia in alcoholic patients is the severity of alcoholism as a disorder. Another unique correlate will be discussed in the next section: the association of insomnia with alcoholic relapse.

INSOMNIA RELAPSE

AND

ALCOHOLIC

Skoloda and colleagues [27] were the first investigators to provide experimental evidence that selfreported insomnia was associated with relapse (Table I). They studied 56 alcoholic men who could choose to drink on an inpatient unit after a one-week baseline period of no drinking. Patients who eventually drank reported more problems with sleep, including difficulty falling asleep, at baseline than non-drinking patients did. Foster and colleagues [28] followed 60 alcoholics for 12 weeks after completing inpatient detoxification. Baseline sleep was measured at 4-5 days after completing detoxification, using the sleep subscale of the Nottingham Health Profile. Relapse during the 12-week follow-up period was defined as drinking more than 168 g of ethanol (~ 14 American drinks) in a 7-day period for men, and > 112 g in a 7-day period for women. Multivariate analyses revealed that disturbed sleep was the most significant predictor of relapse, even after controlling for depression, severity of alcohol dependence, cigarette smoking, and social class. In a second article using what appeared to be the same sample, Foster and Peters [18] analyzed the five individual items that comprise the sleep subscale of the Nottingham Health Profile. The relapsed group endorsed three items of impaired sleep at baseline more frequently than did the non-relapsed group. After applying a Bonferroni correction, only one baseline item remained significantly higher (P< 0.005) in the relapsed group: "It takes me a long time to get to sleep." Similarly, Brower et al. [25] analyzed five insomnia items from the Sleep Disorders Questionnaire [29], which was administered at baseline after starting treatment for alcoholism. Only one, "1 have trouble getting to sleep at night," was significantly associated with subsequent relapse after controlling for severity

of alcohol dependence, psychiatric severity, and one other significant sleep item ("1 feel that my sleep is abnormal"). In a second analysis of the same sample, Brower et al. [I I], defined insomnia as scoring highly on at least one of eight items from the Sleep Disorders Questionnaire, including "1 have trouble getting to sleep at night." Relapse, defined as any drinking during the follow-up period (mean of 5 months), was more frequent in alcoholic patients with insomnia than without insomnia at baseline (60 vs 30%, P = 0.02). Contrary to these studies, Foster et al. [12] failed to find a correlation between alcoholic relapse at 12 weeks and poor sleep at baseline, as measured by a single item from the Life Situation Survey. Therefore, insomnia items from the Sleep Disorders Questionnaire [29] and the Nottingham Health Profile [18] appeared more likely than an item from the Life Situation Survey [I 2] to predict relapse. It is tempting to speculate that using alcohol to self-medicate insomnia represents the mechanism by which insomnia leads to relapse. However, two studies failed to find that a history of self-medicating insomnia with alcohol predicted subsequent relapse among alcoholics [I I, 30], although the finding approached significance (P= 0.07) in one study [I I].

Polysomnographic correlates of alcoholic relapse SL is generally recognized as the polysomnographic correlate of subjectively reported initial insomnia. Brower et al. [25] entered objectively measured SL and subjectively reported initial insomnia into a logistic regression and found that only SL remained as a predictor of alcoholic relapse. Drummond et al. [3 I] reported that prolonged SL and decreased SE predicted relapse at 14 months among alcoholic patients who had been abstinent for 19 weeks. However, three studies failed to find an association between SL and relapse [24, 32, 33], although two of these studies did find an association between low levels of TST and relapse [32, 33] (Table I). In addition to sleep continuity variables (i.e. SL, SE, TST), various REM sleep indices have been correlated with relapse. Gillin et al. [24] were the first group to demonstrate an association between REM pressure (shortened REM latency, and increased REM% and REM density) and subsequent relapse. Gillin's group also reported that elevated REM density predicted relapse in alcoholics with and without a history of depression [32, 33]. However, they did not find an

56 males on in patient unit

45 male inpatients

62 men and 12 women

21 male inpatients with primary alcoholism and secondary depression

23 male inpatients who abstained for 19 weeks

39 male and 2t female inpatients

Skoloda et al.. 1979 [27]

Gillin et al., 1994 [24]

Brower et al., 1998 [25]

Clark et al., 1998 [32]

Drummond et al.,

Foster et al.,

1998 [28]

r998 [31]

9 male inpatients

Allen et al., 1977 [35]

Allen & Wagman, 1975 [34]

Sample characteristics 4 male in patients

Sleep subscale of Nottingham Health Profile

PSG; no subjective sleep measures

PSG; no subjective sleep measures

PSG and 5 items from the SDQ

PSG

4-item questionnaire given each morning

PSG

Baseline measure of insomnia PSG

Self-reported drinking that exceeded 168 g for men and I 12 g for women in any I of 12 weeks after treatment

Any drinking from 19 weeks to 14 months, measured by self-report, collateral informant, increased liver enzymes, and urine toxicology screens

Same as Gillin et al., 1994

Any self-reported drinking during a S-month mean follow-up period

Any drinking during a 12-week period after inpatient discharge, measured by self-report, collateral informant, increased liver enzymes, and urine toxicology screens

Any observed drinking on inpatient unit with access to alcohol for 4 weeks, after baseline period of no drinking

"Amount of sobriety" during 2-month follow-up period

Frequency of button pressing to obtain alcoholic drink

Outcome measure of drinking

Sleep predicted drinking after controlling for depression, severity of alcoholism, smoking, and social class

Prolonged SL and decreased SE at 19 weeks predicted relapse at 14 months

TST and increased REM density predicted relapse

Both PSG-measured SL and self-reported DFA predicted relapse; decreased REM latency and stage 4% were predictors in univariate analyses

Relapse predicted by short REM latency, increased REM% and REM density, but not by SL, SE, or TST

Patients who drank had worse sleep quality and more DFA at baseline than patients who did not drink

Low levels of SWS predicted poor sobriety outcomes

Low REM% correlated with high frequency of button pressing

Results and comments

Studies of baseline sleep disturbance and subsequent relapse to drinking in aJcoholic patients

Author(s) Year [reference]

Table I

3

21 male inpatients from Clark et al., 1998 and 46 male non-depressed inpatients

Same as Foster and Peters, 1998

41 male and 41 female inpatients

Same as Brower et al., 1998

29 male and II female inpatients

Clark et al., 1999 [33]

Foster and Peters 1999 [ 18]

Foster et al., 2000 [I 2]

Brower et al., 2001 [I I]

Gann et aL, 2001 [23]

PSG & PSQI

8-item scale derived from the SDQ and PSG

Single item from Life Situation Survey

Sleep scale items of Nottingham Health Profile

PSG

Baseline measure of insomnia

Any self-reported drinking between hospital discharge and 6-month follow-up, or elevated liver enzymes

Same as Brower et al., 1998

Same as Foster and Peters, 1998

Same as Foster and Peters, 1998

Same as Gillin et al., 1994

O u t c o m e measure of d r i n k i n g

Increased REM pressure predicted relapse; PSQI not reported nor analyzed as a predictor

Patients with insomnia had increased SL and decreased SE and were twice as likely to relapse as patients without insomnia

Negative study

Prolonged SL predicted alcoholic relapse

Increased REM density predicted relapse in both patient groups, TST was a marginal predictor (P = 0.05)

Results and comments

Questionnaire [29]; SL = sleep latency; SWS = slow wave sleep; TST = total sleep time.

Note: DFA= difficulty falling asleep; PSG= polysomnography; PSQI= Pittsburgh Sleep Quality Index; REM = rapid eye movement; SE=sleep efficiency; SDQ =Sleep Disorders

Sample

characteristics

Continued

[reference]

I

Author(s) Year

Table

INSOMNIA AND ALCOHOLISM association between REM sleep indices after 19 weeks of abstinence and subsequent relapse after 14 months [3 I], suggesting that REM sleep predicts relapse only during early abstinence. Aldrich et aL found an association between increased REM% and relapse in preliminary studies and between shortened REM latency and relapse in a larger sample [25]. Recently, Gannet al. [23] replicated the findings of Gillin et aL [24] that increased REM pressure predicted relapse. By contrast, Allen and Wagman [34] reported a correlation between low REM% and subsequent drinking (Table I). Immediately after 2 to 3 days of inpatient detoxification, four alcoholic men had polysomnography for at least the first 7 nights (range: 7 to 28 nights). Each subsequent morning, subjects' disposition to drink was tested via a behavioral paradigm. Subjects could press a button to obtain one alcoholic drink (2 oz of 95 proof alcohol). By pressing the button more frequently, subjects could obtain the drink more quickly. Results revealed that low REM% on a given night was correlated with a high frequency of button pressing the next morning. However, the results must be interpreted cautiously because of the small number of subjects studied and the fact that disposition to drink was tested only in the early morning (at 7:45 aom.). Moreover, the investigators failed to find in another experiment that REM sleep deprivation increased the disposition to drink [34]. Other studies implicate low amounts of SWS as a marker of alcoholic relapse. Allen et al. [35] performed sleep recordings on nine inpatients and later classified them as having either good or poor treatment outcomes based on amounts of sobriety at a two-month follow-up period. Patients with poor outcomes had lower levels of baseline SWS than patients with good outcomes (P<0.10). Aldrich et al. [25] reported low baseline levels of stage 4% (but not SWS%) among patients that subsequently relapsed. Other studies have not found a relationship between SWS and relapse [24, 31, 32]. In summary, polysomnographic correlates of insomnia - prolonged SL, decreased SE, decreased TST - have been associated with alcoholic relapse in 4 of 5 studies that examined the relationship [25, 31-33]. Other studies demonstrated that increased REM pressure and decreased SWS also predicted subsequent relapse. However, some inconsistencies in results across studies exist, which likely reflect differences in sampling, methods for assessing relapse, and timelines for measurements. More research is needed to assess the categories of polysomnographic variables (i.e. sleep continuity, REM sleep, SWS) that

529 have the greatest value in predicting relapse among alcoholics.

A M O D E L OF T H E RELATIONSHIPS BETWEEN INSOMNIA AND ALCOHOLISM Although the literature is very clear that insomnia and alcoholism are significantly associated, causal explanations for the association remain speculative. The nature of relationships between insomnia and alcoholism is undoubtedly complex and a plausible model needs to account for the following experimental observations. First, epidemiological studies suggest that insomnia can precede and predict the developmenthol new-onset alcoholism [4, 36]. Second, people with insomnia are more likely than people without insomnia to use alcohol as a sleeping aid and to perceive alcohol as emotionally reinforcing [37]. Third, experimental administration of alcohol to alcoholic and non-alcoholic subjects results in wellcharacterized disruptions to sleep architecture and sleep continuity [I, 38]. Fourth, chronic, heavy ethanol consumption alters a number of neurochemical systems that are believed to regulate sleep [I]. Fifth, sleep problems in alcoholics can persist despite sustained abstinence [3 I]. Sixth, sleep problems can predict relapse and return to drinking in alcoholic patients [I I, 18, 31]. Based on these observations, a reciprocal, causal model is proposed in which (a) insomnia leads to alcoholism due to prolonged and excessive self-medication of sleep problems with alcohol, and (b) chronic, heavy alcohol consumption leads to insomnia via ethanors toxic effects on brain systems involved in the regulation of sleep (Figure I). Although not emphasized in this model, chronic alcoholism is associated with comorbid medical and psychiatric disorders (e.g. depression) that can also contribute to insomnia.

Insomnia m a y lead to alcoholism Ford and Kamerow [4], using data collected from the Epidemiological Catchment Area survey, reported that the incidence of developing alcohol abuse was 2.4 times higher in household adults who had persistent insomnia than in adults without insomnia 6-12 months earlier. However, they did not exclude individuals with other psychiatric disorders at baseline. In further analyses of these data, Weissman et aL [36] calculated

530

K.J. BROWER Insomnia Se|f-m

1" A~cohol Consumption ' x ~

~

~ ~

Alcoholism ment

Relapse

Figure I Model of the reciprocal relationships between heavy alcohol consumption and insomnia. Insomnia may lead to increased alcohol consumption via self-medication, and alcohol consumption may lead to insomnia via neurotoxicity. Insomnia and heavy alcohol consumption are risk factors for developing alcoholism. Treatment of alcoholism can facilitate abstinence, but insomnia may persist despite abstinence. Insomnia at the time of treatment is a risk factor for relapse to drinking. Relapse contributes to neurotoxicity and persistent insomnia. The clear arrow represents the untested hypothesis that treatment of insomnia can facilitate abstinence when provided as an adjunct to alcoholism treatment.

a significant odds ratio of 2.3 for developing alcohol abuse in adults with a history of insomnia vs no insomnia after excluding those with psychiatric disorders at baseline. A third study [39] showed a non-significant trend for new-onset alcohol abuse or dependence to follow a history of insomnia (odds ratio 1.7). Together, these studies suggest that insomnia precedes the development of alcohol problems in at least some adults. Between 15 and 28% of people with insomnia, for example, use alcohol as an aid to sleep [40]. Even more, 44-60% of alcoholic patients report using alcohol to help them sleep [11, 30]. However, alcohol is not a reliably effective sedative among alcoholic patients [I]. Skoloda et aL [27] observed that alcoholic patients who returned to drinking under experimental

conditions reported improvements in sleep that were mainly confined to the first week of drinking. A reasonable hypothesis, therefore, is that alcoholic patients develop tolerance to the sedative effects of alcohol, rendering it ineffective unless they escalate their consumption. It is also possible that escalating attempts to self-medicate insomnia with alcohol may contribute to the development of alcoholism (Fig. I). If alcohol is not an effective sedative, then why do people with insomnia take it? Roehrs et al. [37] studied I I subjects with insomnia and 9 subjects with normal sleep. After 2 nights in which subjects learned to distinguish ethanol vs placebo beverages by colorcoded cups, they chose their bedtime beverage for the next 3 nights. Subjects with insomnia chose ethanol 67% of nights compared to 22% of nights for controls. Moreover, alcohol improved pre-sleep mood in insomniacs vs'controls. Therefore, people with insomnia may perceive alcohol to have benefits in addition to its sedative effects. Taken together, epidemiological and laboratory studies suggest the possibility that insomnia could contribute to the development of alcohol problems in vulnerable individuals.

Alcoholic neurotoxicity may lead to insomnia The neurobiological mechanisms underlying the effects of alcohol on sleep are poorly studied. However, much is known about the neurobiology of alcoholism [4 I, 42] and the neurobiology of sleep [43]. The overlap between these two areas of knowledge, therefore, provides a starting point for understanding the neurobiological relationships between alcoholism and sleep [I]. Early on, investigators speculated that low levels of SWS found in recently abstaining alcoholics were related to diffuse cortical damage and neuronal cell loss [I]. Consistent with this hypothesis, Ishibashi et al. [44] observed that improvement in slow wave sleep over a 6-month period among nine alcoholic men was associated with reversibility of cerebral atrophy as measured by computed tomography (CT) scanning. Early theories regarding the neurochemistry of sleep focused on monoamine neurotransmitters, particularly serotonin and norepinephrine. Because alcohol was also known to affect monoamine neurotransmitters, investigators proposed that alcohol disrupted sleep via these mechanisms [20]. Consistent with the monoamine hypothesis, Zarcone [20] cited evidence

INSOMNIA AND ALCOHOLISM that alcohol-related sleep disturbance improved with 5-hydroxytryptophan, a serotonin precursor. A later study failed to find that L-tryptophan improved sleep in alcoholic patients, but subjects slept relatively well at baseline prior to receiving medication [45]. Nevertheless, the simple notion that increasing serotonin levels will improve sleep in alcoholic patients is unlikely [I]. Sleep regulation involves multiple neurotransmitter systems and sleep factors [43], many of which are also affected by alcohol [41, 42]. Moreover, studies have begun to reveal patterns of neurochemical activity during alcoholic drinking and withdrawal that favor the changes in sleep and arousal observed in alcoholic patients [I]. Selected neurochemical systems will be discussed below, while other systems are reviewed elsewhere [I, 38].

GABA A general principle of addiction neurobiology is that acute administration of a substance induces acute neurochemical effects to which the brain over time responds with neuroadaptation [4 I, 46]. For example, alcohol can acutely increase GABA activity, which may mediate some of its sedative properties. After chronic administration of alcohol (as happens with alcoholism), the brain adapts via homeostatic processes to decrease the overall tone of central GABA activity. Neuroadaptation of GABA activity to chronic alcohol administration manifests clinically in at least two ways. First, the patient develops tolerance to the sedative effects of alcohol, in part because it takes more alcohol to overcome the decreased tone of GABA activity. Second, when alcohol is withdrawn, the decreased tone of GABA activity becomes unmasked and contributes to hyperarousal. Further evidence of GABA involvement in the sleep disruptions of alcohol withdrawal is suggested by the finding that GABAA agonists improve sleep during acute and subacute alcohol withdrawal [I 6, 47].

Glutamate Glutamate activity is decreased during acute alcohol administration, which is consistent with sedation [I]. As a result of neuroadaptation to chronic alcohol administration, the early stages of abstinence are characterized by increased glutamate activity, which is associated with hyperarousal.

Acetylcholine Acetylcholine activity decreases during SWS and increases during REM sleep [I, 43]. Acutely, alcohol

531 inhibits acetylcholine release in the brain [42]. Therefore, SWS augmentation and REM sleep suppression on nights of alcohol administration may result in part from decreased cholinergic activity.

Norepinephrine Noradrenergic activity is enhanced during alcohol withdrawal, which likely contributes to increased arousal when alcohol-dependent people stop drinking [I]. Agents that reduce noradrenergic activity (e.g. benzodiazepines, clonidine, and propanolol) both have sedative effects and are used to treat alcohol withdrawal [I, 8].

Dopamine Dopamine activity decreases during sleep [I]. Dopamine activity is also hypothesized to mediate the reinforcing properties of most drugs of abuse including alcohol [41]. Acute alcohol administration increases dopamine release, especially in the mesolimbic system that is associated with reward. Dopamine augmentation, along with noradrenergic activation, may contribute to alcohol's stimulating properties.

Adenosine Adenosine has inhibitory effects on the central nervous system - including the cholinergic system that it exerts at adenosine receptor sites [43]. Brain levels of adenosine increase with prolonged waking and before sleeping, suggesting that it may have a role in sleep induction. Acutely, alcohol enhances adenosine activity by inhibiting its reuptake [41], which in turn inhibits the cholinergic system, so adenosine may also have a role in decreasing REM sleep following alcoholic intoxication. Conversely, during alcohol withdrawal adenosine activity is relatively reduced due to neuroadaptation, which favors arousal and REM rebound.

Summary A number of neurobiological systems regulate sleep, many of which are altered by chronic and heavy drinking. It is hypothesized, therefore, that the disturbances of sleep commonly observed in alcoholic patients, result from alcohol-induced neurotoxicity and neuroadaptation. Neuroadaptation refers to the process by which the central nervous system (CNS) compensates for chronic exposure to alcohol, a toxin, in order to maintain homeostasis and optimize CNS functioning. Because alcohol is a CNS depressant for the most part, the brain compensates by modulating its systems to favor CNS arousal. In general,

532 neuroadaptations to chronic alcohol consumption, as well as neurochemical activity during alcohol withdrawal, favor central nervous system arousal and, thus, interfere with sleep-regulating mechanisms.

TREATMENT IMPLICATIONS Both pharmacological and nonpharmacological treatments have demonstrated efficacy to treat primary insomnia in non-alcoholic patients [48]. Such treatments may also be indicated to treat insomnia in selected alcoholic patients. Unfortunately, few controlled studies of treating insomnia in alcoholic patients have been published and, therefore, no consensus exists about the optimal treatment of insomnia in alcoholic patients [49, 50]. Alcohol treatment programs typically assume that sobriety is the best treatment for restoring the patient's sleep patterns and rhythms that have been disrupted by alcohol. Although abstinence and a sober lifestyle are necessary, they do not always provide sufficient treatment of alcohol-associated insomnia, because sleep disturbances can both persist during abstinence [31] and increase the risk of alcoholic relapse [I I, 18, 31]. Accordingly, some investigators and clinicians have reported on potential treatments for alcoholassociated insomnia that will now be reviewed.

Nonpharmacological treatment Recent reviews of the literature support the efficacy of nonpharmacological treatments for insomnia [51, 52] and some authors have concluded that stimulus control and sleep restriction techniques are especially beneficial [48, 53]. With two exceptions [54, 55], however, studies have excluded subjects with alcoholism, and no studies of stimulus control or sleep restriction have been conducted in alcoholic subjects. One study of alcoholic patients during withdrawal utilized bright light therapy to improve sleep quality [54]. The rationale for treatment assumed that sleep onset latency is phase delayed during alcohol withdrawal, and that bright light exposure in the daytime should advance the sleep/wake cycle. Accordingly, bright light therapy was administered to 10 inpatients during acute alcohol withdrawal for 6 h on day 3 of abstinence. After one night of adaptation, sleep was measured the night before treatment (baseline), the night of treatment, and the night after treatment. Both polysomnographically-measured SL and subjective

K.J. BROWER sleep quality improved after treatment. Unfortunately, the absence of a control group and the short follow-up period severely limits the conclusions that may be drawn. Greeff and Conradie [55] randomized 22 alcoholic patients who met DSM-III-R criteria for insomnia to either 10 I-hour sessions of progressive relaxation training over a 2-week period (treatment group) or to delayed training (control group), after completing at least I month of residential treatment for alcoholism. The treatment group reported significantly more improvement in its quality of sleep than the control group at the end of the 2-week period. However, objective sleep measures were not obtained. Nevertheless, this controlled study demonstrated the potential of a behavioral therapy to improve sleep in abstinent alcoholic inpatients. Studies of other therapies°~-.such as cognitivebehavioral therapy, stimulus control techniques, sleep hygiene, and sleep restriction strategies are clearly needed. As described below, there are good reasons to avoid using certain medications, especially sedative-hypnotic medication, in alcohol-dependent patients. Therefore, further observations and trials of non-pharmacological therapies for insomnia in alcoholdependent patients are strongly encouraged.

Pharmacotherapy Sedative-hypnotic medications (i.e. the benzodiazepines and related GABA receptor agonists such as zolpidem and zaleplon) are safe, efficacious, and often the treatment of choice for short-term management of insomnia in nonalcoholic patients [56]. Although the abuse potential of sedative-hypnotics is low in most patients, addiction specialists disagree on the risk for abuse among alcoholics [49, 57, 58]. Moreover, sedative-hypnotic medications have a high potential for overdose and toxicity when mixed with alcohol. Thus, sedative-hypnotic use in alcohol-dependent patients remains controversial [49], except for using benzodiazepines to treat acute alcohol withdrawal [8]. Antidepressant medications with sedative properties have increasingly been used to treat insomnia in the United States [59]. The use of sedating antidepressants to treat insomnia among depressed patients finds moderately good support from polysomnographic studies according to recent reviews of the topic [60, 61]. When alcoholic patients with insomnia suffer from comorbid major depression, the same treatment guidelines [60, 61] may be applied with

INSOMNIA AND ALCOHOLISM some important caveats. Most importantly, the overdose potential of the medication must be carefully considered, especially for patients who either are suicidal due to depression or have a history of suicide attempts when drinking. In this regard, the tricyclic antidepressants - including amitriptyline and doxepin, t h e most commonly used tricyclics to treat insomnia [59] - are highly lethal when taken as an overdose. Trazodone - the other most commonly prescribed antidepressant to treat insomnia - has limited toxicity when taken alone in overdose, but can be lethal when taken with alcohol or other drugs [62]. The association of trazodone with priapism, albeit rare, can cause irreversible impotence in males, who are more likely than women to have alcoholism. Finally, the dosing of medications in alcoholics may be complicated by alcohol-associated changes in liver function. For exampler induction of the liver enzymes by alcohol can result in decreased blood concentrations and efficacy of the tricyclic antidepressants. There are few published observations of using antidepressants to treat insomnia in alcoholic patients, but trazodone is the one best represented in the literature. One group reported that 100mg/d of trazodone significantly decreased insomnia (as measured by the Hamilton Rating Scale for Anxiety) over a 10-day period in 17 patients undergoing acute withdrawal from alcohol [63]. Another group reported that 50-150 mg/d oftrazodone improved insomnia symptoms in 10 (56%) of 18 substance abusers with comorbid anxiety disorders [64]. Lastly, a study compared trazodone to gabapentin (an anticonvulsant) in 10 alcoholic patients who had insomnia that persisted for at least 4 weeks of abstinence [65]. After 4-6 weeks of treatment, both groups improved in sleep as measured by the Sleep Problems Questionnaire [66], but the trazodone-treated patients were more likely to awaken feeling tired and worn out. These results have now been extended to 50 alcoholic patients in which 16 took trazodone (mean dose 105mg at bedtime; range 50-300 mg) and 34 took gabapentin (unpublished data). Collectively, none of these studies of trazadone were controlled trials and none used polysomnography to document improvements in sleep. Nevertheless, they suggest a dose range for trazodone as well as change-sensitive, sleep measures that could be utilized in randomized, double blind, placebo-controlled trials. Nefazodone is similar to trazodone in having dual activity as a serotonin-type-2 receptor antagonist and serotonin reuptake inhibitor [60]. Nevertheless, trazodone is more sedating than nefazodone [60].

533 Although nefazodone has been suggested as a potentially useful treatment for insomnia in substance abusing patients [50], the author is unaware of any published data to recommend it for this purpose. Another antidepressant, mirtazapine, has been associated with somnolence in 54% of patients treated for major depression during clinical trials [60]. The author has used mirtazapine successfully for treating insomnia in his clinical practice of alcoholic patients. Further clinical observations are warranted before controlled studies of mirtazapine are conducted. The remaining antidepressants - selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, bupropion, and venlafaxine - cannot be recommended to treat insomnia in alcoholic patients, because they are generally not sedating [60]. Also, monoamine oxidase inhibitors interact adversely with alcohol.

Gabapentin and other anticonvulsants Several anticonvulsant drugs have sedative effects and the therapeutic potential to aid sleep [67]. Anticonvulsant drugs also have been used to treat alcohol withdrawal and alcoholism, in part because of their anti-kindling effects [68, 69]. Kindling is a process by which the brain becomes sensitized after repeated exposure to a stimulus such as electrical current or medication. Consequently, a stimulus that did not initially elicit a response from the brain, may elicit a response such as a seizure after repeated presentations. An episode of alcohol withdrawal may be considered as a stimulus to the brain. According to this line of reasoning, alcoholics become increasingly vulnerable to alcohol-related seizures after repeated episodes of alcohol withdrawal due to kindling [46]. It is further theorized that protracted, subacute withdrawal symptoms that can lead to relapse (such as insomnia, dysphoria and craving) become activated more easily in response to psychosocial and environmental stimuli due to kindling [46]. Carbamazepine, divalproex sodium, and gabapentin all manifest anti-kindling effects in animal models. However, carbamazepine and divalproex sodium have not been tested specifically for their effects on sleep in alcoholic patients. Moreover, they require blood monitoring and are associated with hepatoxicity (in a population already vulnerable to liver disease). By contrast, gabapentin has been studied as a treatment for insomnia in alcoholic patients [65, 70, 71], due to its effects on sleep and other advantages. Unlike carbamazepine and valproate, gabapentin does not undergo liver metabolism, cause hepatotoxicity,

s34 require blood monitoring, or interact adversely with other medications. Importantly, gabapentin has a low potential for fatal or complicated overdoses even when mixed with alcohol [72]. The notion that gabapentin may improve alcoholassociated insomnia was suggested by a report of 4 alcoholic patients with comorbid anxiety disorders, but the authors did not quantify the improvement in sleep [73]. Karam-Hage and Brower [70] described 15 alcoholic outpatients who were abstinent for at least 4 weeks and then received once nightly doses of gabapentin (mean=953mg at bedtime; range 200-1500mg). After 4-6 weeks of treatment, sleep was significantly improved as measured by the selfadministered Sleep Problems Questionnaire [66], and only 2 patients relapsed. Similarly, I 0 alcoholic patients with persisting insomnia after 4 or more weeks of sobriety were non-randomly assigned to either trazodone or gabapentin treatment [65]. Both the trazodone (n = 4) and the gabapentin (n = 6) groups had significant improvement in subjective sleep, but the trazodone group was more likely to complain of nonrestorative sleep as noted above. These results have recently been extended to 34 alcoholic patients who received a mean dose of 888mg (range 300-1800 mg) of gabapentin at bedtime (unpublished data). Other studies of gababentin have revealed polysomnographic increases in SWS among healthy subjects [67], in SE among patients with restless legs and periodic limb movements [74], and in TST among alcoholic patients [71]. However, sample sizes were small in these polysomnographic studies (ranging from 2 to 6) and dosing was modest (ranging from 300 to 900 mg at bedtime).

Miscellaneous agents Ritanserin, a serotonin (type 2) receptor antagonist, was shown to improve sleep and mood compared to placebo in dysthymic, alcoholic patients [75]. Antipsychotic agents such as olanzapine and quetiapine have known sedative effects, but their use is best reserved for alcoholic patients with comorbid psychosis or extreme agitation because of other side effects. Disulfiram causes drowsiness more frequently than placebo, but its utility is compromised by low compliance rates in alcoholic patients [76]. Whether patients with insomnia are more likely to comply with disulfiram than are patients without insomnia is unstudied. Some studies suggest that melatonin levels are decreased in patients with alcoholism [77]. Supplemental melatonin has been used with mixed

K.j. BROWER results to treat insomnia, but appears most effective when endogenous melatonin levels are low. Melatonin has not been investigated in alcoholic patients, but could be hypothesized to treat insomnia effectively in alcoholic patients who have low levels of endogenous melatonin.

Treatment

guidelines

Eight guidelines for assessing and treating alcoholic patients with symptoms of insomnia are now discussed (see also box for summary of guidelines as Practice Points).

I. Insomnia treatment should begin with treating alcoholism, a diagnosis that requires proper screening and, frequently, referral to addiction treatment specialists. Attempting to treat insomnia'-exclusively is highly unlikely to initiate sobriety and provide sufficient treatment for alcoholism. Consequently, continued drinking will undermine treatment for insomnia because heavy drinking disrupts sleep. Even if insomnia preceded the development of alcoholism and now contributes to drinking, alcoholism (once it is established) requires primary treatment because of the complex array of biopsychosocial factors that maintain pathological drinking patterns. Since most non-specialists are not trained to provide alcoholism treatment, the referring practitioner needs familiarity with local addiction treatment providers and with techniques to motivate patients to accept treatment [8]. Treating alcoholism also facilitates the period of sobriety required to assess the contribution of patients' drinking to their insomnia. For an unknown percentage of alcoholic patients, insomnia may remit after 4 weeks of sobriety. 2. Monitor insomnia with rating scales or sleep diaries for at least 4 weeks of sobriety to rule out the immediate effects of alcohol withdrawal as the cause for insomnia. If insomnia remits, then its likely cause was stress associated with acute withdrawal. Insomnia that persists beyond 4 weeks of sobriety may result from comorbid medical and psychiatric disorders, other sleep disorders (e.g. sleep apnea and PLM disorder), and protracted withdrawal symptoms related to alcohol-associated neurotoxicity. In addition, a childhood history of sleep problems or a history of insomnia that preceded the development of alcoholism raises the likelihood that the patient has an underlying primary insomnia, now exacerbated by other factors. 3. Assess for all possible contributors to insomnia (e.g. poor sleep hygiene and sleep environment; medical,

INSOMNIA AND ALCOHOLISM

psychiatric, and sleep disorders; and other drug use). Do not assume that alcoholism is the only cause of insomnia in alcoholic patients. Alcoholics have high rates of tobacco smoking, chronic obstructive pulmonary disease, gastritis, peripheral neuropathies, depression, and anxiety that can cause or exacerbate insomnia. Alcoholics also have higher rates of sleep apnea [26] and PLM disorder [ I ] than non-alcoholics have. Thus, a suggestive history from the patient, corroborative history from a bed partner, or physical risk factors such as a high body mass index will indicate the use of polysomnography to rule out sleep apnea or PLM disorder as contributors to insomnia. In summary, it is important to rule out non-alcohol-related causes of insomnia in alcoholic patients, and to explore contributing factors such as poor sleep hygiene, a less than optimal sleep environment, and the use of medications that interfere with sleep. For the purposes of the remaining discussion, "alcohol-associated insomnia" (i.e. insomnia due to protracted alcohol withdrawal and alcoholic neurotoxicity) is distinguished from "non-alcoholic insomnia" (i.e. insomnia related to medical, psychiatric, and sleep disorders as well as insomnia related to poor sleep hygiene and environmental causes). Both types of insomnia may coexist in alcoholic patients. 4. Treat non-alcoholic causes of insomnia, but adjust that treatment to accommodate the special characteristics of alcoholic patients. First, patients may complain about their insomnia but not their drinking. Without proper screening, the diagnosis of alcoholism is easy to miss because of the patient's defensiveness [8], Alcoholic patients may rationalize their use of alcohol to treat insomnia or deny their problem completely. Second, refer alcoholic patients to treatment for alcoholism. Third, avoid medications with a potential for abuse or lethal overdose, especially when mixed with alcohol. 5. Treat alcohol-associated insomnia that persists despite four or more weeks of sobriety when it is associated with significant daytime impairment or psychological distress. If clinically significant insomnia persists despite 4 or more weeks of sobriety and despite treatment for non-alcoholic causes of insomnia, then initiate treatment for insomnia related to protracted withdrawal. In addition to significant impairment and distress, untreated insomnia may lead to alcoholic relapse. However, no study has tested the hypothesis that treating alcohol-related insomnia prevents alcoholic relapse (Fig. I). 6. All alcoholic patients should receive education about good sleep hygiene and about the effects of alcohol on sleep. Patients need to know that drinking alcohol can

535 cause insomnia as well as exacerbate insomnia due to non-alcoholic causes. Improvement of insomnia can be framed as one of several incentives to stop drinking. Educating patients about the course of insomnia as a protracted withdrawal symptom will help to facilitate reasonable expectations about the rate of improvement. Patients require reassurance that if insomnia continues to cause significant distress or impairment after a 4-week period of sobriety, then non-alcoholic causes of insomnia will be thoroughly investigated and treated. Finally, clinicians should inform patients about the relationship between drinking and sleepdisordered breathing as well as the consequences of untreated sleep apnea. 7. Behavioral therapies and medications may help treat alcohol-associated insomnia, but these treatments are mostly unstudied in alcoholic patients. Behavioral therapy for insomnia is well accepted by non-alcoholic patients, although the preference of alcoholic patients for behavioral therapy vs pharmacotherapy of insomnia has not been studied. Behavioral therapy also counters the maladaptive thinking of some alcoholic patients: "There is a pill for every ill." 8. Avoid medications that have a potential for addiction or overdose when mixed with alcohol (including selective and non-selective benzodiazepine agonists). Some antidepressants should also be avoided for these reasons, particularly doxepin and amitriptyline. Of the antidepressants, trazodone (usual doses of 50-150 mg at bedtime) and mirtazapine (I 5-30 mg at bedtime) show some promise and may be used judiciously, but alcohol can potentiate their CNS depressant effects. The anticonvulsant, gabapentin (usual doses of 3001800 mg at bedtime), has the advantage of low' overdose potential even when mixed with alcohol. However, the safety and efficacy of medications to treat insomnia in alcoholic patients has not been tested in randomized controlled trials.

CONCLUSIONS Insomnia and alcoholism frequently co-occur which is clinically significant because (a) alcoholism can exacerbate the adverse consequences of insomnia (such as daytime impairment, the development of depression, and premature mortality) and (b) insomnia has been linked to subsequent drinking episodes and relapse in alcoholic patients. Insomnia is a common problem in alcoholic patients (36-72%) that can occur during active drinking, acute

536 alcohol withdrawal, and subacute (or protracted) withdrawal. Although alcohol-associated insomnia appears to improve over time with abstinence in many patients, it may persist for weeks to months after initiating abstinence. Insomnia that persists beyond 4 weeks of sobriety may result from comorbid medical and psychiatric disorders, other sleep disorders (e.g. sleep apnea and PLM disorder), protracted withdrawal symptoms related to alcohol-associated neurotoxicity (so-called alcohol-associated insomnia), and primary insomnia. Regarding primary insomnia, there is epidemiological evidence that insomnia may precede, and increase the risk for, the development of alcoholism in some individuals. Regarding sleep disorders, studies suggest that recently sober alcoholics are more likely than non-alcoholics to have sleep-disordered breathing and periodic limb movements. Correlates of insomnia in alcoholic patients include severity of alcohol dependence and consumption, psychiatric symptoms (anxiety, depression and hostility), disrupted sleep continuity on polysomnography, and using alcohol to aid sleep. Although 44-60% of alcoholic patients use alcohol to selfmedicate insomnia, tolerance to the sedative effects of alcohol may develop within I week among alcoholic patients, leaving patients vulnerable to the sleepdisrupting effects of alcohol. Polysomnographic studies clearly indicate that experimental administration of alcohol at bedtime to alcoholic patients disrupts sleep by increasing SL, decreasing SE, and decreasing TST. Therefore, self-medication of insomnia may be common in alcoholics because of perceived benefits, but it is not particularly effective when measured objectively. A number of studies have demonstrated a relationship between baseline sleep problems when patients enter alcoholism treatment and subsequent relapse to drinking (Table I). Sleep predictors of relapse include insomnia, especially difficulty falling asleep, and various polysomnographic abnormalities that are often associated with insomnia. The neurobiological mechanisms linking insomnia and alcoholism are not fully known, but a working hypothesis is that alcoholism is associated with neurotoxic effects to neurotransmitter systems that are involved in regulating sleep (Fig. I). Preliminary studies of treating alcohol-related insomnia with either medication or behavioral therapy appear promising, but the hypothesis that effectively treating sleep problems reduces relapse rates in alcoholic patients warrants testing in controlled clinical trials.

K.J. BROWER

Practice Points In alcoholic patients with symptoms of insomnia: I. Monitor insomnia with rating scales or sleep diaries for at least 4 weeks of sobriety to rule out the immediate effects of alcohol withdrawal as the cause for insomnia. If insomnia remits, then its likely cause was stress associated with acute withdrawal. 2. Assess for all possible contributors to insomnia (e.g. poor sleep hygiene and sleep environment; medical, psychiatric, and sleep disorders; and other drug use). Do not assume that alcoholism is the only cause of insomnia in alcoholic patients. 3. Insomnia treatment should begin with treating alcoholism, a diagnosis that requires proper screening and, frequently, referral to addiction treatment specialists. 4. Treat non-alcoholic causes of insomnia, but adjust that treatment to accommodate the special characteristics of alcoholic patients (see text). 5. Treat alcohol-associated insomnia that persists despite four or more weeks of sobriety when it is associated with significant daytime impairment or psychological distress. 6. All alcoholic patients should receive education about good sleep hygiene and about the effects of alcohol on sleep. 7. Behavioral therapy and medications may help treat alcohol-associated insomnia, but these treatments are mostly unstudied in alcoholic patients. 8. Avoid medications that have a potential for addiction or overdose when mixed with alcohol (including selective and non-selective benzodiazepine agonists).

Research Agenda I. Conduct studies to determine whether sleep disturbance in early adolescence ;predicts subsequent use and abuse of alcohol. If yes, determine whether early treatment of insomnia will prevent the development of alcohol dependence. 2. DevelOp assessment tools for insomnia that are validated in alcoholic patients to (a) facilitate a diagnosis of insomnia, (b) elaborate its potential causes, (c) predict alcoholic relapse, and (d) measure response of insomnia to treatments.

INSOMNIA A N D ALCOHOLISM 3. Determine w h e t h e r polysomnography o r subjectively measured insomnia has more value at predicting the development of, and relapse to, alcoholism. 4. Conduct basic and clinical research to investigate the neurobiological mechanisms by which chronic alcohol consumption and dependence disrupt sleep. 5. Test the safety, efficacy, and acceptance of targeted behavioral and pharmacological therapies to treat insomnia in alcoholic patients using randomized controlled trials. The need to test and implement non-pharmacological treatments for insomnia deserves special emphasis in a population at risk for substance dependence, 6. Determine whether successful treatment of insomnia is associated with reductions in alcoholic relapse rates.

537

9. 10.

II.

12.

13.

14.

15.

ACKNOWLEDGMENT 16. This research was supported by grant K24 AA00304 from the National Institute on Alcohol Abuse and Alcoholism. 17.

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