Shift workers often use drugs to try to sleep during the day or stay awake at night, but limited evidence supports the efficacy of these agents, according to a Cochrane Database review of 15 placebo-controlled studies.
"The evidence was of low quality and mostly from small trials," said Dr. Juha Liira of the Finnish Institute of Occupational Health in Helsinki and her associates. "Both sleep- and alertness-promoting agents have potentially serious adverse effects. Therefore, we need more trials to determine the beneficial and harmful effects of these drugs."
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There is limited evidence to support the usage of drugs that help workers on shifts to sleep during the day or stay awake at night.
The strongest evidence was for the ability of modafinil and armodafinil to promote wakefulness during shift work, but these drugs can pose substantial risks, the authors said.
The review uncovered low-quality evidence for melatonin as a daytime sleep promoter and for caffeine to enhance nighttime wakefulness, the authors said, adding that hypnotics did not affect sleep length or quality after night work.
For the study, reviewers searched the CENTRAL, MEDLINE, EMBASE, PubMed, and PsycINFO databases through September 2013 and ClinicalTrials.gov up to July 2013. They included all randomized, controlled trials, including crossover trials, of pharmacologic agents in shift workers, whether or not the subjects had sleep problems (Cochrane Database Syst. Rev. 2014 Aug. 12 [doi:10.1002/14651858.CD009776.pub2]) They excluded trials that simulated shift work tasks, noting that such studies probably do not approximate shift work in real life. They also excluded studies of airline and military personnel because melatonin has already been reviewed for jet lag (Cochrane Database Syst. Rev. 2002;2:CD001520).
The search yielded 15 randomized, placebo-controlled trials with a total of 718 participants. Nine trials assessed melatonin, two examined hypnotics, three looked at modafinil or armodafinil, and one assessed caffeine, they reported.
Modafinil (200 mg) and armodafinil (150 mg) improved wakefulness and alertness during night shifts at 3-month follow-up, compared with placebo, the researchers said. But armodafinil cut sleepiness by a mean of just one point on the Karolinska Sleepiness Scale (KSS) (range, 1-9 points; 95% confidence interval, -1.32 to -0.67), and improved reaction time by only 50 ms (95% CI, -85.5 to -15.5 ms), they added. "Modafinil probably has similar effects on sleepiness," the reviewers concluded, noting that the drug decreased sleepiness by 0.9 points on the KSS (95% CI, -1.45 to -0.35) while also heightening alertness in a psychomotor vigilance test.
Armodafinil and modafinil also have been linked to serious skin disorders in postmarketing reports, the researchers emphasized. And the drugs caused headache, nausea, and increased blood pressure in clinical trials, they said.
Caffeine at a dose of 300 mg or 4 mg/kg improved alertness during night shifts when combined with a preshift nap, the reviewers said. But the effect size in the single trial was small, with a mean improvement of only 0.63 points on the KSS (95% CI, -1.09 to -0.17), they added.
Melatonin had only low-quality evidence as a sleep promoter, the reviewers said. A dose of 1-10 mg lengthened daytime sleep by an average of 24 minutes, compared with placebo in seven trials of 263 shift workers (95% CI, 9.82-38.86), and added 17 minutes to nighttime sleep in three trials of 234 participants (95% CI, 3.71-30.22), but did not significantly affect other sleep parameters such as sleep latency, they reported.
The only trial of the hypnotic drug zopiclone (7.5 mg) included just 28 participants and found that the agent did not lengthen daytime sleep significantly more than did placebo (mean difference, 44 minutes; 95% CI, -22.67-110.67), while no trials examined adverse effects of hypnotics in shift workers, the reviewers said.
"We need more and better quality trials on the beneficial and adverse effects and costs of all pharmacological agents that induce sleep or promote alertness in shift workers, both with and without a diagnosis of shift work sleep disorder," Dr. Liira and associates concluded. "We also need systematic reviews of their adverse effects."
Most of the melatonin trials had a high risk of bias, so the reviewers downgraded their rating from a high to a low level of quality, they said. They similarly downgraded trials for armodafinil, modafinil, caffeine, and hypnotics.
The Finnish Institute of Occupational Health pays the salary of Dr. Liira and four coauthors. There were no external funding sources or conflicts of interest.