Getting a Good Day's Sleep

Pauline Anderson

August 13, 2014

Shift workers who take melatonin may get 24 more minutes of sleep after a night shift and some who take the stimulants modafinil or armodafinil during a shift may be more alert, although these medications have adverse effects, according to a new literature review.

The review also showed that caffeine plus naps reduces sleepiness during the night shift.

However, studies included in the review were mostly small and the reviewers deemed most of them to be of low quality, even though their randomization methods and allocation concealments were not described.

"We need more and better quality trials on the beneficial and adverse effects and cost of all pharmacological agents that induce sleep or promote alertness in shift workers. We also need systematic reviews of their adverse effects," the authors, led by Juha Liira, chief physician, research and development in occupational health services, Finnish Institute of Occupational Health, Helsinki, Finland, write.

The review was published online August 12 in the Cochrane Database of Systematic Reviews.

Real Working Life

Researchers searched CENTRAL, MEDLINE, EMBASE, PubMed, PsychINFO, and ClinicalTrials.gov for randomized controlled trials of pharmacologic products among shift workers with or without sleep problems. Outcomes included sleep length and sleep quality while off work, and alertness and fatigue at work.

The included studies investigated the "real life working environment"; in other words, researchers excluded all trials that used simulated shift work tasks. They also excluded studies of airline staff, military personnel, or others who frequently cross time zones.

The analysis included 15 trials with 718 participants. Nine trials evaluated the effect of melatonin, a hormone secreted by the pineal gland, and 2 the effect of hypnotics for improving sleep problems. One trial assessed the effect of modafinil, 2 the effect of armodafinil, and 1 the effect of caffeine plus naps on decreasing sleepiness or increasing alertness.

Reviewers found that melatonin (1 to 10 mg) may increase sleep length during the day after a night shift (mean difference [MD], 24 minutes [95% confidence interval (CI), 9.8 - 38.9] in 7 trials with 263 participants) and at night (MD, 17 minutes [95% CI, 3.71 - 30.22] in 3 trials with 234 participants). Melatonin may lead to similar sleep latency times as placebo (MD, 0.37 minutes [95% CI, –1.55 to 2.29] in 5 trials with 74 participants).

All evidence related to melatonin was of low quality, according to the authors. Interventions such as melatonin aim to realign the disruption of the circadian system.

"Melatonin comes closest to a substance that could potentially achieve this," the authors note. "The melatonin signal forms part of the system that regulates the sleep-wake cycle by chemically causing drowsiness and lowering the body temperature."

The authors also noted that melatonin, which is available in the United States without a prescription in tablet, capsule, liquid, or patch form, appears to be useful for other circadian rhythm disorders, including jet lag.

Given the low quality of evidence for melatonin, the authors said additional placebo- controlled trials are needed. Such trials "should use objective electrophysiological monitoring of sleep length and quality," they write.

Hypnotic Agents

The 1 study of the hypnotic medication zopiclone didn't show a significantly longer daytime sleep length compared with placebo in 1 low-quality trial. The researchers could not use the data from the 1 study of lormetazepam.

The authors noted that most hypnotic drugs have adverse effects, such as dependence and tolerance, after long-term use and that these agents may cause drowsiness after the sleep period in short-term use.

"Based on the available evidence, it is unclear whether or not hypnotics improve sleep length and quality after a night shift," write the authors.

Increased Alertness

Moderate-quality evidence suggested that taking armodafinil before the night shift reduces sleepiness by 1 point on the Karolinska Sleepiness Scale (KSS) (MD, –0.99 [95% CI, –1.32 to –0.67] in 2 trials with 572 participants). There was also evidence that this drug increases alertness by 50 minutes at 3 months in patients with shift work sleep disorder. The disorder involves persistent difficulties with sleep after working a night shift and sleepiness during the night shift.

There was also moderate-quality evidence that modafinil has similar effects on sleepiness (MD on KSS, –0.90 [95% CI, –1.45 to –0.35] in 1 trial with 183 participants) and on alertness.

In these studies, headache, nausea, and rise in blood pressure were the most common adverse effects. However, since coming on the market, these stimulant agents have been associated with severe skin reactions.

In 1 trial, caffeine plus preshift naps decreased sleepiness (MD in KSS, –0.63 [95% CI, –1.09 to –0.17]). The authors found no evidence that caffeine reduces work-related injuries compared with other interventions.

The authors called for studies of caffeine in shift workers that measure adverse effects. Long-term adverse effects of modafinil and armodafinil should also be studied, they said.

According to the authors, an increasing proportion of workers spend at least some time doing shift work. In 2014, the US Bureau of Labor Statistics found that almost 15% of full-time salaried workers in the United States usually worked shifts, including nights. The likelihood of undertaking shift work appears to decrease progressively with age.

Shift work can lead to health issues beyond just sleepiness interrupted sleep. "The International Agency for Research on Cancer has concluded that shift work that involves circadian disruption (i.e. having to adjust to working at night and sleeping during the day, and then having to readjust back) is probably carcinogenic to humans," the investigators write.

Safety Hazard?

Commenting on the findings for Medscape Medical News, Timothy Morgenthaler, MD, president of the American Academy of Sleep Medicine (AASM), said the study findings are not dissimilar to a practice guideline commissioned by the AASM (Sleep. 2007;30:1445-1449), particularly as they relate to the potential for melatonin to increase sleep duration if taken after a night shift.

Although the 24 minutes by which melatonin might increase daytime sleep may seem like a small effect, the sleep of typical workers is reduced by 2 to 4 hours after a night shift compared with a nonshift schedule, said Dr. Morgenthaler. "That 24 minutes would therefore comprise a 10% or higher increase in sleep duration."

The fact that no data were found to support the use of zopiclone as an aid for daytime sleep was also similar to the previous research, said Dr. Morgenthaler. He pointed out that this drug isn't approved in the United States and that patients often use alternative hypnotics, such as zolpidem, or over-the-counter antihistamine agents, which haven't been well studied for this use and carry a warning against use when activities that require alertness within 7 hours are planned.

"This may be a safety hazard and highlights the need both for clinical trial funding to address this area and for making use of nonpharmacologic interventions, such as ensuring a quiet and dark sleep environment, use of timed sleep and nap schedules, timed light exposure, and smart scheduling of shift changes," said Dr. Morgenthaler.

AASM is updating its clinical practice guideline for the treatment of circadian rhythm sleep disorders. The guideline is expected to be published in 2015.

The authors have disclosed no relevant financial relationships.

Cochrane Database Syst Rev. Published online August 12, 2014. Abstract

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