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Effect on sleep for some medications not reflected in prescribing information

A meta-analysis of randomized controlled trials published in Mayo Clinic Proceedings revealed that sleep disturbance is an adverse effect of several drug classes for a variety of conditions, yet the prescription information of these drugs do not fully reflect clinical evidence.

“Impaired sleep is a major, yet unmet, public health challenge associated with enormous economic and societal cost,” Anthony G. Doufas, MD, PhD, from the department of anesthesiology, perioperative and pain medicine at the Stanford University Medical Center, and colleagues wrote. “Although disturbed sleep can be a symptom or an independent disorder (insomnia), it is most frequently encountered as a comorbid condition with another medical or psychiatric disease and has been identified as a risk factor for chronic mental and physical illnesses. In that context, it is important to recognize that many drugs used to treat diverse clinical conditions may adversely affect the quality and duration of sleep.”

Doufas and colleagues investigated the effect that drugs used to treat diverse conditions have on sleep disturbance (insomnia-related outcomes) and whether their prescription information aligned with evidence from randomized controlled trials (RCTs). They included RCTs that analyzed sleep and any drug compared to a placebo in their assessment. They obtained package inserts for drugs using the Physicians’ Desk Reference (PDR) and compared any insomnia symptoms listed for drugs with RCT evidence.

The researchers identified 74 Cochrane systematic reviews relating to 274 RCTs which evaluated 88 drugs for 27 conditions in 109 drug-condition pairs. Data indicated that five of the assessed drugs reduced sleep problems and 19 increased sleep problems, while 64 did not have a statistically significant effect on sleep. Of the drugs that increased sleep disturbance, 11 more than doubled the risk.

The drug classes that were most significantly associated with sleep disturbance included acetylcholinesterase inhibitors, dopamine agonists and selective serotonin reuptake inhibitors. In the PDR, 35 drugs identified disturbed sleep as an adverse effect, yet data showed that only 14 had RCT evidence to support such a claim. In addition, RCT evidence demonstrated that two drugs increased and decreased sleep problems; however, the PDR did not indicate such findings. Agreement between the PDR and RCTs was weak, according to the researchers.

“A stronger connection between randomized evidence and information in drug package inserts could benefit clinical decision making and influence therapeutics,” Doufas and colleagues concluded. “This is especially true for the [adverse effect] of dysfunctional sleep, which is a strong independent contributor to psychiatric illness, and may have the potential to influence response to treatment or alter disease prognosis. Instead of reporting qualitative reviews regarding various, potentially important, adverse effects, moving to a more quantitative and systematic communication of clinical evidence to drug package inserts may enable prescribing physicians to make more informed therapeutic decisions and ultimately improve disease outcomes.” – by Alaina Tedesco

Disclosure: The researchers report no relevant financial disclosures.