Insomnia and other sleep abnormalities are common, persistent, and associated with relapse in alcohol-dependent patients. The overall, long-term objectives of the proposed research are to investigate the neurophysiologic mechanisms of sleep disturbance that are associated with relapse in patients with alcohol dependence, and to target those mechanisms with medication in order to reduce relapse risk.

The specific research aims are:

1. To investigate three potential mechanisms of sleep disturbance in alcoholic patients: impaired sleep drive, impaired circadian regulation of alertness, and brain hyperactivation;
2. To investigate short-term effects of medication on sleep and its regulatory mechanisms in alcoholics;
3. To investigate the short-term clinical course of alcoholism as a function of baseline sleep parameters.

In Study Phases I & II (Screening & Baseline: 10+ days), subjects are assessed to diagnose alcohol dependence, determine baseline values for drinking and sleeping, and rule out confounding sleep-impairing causes.

Phase III (Medication: 10 days), is a randomized, double-blind parallel design comparison of gabapentin vs. placebo on mechanisms of sleep. It is not a therapeutic or clinical trial. Phases II & III each have 7 days of monitoring sleep and activity, followed by 3 nights in the University of Michigan (UM) sleep laboratory to assess all-night EEG activity and Dim-Light Melatonin Onset (DLMO), a measure of circadian rhythm.

Phase IV is a 2-day medication taper and Phase V (Follow-up) consists of one visit or telephone call after 12 weeks to assess course of drinking.

In summary, sleep disturbance in alcoholic patients increases their risk of relapse. This study proposes to investigate the mechanisms causing sleep disturbance in alcoholics and to determine if those mechanisms predict return to drinking after 12 weeks.

Relevance: Alcoholism is a devastating chronic disorder that in any one year affects 10% of adults, costs over $185 billion, and causes more than 100,000 deaths in the U.S. Despite treatment, most alcoholic patients achieve only short-term abstinence. Medically-based treatment improvements are needed that target neurophysiologic mechanisms of relapse. Overall public health will be improved by developing science-based treatments that can augment existing, but only partially effective, treatment approaches.

Inclusion Criteria:

• Meet DSM-IV criteria for alcohol dependence (as confirmed by the SCID)
• Between 3 and 12 weeks since last drink (as measured by the TLFB)
• At least 2 weeks since last detoxification medication, if relevant
• An alcohol withdrawal rating score < 8 (as measured by the CIWA-Ar) to rule out acute alcohol withdrawal effects on sleep.
• Expresses a desire to stop drinking or a willingness to abstain from alcohol and/or other drugs of abuse (except nicotine) during the course of the study

Exclusion Criteria:

• Subjects who meet DSM-IV criteria for dependence on any psychoactive substance other than alcohol (except nicotine) in the past 3 months (per SCID interview).
• Subjects with a current (past 1 month) DSM-IV diagnosis of panic disorder, generalized anxiety disorder, post-traumatic stress disorder, major depression, anorexia nervosa, or bulimia nervosa (per SCID interview) and/or that require ongoing psychotropic medication.
• Subjects who have a lifetime diagnosis meeting DSM-IV criteria for bipolar disorder, schizophrenia, schizoaffective disorder, delusional (paranoid) disorders, or obsessive-compulsive disorder.
• Urine drug screen positive for amphetamines, barbiturates, benzodiazepines, cocaine, marijuana, or opioids. (If positive, subjects have one opportunity to test negative after a week of abstinence).
• Medical disorders or pain syndromes that may affect sleep; history of head trauma with loss of consciousness; history of seizures (except alcohol-related seizures).
• Subjects with elevated renal tests (blood urea nitrogen or creatinine), because gabapentin is renally eliminated, or elevated liver transaminases (>3X normal), or abnormal thyroid tests as thyroid problems can affect sleep.
• Sleep disorders other than insomnia such as sleep apnea/hypopnea index >10 per hour or periodic limb movement disorder; PLM>15 movements per hour with arousals.
• Taking medications known to affect sleep (e.g., antidepressants, anticonvulsants, centrally acting antihistamines, neuroleptics, sedative-hypnotics, stimulants, centrally acting antihypertensives [alpha-methyldopa, reserpine, clonidine], oral corticosteroids, and theophylline within the past 2 weeks or 5 weeks for fluoxetine).
• Subjects taking medications used to treat addiction (e.g., disulfiram, naltrexone or acamprosate) are excluded because of unknown effects on sleep.
• Subjects who do evening or midnight shift work. (Subjects who have traveled across multiple time zones in the previous two weeks will be included only at the discretion of the P.I.)
• Pregnancy, breast feeding, or inadequate contraception in women of child-bearing potential.
• Subjects who are unable or unlikely to follow the study protocol in the investigator 's opinion, because of cognitive deficits (Mini-Mental State Exam score < 27), a personality disorder, a serious suicide risk, dangerousness to others, illiteracy, or unstable or distant living situation.
• Subjects with a known allergy, hypersensitivity or contraindication to study medication.

10 days