Pharmacological interventions for sleepiness and sleep disturbances caused by shift work



Shift work results in sleep‐wake disturbances, which cause sleepiness during night shifts and reduce sleep length and quality in daytime sleep after the night shift. In its serious form it is also called shift work sleep disorder. Various pharmacological products are used to ameliorate symptoms of sleepiness or poor sleep length and quality.


To evaluate the effects of pharmacological interventions to reduce sleepiness or to improve alertness at work and decrease sleep disturbances whilst off work, or both, in workers undertaking shift work in their present job and to assess their cost‐effectiveness.

Search methods

We searched CENTRAL, MEDLINE, EMBASE, PubMed and PsycINFO up to 20 September 2013 and up to July 2013. We also screened reference lists of included trials and relevant reviews.

Selection criteria

We included all eligible randomised controlled trials (RCTs), including cross‐over RCTs, of pharmacological products among workers who were engaged in shift work (including night shifts) in their present jobs and who may or may not have had sleep problems. Primary outcomes were sleep length and sleep quality while off work, alertness and sleepiness, or fatigue at work.

Data collection and analysis

Two authors independently selected studies, extracted data and assessed risk of bias in included trials. We performed meta‐analyses where appropriate.

Main results

We included 15 randomised placebo‐controlled trials with 718 participants. Nine trials evaluated the effect of melatonin and two the effect of hypnotics for improving sleep problems. One trial assessed the effect of modafinil, two of armodafinil and one examined caffeine plus naps to decrease sleepiness or to increase alertness.

Melatonin (1 to 10 mg) after the night shift may increase sleep length during daytime sleep (mean difference (MD) 24 minutes, 95% confidence interval (CI) 9.8 to 38.9; seven trials, 263 participants, low quality evidence) and night‐time sleep (MD 17 minutes, 95% CI 3.71 to 30.22; three trials, 234 participants, low quality evidence) compared to placebo. We did not find a dose‐response effect. Melatonin may lead to similar sleep latency times as placebo (MD 0.37minutes, 95% CI ‐ 1.55 to 2.29; five trials, 74 participants, low quality evidence).

Hypnotic medication, zopiclone, did not result in significantly longer daytime sleep length compared to placebo in one low quality trial and we could not use the data from the study on lormetazepam.

Armodafinil taken before the night shift probably reduces sleepiness by one point on the Karolinska Sleepiness Scale (KSS) (MD ‐0.99, 95% CI ‐1.32 to ‐0.67; range 1 to 10; two trials, 572 participants, moderate quality evidence) and increases alertness by 50 ms in a simple reaction time test (MD ‐50.0, 95% CI ‐85.5 to ‐15.5) at three months' follow‐up in shift work sleep disorder patients. Modafinil probably has similar effects on sleepiness (KSS) (MD ‐0.90, 95% CI ‐1.45 to ‐0.35; one trial, 183 participants, moderate quality evidence) and alertness in the psychomotor vigilance test in the same patient group. Post‐marketing, severe skin reactions have been reported. Adverse effects reported by trial participants were headache, nausea and a rise in blood pressure. There were no trials in non‐patient shift workers.

Based on one trial, caffeine plus pre‐shift naps taken before the night shift decreased sleepiness (KSS) (MD ‐0.63, 95% CI ‐1.09 to ‐0.17).

We judged most trials to have a low risk of bias even though the randomisation method and allocation concealment were often not described.

Authors' conclusions

There is low quality evidence that melatonin improves sleep length after a night shift but not other sleep quality parameters. Both modafinil and armodafinil increase alertness and reduce sleepiness to some extent in employees who suffer from shift work sleep disorder but they are associated with adverse events. Caffeine plus naps reduces sleepiness during the night shift, but the quality of evidence is low. Based on one low quality trial, hypnotics did not improve sleep length and quality after a night shift.

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. We also need systematic reviews of their adverse effects.


Juha Liira, Jos H Verbeek, Giovanni Costa, Tim R Driscoll, Mikael Sallinen, Leena K Isotalo, Jani H Ruotsalainen


Plain language summary

Drugs for treating people with sleepiness during shift work and sleep problems after shift work

People who work shifts often report sleepiness at work and problems with sleep between work shifts. This is called shift work sleep disorder when the difficulties with sleep after the night shift and sleepiness during the night shift are persistent. We evaluated the effect of drugs, such as melatonin, to improve shift workers' sleep quality after night shift work. We also examined the effect of drugs, such as caffeine, to help shift workers stay awake. We also wanted to evaluate cost‐effectiveness but there were no studies.

Studies found

We performed a literature search up to 20 September 2013. We included 15 trials with 718 participants. Trials evaluated the effect of melatonin and hypnotics on sleep after the shift and the effect of modafinil, armodafinil and caffeine plus naps on sleepiness during the shift.

Effect on sleep length and quality

People who take melatonin may sleep for 24 minutes longer during the daytime after the night shift but there may be no effect on other sleep outcomes, such as time needed to fall asleep (low quality evidence). Side effects of melatonin use were rare.

For hypnotics (zopiclone), there is insufficient evidence to know whether or not they affect sleep length (very low quality evidence). We did not find reports on their side effects in shift workers.

Effect on alertness or sleepiness during the shift

People that take modafinil and armodafinil probably have a small reduction in sleepiness and an increase in alertness during the night shift, based on evidence at three months' follow‐up in people with shift work sleep disorder (moderate quality evidence). Headache and nausea were the most common side effects both in the short and long term follow‐up. However, serious skin disorders have been reported since these drugs have come on the market. We found no trials in shift workers without a diagnosis of shift work sleep disorder.

We found one trial which showed that people that took caffeine before the night shift in combination with a nap before the shift had increased alertness during the night shift.

What do we still need to find out?

The evidence was of low quality and mostly from small trials. 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.


Juha Liira, Jos H Verbeek, Giovanni Costa, Tim R Driscoll, Mikael Sallinen, Leena K Isotalo, Jani H Ruotsalainen

Reviewer's Conclusions

Authors' conclusions 

Implications for practice 

Melatonin may improve sleep length after a night shift but may not improve other sleep parameters (low quality evidence). Modafinil and armodafinil increase alertness and reduce sleepiness to some extent during the night shift in employees who suffer from shift work sleep disorder but both drugs have been associated with adverse events (moderate quality evidence) . Pre‐shift caffeine plus pre‐shift naps increases alertness during the night shift, but this is based on one small trial only. Based on the available evidence, it is unclear whether or not hypnotics improve sleep length and quality after a night shift (low quality evidence).

Implications for research 

Given the low quality evidence, additional placebo‐controlled trials of melatonin are needed. Trials should use objective electrophysiological monitoring of sleep length and quality.

More RCTs are needed of caffeine for shift workers under field conditions and they should also measure adverse effects. Long term adverse effects of modafinil and armodafinil should be studied in cohort and case‐control studies. These studies should also be summarised in a systematic review.

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