Assessment of Patterns of Potentially Unsafe Use of Zolpidem | Clinical Pharmacy and Pharmacology | JAMA Internal Medicine | JAMA Network
[Skip to Navigation]
Table 1.  Characteristics of US Adults Exposed to Zolpidem
Characteristics of US Adults Exposed to Zolpidem
Table 2.  Increased Risks Among Zolpidem Users
Increased Risks Among Zolpidem Users
Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    Research Letter
    September 2018

    Assessment of Patterns of Potentially Unsafe Use of Zolpidem

    Author Affiliations
    • 1Institute for Safe Medication Practices, Alexandria, Virginia
    • 2Department of Epidemiology and Biostatistics, Milken Institute School of Public Health, Washington, DC
    • 3Risk Sciences International, Ottawa, Ontario, Canada
    JAMA Intern Med. 2018;178(9):1275-1277. doi:10.1001/jamainternmed.2018.3031

    Zolpidem was the most widely used prescription hypnotic medication and the fourth most frequently prescribed psychiatric drug in 2013.1 It achieves its effects as an agonist of γ-aminobutyric acid (GABA) receptors. However, the prescribing information2 and US Food and Drug Administration (FDA) Drug Safety Communications3 include limitations to reduce adverse effects, including (1) short-term use because of loss of efficacy; (2) a lower dose of 5 mg/d for those 65 years or older, and the lower starting dose for women because of 45% to 50% higher blood concentrations2; and (3) increased risks when combined with other central nervous system (CNS)-depressant drugs. These precautions were intended to reduce the risks of next-day impairment, abnormal behavioral changes, and dependency. We compared patterns of reported use with these recommendations in data from the largest publicly available national survey of prescription medication.

    Methods

    We used the US Medical Expenditure Panel Survey (MEPS) for 20154 to calculate the noninstitutionalized adult population characteristics and patterns of zolpidem use. The lower recommended daily dose was 5 mg for immediate and 6.25 mg for extended release products; the higher daily dose was 10 mg or 12.5 mg. Sustained use was defined as 3 or more prescriptions or 61 days or more of supply. Other drugs sharing CNS-depressant effects were any opioid agonist, any other GABA agonist (primarily benzodiazepines), and any form of synthetic GABA (primarily gabapentin). Multiple CNS-depressant risks were limited to those reporting sustained use of the CNS medications. We estimated the exposed populations and 95% confidence intervals (CIs) using the MEPS multistage probability design, based on a clustered sample of 35 427 individuals and 330 453 reported prescriptions during 2015. Because this was not a study with direct patient participants, no informed consent was needed, and since any personal information was deidentified in this publicly available research survey, institutional review board approval was not sought.

    Results

    Overall, 3.8 million adults (95% CI, 3.2-4.4 million) aged 18 to 85 years reported 1 or more prescriptions for zolpidem in 2015. Population characteristics, detailed in Table 1, indicate that women were nearly twice as likely as men to use zolpidem, and use grew with increasing age. Percentages of patients at increased risk for adverse events are summarized in Table 2. The higher dose was being taken by 64.0% (95% CI, 53.0%-75.0%) of adults 65 years or older and 68.0% (95% CI, 60.7%-75.3%) of women. Sustained—vs short-term—use was reported by 68.2% (95% CI, 62.5%-73.9%) of those exposed to zolpidem. The sustained-use zolpidem group reported a median of 192 days’ supply (interquartile range, 117-297 days). Among zolpidem users, sustained use of at least 1 other CNS-depressant medication was reported by 41.4% (95% CI, 34.9%-47.9%), including 26.5% taking opioids, and 20.3% using benzodiazepines. Overall, 77.4% (95% CI, 70.5%-84.3%) were not observing 2 or more recommendations to reduce risk.

    Discussion

    These data show that optimal safe use of zolpidem is uncommon. Although efficacy declines substantially after 14 days of continuous administration,5 most zolpidem patients reported sustained use, with increased risk of dependence, given that zolpidem is a class IV controlled substance. Overdose and next-day impairment risks were increased with the 41.4% combining zolpidem with sustained use of other CNS-depressant drugs.

    These data have several limitations. They are not capable of assessing the harms of zolpidem, only self-reported patterns of drug use. Some women reporting the higher zolpidem dose could have been started at the recommended 5-mg daily dose and later increased the dose. MEPS data likely underestimate exposure because they are self-reported, and the data could not account for the start of medication use and permanent discontinuation occurring part way through the 12-month survey period. Other key safe use recommendations—abstaining from alcohol, avoiding over-the-counter sleep aids, and limiting next-day driving—could not be assessed in these data. In conclusion, this study of zolpidem shows that there are many opportunities to reduce the risks of next-day impairment, abnormal behavior changes, and dependence.

    Back to top
    Article Information

    Accepted for Publication: May 7, 2018.

    Corresponding Author: Thomas J. Moore, AB, Institute for Safe Medication Practices, 815 King St, Ste 302, Alexandria, VA 22314 (tmoore@ismp.org).

    Published Online: July 16, 2018. doi:10.1001/jamainternmed.2018.3031

    Author Contributions: Mr Moore had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

    Concept and design: All authors.

    Acquisition, analysis, or interpretation of data: Moore.

    Drafting of the manuscript: Moore.

    Critical revision of the manuscript for important intellectual content: All authors.

    Statistical analysis: Moore.

    Administrative, technical, or material support: Mattison.

    Conflict of Interest Disclosures: None reported.

    References
    1.
    Moore  TJ, Mattison  DR.  Adult utilization of psychiatric drugs and differences by sex, age, and race.  JAMA Intern Med. 2017;177(2):274-275. doi:10.1001/jamainternmed.2016.7507PubMedGoogle ScholarCrossref
    2.
    AMBIEN—Zolpidem Tartrate Tablet [package insert]. Bridgewater, NJ: Sanofi-Aventis US, LLC; 2014.
    3.
    FDA Drug Safety Communication. FDA approves new label changes and dosing for zolpidem products and a recommendation to avoid driving the day after using Ambien CR. Published May 14, 2013. https://www.fda.gov/Drugs/DrugSafety/ucm352085.htm. Accessed March 8, 2018.
    4.
    AHRQ Agency for Healthcare Research and Quality. Medical Expenditure Panel Survey. https://www.meps.ahrq.gov/mepsweb/. Accessed March 15, 2018.
    5.
    Moore  TJ, Furberg  CD, Mattison  DR, Cohen  MR. QuarterWatch 2014, Quarter 2: New Safety Perspectives. Institute for Safe Medication Practices. Published May 6, 2015. https://www.ismp.org/sites/default/files/attachments/2018-01/2014Q2_0.pdf. Accessed March 8, 2018.
    ×