Economic Burden and Managed Care Considerations for the Treatment of Insomnia

Insomnia is a common sleep disorder in adults that can have many negative health impacts. The aggregate total of direct and indirect insomnia healthcare costs has been estimated to be as high as $100 billion US dollars per year. In addition to the societal cost burden, insomnia also negatively affects patients’ quality of life (QOL), including social and occupational functioning or productivity as well as impaired cognition or mood. Insomnia may also exacerbate and increase morbidity and complications from psychological disorders, such as depression, as well as have serious consequences, such as increased risk of suicide. Comorbidities, medications, and/or psychosocial contributors may negatively influence QOL. Many medications for the treatment of insomnia have adverse effect (AE) profiles that increase the risk of falls and related injuries, cognitive impairment, and motor vehicle accidents. These AEs place additional burden on the already vulnerable older adult population and those with comorbidities. Managed care organizations must evaluate clinical considerations, including safety profiles and the negative impact of disease on patients’ QOL, to develop strategies for cost-effective treatment plans for patients with insomnia and to ensure appropriate use of these medications.

Am J Manag Care. 2020;26:S91-S96. https://doi.org/10.37765/ajmc.2020.43008Introduction

Insomnia is defined by the American Academy of Sleep Medicine (AASM) Clinical Practice Guidelines as a complaint of sleep associated with daytime consequences that are not attributable to environmental circumstances or inadequate opportunity to sleep.¹ When evaluating the economic burden of insomnia, it is important to consider both direct costs (eg, office visits, medication costs, testing) as well as indirect costs, which result in lost resources (eg, absenteeism, presenteeism, work- and non—work-related accidents).¹ Estimating healthcare costs of untreated insomnia has been both difficult and varying due to contributing comorbid conditions, limited studies that differentiate primary versus comorbid insomnia, the significant percentage of patients who self-medicate, and difficulty in accurately quantifying indirect costs.²

Direct and Indirect Costs of Insomnia

The direct costs of patients with untreated insomnia have been shown to be significantly higher when compared with those of patients without insomnia. One retrospective study aimed to better understand the direct healthcare costs of insomnia by analyzing claims from a large health plan. Anderson and colleagues found that a diagnosis of insomnia was associated with 26% higher costs at baseline and 46% higher costs at 12 months after diagnosis. When comorbidities were recognized, the insomnia cohort had 80% higher costs, on average, than the matched control cohort. The insomnia cohort experienced greater general health decline as measured by increases in Charlson Comorbidity Index scores, as well as by greater proportion of patients with mental health diagnoses and use of psychiatric medications, which were drivers in the increase in overall cost.³

A recent study evaluated the economic consequences of untreated insomnia using a sample of claims data obtained from the CMS Chronic Conditions Data Warehouse (CCW); it included all-cause inpatient and outpatient visits, emergency department (ED) visits, nursing home stays, prescription medication use, and all-cause costs. The study found that patients with insomnia had higher rates of healthcare resource utilization (HRU) in all points of service locations evaluated, with HRU being highest for inpatient care (rate ratio [RR], 1.61; 95% CI, 1.59-1.64) and lowest for prescription fills (RR, 1.17; 95% CI, 1.16-1.17).⁴ Similarly, when compared with controls, patients with insomnia demonstrated $63,607 (95% CI, $60,532-$66,685) higher all-cause costs, which were driven primarily by inpatient care ($60,900; 95% CI, $56,609-$65,191).⁴ Further, Wickwire et al estimated that total costs of untreated insomnia may be as high as $100 billion US dollars per year, with a majority of costs being indirect. These indirect costs include not only inpatient admissions, but also ED visits, days hospitalized, and outpatient provider visits.⁵

As insomnia is associated with daytime sleepiness, fatigue, psychomotor deficits, and mood dysregulation, it may be expected to have negative impacts on US workers. Studies have demonstrated the impact of insomnia on impaired workplace functioning, including absenteeism due to sickness, injuries, and disability.⁶ Insomnia is a risk factor for workplace accidents and increased risk of associated falls and injuries, such as hip fractures.⁷ The American Insomnia Survey of 4991 respondents revealed that the average costs of insomnia-related accidents and errors are $32,062; these costs were significantly higher than those of other accidents and errors not associated with insomnia ($21,914). Simulations associated insomnia with an estimated 7.2% of all costly workplace accidents and errors, and with 23.7% of the total costs of overall incidents. Annualized US population projected estimates of 274,000 insomnia-related workplace accidents and errors had a combined value of $31.1 billion.⁶

Insomnia has been shown to have substantial burdens on the US workforce. After evaluating a sample of more than 7000 employed health plan subscribers via the Brief Insomnia Questionnaire, Kessler and colleagues found that the prevalence of insomnia was more than 23%, with an annualized individual-level association of insomnia with presenteeism equivalent to 11.3 days of lost work performance, accounting for $2280 of individual-level lost capital. When generalizing to the US workforce, this approximates to an annualized population-level estimate of more than 252 days and $63.2 billion per year in lost productivity resulting from insomnia.⁸ In a study that evaluated the results of a US National Health and Wellness survey, patients with anxiety who experienced insomnia characterized by nighttime awakenings reported 3.0 more provider visits in the past 12 months compared with those without chronic insomnia, 15.8% greater work impairment (among full-time employed), and 20.4% greater activity impairment (P <.001 for all). Patients with depression who experienced insomnia characterized by nighttime awakenings reported 2.4 more provider visits, 13.2% greater work impairment, and 18.2% greater activity impairment (P <.001 for all).⁹

Healthcare costs may also be higher in those with more severe insomnia. A retrospective study linking health claims data with a telephone survey of health plan members sought to compare the association between insomnia severity (using the Insomnia Severity Index) and healthcare productivity and cost. It found that, compared with the group without insomnia, mean total healthcare costs were 75% higher in the group with moderate to severe insomnia ($1323 vs $757; P <.05) and mean lost productivity costs were 33% greater for the subthreshold insomnia group ($1352 vs $1013; P <.001). Healthcare cost trend drivers were chronic medical and psychiatric comorbidities. Similarly, lost productivity costs were 72% greater in the moderate to severe insomnia group compared with the group without insomnia ($1739 vs $1013; P <.001).¹⁰

Effect on Quality of Life

The societal burden of insomnia is not limited to economic impacts. It also has profound effects on quality of life (QOL). Insomnia is more prevalent in psychiatrically and medically ill patients and is associated with numerous negative health outcomes.¹

An estimated 85% to 90% of chronic insomnia is attributed to comorbidities, which may have a substantial impact on QOL.¹¹ Insomnia occurs prior to and represents a risk factor for new-onset depression, and it has been suggested that treatment of insomnia may improve depression.¹² Many patients with depression attribute their inability to obtain an adequate amount of nighttime sleep to low daytime functioning (including poor concentration and memory), decreased reaction time and coordination, fatigue, mood disturbance, and anxiety.¹¹ Decreased sleep levels may contribute to impulsivity and may increase unplanned suicidal behaviors, and therefore should be considered as a potential therapeutic target.¹³ Patients with chronic obstructive pulmonary disease who had insomnia were found to have a poorer QOL.¹⁴ Military members returning from combat with posttraumatic stress disorder report insomnia as their most common symptom.¹⁵ Insomnia is a common symptom of patients with cancer and is associated with increased depression, pain, and tiredness.¹⁶ Insomnia has also been associated with increased risk for incident hypertension.¹⁷ When developing an insomnia treatment plan, it is important to consider treatment of comorbidities that may be exacerbating insomnia symptoms as well as potential benefits of possibly improving comorbidities in order to improve overall QOL.

Limited studies have assessed specific treatment plans and measurement of effect on QOL. Both behavioral and pharmacologic interventions may be considered in a treatment plan.¹ The American College of Physicians as well as the AASM recommend the use of cognitive behavior therapy for insomnia (CBTI) as first-line treatment for insomnia.¹⁸ CBTI generally consists of 4 to 7 therapy sessions and has been found to be as effective as medication treatment in the short term.^1,18 The majority of available studies evaluating pharmacotherapy treatments on QOL—including zolpidem, zopiclone, and eszopiclone&mdash;have demonstrated positive impact on patients’ perceptions of QOL.⁵

Using the Medical Outcomes Study 8-item Short-Form Survey (SF-8), Bolge and colleagues found that patients with anxiety and depression as well as insomnia had impaired QOL. Responses from the US National Health and Wellness survey revealed that patients with depression and chronic insomnia had SF-8 physical component summary scores that were 5.2 points lower and SF-8 mental component summary scores that were 7.0 points lower than those of patients without insomnia. SF-8 physical component summary scores were 5.9 points lower and SF-8 mental component summary scores were 7.9 points lower for patients with anxiety and chronic insomnia than for those without insomnia (P <.001 for all).⁹

Considerations for Vulnerable Populations

Older adults have an increased risk of insomnia due to comorbid medical conditions.^1,7 It is important to consider the adverse effect (AE) profiles of insomnia treatments and associated risks for this patient population when evaluating whether treatment is appropriate and making appropriate recommendations for pharmacotherapy.

The American Geriatrics Society Beers Criteria recommend against benzodiazepine use in older adults due to known increased risk of cognitive impairment, delirium, falls, fractures, and motor vehicle accidents.¹⁹ The criteria also recommend avoiding use of nonbenzodiazepine GABA-A receptor agonist hypnotics (such as eszopiclone, zolpidem, and zaleplon) as they have AEs similar to those of benzodiazepines and are also associated with increased ED visits and hospitalizations with minimal improvement of sleep latency and duration.¹⁹

The treatment of choice for older adults, rather than pharmacologic therapy, is CBTI. However, for patients who require pharmacologic therapy, careful attention must be given with regard to dose and drug, as older adults may experience slower drug metabolism. This can result in older patients being vulnerable to AEs, particularly related to age-related deficits, such as gait instability, sedation, and cognitive dysfunction. In addition to increased risk of AEs, the literature has also documented possible links of hypnotics to infection, depression, and overall mortality risks that are most frequently observed in the older adult population.¹ Older patients—who commonly experience declining renal function&mdash;are also at increased risk of prolonged drug exposure to hypnotics due to reduced metabolism and/or excretion. The risks of hypnotics increase when used in patients with comorbidities, such as Alzheimer disease; when used at dose levels higher than those recommended; or when combined with other psychoactive medications.¹ Clinicians should be cautious and warn patients of risks of hypnotics regarding sedation, especially with agents with longer half-lives or intended long-term use, such as extended-release zolpidem, eszopiclone, and temazepam.¹ Due to the risks of hypnotic agents and the potential of drug—drug interactions for patients with comorbidities whose current medication profile includes medications that may be sedating or increase the risk of AE occurrence, it is important to weigh medication safety profiles when evaluating initial insomnia treatment for vulnerable patient populations.

Cost-Effectiveness of Insomnia Treatment

Evaluating the cost-effectiveness of medications is a primary focus when making appropriate recommendations for treatment of insomnia. A large number of study designs have aimed to compare the cost-effectiveness of insomnia treatments using quality-adjusted life-years (QALYs). This measure is meant to determine both survival and QOL by incorporating a utility score of health-related QOL (HRQOL), such as the Medical Outcomes Study 36-item Short-Form (SF-36), which is often used in insomnia cost-effectiveness studies. If the QALY is 1, that suggests 1 year of perfect health, with 0 representing death. The ratio of $50,000 to $150,000 per QALY gained by using an intervention has been a commonly accepted threshold for cost-effectiveness in the United States. Varying models have been used to measure QALY in relation to direct and indirect costs, including absenteeism, presenteeism, and fall-related costs.⁵

The first study to evaluate cost-effectiveness of insomnia pharmacotherapy treatment examined the cost-effectiveness of 6-month duration nightly eszopiclone. The study used previously published data and claims information from a payer database with more than 5 million enrollees. The study incorporated both direct costs from the payer perspective, including prescription costs, dispensing fees, and 1 physician visit, in addition to indirect costs, such as days-out-of-role (including worker compensation and disability) and presenteeism costs (using averages from previously published data). Patients receiving eszopiclone were 2.5 times more likely than those receiving placebo to have remitted from insomnia (95% CI, approximately 1.75-3.60).²⁰ The total 6-month cost of insomnia due to lost productivity time, including absenteeism and presenteeism, was found to be $1091 per person (or $182 per person per month). Presenteeism occurs when an employee does not miss work, but is unable to work to their full productivity. Many patients with insomnia report impairment in next-day functioning and alertness. Absenteeism occurs when an employee is unable to work due to issues associated with the disease state, which has an effect on overall productivity.²⁰ Treatment with eszopiclone was associated with a total cost of $497.15 per person over 6 months (including physician visit, drug costs, and time taken for physician visit). However, when incorporating total savings from indirect and direct costs of treatment, the net cost of eszopiclone therapy was $67.83 per person over 6 months. The incremental cost, including direct and indirect costs, per QALY gained was $9930 relative to placebo.²⁰ The study found 6-month treatment with eszopiclone for adults to be cost-effective when accounting for indirect costs.

Another study evaluated the use of many insomnia medications on reduction of healthcare costs from the payer perspective using a medical claims database of more than 55 million covered lives. Healthcare costs included physician visits, hospitalizations, ED visits, and prescription drugs (excluding insomnia medications). The unadjusted mean reduction in per-person total health costs for pharmacotherapy treatment of insomnia was $1100.^20,21 The medications that showed the greatest impact on per person per year (PPPY) cost savings when using total sleep time as the primary value of efficacy were low-dose trazodone at $1022 PPPY (95% CI, —$1151 to –$894), zolpidem at $1158 PPPY (95% CI, –$1281 to –$1036), and zolpidem extended-release at $2573 PPPY (95% CI, –$3681 to –$1465).²¹ Of note, ramelteon was predicted to increase costs by $763 PPPY (95% CI, —$641 to $2125).²¹ The study did not evaluate indirect costs or impact on QOL.

The most encompassing evaluation of pharmacotherapy cost-effectiveness included efficacy data from a previous study on eszopiclone and costs data from a claims database. HRQOL was measured using the SF-36. Direct healthcare costs included medication use, physician visits, the wholesale price of eszopiclone, and dispensing fees. Indirect costs, such as days-out-of-role, were measured using absences, disability, and worker compensation. Presenteeism was included and measured using the Work Limited Questionnaire. Although treatment with eszopiclone resulted in a net cost increase of $67, eszopiclone showed a net gain of 0.0137 QALYs over placebo.²² Treatment with eszopiclone increased HRQOL with incremental cost per QALY of less than $5000.²² When absenteeism and presenteeism costs were excluded, the cost-effectiveness ratio increased to $33,000 per QALY gained, which is below the common threshold of $50,000 used to determine cost-effectiveness.²²

A more recent 2019 study evaluated the economic aspects of insomnia and insomnia medication treatment among a nationally representative sample of older adult Medicare beneficiaries using claims from the CMS CCW between 2006 and 2013. The study evaluated HRU and costs in the year following insomnia diagnosis. No significant differences in pre- and postdiagnosis costs were found between individuals who received insomnia medication treatment and those who were untreated.⁴ However, this study did not account for impact on QOL or potential indirect costs, possibly due to being limited to the Medicare population and likely minimal impact on the US workforce.

Application of Clinical Practice Guidelines and Managed Care Considerations

The 2017 AASM guideline recommends CBTI as first-line treatment for insomnia.^1,23 Nonpharmacologic treatment with CBTI is effective for adults, as demonstrated in many studies.²³ When pharmacologic intervention is recommended, the AASM recommends all pharmacotherapy treatment with a “WEAK” recommendation rating. The “WEAK” rating denotes less of a degree of certainty that the recommendation should apply to all patients both in outcomes and appropriateness, but it does not necessarily denote ineffectiveness of the treatment option. The AASM states that the recommendations were downgraded due to the lack of quality data in the literature regarding efficacy, treatment-emergent AEs, and outcomes.¹ Managed care decision makers must consider the safety and potential harm associated with pharmacologic use, especially in the vulnerable patient populations previously mentioned.

The Table^24-35 shows currently available insomnia medications. Given the varying differences in cost among insomnia agents and recommendations outlined by the AASM, managed care organizations may want to take additional measures to ensure appropriate use of high-cost insomnia medications for those patients most likely to benefit from therapy. Additional measures may also be considered for patients, such as older adults, who are most likely to experience negative effects due to the AE profile of these agents. HRU management programs or clinical pathway protocols should guide providers to begin with CBTI for all patients. If pharmacologic therapy is warranted, dosing and drug choice selection should be guided by age, comorbidities, and potential fall risk or next-day sedation. In addition, therapy should not be continued indefinitely, and patients should be reevaluated often to ensure that the benefit of the pharmacologic therapy is not outweighing any potential risk from the medication.

Step Therapies, Age Screening, and Quantity Limits

Step therapies require utilizing a clinically effective prescription prior to trying a medication with less evidence of clinical effectiveness or higher cost.³⁶ Step therapies may be considered for moderate- to high-cost agents to ensure that cost-effective or safer alternatives are being used before initiating agents that are even more costly or associated with greater risks. Step therapies may also incorporate the consideration of age, for older adults, to ensure that safer alternatives are used first. Step therapies do not require a high payer burden, as they do not require manual review and are incorporated into the electronic claims adjudication system. However, step therapies may still delay treatment if a provider is unaware of the step therapy requirements. Best practices recommend that payers provide rejection messages with an included list of required step 1 agents at point of sale at the pharmacy to decrease delay to treatment. This may result in primary medication nonadherence, in which a patient never receives treatment for insomnia, despite obtaining a prescription from their provider.

Age screening edits are an important tool for managed care professionals to utilize to help ensure appropriate use of insomnia medications with minimal patient disruption. Particularly in patients older than 65 years, the Beers criteria recommend against the use of benzodiazepines due to increased risks, and they recommend a short maximum duration (less than 90 days) for the newer-generation nonbenzodiazepine GABA-A receptor agonists.

Limiting the quantity of medication prescribed in a given timeframe may be considered to ensure that agents that are approved for short-term use are not being used for longer periods without proper physician evaluation. Quantity limits may also ensure appropriate dosing, especially for medications with recommended starting dosages for older adults and maximum daily doses.

Prior Authorizations

Prior authorizations may be considered for the highest-cost agents to ensure appropriate use. Despite the costs for payers that are associated with providing the clinical support and resources to review prior authorizations, the delay in treatment therapy for patients, and the administration burden for prescribers, managed care organizations may want to review additional documentation from patients’ prescribers to ensure that these agents are being reserved for those who are most likely to benefit from therapy.³⁷ Managed care organizations developing coverage criteria may consider the following general requirements, then present them for approval to the organization’s Pharmacy and Therapeutics Committee:

• Diagnosis of chronic insomnia lasting at least 3 months
• Potential underlying causes of insomnia have been addressed
• Patient has tried and failed sleep hygiene practices or CBTI
• Lower-cost alternatives were already tried and failed OR specific patient factors explain why cost-effective alternatives are not appropriate
• Patient is being evaluated by a provider every 6 to 12 months to attest that benefit of treatment continues to outweigh risk and that patient is benefiting from therapy

Conclusions

Insomnia is prevalent among adults, results in high HRU costs, and negatively impacts patients’ QOL. Untreated insomnia is associated with higher healthcare costs, largely attributed to indirect costs that include absenteeism, presenteeism, and work-related accidents and errors. The severity of insomnia has been shown to have a direct correlation to healthcare costs. The AASM recommends CBTI and sleep hygiene practices as first-line treatment for insomnia. Additionally, the AASM provides “WEAK” strength of recommendations for the use of all pharmacologic treatments for insomnia, mostly due to lack of quality data in the peer-reviewed literature. The Beers Criteria recommend avoiding hypnotic medications for insomnia in the elderly population due to potential AEs, including cognitive impairment, delirium, falls, fractures, and motor vehicle accidents. These agents are sedating and pose increased risk for vulnerable patient populations who are at increased fall risk and have an increased sensitivity to AE profiles. The benefits of treating insomnia, such as improved QOL, must be weighed against potential risks of these agents. Managed care decision makers may want to implement HRU strategies to ensure safe, appropriate, cost-effective use

for patients.&ensp;

Author affiliation: Patty Taddei-Allen, PharmD, MBA, BCACP, BCGP, is a senior director, Clinical Analytics, WellDyne, Lakeland, FL; and a clinical assistant professor, University of Florida College of Pharmacy, Gainesville, FL.

Funding source: This activity is supported by an educational grant from Eisai.

Author disclosure: Dr Taddei-Allen has the following relevant financial relationship with a commercial interest to disclose:

• Advisory Board Member — Novo Nordisk

Authorship information: Substantial contributions to the intellectual content including concept and design, analysis and interpretation of data, drafting of the manuscript, and critical revision of the manuscript for intellectual content.

Address correspondence to: ptaddei-allen@welldyne.com.

Medical writing and editorial support provided by: Jenna Wood, PharmD.

1. Sateia MJ, Buysse DJ, Krystal AD, Neubauer DN, Heald JL. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2017;13(2):307-349. doi: 10.5664/jcsm.6470.
2. Daley M, Morin CM, LeBlanc M, Grégoire JP, Savard J. The economic burden of insomnia: direct and indirect costs for individuals with insomnia syndrome, insomnia symptoms, and good sleepers. Sleep. 2009;32(1):55-64.
3. Anderson LH, Whitebird RR, Schultz J, McEvoy CE, Kreitzer MJ, Gross CR. Healthcare utilization and costs in persons with insomnia in a managed care population. Am J Manag Care. 2014;20(5):e157-e165.
4. Wickwire EM, Tom SE, Scharf SM, Vadlamani V, Bulatao IG, Albrecht JS. Untreated insomnia increases all-cause health care utilization and costs among Medicare beneficiaries. Sleep. 2019;42(4). pii: zsz007. doi: 10.1093/sleep.zsz007.
5. Wickwire EM, Shaya FT, Scharf SM. Health economics of insomnia treatments: the return on investment for a good night’s sleep. Sleep Med Rev. 2016;30:72-82. doi: 10.1016/j.smrv.2015.11.004.
6. Shahly V, Berglund PA, Coulouvrat C, et al. The associations of insomnia with costly workplace accidents and errors: results from the America Insomnia Survey. Arch Gen Psychiatry. 2012;69(10):1054-1063. doi: 10.1001/archgenpsychiatry.2011.2188.
7. Wade AG. The societal costs of insomnia. Neuropsychiatr Dis Treat. 2010;7:1-18. doi: 10.2147/NDT.S15123.
8. Kessler RC, Berglund PA, Coulouvrat C, et al. Insomnia and the performance of US workers: results from the America insomnia survey [published corrections appear in Sleep. 2011;34(11):1608; and Sleep. 2012;35(6):725]. Sleep. 2011;34(9):1161-1171. doi: 10.5665/SLEEP.1230.
9. Bolge SC, Joish VN, Balkrishnan R, Kannan H, Drake CL. Burden of chronic sleep maintenance insomnia characterized by nighttime awakenings among anxiety and depression sufferers: results of a national survey. Prim Care Companion J Clin Psychiatry. 2010;12(2). pii: PCC.09m00824. doi: 10.4088/PCC.09m00824gry.
10. Sarsour K, Kalsekar A, Swindle R, Foley K, Walsh JK. The association between insomnia severity and healthcare and productivity costs in a health plan sample. Sleep. 2011;34(4):443-450. doi: 10.1093/sleep/34.4.443.
11. Ishak WW, Bagot K, Thomas S, et al. Quality of life in patients suffering from insomnia. Innov Clin Neurosci. 2012;9(10):13-26.
12. Li L, Wu C, Gan Y, Qu X, Lu Z. Insomnia and the risk of depression: a meta-analysis of prospective cohort studies. BMC Psychiatry. 2016;16(1):375. doi: 10.1186/s12888-016-1075-3.
13. Porras-Segovia A, Pérez-Rodríguez M, López-Esteban P, et al. Contribution of sleep deprivation to suicidal behaviour: a systematic review. Sleep Med Rev. 2019;44:37-47. doi: 10.1016/j.smrv.2018.12.005.
14. Budhiraja R, Parthasarathy S, Budhiraja P, Habib MP, Wendel C, Quan SF. Insomnia in patients with COPD. Sleep. 2012;35(3):369-375. doi: 10.5665/sleep.1698.
15. McLay RN, Klam WP, Volkert SL. Insomnia is the most commonly reported symptom and predicts other symptoms of post-traumatic stress disorder in U.S. service members returning from military deployments. Mil Med. 2010;175(10):759-762. doi: 10.7205/milmed-d-10-00193.
16. Davis MP, Khoshknabi D, Walsh D, Lagman R, Platt A. Insomnia in patients with advanced cancer. Am J Hosp Palliat Care. 2014;31(4):365-373. doi: 10.1177/1049909113485804.
17. Fernandez-Mendoza J, Vgontzas AN, Liao D, et al. Insomnia with objective short sleep duration and incident hypertension: the Penn State Cohort. Hypertension. 2012;60(4):929-935. doi: 10.1161/HYPERTENSIONAHA.112.193268.
18. Krystal AD, Prather AA, Ashbrook LH. The assessment and management of insomnia: an update. World Psychiatry. 2019;18(3):337-352. doi: 10.1002/wps.20674.
19. 2019 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society. 2019 Updated AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2019;67(4):674-694. doi: 10.1111/jgs.15767.
20. Botteman MF, Ozminkowski RJ, Wang S, Pashos CL, Schaefer K, Foley DJ. Cost effectiveness of long-term treatment with eszopiclone for primary insomnia in adults: a decision analytical model. CNS Drugs. 2007;21(4):319-334. doi: 10.2165/00023210-200721040-00005.
21. Jhaveri M, Seal B, Pollack M, Wertz D. Will insomnia treatments produce overall cost savings to commercial managed-care plans? a predictive analysis in the United States. Curr Med Res Opin. 2007;23(6):1431-1443. doi: 10.1185/030079907X199619.
22. Snedecor SJ, Botteman MF, Bojke C, Schaefer K, Barry N, Pickard AS. Cost-effectiveness of eszopiclone for the treatment of adults with primary chronic insomnia. Sleep. 2009;32(6):817-824. doi: 10.1093/sleep/32.6.817.
23. Gooneratne NS, Vitiello MV. Sleep in older adults: normative changes, sleep disorders, and treatment options. Clin Geriatr Med. 2014;30(3):591-627. doi: 10.1016/j.cger.2014.04.007.
24. Halcion [prescribing information]. New York, NY: Pfizer Inc; 2019. labeling.pfizer.com/ShowLabeling.aspx?format=PDF&id=586. Accessed March 2, 2020.
25. Restoril [prescribing information]. Hazelwood, MO: Mallinckrodt Inc; 2016. accessdata.fda.gov/drugsatfda_docs/label/2016/018163s064lbl.pdf. Accessed March 2, 2020.
26. Sonata [prescribing information]. Bristol, TN: King Pharmaceuticals, Inc; 2013. fda.gov/media/85713/download. Accessed March 2, 2020.
27. Belsomra [prescribing information]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp; 2020. merck.com/product/usa/pi_circulars/b/belsomra/belsomra_pi.pdf. Accessed March 2, 2020.
28. Desyrel [prescribing information]. Locust Valley, NY: Pragma Pharmaceuticals; 2017. accessdata.fda.gov/drugsatfda_docs/label/2017/018207s032lbl.pdf. Accessed March 2, 2020.
29. Rozerem [prescribing information]. Deerfield, IL: Takeda Pharmaceuticals America, Inc; 2018. general.takedapharm.com/rozerempi/. Accessed March 2, 2020.
30. Sinequan [prescribing information]. New York, NY: Pfizer Inc; 2014. labeling.pfizer.com/ShowLabeling.aspx?id=1759. Accessed March 2, 2020.
31. Ambien [prescribing information]. Bridgewater, NJ: sanofi-aventis U.S. LLC; 2019. products.sanofi.us/ambien/Ambien.pdf. Accessed March 2, 2020.
32. Ambien CR [prescribing information]. Bridgewater, NJ: sanofi-aventis U.S. LLC; 2019. products.sanofi.us/ambien_cr/ambien_CR.pdf. Accessed March 2, 2020.
33. Intermezzo [prescribing information]. Pt. Richmond, CA: Transcept Pharmaceuticals, Inc; 2011. accessdata.fda.gov/drugsatfda_docs/label/2011/022328lbl.pdf. Accessed March 2, 2020.
34. Zolpimist [prescribing information]. Flemington, NJ: NovaDel Pharma Inc; 2019. myzolpimist.com/wp-content/uploads/2019/10/Zolpimist-Full-Prescribing-Information.pdf. Accessed March 2, 2020.
35. Lunesta [prescribing information]. Marlborough, MA: Sunovion Pharmaceuticals Inc; 2019. lunesta.com/PostedApprovedLabelingText.pdf. Accessed March 2, 2020.
36. Managed care pharmacy 101. AMCP (Academy of Managed Care Pharmacy) website. amcp.org/about/managed-care-pharmacy-101#MCP. Accessed January 1, 2020.
37. Balkrishnan R, Joish VN, Bhosle MJ, Rasu RS, Nahata MC. Prior authorization of newer insomnia medications in managed care: is it cost saving? J Clin Sleep Med. 2007;3(4):393-398.