Double-Blind, Placebo-Controlled Study of the Efficacy of Trazodone in Alcohol Post-Withdrawal Syndrome: Polysomnographic and Clinical Evaluations

Brugmann University Hospital, CHU Brugmann S78, Université Libre de Bruxelles, 1040 Brussels, Belgium.
Journal of Clinical Psychopharmacology (Impact Factor: 3.24). 09/2003; 23(4):377-83. DOI: 10.1097/
Source: PubMed


Alcohol detoxification is accompanied by sustained difficulties in sleep initiation and maintenance. These difficulties are thought to be an important cause of relapse to alcohol use. However, the treatment of sleep problems with hypnotic drug is made difficult by cross-tolerance between benzodiazepines and alcohol. In this report, we evaluated the capacity of trazodone (TRZ), a second-generation antidepressant with anxiolytic and sedative properties, to increase the sleep efficiency in alcohol-dependent patients after detoxification. Sixteen patients completed the TRZ (n = 8) or the placebo (PL; n = 8) treatment arms. Polysomnographies were performed at baseline, after the 1st drug dose, and after 4 weeks of treatment. The main outcome was sleep efficiency. Secondary outcomes included changes in other sleep parameters, Hamilton Depression Rating and Clinical Global Impression scales. Sleep efficiency was increased in the TRZ group when it was computed after sleep onset, both immediately after 1st administration of the drug and after 4 weeks of treatment. No benefit was observed in the PL group. Sleep improvement under TRZ also included the number of awakenings, intermittent wake sleep time, and non-rapid eye movement sleep. Hamilton and Clinical Global scales were better for the TRZ group. TRZ is thus a potential option in the treatment of alcohol post-withdrawal insomnia.

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    • "These trials enrolled sleepdisturbed alcohol-dependent patients following detoxification. In a small study in which sleep was measured with polysomnography, trazodone reduced awakenings and enhanced sleep maintenance (Le Bon et al., 2003). However, in a larger trial, trazodone was associated with improved subjective sleep quality (Pittsburgh Sleep Quality Index) over three months, but produced an increase in the number of drinks per drinking days and a lowering of abstinence after its cessation (Friedmann et al., 2008). "
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    ABSTRACT: To test whether trazodone, one of the most commonly prescribed medications for treatment of insomnia, improves subjective and/or objective sleep among methadone-maintained persons with sleep complaints, we performed a randomized, double-blind, placebo-controlled trial with 6-month follow-up. From eight methadone maintenance programs in the northeastern United States, we recruited 137 persons receiving methadone for at least 1 month who reported a Pittsburgh Sleep Quality Index (PSQI) score of six or higher. Two-night home polysomnography (PSG) was completed at baseline and 1 month later, with morning surveys and urine drug toxicologies. Interviews assessed sleep over the past 30 days at baseline and 1-, 3-, and 6-month follow-ups. Participants averaged 38 years of age, were 47% male, and had a mean PSQI total score of 12.9 (±3.1). At baseline, intervention groups did not significantly differ on 10 PSG-derived objective sleep measures and 11 self-reported measures. Over 88% (n=121) of participants completed the PSG at 1-month. Without adjusting p-values for multiple comparisons, only 1 of 21 sleep measure comparisons was statistically significant (p<.05). The effect of trazodone on mean PSQI scores during the 6-month follow-up was not statistically significant (p=.10). Trazodone neither significantly increased nor decreased illicit drug use relative to placebo. Trazodone did not improve subjective or objective sleep in methadone-maintained persons with sleep disturbance. Other pharmacologic and non-pharmacologic treatments should be investigated for this population with high rates of insomnia.
    Drug and alcohol dependence 07/2011; 120(1-3):65-73. DOI:10.1016/j.drugalcdep.2011.06.026 · 3.42 Impact Factor
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    • "Empirical evidence of trazodone's safety and effectiveness as a soporific agent in alcoholdependent patients is limited. One small placebo-controlled trial suggested that trazodone improved sleep efficiency after alcohol detoxification (Le Bon et al., 2003). To examine whether trazodone improves drinking outcomes and sleep quality among sleep-disturbed, alcohol-dependent patients after detoxification, we performed a randomized, double-blind, placebo-controlled trial of short term, low dose trazodone (50−150 mg) at bedtime. "
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    ABSTRACT: Trazodone is a commonly prescribed off-label for sleep disturbance in alcohol-dependent patients, but its safety and efficacy for this indication is unknown. We conducted a randomized, double-blind, placebo-control trial of low-dose trazodone (50 to 150 mg at bedtime) for 12 weeks among 173 alcohol detoxification patients who reported current sleep disturbance on a validated measure of sleep quality or during prior periods of abstinence. Primary outcomes were the proportion of days abstinent and drinks per drinking day over 6-months; sleep quality was also assessed. Urn randomization balanced baseline features among the 88 subjects who received trazodone and 85 who received placebo. The trazodone group experienced less improvement in the proportion of days abstinent during administration of study medication (mean change between baseline and 3 months: -0.12; 95% CI: -0.15 to -0.09), and an increase in the number of drinks per drinking day on cessation of the study medication (mean change between baseline and 6 months, 4.6; 95% CI: 2.1 to 7.1). Trazodone was associated with improved sleep quality during its administration (mean change on the Pittsburgh Sleep Quality Index between baseline and 3 months: -3.02; 95% CI: -3.38 to -2.67), but after it was stopped sleep quality equalized with placebo. Trazodone, despite a short-term benefit on sleep quality, might impede improvements in alcohol consumption in the postdetoxification period and lead to increased drinking when stopped. Until further studies have established benefits and safety, routine initiation of trazodone for sleep disturbance cannot be recommended with confidence during the period after detoxification from alcoholism.
    Alcoholism Clinical and Experimental Research 07/2008; 32(9):1652-60. DOI:10.1111/j.1530-0277.2008.00742.x · 3.21 Impact Factor
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    • "Other medications such as trazodone and gabapentin are commonly prescribed for their sleep promoting properties (Friedmann et al., 2003) and have shown some potential as sleep aids in alcohol-dependent patients in openlabel studies employing subjective measures (Karam-Hage and Brower, 2000, 2003). Yet placebo-controlled studies of these medications utilizing objective sleep polysomnographic parameters are virtually unknown in alcohol-dependent patients with at least one exception (Le Bon et al., 2003). Systematically investigating the sleep effects of medications in alcohol-dependent patients could identify sleep promoting, sleep neutral, and sleep disruptive agents. "
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    ABSTRACT: 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. 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. 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. 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.
    Alcoholism Clinical and Experimental Research 07/2008; 32(8):1429-38. DOI:10.1111/j.1530-0277.2008.00706.x · 3.21 Impact Factor
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