Skip to main content
Browse Subject Areas

Click through the PLOS taxonomy to find articles in your field.

For more information about PLOS Subject Areas, click here.

  • Loading metrics

Patterns of zolpidem use among Iraq and Afghanistan veterans: A retrospective cohort analysis

  • Ramona Shayegani ,

    Contributed equally to this work with: Ramona Shayegani, Kangwon Song, Mary Jo Pugh

    Roles Conceptualization, Formal analysis, Investigation, Methodology, Project administration, Writing – original draft, Writing – review & editing

    Affiliation VA Southern Nevada Healthcare System, North Las Vegas, Nevada, United States of America

  • Kangwon Song ,

    Contributed equally to this work with: Ramona Shayegani, Kangwon Song, Mary Jo Pugh

    Roles Conceptualization, Formal analysis, Investigation, Methodology, Project administration, Visualization, Writing – original draft, Writing – review & editing

    Affiliations South Texas Veterans Health Care System, San Antonio, Texas, United States of America, University of Texas Health Science Center San Antonio, San Antonio, Texas, United States of America

  • Megan E. Amuan ,

    Roles Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Software, Writing – original draft, Writing – review & editing

    ‡ These authors also contributed equally to this work.

    Affiliation Center for Health Quality, Outcomes and Economic Research, Edith Nourse Rogers Memorial Veterans Hospital, Bedford, Massachusetts, United States of America

  • Carlos A. Jaramillo ,

    Roles Conceptualization, Formal analysis, Investigation, Methodology, Writing – review & editing

    ‡ These authors also contributed equally to this work.

    Affiliations South Texas Veterans Health Care System, San Antonio, Texas, United States of America, University of Texas Health Science Center San Antonio, San Antonio, Texas, United States of America

  • Blessen C. Eapen ,

    Roles Formal analysis, Investigation, Methodology, Writing – review & editing

    ‡ These authors also contributed equally to this work.

    Affiliations South Texas Veterans Health Care System, San Antonio, Texas, United States of America, University of Texas Health Science Center San Antonio, San Antonio, Texas, United States of America

  • Mary Jo Pugh

    Contributed equally to this work with: Ramona Shayegani, Kangwon Song, Mary Jo Pugh

    Roles Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Writing – original draft, Writing – review & editing

    Affiliations South Texas Veterans Health Care System, San Antonio, Texas, United States of America, University of Texas Health Science Center San Antonio, San Antonio, Texas, United States of America, VA Salt Lake City Health Care System, Salt Lake City, Utah, United States of America, University of Utah Health, Division of Epidemiology, Salt Lake City, Utah, United States of America



Although concern exists regarding the adverse effects and rate of zolpidem use, especially long-term use, limited information is available concerning patterns of zolpidem use.


To examine the prevalence and correlates of zolpidem exposure in Iraq and Afghanistan Veterans (IAVs).


A retrospective cohort study of zolpidem prescriptions was performed with National Veterans Health Administration (VHA) data. We gathered national VA inpatient, outpatient, and pharmacy data files for IAV’s who received VA care between fiscal years (FY) 2013 and 2014. The VA pharmacy database was used to identify the prevalence of long term (>30 days), high-dose zolpidem exposure (>10mg immediate-release; >12.5mg extended-release) and other medications received in FY14. Baseline characteristics (demographics, diagnoses) were identified in FY13. Bivariate and multivariable analyses were used to examine the demographic, clinical, and medication correlates of zolpidem use.


Of 493,683 IAVs who received VHA care in FY 2013 and 2014, 7.6% (n = 37,422) were prescribed zolpidem in FY 2014. Women had lower odds of high-dose zolpidem exposure than men. The majority (77.3%) of IAVs who received zolpidem prescriptions had long-term use with an average days’ supply of 189.3 days and a minority (0.9%) had high-dose exposure. In multivariable analyses, factors associated with long-term zolpidem exposure included age greater than 29 years old, PTSD, insomnia, Selim Index, physical 2–3 conditions, opioids, antidepressants, benzodiazepines, atypical antipsychotics, and stimulants. High dose exposure was associated with PTSD, depression, substance use disorder, insomnia, benzodiazepines, atypical antipsychotics, and stimulant prescriptions.


The current practices of insomnia pharmacotherapy in IAVs fall short of the clinical guidelines and may reflect high-risk zolpidem prescribing practices that put Iraq and Afghanistan Veterans at risk for adverse effects of zolpidem and poor health outcomes.


Once the mainstay of insomnia treatment, benzodiazepine prescription rates have fallen as a result of clinical practice guidelines discouraging their use [14]. Subsequently, a steady increase in the use of non-benzodiazepine hypnotics, specifically zolpidem, has been observed within the U.S. Department of Veterans Affairs (VA) healthcare system and non-VA settings [2,5]. Although zolpidem is marketed as a safe alternative for treatment of insomnia, emerging data suggests that its use is associated with safety concerns resembling those seen with benzodiazepines [6].

In addition to causing cognitive impairment and dizziness along with adverse events such as complex sleep related behaviors, falls, head injuries, fractures and traffic accidents [711], data now shows that zolpidem is the leading psychiatric medication linked to emergency department (ED) visits with 25% requiring hospital admissions [12], in part due to co-ingestion of another CNS depressant (e.g., benzodiazepine, opioid, alcohol) [13,14]. Data from the national Drug Abuse Warning Network (DAWN) showed that the estimated number of ED visits involving zolpidem-related suicide attempts tripled from 2004 to 2011, reaching over 14,000 visits in the latter year [15]. The rates of abuse and dependency for zolpidem are comparable to benzodiazepines and are especially concerning in patients with mental health conditions and substance use disorders (SUD)[16]. On this basis, zolpidem is classified as a Schedule IV controlled substance in the U.S. along with benzodiazepines [17].

As with any sedative hypnotic agent, the risk for adverse health outcomes is especially concerning with higher doses and long-term use. In January 2003, the U.S. Food and Drug Administration (FDA) issued a drug safety communication to lower the recommended dose for zolpidem products partly because of the lingering next-day psychomotor and cognitive effects for women and older adults who physiologically eliminate zolpidem more slowly due to the increased half-life [18,19]. Although some studies have demonstrated repeated nightly use to be safe and effective for up to one year [2022], zolpidem is recommended for short-term use to temporarily relieve symptoms of insomnia [23]. However, the specific period of short-term use has not been delineated. Nevertheless, there is growing anecdotal evidence that zolpidem is routinely used contrary to FDA and manufacturer recommendations despite the greater awareness of its potential risks of harm [2426].

Iraq and Afghanistan war veterans (IAVs) may be particularly vulnerable to zolpidem exposure given their behavioral and medical risk factors for adverse health outcomes, including: suicide, accidental overdose from prescription medications, and motor vehicle accidents [2730]. However, no prior work to our knowledge has examined the extent to which zolpidem is used contrary to FDA and manufacturer recommendations in the IAV population. Thus, we aimed to describe the prevalence, duration, and mean daily dose of zolpidem prescriptions among a national cohort of IAVs, in addition to identifying key patient sociodemographic and clinical factors associated with these prescription patterns.



This retrospective cohort study was approved by the Institutional Review Boards at the University of Texas Health Science Center at San Antonio and the Edith Nourse Rogers Memorial Veterans Hospital; a waiver of informed consent was granted prior to initiation.


We first identified IAVs using the national Operations Enduring and Iraqi Freedom and New Dawn (OEF/OIF/OND) roster file, which is provided by the VA Office of Public Health. This roster identifies individuals who were deployed in support of combat operations in Iraq and Afghanistan or provided direct support from outside the designated combat zones and who were discharged from military service (active duty) or who returned from deployments (Reserve and National Guard) prior to the end of 2011. Those IAVs that accessed VA inpatient or outpatient care at least once annually in fiscal year (FY) 2013 and 2014 (October 1, 2012 to September 30, 2014) were selected for inclusion.

Data sources

We obtained VA inpatient and outpatient administrative data using the national VA data repository in Austin, Texas, and pharmacy records from the VA Pharmacy Benefits Management Strategic Health Group. These national data sources were then linked to the OEF/OIF/OND roster using an encrypted identifier, consistent for each individual across all databases. Prescriptions for zolpidem and other medications were identified in FY 2014 and baseline demographic characteristics and comorbid conditions were identified in FY 2013.


Study outcome definitions

The main study outcomes were related to zolpidem prescriptions in FY 2014. We first identified all individuals who were dispensed any zolpidem prescriptions based on the generic drug name. Duration of treatment was calculated by adding the days’ supply of zolpidem dispensed during FY 2014. The average daily dose was computed using the following formula: Because there is no consensus in the literature on what constitutes long-term zolpidem treatment, we considered zolpidem exposure as long-term if prescriptions were dispensed for more than 30 days because clinical trials found zolpidem treatment to be clinically significant for only four weeks and the FDA approval is for short-term use [23]. High-dose exposure was defined by an average daily dose exceeding 12.5mg for extended-release formulations and 10 mg for immediate-release formulations based on the latest FDA warning [18].

Sociodemographic covariates

We obtained date of birth, sex, race/ethnicity, and educational attainment using the OEF/OIF/OND roster and supplemented with VA data when missing. Age was based on the first day of FY 2013 (October 1st, 2012) and was classified as follows: 18 to 29 years, 30 to 39 years, 40 to 49 years, and 50 years and older. Race/ethnicity was categorized as African American, Asian, Hispanic, Native American/Pacific Islander, non-Hispanic White, and unknown. Education at the time of discharge included less than high school, high school graduate, some college, college or higher degree graduate, and unknown. We obtained marital status (married vs not married) using VA inpatient and outpatient data in FY 2013.

Comorbid condition covariates

We used International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes from national VA inpatient and outpatient data to characterize baseline psychiatric and medical comorbidities in FY 2013 as dichotomous variables (yes/no). We used a validated approach to identify chronic conditions (except for TBI- see below) that required ICD-9-CM diagnosis codes based on a minimum of one inpatient clinical encounter or two outpatient clinical encounters at least seven days apart [31]. Based on guidance recommending clinicians code TBI only on the first visit [32], TBI was based on a single inpatient or outpatient diagnosis. Conditions that are prevalent in IAVs and may be associated with zolpidem prescriptions were identified, including: TBI, PTSD, depression, SUD, anxiety, headache, pain other than headache, insomnia, chronic pulmonary disease, and sleep apnea. Finally, the Selim physical comorbidity index (excluding back pain and chronic pulmonary disease) was calculated to measure the burden of medical conditions [33]. Due to non-normal distribution, we classified comorbidity count as zero, one, two to three, and four or more.

Because Central Nervous System (CNS) polypharmacy is common among IAVs, with zolpidem as a common contributor [34], the following VA medication classes prescribed in FY 2014 were identified: antidepressants, benzodiazepines, stimulants, opioid analgesics, atypical antipsychotics, and sedating antihistamines. We classified each medication by days’ supply (e.g., 0, 1–30, 31–60, 61–90. 91–180, and more than 180 days); however, this did not result in any significant differences. Therefore, the CNS acting medications were summed up as any or no use.

Statistical analysis

Bivariate analyses using the χ2 statistic were performed to describe characteristics of individuals with and without zolpidem prescriptions, and those with and without long-term and high-dose zolpidem exposure. Multivariable logistic regression analyses were used to identify demographic characteristics, comorbidities, and medications associated with receipt of: 1) any zolpidem prescriptions, 2) long-term, and 3) high-dose exposures. Results are reported as adjusted odds ratios (AORs) with 95% confidence intervals (CI). All statistical analyses were conducted using SAS version 9.3 software® (SAS Institute, Inc., Cary, North Carolina); P < 0.05 was used as the level of statistical significance.


Of the 493,683 individuals who received VA care in FY 2013 and FY 2014, 37,422 (7.6%) received zolpidem. Of those who received zolpidem, 28,937 (77.3%) had long-term exposure and 351 (0.9%) received high-dose zolpidem (Fig 1).

Fig 1. Derivation of study cohort of Iraq and Afghanistan veterans with zolpidem exposure in fiscal year 2014.

Any zolpidem exposure

Table 1 shows sociodemographic and clinical characteristics for those with and without zolpidem prescriptions, and adjusted odds ratios (AOR) from logistic regression predicting zolpidem exposure in FY14. For those with zolpidem prescriptions dispensed, the mean daily dose was 8.2 ±2.4mg for immediate-release (IR) zolpidem and 11.4 ±2.4mg for extended-release (ER) zolpidem.

Table 1. Adjusted odds ratios (AOR) of correlates of zolpidem use among Iraq and Afghanistan veterans in fiscal year 2014.

Sociodemographic characteristics

Blacks and unknown races had significantly lower odds than whites for receiving zolpidem while Hispanics and Asians had higher odds. Zolpidem exposure increased with education above the high school level and in unmarried individuals.

Comorbid and medication characteristics.

Logistic regression analysis indicated that IAVs with PTSD, headache, other pain, and insomnia had higher odds of zolpidem exposure than individuals without these comorbidities. Decreased odds of zolpidem exposure was associated with SUD. Finally, IAVs who were prescribed opioids, antidepressants, benzodiazepines, atypical antipsychotics, sedating antihistamines, or stimulants in FY14 also had higher odds of receiving any outpatient zolpidem prescription.

Long-term zolpidem exposure

Individuals with long-term zolpidem exposure had a mean daily dose of 8.4 ±2.3mg IR zolpidem and 11.4 ±2.3mg ER zolpidem while those with short-term zolpidem exposure had a mean daily dose of 7.6 ±2.6mg IR zolpidem and 10.6 ±2.9mg ER zolpidem. Table 2 shows the socio-demographic and clinical characteristics for individuals with long-term zolpidem use and AORs from logistic regression analysis predicting long-term zolpidem exposure. IAVs 30 years and older had higher odds of long-term zolpidem exposure. On the contrary, those with Black, Asian, or Native American/Pacific Islander racial backgrounds had lower odds of long-term zolpidem exposure. Individuals with PTSD, insomnia, and two to three physical comorbidities had significantly higher odds of long-term zolpidem exposure while IAVs with SUD had lower odds. Regarding medications, individuals who also received opioids, antidepressants, benzodiazepines, atypical antipsychotics, or stimulants had significantly higher odds of long-term zolpidem exposure. Also, Veterans with zolpidem use in FY13 and FY14, and individuals with high dose zolpidem in FY14 had significantly higher odds of long-term zolpidem use in FY14.

Table 2. Adjusted odds ratios (AOR) of correlates of long-term zolpidem use among Iraq and Afghanistan veterans in fiscal year 2014.

High-dose zolpidem exposure

Individuals with high-dose zolpidem exposure had a mean daily dose of 15.7 ±3.4mg IR zolpidem and 17.4 ±6.7mg ER zolpidem while those with low-dose zolpidem exposure had a mean daily dose of 8.2 ±2.3mg IR zolpidem and 11.3 ±2.2mg ER zolpidem. Table 3 shows descriptive statistics and AOR for logistic regression analyses predicting high-dose zolpidem exposure. Women had lower odds of high-dose zolpidem prescriptions (AOR = 0.57; 95% CI = 0.37, 0.86) compared to men. Individuals with PTSD, depression, SUD, and insomnia had significantly higher odds of receiving high-dose zolpidem. Furthermore, those Veterans who were prescribed benzodiazepines, atypical antipsychotics, and stimulants also had significantly higher odds of high-dose zolpidem exposure than individuals without these medications. Individuals with zolpidem use in FY13 had increased odds of high-dose zolpidem exposure in FY14.

Table 3. Adjusted odds ratios (AOR) of correlates of high-dose zolpidem use among Iraq and Afghanistan veterans in fiscal year 2014.


We found that approximately 7.6% of IAVs were dispensed one or more zolpidem prescriptions in FY 2014 and more than three-quarters of those individuals (77.3%) had long-term exposure. A Danish study reported similar findings that approximately 94% of individuals who were prescribed Z-drugs (zaleplon, zolpidem, and zopiclone) had longer treatment exposure than the recommended four weeks [35]. Nonetheless, our finding that women were less likely to receive higher dosages is promising. This observation is consistent with a previous study that demonstrated FDA’s January 2013 Drug Safety Communication release has been effective [26], or that prescribing for women largely met the FDA criteria prior to the recommendation.

Suboptimal zolpidem prescribing practices may lead to high-risk drug interactions with serious adverse health outcomes, namely due to potentiation of CNS depressant effects [14,3641]. We found that individuals prescribed zolpidem long-term were significantly more likely to also receive antidepressants (83.7%), benzodiazepines (48.5%), opioids (49.6%), stimulants (28.6%), or atypical antipsychotics (36.3%) prescriptions. Veterans on high-doses of zolpidem received benzodiazepine (99.5%), opioid (99.5%), and atypical antipsychotics (99.35%) prescriptions. The prescription of additional CNS acting medications is concerning given the potential for drug interactions because CNS polypharmacy is independently associated with overdose and suicide-related behaviors [34]. It is not known whether specific combinations of medications or total number of medications lead to adverse events, but this topic deserves further study.

We found that approximately 7% of the zolpidem cohort also received prescriptions for neuro-stimulants. Stimulant pharmacotherapy is commonly used for the treatment of ADHD and was recommended for the treatment of fatigue and cognitive symptoms by the 2009 VA TBI clinical practice guidelines which were in effect at the time of this study [42,43]. However, stimulants can further exacerbate sleep disturbance symptoms due to their wake-promoting effects [43]. It is not clear whether zolpidem is prescribed for insomnia secondary to ADHD and TBI or as part of a "prescribing cascade,” treating the undesired effects of stimulant medications [44].

Adverse reactions with zolpidem include abnormal thinking and behavioral changes which could complicate the diagnostic picture regarding depression and PTSD [45]. In this study, depression and PTSD were consistently associated with all aspects of zolpidem exposure. Surprisingly, we found that the likelihood of high-dose zolpidem exposure was significantly greater for individuals with PTSD than those with insomnia This reflects the fact that zolpidem is recommended as a second-line treatment option for management of sleep disturbances in patients with PTSD [46]. However, since psychiatric disorders such as PTSD and depression carry an inherent risk for overdose death on their own [47,48], the FDA warning for zolpidem regarding an increased risk of worsening depression or suicidality should be considered [23]. This risk can be further potentiated with the addition of high-dose or long duration zolpidem treatment to existing regimens of antidepressants and benzodiazepines [49].

Sedative-hypnotic abuse is commonly seen in individuals with substance use disorders [50,51]. Although initial zolpidem clinical trials reported a lack of abuse and dependence potential, the emerging evidence from epidemiological studies and post-marketing surveillance show that individuals with mental health conditions and substance use disorders are at higher risk for misuse of prescribed zolpidem [5254]. In this study, it is reassuring that the zolpidem exposure was less likely for those with substance use disorder (SUD). However, among those who had zolpidem exposure, SUD was associated with high-dose zolpidem use. This may suggest suboptimal prescribing practices, tolerance (i.e., physical dependence) to the sedating effects, or drug seeking behavior to alleviate withdrawal effects or enhance the effects of other drugs in this cohort. This finding has clinical implications as individuals with SUDs may be using high-doses of zolpidem with other CNS depressing drugs.

We hope that clinicians consider a broad assessment of insomnia symptoms and optimize the management of the underlying conditions (e.g., sleep apnea, pain, ADHD, SUD) and substance use (e.g., stimulants, illicit drugs, alcohol) prior to initiating pharmacotherapy [55]. If a hypnotic such as zolpidem is initiated, it should be offered short-term for intermittent use and only as an adjunct to cognitive behavioral therapy for insomnia (CBT-I). CBT-I is now considered an important treatment approach for chronic insomnia and recommended as the initial treatment in current treatment practice guidelines [5558]. Because of the limited number of CBT therapists, new models of delivering CBT for insomnia have been developed to meet the high demand [5962]. It is important for providers to incorporate CBT to sustain improved sleep and to limit the use of hypnotics [6365].

Strengths and limitations

The present study had several strengths. To our knowledge, it is the first national-level study investigating the prevalence of zolpidem use and its prescribing patterns among IAVs. However, several limitations should be noted. Our data represents only IAVs enrolled in the VA healthcare system; thus, our results may not be generalized to all OEF/OIF/OND veterans, other veteran groups, or the U.S. general population. Because the current study used VA administrative data obtained from veterans’ medical records in a retrospective manner, our estimates of medications and diagnoses may be conservative as outside care was not included. Additionally, medication adherence and the use of "as needed" therapy cannot be confirmed. Although our models adjusted for important demographic and clinical covariates, our results may be confounded by other variables not captured in the analysis such as disease severity and the use of non-pharmacological approaches (e.g., psychotherapy). Lastly, given that patients with consistent utilization of VA services (at least one annual visit in FY 2013–2014) were included, we may have inadvertently selected for veterans with poorer health status compared to that of the OEF/OIF/OND general population. However, our cohort included about 80% of those who had VA care in FY 2014. Despite these limitations, our results elucidate that the prevalent use of zolpidem is associated with higher-risk prescribing patterns in IAV population, particularly those veterans with PTSD or on CNS activating medications. Future studies with trajectory-based models are needed to assess the potential adverse clinical outcomes associated with these prescribing patterns.


As benzodiazepines have fallen out of favor due to safety concerns, an apparent trend towards zolpidem prescribing for treatment of insomnia has become increasingly widespread. The current study found that zolpidem use is common and approximately 80% of IAVs who were prescribed zolpidem had long-term exposure. Additionally, both high-dose and long-term zolpidem exposure were consistently associated with PTSD and CNS polypharmacy (e.g., benzodiazepines and opioids) which may suggest high-risk prescribing practices and subsequent increased risk of adverse health outcomes in this population. We believe our findings can inform the development of future clinical resources and treatment algorithms to guide providers in the optimal dosing and monitoring of zolpidem treatment.


We thank Dr. Michael Dawes for editorial advice on early versions of the manuscript, and the VA Office of Public Health for access to the OEF/OIF Roster.


  1. 1. Lund BC, Bernardy NC, Alexander B, Friedman MJ. Declining benzodiazepine use in veterans with posttraumatic stress disorder. J Clin Psychiatry. 2012;73: 292–296. pmid:22152399
  2. 2. Bernardy NC, Lund BC, Alexander B, Friedman MJ. Prescribing trends in veterans with posttraumatic stress disorder. J Clin Psychiatry. 2012;73: 297–303. pmid:22490256
  3. 3. Management of Post-Traumatic Stress Disorder and Acute Stress Reaction (2010)—VA/DoD Clinical Practice Guidelines [Internet]. [cited 11 Dec 2017].
  4. 4. Management of Concussion-mild Traumatic Brain Injury (mTBI) (2016)—VA/DoD Clinical Practice Guidelines [Internet]. [cited 8 Feb 2016].
  5. 5. Kaufmann CN, Spira AP, Alexander GC, Rutkow L, Mojtabai R. Trends in prescribing of sedative-hypnotic medications in the USA: 1993–2010. Pharmacoepidemiol Drug Saf. 2016;25: 637–645. pmid:26711081
  6. 6. QuarterWatch: May 2015 [Internet]. [cited 18 Jan 2017].
  7. 7. Verster JC, Volkerts ER, Schreuder AHCML, Eijken EJE, van Heuckelum JHG, Veldhuijzen DS, et al. Residual effects of middle-of-the-night administration of zaleplon and zolpidem on driving ability, memory functions, and psychomotor performance. J Clin Psychopharmacol. 2002;22: 576–583. pmid:12454557
  8. 8. Kolla BP, Lovely JK, Mansukhani MP, Morgenthaler TI. Zolpidem is independently associated with increased risk of inpatient falls. J Hosp Med. 2013;8: 1–6. pmid:23165956
  9. 9. Wang PS, Bohn RL, Glynn RJ, Mogun H, Avorn J. Zolpidem Use and Hip Fractures in Older People. J Am Geriatr Soc. 2001;49: 1685–1690. pmid:11844004
  10. 10. Morgenthaler TI. The sirens of sleep? Mayo Clin Proc. 2014;89: 579–582. pmid:24708930
  11. 11. Lai M-M, Lin C-C, Lin C-C, Liu C-S, Li T-C, Kao C-H. Long-term use of zolpidem increases the risk of major injury: a population-based cohort study. Mayo Clin Proc. 2014;89: 589–594. pmid:24684782
  12. 12. Hampton LM, Daubresse M, Chang H-Y, Alexander GC, Budnitz DS. Emergency Department Visits by Adults for Psychiatric Medication Adverse Events. JAMA Psychiatry. 2014;71: 1006–1014. pmid:25006837
  13. 13. Zosel A, Osterberg EC, Mycyk MB. Zolpidem misuse with other medications or alcohol frequently results in intensive care unit admission. Am J Ther. 2011;18: 305–308 pmid:20458214
  14. 14. Turner BJ, Liang Y. Drug Overdose in a Retrospective Cohort with Non-Cancer Pain Treated with Opioids, Antidepressants, and/or Sedative-Hypnotics: Interactions with Mental Health Disorders. J Gen Intern Med. 2015;30: 1081–1096. pmid:25650263
  15. 15. Drug Abuse Warning Network, 2011: National Estimates of Drug-Related Emergency Department Visits [Internet]. [cited 14 Dec 2016].
  16. 16. Hajak G, Müller WE, Wittchen HU, Pittrow D, Kirch W. Abuse and dependence potential for the non-benzodiazepine hypnotics zolpidem and zopiclone: a review of case reports and epidemiological data. Addict Abingdon Engl. 2003;98: 1371–1378.
  17. 17. Victorri-Vigneau C, Feuillet F, Wainstein L, Grall-Bronnec M, Pivette J, Chaslerie A, et al. Pharmacoepidemiological characterisation of zolpidem and zopiclone usage. Eur J Clin Pharmacol. 2013;69: 1965–1972. pmid:23877252
  18. 18. Research C for DE and. Drug Safety and Availability—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 [Internet]. [cited 14 Dec 2016].
  19. 19. Research C for DE and. Drug Safety and Availability—FDA Drug Safety Communication: Risk of next-morning impairment after use of insomnia drugs; FDA requires lower recommended doses for certain drugs containing zolpidem (Ambien, Ambien CR, Edluar, and Zolpimist) [Internet]. [cited 14 Dec 2016].
  20. 20. Roehrs TA, Randall S, Harris E, Maan R, Roth T. Twelve months of nightly zolpidem does not lead to rebound insomnia or withdrawal symptoms: a prospective placebo-controlled study. J Psychopharmacol Oxf Engl. 2012;26: 1088–1095. pmid:22004689
  21. 21. Roehrs TA, Randall S, Harris E, Maan R, Roth T. Twelve months of nightly zolpidem does not lead to dose escalation: a prospective placebo-controlled study. Sleep. 2011;34: 207–212. pmid:21286241
  22. 22. Randall S, Roehrs TA, Roth T. Efficacy of eight months of nightly zolpidem: a prospective placebo-controlled study. Sleep. 2012;35: 1551–1557. pmid:23115404
  23. 23. Ambien (Sanofi-aventis U.S. LLC): FDA Package Insert. In: [Internet]. [cited 14 Dec 2016].
  24. 24. ISMP-zolpidem [Internet]. [cited 12 Dec 2016].
  25. 25. ISMP Quarterly Action Agenda [Internet]. [cited 12 Dec 2016].
  26. 26. Ambien, Similar Sleep Drugs Most Often Used In An Unsafe Manner: ISMP Report [Internet]. [cited 12 Dec 2016].
  27. 27. Finley EP, Zeber JE, Pugh MJV, Cantu G, Copeland LA, Parchman ML, et al. Postdeployment Health Care for Returning OEF/OIF Military Personnel and Their Social Networks: A Qualitative Approach. Mil Med. 2010;175: 953–957. pmid:21265301
  28. 28. Bohnert ASB, Ilgen MA, Galea S, McCarthy JF, Blow FC. Accidental Poisoning Mortality Among Patients in the Department of Veterans Affairs Health System: Med Care. 2011;49: 393–396 pmid:21407033
  29. 29. Knapik JJ, Marin RE, Grier TL, Jones BH. A systematic review of post-deployment injury-related mortality among military personnel deployed to conflict zones. BMC Public Health. 2009;9: 231. pmid:19594931
  30. 30. Jaramillo CA, Cooper DB, Wang C-P, Tate DF, Eapen BC, York GE, et al. Subgroups of US IRAQ and Afghanistan veterans: associations with traumatic brain injury and mental health conditions. Brain Imaging Behav. 2015;9: 445–455. pmid:25963862
  31. 31. Borzecki AM, Wong AT, Hickey EC, Ash AS, Berlowitz DR. Identifying hypertension-related comorbidities from administrative data: what’s the optimal approach? Am J Med Qual. 2004;19: 201–206. pmid:15532912
  32. 32. Surveillance Case Definitions. In: Military Health System [Internet]. [cited 10 Feb 2017].
  33. 33. Selim AJ, Fincke G, Ren XS, Lee A, Rogers WH, Miller DR, et al. Comorbidity assessments based on patient report: results from the Veterans Health Study. J Ambulatory Care Manage. 2004;27: 281–295. pmid:15287217
  34. 34. Collett GA, Song K, Jaramillo CA, Potter JS, Finley EP, Pugh MJ. Prevalence of Central Nervous System Polypharmacy and Associations with Overdose and Suicide-Related Behaviors in Iraq and Afghanistan War Veterans in VA Care 2010–2011. Drugs—Real World Outcomes. 2016;3: 45–52. pmid:27073756
  35. 35. Anderson BJ, Dare T. We need to confirm, not relearn old information. Pediatr Anesth. 2014;24: 549–552. pmid:24809836
  36. 36. Zedler B, Xie L, Wang L, Joyce A, Vick C, Kariburyo F, et al. Risk factors for serious prescription opioid-related toxicity or overdose among Veterans Health Administration patients. Pain Med Malden Mass. 2014;15: 1911–1929. pmid:24931395
  37. 37. Sun EC, Dixit A, Humphreys K, Darnall BD, Baker LC, Mackey S. Association between concurrent use of prescription opioids and benzodiazepines and overdose: retrospective analysis. The BMJ. 2017;356. pmid:28292769
  38. 38. Jones CM, McAninch JK. Emergency Department Visits and Overdose Deaths From Combined Use of Opioids and Benzodiazepines. Am J Prev Med. 2015;49: 493–501. pmid:26143953
  39. 39. Dunn KM, Saunders KW, Rutter CM, Banta-Green CJ, Merrill JO, Sullivan MD, et al. Opioid Prescriptions for Chronic Pain and OverdoseA Cohort Study. Ann Intern Med. 2010;152: 85–92. pmid:20083827
  40. 40. Park TW, Saitz R, Ganoczy D, Ilgen MA, Bohnert ASB. Benzodiazepine prescribing patterns and deaths from drug overdose among US veterans receiving opioid analgesics: case-cohort study. The BMJ. 2015;350. pmid:26063215
  41. 41. Yang Z, Wilsey B, Bohm M, Weyrich M, Roy K, Ritley D, et al. Defining risk of prescription opioid overdose: pharmacy shopping and overlapping prescriptions among long-term opioid users in medicaid. J Pain Off J Am Pain Soc. 2015;16: 445–453. pmid:25681095
  42. 42. Yoon JR, Jeon Y, Yoo Y, Shin HJ, Ahn JH, Lim CH. The analgesic effect of remifentanil on prevention of withdrawal response associated with the injection of rocuronium in children: no evidence for a peripheral action. J Int Med Res. 2010;38: 1795–1800. pmid:21309495
  43. 43. Management of Concussion/mTBI Working Group. VA/DoD Clinical Practice Guideline for Management of Concussion/Mild Traumatic Brain Injury. J Rehabil Res Dev. 2009;46: CP1–68. pmid:20108447
  44. 44. Pa R, Jh G. Optimising drug treatment for elderly people: the prescribing cascade. BMJ. 1997;315: 1096–1099. pmid:9366745
  45. 45. Seal KH, Bertenthal D, Miner CR, Sen S, Marmar C. Bringing the War Back Home: Mental Health Disorders Among 103 788 US Veterans Returning From Iraq and Afghanistan Seen at Department of Veterans Affairs Facilities. Arch Intern Med. 2007;167: 476–482. pmid:17353495
  46. 46. VA/DoD Clinical Practice Guideline. Managment of Post-Traumatic Stress Disorder [Internet]. Washington DC; 2010 pp. 1–254.
  47. 47. Bohnert ASB, McCarthy JF, Ignacio RV, Ilgen MA, Eisenberg A, Blow FC. Misclassification of suicide deaths: examining the psychiatric history of overdose decedents. Inj Prev J Int Soc Child Adolesc Inj Prev. 2013;19: 326–330. pmid:23322257
  48. 48. Copeland LA, Finley EP, Bollinger MJ, Amuan ME, Pugh MJV. Comorbidity Correlates of Death Among New Veterans of Iraq and Afghanistan Deployment. Med Care. 2016;54: 1078–1081 pmid:27367868
  49. 49. Kripke DF. Mortality Risk of Hypnotics: Strengths and Limits of Evidence. Drug Saf. 2016;39: 93–107. pmid:26563222
  50. 50. Tjagvad C, Clausen T, Handal M, Skurtveit S. Benzodiazepine prescription for patients in treatment for drug use disorders: a nationwide cohort study in Denmark, 2000–2010. BMC Psychiatry. 2016;16. pmid:27234965
  51. 51. Malcolm R, Brady KT, Johnston AL, Cunningham M. Types of benzodiazepines abused by chemically dependent inpatients. J Psychoactive Drugs. 1993;25: 315–319. pmid:7907366
  52. 52. Weaver MF. Prescription Sedative Misuse and Abuse. Yale J Biol Med. 2015;88: 247–256. pmid:26339207
  53. 53. Hajak G, Müller WE, Wittchen HU, Pittrow D, Kirch W. Abuse and dependence potential for the non-benzodiazepine hypnotics zolpidem and zopiclone: a review of case reports and epidemiological data. Addiction. 2003;98: 1371–1378. pmid:14519173
  54. 54. Licata SC, Rowlett JK. Abuse and dependence liability of benzodiazepine-type drugs: GABAA receptor modulation and beyond. Pharmacol Biochem Behav. 2008;90: 74–89. pmid:18295321
  55. 55. Schutte-Rodin S, Broch L, Buysse D, Dorsey C, Sateia M. Clinical Guideline for the Evaluation and Management of Chronic Insomnia in Adults. J Clin Sleep Med JCSM Off Publ Am Acad Sleep Med. 2008;4: 487–504.
  56. 56. Morin CM, Bootzin RR, Buysse DJ, Edinger JD, Espie CA, Lichstein KL. Psychological and behavioral treatment of insomnia:update of the recent evidence (1998–2004). Sleep. 2006;29: 1398–1414. pmid:17162986
  57. 57. Morgenthaler T, Kramer M, Alessi C, Friedman L, Boehlecke B, Brown T, et al. Practice parameters for the psychological and behavioral treatment of insomnia: an update. An american academy of sleep medicine report. Sleep. 2006;29: 1415–1419. pmid:17162987
  58. 58. Qaseem A, Kansagara D, Forciea MA, Cooke M, Denberg TD, for the Clinical Guidelines Committee of the American College of Physicians. Management of Chronic Insomnia Disorder in Adults: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2016;165: 125. pmid:27136449
  59. 59. Ho FY-Y, Chung K-F, Yeung W-F, Ng TH, Kwan K-S, Yung K-P, et al. Self-help cognitive-behavioral therapy for insomnia: a meta-analysis of randomized controlled trials. Sleep Med Rev. 2015;19: 17–28. pmid:25104471
  60. 60. Ye Y-Y, Chen N-K, Chen J, Liu J, Lin L, Liu Y-Z, et al. Internet-based cognitive-behavioural therapy for insomnia (ICBT-i): a meta-analysis of randomised controlled trials. BMJ Open. 2016;6: e010707. pmid:27903557
  61. 61. Vincent N, Walsh K. Stepped Care for Insomnia: An Evaluation of Implementation in Routine Practice. J Clin Sleep Med JCSM Off Publ Am Acad Sleep Med. 2013;9: 227–234. pmid:23493468
  62. 62. Blom K, Jernelöv S, Rück C, Lindefors N, Kaldo V. Three-Year Follow-Up of Insomnia and Hypnotics after Controlled Internet Treatment for Insomnia. Sleep. 2016;39: 1267–1274. pmid:27091535
  63. 63. Buysse DJ. Insomnia. JAMA. 2013;309: 706–716. pmid:23423416
  64. 64. Morin CM, Bootzin RR, Buysse DJ, Edinger JD, Espie CA, Lichstein KL. Psychological and behavioral treatment of insomnia:update of the recent evidence (1998–2004). Sleep. 2006;29: 1398–1414. pmid:17162986
  65. 65. Seyffert M, Lagisetty P, Landgraf J, Chopra V, Pfeiffer PN, Conte ML, et al. Internet-Delivered Cognitive Behavioral Therapy to Treat Insomnia: A Systematic Review and Meta-Analysis. PLoS ONE. 2016;11. pmid:26867139