Trazodone for sleep disturbance during methadone maintenance: A double-blind, placebo-controlled trial

Abstract

BACKGROUND 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 six month follow-up. METHODS From eight methadone maintenance programs in the northeastern United States, we recruited 137 persons receiving methadone for at least one month who reported a Pittsburgh Sleep Quality Index (PSQI) score of six or higher. Two-night home polysomnography (PSG) was completed at baseline and one 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. RESULTS 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 six-month follow-up was not statistically significant (p = .10). Trazodone neither significantly increased nor decreased illicit drug use relative to placebo. CONCLUSIONS 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.

The diversion of nonscheduled psychoactive prescription medications in the United States, 2002 to 2017

“…Trazodone, approved by the FDA in 1981, is a serotonin antagonist and reuptake inhibitor (SARI) antidepressant that has been extensively prescribed for off‐label use as a treatment for insomnia. Findings from recent studies using other medications or placebo as control are mixed; trazodone was found to improve sleep among patients with primary and secondary insomnia, although it was not effective among methadone maintenance patients with insomnia . Trazodone has been shown to alleviate opioid and benzodiazepine withdrawal symptoms in dependent patients.…”

“…Findings from recent studies using other medications or placebo as control are mixed; trazodone was found to improve sleep among patients with primary and secondary 18 insomnia, although it was not effective among methadone maintenance patients with insomnia. 19 Trazodone has been shown to alleviate opioid 20,21 and benzodiazepine 22 withdrawal symptoms in dependent patients. No systematic national data on trazodone abuse/misuse are apparent in the literature.…”

Sleep disturbances and pain among individuals with prescription opioid dependence

“…For example, actigraphy may be less accurate in measuring sleep latency and is prone to first night effects. Future research would benefit from the collection of more in-depth sleep quality data utilizing polysomnographic methods that alleviate first night effects and allow for assessment of sleep apneic events (Krystal & Edlinger, 2008; Kurth et al, 2009; Sharkey et al, 2011; Stein et al, 2012). Finally, future research may also be informed by the extension of the assessment timeframe and environment (i.e., to naturalistic home environment).…”

Self-reported psychopathology and health-related quality of life in heroin users treated with methadone

“…Additional symptoms on BSRS refers to poor appetite and sleep difficulty. Poor appetite and sleep difficulty are common symptoms and very highly prevalent in heroin users 29,30. Short sleep duration (<6 hours) is associated with poor physical and self-perceived mental health status, as well as increased morbidity and mortality 31,32.…”