Abstract
Objective
To determine whether drugs used to treat diverse conditions cause insomnia symptoms
and whether their prescription information is concordant with this evidence.
Methods
We conducted a survey of meta-analyses (Cochrane Database of Systematic Reviews) and
comparisons with package inserts compiled in the Physicians' Desk Reference (PDR). We identified randomized controlled trials (RCTs) in which any drug had been evaluated
vs placebo and sleep had been assessed. We collectively referred to insomnia-related
outcomes as sleep disturbance. We also searched the PDR to identify any insomnia symptoms listed for drugs with RCT evidence available.
Results
Seventy-four Cochrane systematic reviews corresponding to 274 RCTs assessed 88 drugs
in 27 different conditions, providing evidence on 109 drug-condition pairs. Of these
88 drugs, 5 decreased sleep problems and 19 increased sleep problems; 64 drugs had
no nominally statistically significant effect on sleep. Acetylcholinesterase inhibitors,
dopamine agonists, and selective serotonin reuptake inhibitors were the drug classes
most importantly associated with sleep disturbance. Of 35 drugs that included disturbed
sleep as an adverse effect in the PDR, only 14 had RCT evidence supporting such effect, and 2 had evidence of increasing
and decreasing sleep problems in RCTs, although this was not shown in the PDR. We identified weak concordance between the PDR and RCTs (weighted κ=0.31; P<.001).
Conclusion
The RCTs offer substantial evidence about the common effects of drugs on the risk
of sleep disturbance; currently, prescription information only partially agrees with
the available randomized evidence.
Abbreviations and Acronyms:
AE (adverse event), CDSR (Cochrane Database of Systematic Reviews), COMTI (catechol-O-methyltransferase inhibitor), DOPA (dopamine), FDA (Food and Drug Administration), GABA (γ-aminobutyric acid), GnRH (gonadotropin-releasing hormone), IQR (interquartile range), MAOI (monoamine oxidase inhibitor), NA (number of events is not applicable because the outcome is continuous), NL (drug is not listed in the PDR), NMDA (N-methyl-d-aspartic acid), NSAID (nonsteroidal anti-inflammatory drug), OR (odds ratio), PDR (Physicians' Desk Reference), RCT (randomized controlled trial), SNRI (serotonin-norepinephrine reuptake inhibitor), SSRI (selective serotonin reuptake inhibitor), TCA (tricyclic antidepressant)To read this article in full you will need to make a payment
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Article Info
Publication History
Published online: November 11, 2016
Footnotes
Dr Wong is now with the Department of Psychiatry, Massachusetts General Hospital, Harvard University School of Medicine, Boston, MA.
Identification
Copyright
© 2016 Mayo Foundation for Medical Education and Research
