Kirk J. Brower

Insomnia, alcoholism and relapse

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.

Sleep problems and suicidality in the National Comorbidity Survey Replication

OBJECTIVE Links between sleep problems and suicidality have been frequently described in clinical samples; however, this issue has not been well-studied in the general population. Using data from a nationally representative survey, we examined the association between self-reported sleep difficulties and suicidality in the United States. METHODS The WHO Composite International Diagnostic Interview was used to assess sleep problems and suicidality in the National Comorbidity Survey Replication (NCS-R). Relationships between three measures of sleep (difficulty initiating sleep, maintaining sleep, early morning awaking), and suicidal thoughts, plans, and attempts were assessed in logistic regression analyses, while controlling for demographic characteristics, 12-month diagnoses of mood, anxiety and substance use disorders, and chronic health conditions. RESULTS In multivariate models, the presence of any of these sleep problems was significantly related to each measure of suicidality, including suicidal ideation (OR=2.1), planning (OR=2.6), and suicide attempt (OR=2.5). Early morning awakening was associated with suicidal ideation (OR=2.0), suicide planning (OR=2.1), and suicide attempt (OR=2.7). Difficulty initiating sleep was a significant predictor of suicidal ideation and planning (ORs: 1.9 for ideation; 2.2 for planning), while difficulty maintaining sleep during the night was a significant predictor of suicidal ideation and suicide attempts (ORs: 2.0 for ideation; 3.0 for attempt). CONCLUSIONS Among community residents, chronic sleep problems are consistently associated with greater risk for suicidality. Efforts to develop comprehensive models of suicidality should consider sleep problems as potentially independent indicators of risk.

A Randomized Double-Blind Pilot Trial of Gabapentin Versus Placebo to Treat Alcohol Dependence and Comorbid Insomnia

BACKGROUND Insomnia and other sleep disturbances are common, persistent, and associated with relapse in alcohol-dependent patients. The purpose of this pilot study was to compare gabapentin versus placebo for the treatment of insomnia and prevention of relapse in alcohol-dependent patients. METHODS Twenty-one subjects, including 10 women who met study criteria for alcohol dependence and insomnia and expressed a desire to abstain from alcohol, were recruited to the study. During a 1 to 2 week placebo lead-in and screening phase, a complete medical history, physical exam, blood tests, urine drug test, and structured interviews were performed to determine eligibility and patterns of alcohol use and sleep. Insomnia due to intoxication or acute withdrawal, psychiatric or medical illness, medications, and other sleep disorders were ruled out. Subjects were then randomized to either placebo (n = 11) or gabapentin (n = 10) for 6 weeks and titrated over a 10-day period to 1,500 mg or 5 pills at bedtime. After a 4-day taper, subjects were reassessed 6 weeks after ending treatment. RESULTS Gabapentin significantly delayed the onset to heavy drinking, an effect which persisted for 6 weeks after treatment ended. Insomnia improved in both treatment groups during the medication phase, but gabapentin had no differential effects on sleep as measured by either subjective report or polysomnography. CONCLUSION Because gabapentin is a short-acting medication that was taken only at nighttime in this study, it may possibly exert a nocturnal effect that prevents relapse to heavy drinking by a physiological mechanism not measured in this pilot study.

Childhood sleep problems, early onset of substance use and behavioral problems in adolescence

BACKGROUND Very few prospective studies examine the relationship between childhood sleep problems and subsequent substance use. In this study, we examined how sleep problems at ages 3-8 predicted onset of alcohol, cigarette, and marijuana use in adolescence. We also investigated the relationships between childhood sleep problems and adolescent internalizing and externalizing problems. METHODS Study participants were 292 boys and 94 girls from a community sample of high risk families and controls in an ongoing longitudinal study. RESULTS Controlling for parental alcoholism, sleep problems at ages 3-8 predicted onset of alcohol, cigarette, and marijuana use among boys and onset of alcohol use among girls. Childhood sleep problems were related to maternal ratings of internalizing and externalizing problems during adolescence for both boys and girls. Adjusting for these problems did not weaken the effects of sleep problems on onset of substance use. CONCLUSIONS This is to our knowledge the first study that prospectively examines gender differences in the relationship between sleep problems and early onset of substance use. Childhood sleep problems predicted early onset of substance use for boys but not girls. If childhood sleep problems indeed increase the probability of substance use onset, greater attention by parents to sleep problems in children and adolescents would potentially have ameliorative long-term effects. Parents are encouraged to explore different ways to help their children sleep better, including obtaining information and suggestions from their primary care physicians.

Sleep problems, suicidal ideation, and self-harm behaviors in adolescence

OBJECTIVE Previous research has found an association between sleep problems and suicidal behavior. However, it is still unclear whether the association can be largely explained by depression. In this study, we prospectively examined relationships between sleep problems when participants were 12-14 years old and subsequent suicidal thoughts and self-harm behaviors--including suicide attempts--at ages 15-17 while controlling for depressive symptoms at baseline. METHODS Study participants were 280 boys and 112 girls from a community sample of high-risk alcoholic families and controls in an ongoing longitudinal study. RESULTS Controlling for gender, parental alcoholism and parental suicidal thoughts, and prior suicidal thoughts or self-harm behaviors when participants were 12-14 years old, having trouble sleeping at 12-14 significantly predicted suicidal thoughts and self-harm behaviors at ages 15-17. Depressive symptoms, nightmares, aggressive behavior, and substance-related problems at ages 12-14 were not significant predictors when other variables were in the model. CONCLUSIONS Having trouble sleeping was a strong predictor of subsequent suicidal thoughts and self-harm behaviors in adolescence. Sleep problems may be an early and important marker for suicidal behavior in adolescence. Parents and primary care physicians are encouraged to be vigilant and screen for sleep problems in young adolescents. Future research should determine if early intervention with sleep disturbances reduces the risk for suicidality in adolescents.

Association Between Val66Met Brain-Derived Neurotrophic Factor (BDNF) Gene Polymorphism and Post-Treatment Relapse in Alcohol Dependence

BACKGROUND The purpose of this study was to examine relationships between genetic markers of central serotonin (5-HT) and dopamine function, and risk for post-treatment relapse, in a sample of alcohol-dependent patients. METHODS The study included 154 patients from addiction treatment programs in Poland, who met DSM-IV criteria for alcohol dependence. After assessing demographics, severity of alcohol use, suicidality, impulsivity, depression, hopelessness, and severity of alcohol use at baseline, patients were followed for approximately 1 year to evaluate treatment outcomes. Genetic polymorphisms in several genes (TPH2, SLC6A4, HTR1A, HTR2A, COMT, and BDNF) were tested as predictors of relapse (defined as any drinking during follow-up) while controlling for baseline measures. RESULTS Of 154 eligible patients, 123 (80%) completed follow-up and 48% (n = 59) of these individuals relapsed. Patients with the Val allele in the Val66Met BDNF polymorphism and the Met allele in the Val158Met COMT polymorphism were more likely to relapse. Only the BDNF Val/Val genotype predicted post-treatment relapse [odds ratio (OR) = 2.62; p = 0.019], and time to relapse (OR = 2.57; p = 0.002), after adjusting for baseline measures and other significant genetic markers. When the analysis was restricted to patients with a family history of alcohol dependence (n = 73), the associations between the BDNF Val/Val genotype and relapse (OR = 5.76, p = 0.0045) and time to relapse (hazard ratio = 4.93, p = 0.001) were even stronger. CONCLUSIONS The Val66Met BDNF gene polymorphism was associated with a higher risk and earlier occurrence of relapse among patients treated for alcohol dependence. The study suggests a relationship between genetic markers and treatment outcomes in alcohol dependence. Because a large number of statistical tests were conducted for this study and the literature on genetics and relapse is so novel, the results should be considered as hypothesis generating and need to be replicated in independent studies.

Childhood Sleep Problems, Response Inhibition, and Alcohol and Drug Outcomes in Adolescence and Young Adulthood

BACKGROUND To our knowledge, no prospective studies examine the relationships among childhood sleep problems, adolescent executive functioning, and substance outcomes (i.e., substance use and substance-related problems). In this study, we examined whether childhood sleep problems predicted adolescent sleep problems and response inhibition. We also tested whether adolescent sleep problems and poor response inhibition mediated the relationship between childhood sleep problems and substance (alcohol and drug) outcomes in young adulthood. METHODS Study participants were 292 boys and 94 girls (M = 4.85, SD = 1.47) from a community sample of high-risk families and controls. RESULTS When compared to their counterparts, those with trouble sleeping in childhood were twice as likely to have the same problem in adolescence. Childhood overtiredness predicted poor response inhibition in adolescence. Persistent trouble sleeping from childhood to adolescence and response inhibition in adolescence mediated the relationship between childhood sleep problems and drug outcomes in young adulthood, whereas overtiredness in childhood directly predicted alcohol use outcomes and alcohol-related problems in young adulthood. CONCLUSIONS This is the first study showing a long-term relationship between childhood sleep measures and subsequent alcohol and drug outcomes. The developmental and clinical implications of these findings were discussed. Prevention and intervention programs may want to consider the role of sleep problems and response inhibition on substance use and abuse.

The prospective relationship between sleep problems and suicidal behavior in the National Longitudinal Study of Adolescent Health

OBJECTIVE Previous research has found a longitudinal relationship between sleep problems and suicidal behavior while controlling for depression and other important covariates in a high risk sample of adolescents and controls. In this paper, we replicated this longitudinal relationship in a national sample and examined whether the relationship was partially mediated by depression, alcohol-related problems and other drug use. METHODS Study participants were 6504 adolescents from the National Longitudinal Study of Adolescent Health (ADD HEALTH). RESULTS In bivariate analyses, sleep problems (i.e., having trouble falling asleep or staying asleep) at Wave 1 were associated with suicidal thoughts and suicide attempts at Waves 1, 2, and 3 (W1, 2 and 3). In multivariate analyses, controlling for depression, alcohol problems, illicit drug use, and important covariates such as gender, age, and chronic health problems, sleep problems at a previous wave predicted suicidal thoughts and suicide attempts at a subsequent wave. In mediation analyses, W2 depression significantly mediated the effect of W1 sleep problems on W3 suicide thoughts. Moreover, W2 suicidal thoughts also significantly mediated the effect of W1 sleep problems on W3 suicidal attempts. CONCLUSIONS Sleep problems appear to be a robust predictor of subsequent suicidal thoughts and attempts in adolescence and young adulthood. Having trouble falling sleeping or staying asleep had both direct and indirect effects (via depression and suicidal thoughts) on suicidal behavior. Future research could determine if early intervention with sleep disturbances reduces the risk for suicidality in adolescents and young adults.

Sleep disturbance as a universal risk factor for relapse in addictions to psychoactive substances.

Relapse to uncontrolled use of a psychoactive substance is arguably the single most defining characteristic of an addiction. Relapse following addiction treatment is very common with serious consequences to individuals, families, and the public system of care, making predictors of relapse a highly significant area of study. Before the turn of the century, most of the addiction treatment outcome literature focused on psychosocial predictors of relapse. More recently, investigating biological predictors of relapse specifically and treatment outcome broadly has gained momentum. This line of research has linked sleep disturbances to the risk of relapse among persons who are recovering from an alcohol addiction. Given common neurobiological and psychosocial processes in sleep and addictive behaviors, we hypothesize that the link between sleep disturbance and relapse risk observed among alcohol addiction generalizes to all other types of psychoactive substances. This hypothesis has the potential for helping develop more effective and targeted treatment approaches for persons with addiction. As initial support for the hypothesis, this paper reviews evidence on common neurobiological processes among various types of psychoactive substances that suggests sleep is a universal risk factor for relapse. A conceptual framework is also presented to articulate causal mechanisms. The paper concludes with implications for research and practice.

Impulsive and non-impulsive suicide attempts in patients treated for alcohol dependence

BACKGROUND Suicidal behavior has been recognized as an increasing problem among alcohol-dependent subjects. The aim of the study was to identify correlates of impulsive and non-impulsive suicide attempts among a treated population of alcohol-dependent patients. METHODS A total of 154 patients with alcohol dependence consecutively admitted for addiction treatment participated in the study. Suicidal behavior was assessed together with severity of alcohol dependence, childhood abuse, impulsivity, and family history. A stop-signal procedure was used as a behavioral measure of impulsivity. RESULTS AND CONCLUSIONS Lifetime suicide attempts were reported by 43% of patients in alcohol treatment; of which 62% were impulsive. Compared to patients without a suicide attempt, those with a non-impulsive attempt were more likely to have a history of sexual abuse (OR=7.17), a family history of suicide (OR=4.09), and higher scores on a personality measure of impulsiveness (OR=2.27). The only significant factor that distinguished patients with impulsive suicide attempts from patients without a suicide attempt and from patients with a non-impulsive suicide attempt was a higher level of behavioral impulsivity (OR=1.84-2.42). LIMITATIONS Retrospective self-report of suicide attempts and family history. Lack of diagnostic measure.