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Home , Armodafinil, Idiopathic hypersomnia

Drug and Biologic Coverage Policy

Effective Date ...... 7/1/2020 Next Review Date… ...... 7/1/2021 Coverage Policy Number ...... 1501

Modafinil / for Individual and Family Plans

Table of Contents Related Coverage Resources

Coverage Policy ...... 1 Obstructive Apnea Treatment Services FDA Approved Indications ...... 2 Recommended Dosing ...... 3 General Background ...... 3 Coding/ Billing Information ...... 6 References ...... 6

INSTRUCTIONS FOR USE The following Coverage Policy applies to health benefit plans administered by Cigna Companies. Certain Cigna Companies and/or lines of business only provide utilization review services to clients and do not make coverage determinations. References to standard benefit plan language and coverage determinations do not apply to those clients. Coverage Policies are intended to provide guidance in interpreting certain standard benefit plans administered by Cigna Companies. Please note, the terms of a customer’s particular benefit plan document [Group Service Agreement, Evidence of Coverage, Certificate of Coverage, Summary Plan Description (SPD) or similar plan document] may differ significantly from the standard benefit plans upon which these Coverage Policies are based. For example, a customer’s benefit plan document may contain a specific exclusion related to a topic addressed in a Coverage Policy. In the event of a conflict, a customer’s benefit plan document always supersedes the information in the Coverage Policies. In the absence of a controlling federal or state coverage mandate, benefits are ultimately determined by the terms of the applicable benefit plan document. Coverage determinations in each specific instance require consideration of 1) the terms of the applicable benefit plan document in effect on the date of service; 2) any applicable laws/regulations; 3) any relevant collateral source materials including Coverage Policies and; 4) the specific facts of the particular situation. Coverage Policies relate exclusively to the administration of health benefit plans. Coverage Policies are not recommendations for treatment and should never be used as treatment guidelines. In certain markets, delegated vendor guidelines may be used to support medical necessity and other coverage determinations.

Coverage Policy

Modafinil (Provigil®) and armodafinil (Nuvigil®) are considered medically necessary when ALL of the following criteria are met: • Age 18 years of age and older • For the treatment of any of the following indications: o confirmed by (PSG) and Multiple Sleep Latency Test (MSLT) o Obstructive / hypopnea syndrome (OSAHS) confirmed by o (SWD) o related fatigue o Modafinil (Provigil) only: Parkinson’s disease related excessive daytime (EDS) AND used in combination with standard Parkinson’s therapy (for example, carbidopa-levodopa, , • Additional specific criteria apply for each drug below:

Drug Additional Specific Criteria Nuvigil • Documented intolerance to 1 generic formulation of Nuvigil AND • Documented intolerance to 1 generic formulation of modafinil Provigil • Documented intolerance to 1 generic formulation of Provigil AND

Page 1 of 8 Coverage Policy Number: 1501 • Documented intolerance to 1 generic formulation of armodafinil

Initial authorization is up to 12 months.

Modafinil (Provigil) and armodafinil (Nuvigil) are considered medically necessary for continued use when BOTH of the following criteria are met: • Initial criteria are met • Evidence of beneficial clinical response as submitted by the provider

Modafinil (Provigil) and armodafinil (Nuvigil) are considered experimental, investigational or unproven for ANY other use including the following: • Addiction, dependence and/or abstinence (including withdrawal symptoms) associated with substance abuse • Amyotrophic lateral sclerosis (ALS) • -induced • Attention-deficit hyperactivity disorder (ADHD) • Cognitive impairment associated with cancer • Fatigue associated with cancer • HIV/AIDS • Huntington’s disease • Major depressive disorder (MDD) • Multiple sclerosis- related nocturnal enuresis • Myotonic dystrophy • Postpoliomyelitis syndrome-related fatigue • Symptomatic or adjunctive treatment of bipolar • Under arousal related to traumatic brain injury

When coverage is available and medically necessary, the dosage, frequency, duration of therapy, and site of care should be reasonable, clinically appropriate, and supported by evidence-based literature and adjusted based upon severity, alternative available treatments, and previous response to therapy.

Note: Receipt of sample product does not satisfy any criteria requirements for coverage.

FDA Approved Indications

FDA Approved Indication Brand Name Approved Indication Provigil Provigil is indicated to improve in adult patients with excessive sleepiness associated with narcolepsy, (OSA), and shift work disorder (SWD).

Limitations of Use: In OSA, Provigil is indicated to treat excessive sleepiness and not as treatment for the underlying obstruction. If continuous positive airway pressure (CPAP) is the treatment of choice for a patient, a maximal effort to treat with CPAP for an adequate period of time should be made prior to initiating and during treatment with Provigil for excessive sleepiness. Nuvigil Nuvigil is indicated to improve wakefulness in adult patients with excessive sleepiness associated with obstructive sleep apnea (OSA), narcolepsy, or shift work disorder (SWD).

Limitations of Use:

Page 2 of 8 Coverage Policy Number: 1501 Brand Name Approved Indication In OSA, Nuvigil is indicated to treat excessive sleepiness and not as treatment for the underlying obstruction. If continuous positive airway pressure (CPAP) is the treatment of choice for a patient, a maximal effort to treat with CPAP for an adequate period of time should be made prior to initiating Nuvigil for excessive sleepiness.

Recommended Dosing

FDA Recommended Dosing Brand Name FDA Recommended Dosing Provigil Dosage in Narcolepsy and Obstructive Sleep Apnea (OSA): The recommended dosage of Provigil for patients with narcolepsy or OSA is 200 mg taken orally once a day as a single dose in the morning. Doses up to 400 mg/day, given as a single dose, have been well tolerated, but there is no consistent evidence that this dose confers additional benefit beyond that of the 200 mg/day dose.

Dosage in Shift Work Disorder (SWD): The recommended dosage of Provigil for patients with SWD is 200 mg taken orally once a day as a single dose approximately 1 hour prior to the start of their work shift Nuvigil Dosage in Obstructive Sleep Apnea (OSA) and Narcolepsy: The recommended dosage of Nuvigil for patients with OSA or narcolepsy is 150 mg to 250 mg taken orally once a day as a single dose in the morning. In patients with OSA, doses up to 250 mg/day, given as a single dose, have been well tolerated, but there is no consistent evidence that these doses confer additional benefit beyond that of the 150 mg/day dose.

Dosage in Shift Work Disorder (SWD): The recommended dosage of Nuvigil for patients with SWD is 150 mg taken orally once a day as a single dose approximately 1 hour prior to the start of their work shift.

Drug Availability Brand Name Drug Availability Provigil Provigil is available as 100 mg or 200 mg capsules. Nuvigil Nuvigil is available as 50 mg, 150 mg, 200 mg or 250 mg capsules.

General Background

Disease Overview Narcolepsy is a central disorder, primarily characterized by excessive daytime sleepiness and (sudden loss of muscular tone). The pathophysiology of narcolepsy involves intrusion of aspects of REM sleep (e.g., muscle atonia and ) into periods of wakefulness. (Billiard, 2011)

Obstructive sleep apnea (OSA) is a treatable form of sleep disordered breathing characterized by repetitive episodes of apnea, hypopnea, or respiratory effort related arousals (RERA) during sleep. Apnea may be obstructive, central, or mixed. Polysomnography is the collective process of monitoring and recording physiologic data during sleep. Patients with OSAHS often experience sleep fragmentation due to breathing fluctuations. The change in sleep often causes daytime sleepiness. Continuous positive airway pressure (CPAP) assists in improving oxygenation and indirectly improves sleep. However, some patients continue to experience daytime sleepiness with CPAP therapy. and modafinil have been studied to improve daytime sleepiness in the patients with OSAHS. (Young, 2004)

Page 3 of 8 Coverage Policy Number: 1501 Patients diagnosed with OSA receive education regarding the pathophysiology of OSA and the impact of lifestyle modifications, including weight loss, reduced alcohol consumption, especially at , and lateral sleeping position (vs. supine). While such noninvasive measures are encouraged, particularly in the obese or those with very poor , OSA does not usually resolve with these measures alone. Potential treatment options for OSA include treatment with positive airway pressure (PAP), the use of oral appliances, and surgical interventions. Treatment decisions are based on condition severity, the presence of comorbidities and complicating factors, and the patient’s tolerance and response to treatment. (Young, 2004)

Pharmacology Provigil and Nuvigil have wake-promoting actions similar to sympathomimetic agents including and , although their pharmacologic profile is not identical to that of the sympathomimetic amines. The specific mechanism(s) through which either drug supports wakefulness is not known. Armodafinil (R-modafinil) has pharmacological properties similar to those of modafinil (a mixture of R- and S-modafinil), to the extent tested in animal and in vitro studies. The R- and S-enantiomers have similar pharmacological actions in animals. (Clinical Pharmacology 2015)

Professional Societies/Organizations European Federation of Neurological Societies (EFNS) The EFNS recommends diagnosis of narcolepsy by first interviewing the patient and a full night polysomnography, directly followed by a multiple sleep latency test (MSLT). A follow up polysomnography would be warranted only if the patient has worsening symptoms or other symptoms occur, but not for the purposes of evaluating response to treatment. Modafinil is recommended for narcolepsy symptoms of excessive daytime sleepiness and irresistible episodes of sleep, but is not suggested for symptoms of poor sleep. The EFNS does mention, however, that some patients do report modafinil ameliorates poor sleep. (Billiard, 2011)

American Academy of (AAN) The American Academy of Neurology state modafinil should be considered for patients to improve their subjective perception of excessive daytime somnolence. The guidelines note that patients who are treated with modafinil may experience an improvement in sleep perception without an actual improvement in objective sleep measurements. (Zesiewicz, 2010) The etiology of Parkinson’s disease excessive daytime somnolence (EDS) may be the result of disease process, medications, or other sleep disorders. Two studies assessed the therapeutic efficacy of modafinil in the treatment of EDS in patients with Parkinson’s disease EDS. These studies found that modafinil improved EDS on a subjective level using the Epworth Sleepiness Score (ESS), however, there was no objective improvement in EDS as measured by the maintenance of wakefulness test or Multiple Sleep Latency Test. (Adler et al 2003, Hogl, 2002)

American Academy of (AASM) The American Academy of Sleep recommends modafinil for the treatment of residual excessive daytime sleepiness in OSA patients who have sleepiness despite effective PAP treatment and who are lacking any other identifiable cause for their sleepiness. (AASM, 2009) The AASM suggests several modalities for treating sleep disorders (CRSD). Suggested methods to treat shift work disorder include non- pharmaceutical approaches such as planning a sleep schedule and light exposure. Pharmaceutical treatments proposed include scheduled , hypnotics, and alerting agents such as modafinil. The AASM mentions that modafinil may be an option for daytime sleepiness due to Parkinson’s disease, multiple sclerosis, myotonic dystrophy or idiopathic . However, supporting data in are limited to case reports, retrospective series, and one small randomized trial. The organization is silent on the use of armodafinil. (Mayer, 2015 Morgenthaler 2008, Zesiewicz 2010)

American Psychiatric Association (APA) The APA published clinical practice guidelines in 2010 for the treatment of patients with major depressive disorder. The APA guidelines address many elements associated with treating major depressive disorder including augmentation therapy in patients who do not respond to initial therapy and potential treatments for side effects associated with antidepressant medications. Modafinil is mentioned in both aforementioned areas. The APA provides several recommendations, with varying levels of supporting evidence, for augmenting therapy in

Page 4 of 8 Coverage Policy Number: 1501 patients who have not responded fully to treatment. Modafinil is identified as a strategy with less evidence for efficacy and is provided a categorical rating equivalent to the lowest level of clinical confidence possible for a recommendation. (Gelenberg, 2010)

Department of Veterans Affairs (VA) / Department of Defense (DOD) The VA/DoD published clinical practice guidelines in 2016 for the treatment of patients with major depressive disorder. The VA/DoD guidelines address many aspects of treating major depressive disorder including the use of augmentation agents. Neither modafinil nor armodafinil are mentioned in the clinical practice guidelines. (VA/DoD, 2016)

National Comprehensive Cancer Network (NCCN) The NCCN published clinical practice guidelines in 2018 for the treatment of cancer related fatigue. The NCCN guidelines address the treatment of cancer related fatigue associated with many stages of cancer treatment including during active treatment, post-treatment, and end of life care. Modafinil is mentioned on several occasions throughout the guidelines however its use is not recommended for the treatment of cancer related fatigue during any stage of cancer treatment. (Berger, 2018)

The American Board of Internal Medicine’s (ABIM) Foundation Choosing Wisely® Initiative: No recommendations are available for modafinil or armodafinil.

Centers for Medicare & Medicaid Services - National Coverage Determinations (NCDs) There are no CMS National Coverage Determinations for modafinil or armodafinil.

Clinical Efficacy FDA Approved Indications Modafinil was compared to placebo in 6 published trials of wakefulness in narcolepsy where all patients were required to have objectively documented excessive daytime sleepiness. Therapeutic response to modafinil was superior to placebo, with little difference in adverse effects, in all clinical trials. No significant difference in efficacy was detected between modafinil 200 mg and 400 mg in the majority of clinical trials. Modafinil demonstrated superior efficacy for improving daytime wakefulness in patients with OSAHS compared to placebo in 3 published clinical trials. Patients suffering from SWD showed greater alertness and quality of life with modafinil therapy compared to placebo in 2 abstracts. (, 2015)

Armodafinil was studied in one 12 week trial of improving wakefulness in narcolepsy. Patients received either 150 mg or 250 mg of armodafinil or placebo. Both active drug regimens demonstrated a statistically significant enhanced ability to remain awake compared to placebo. The 250 mg dosage regimen produced a greater magnitude of effect. Armodafinil showed a statistically significant improvement in the ability to remain awake, as compared to placebo in 2 trials of patients with OSAHS, who received either 150 mg or 250 mg of armodafinil. No difference in efficacy was detected between the two dosing regimens. Patients experiencing SWD showed a statistically significant prolongation in time to compared to placebo in one 12 week trial. Patients with all conditions were reported to have improvement in their overall clinical condition. (Cephalon, 2017)

Off Label Uses AHFS Drug Information 2020 Edition does not support any off-label uses of Provigil (modafinil) or Nuvigil (armodafinil).

Experimental, Investigational, Unproven Uses Case series, randomized controlled trials, systematic reviews, and/or meta-analysis have investigated Provigil/ Nuvigil for numerous conditions/indications, including multiple sclerosis- related nocturnal enuresis (Carrieri, 2007), under arousal related to traumatic brain injury (Jha, 2008), fatigue associated with cancer (Jean-Pierre, 2010), amyotrophic lateral sclerosis (Rabkin, 2009), Huntington’s disease (Blackwell, 2008), HIV/AIDS (Rabkin, 2010), myotonic dystrophy (Orlikowski, 2009), Cognitive impairment associated with cancer (Boele, 2013), addiction, dependence and/ or abstinence (including withdrawal symptoms) associated with substance abuse (Joos, 2013), symptomatic or adjunctive treatment of bipolar depression (Frye, 2007), antipsychotic-induced Parkinsonism (Lohr, 2013) and fatigue associated with fibromyalgia (Schwartz, 2010).

Page 5 of 8 Coverage Policy Number: 1501

Studies in adults, adolescents and children have shown improvement in attention-deficit hyperactivity disorder (ADHD) symptoms, and various studies report the efficacy of modafinil similar to . In 2000, a phase III study conducted by Cephalon, Inc. demonstrated no benefit in decreasing ADHD symptoms in adults when modafinil was compared to placebo. Cephalon, Inc. submitted an NDA for pediatric ADHD in 2005, which led to review of safety data by the FDA Advisory Committee. Despite modafinil’s ability to treat ADHD in children and adolescents, safety signals such as a possible incident of Stevens-Johnson syndrome, psychiatric adverse reactions and lab abnormalities resulted in the drug not receiving approval for this indication. Further safety data was requested by the FDA. Cephalon, Inc. is no longer seeking a pediatric ADHD indication. (Biederman et al 2006, Goez et al 2012, Greenhill et al 2006, Swanson et al 2006, Clinical Pharmacology 2015)

Fatigue and sleepiness are common symptoms in major depressive disorder (MDD) patients. These symptoms can result in early discontinuation of treatment which may lead to inadequate treatment. Adjunct therapy to antidepressant therapy may be useful and also improve the Hamilton Rating Scale for Depression (HAM-D). This may be particularly important in patients who are non-responders or only partial responders to antidepressant therapy. Randomized controlled trials with modafinil have demonstrated limited short term benefit (for example, 2 weeks) for wakefulness and fatigue in these patients. In a few studies, an improvement in Clinical Global Impression of change (CGI-c) was noted to favor modafinil, however, there was no statistically significant differences noted with modafinil treatment versus placebo for HAM-D scores. In a multi-center randomized controlled trial, no significant differences were found between modafinil and placebo for daytime sleepiness measured by the rate of change in the (ESS) score from baseline to week 6 in patients with primary MDD initiating SSRI treatment (n = 72). In addition, the mean end point ESS scores were not statistically significantly between placebo and modafinil. In addition, modafinil was not statistically significant compared to placebo for secondary outcome measures of proportion of subjects achieving response for ESS score, Fatigue Severity Scale (FSS) score, Hamilton Depression Rating Scale or Montgomery-Asberg Depression Rating Scale (MADRS) score. These results suggest only a short-term benefit for wakefulness and fatigue in patients with MDD receiving adequate SSRI treatment. (Dunlop et al 2007, DeBattista et al 2003, Fava et al 2005, Clinical Pharmacology 2015)

Results of controlled studies and meta analyses do not indicate improvement in symptoms of postpoliomyelitis syndrome-related fatigue as compared to placebo, therefore, use in this condition is not supported by evidence. (Chan, 2006)

Coding/ Billing Information

Note: Modafinil and armodafinil are typically covered under pharmacy benefit plans. Certain prescription drugs require an authorization for coverage to ensure that appropriate treatment regimens are followed. Medical drug coding and diagnosis codes, however, are generally not required for pharmacy claims submissions, therefore, this section is not in use.

References

1. Adler CH et al. Randomized trial of modafinil for treating subjective daytime sleepiness in patients with Parkinson’s Disease. Mov Disord 2003 March; 18(3): 287-93 2. AASM. Adult Obstructive Sleep Apnea Task Force of the American Academy of Sleep Medicine. Clinical Guideline for the Evaluation, Management and Long-term Care of Obstructive Sleep Apnea in Adults. Journal of Clinical Sleep Medicine. J Clin Sleep Med. 2009 Jun 15; 5(3): 263–276. 3. Berger AM, Mooney K, Banerjee C, et al. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Cancer-Related Fatigue. Version 2.2018. 4. Biederman J, Swanson J, Wigal S et al. A comparison of once-daily and divided doses of modafinil in children with attention-deficit/hyperactivity disorder: a randomized, double-blind, and placebo-controlled study. J Clin . 2006 May;67(5):727-35. 5. Billiard M, Davilliers Y, Dolenc-Groselj L. Management of Narcolepsy in adults. In: Gilhus N, Barnes M, Branin M, editor(S). European handbook of neurological management. 2nd ed. Vol 1. Oxford (UK): Wiley- Blackwell 2011. P.513-28.

Page 6 of 8 Coverage Policy Number: 1501 6. Blackwell AD, Paterson NS, Barker RA, et al. The effects of modafinil on mood and cognition in Huntington's disease. Psychopharmacology (Berl). 2008 Jul;199(1):29-36. 7. Boele, F, Douw L, de Groot M et al. The effect of modafinil on fatigue, cognitive functioning, and mood in primary brain tumor patients: a multicenter randomized controlled trial. Neuro Oncol. 2013 Oct;15(10):1420-8 8. Carrieri PB, de Leva MF, Carrieri M, Buongiorno M. Modafinil improves primary nocturnal enuresis in multiple sclerosis. Eur J Neurol. 2007;14(3). 9. Cephalon Inc. Nuvigil® (armodafinil) package insert. Frazer, PA. Cephalon Inc. February 2017. 10. Cephalon Inc. Provigil® (modafinil) package insert. Frazer, PA. Cephalon Inc. January 2015. 11. Chan KM, Strohschein FJ, Rydz D, Allidina A, Shuaib A, Westbury CF. Randomized controlled trial of modafinil for the treatment of fatigue in postpolio patients. Muscle Nerve. 2006;33(1):138-141 12. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2014. URL: http://www.clinicalpharmacology.com. Updated October 2015 13. DeBattista C, Doghramji K, Menza MA, et al; Modafinil in Depression Study Group. Adjunct modafinil for the short-term treatment of fatigue and sleepiness in patients with major depressive disorder: a preliminary double-blind, placebo-controlled study. J Clin Psychiatry. 2003;64:1057-1064. 14. Dunlop BW, Crits-Christoph P, Evans DL, et al. Coadministration of modafinil and a selective serotonin reuptake inhibitor from the initiation of treatment of major depressive disorder with fatigue and sleepiness: a double-blind, placebo-controlled study. J Clin Psychopharmacol 2007;27:614-9 15. Fava M, Thase ME, DeBattista C, et al. A multicenter, placebo-controlled study of modafinil augmentation in partial responders to selective serotonin reuptake inhibitors with persistent fatigue and sleepiness. J Clin Psychiatry 2005;66:85-93. 16. Frye M, Grunze H, Suppes T et al. A placebo-controlled evaluation of adjunctive modafinil in the treatment of bipolar depression. Am J Psychiatry. 2007 Aug;164(8):1242-9. 17. Gelenberg AJ, Freeman MP, Markowitz JC, et al. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Major Depressive Disorder. 3rd ed. Arlington (VA): American Psychiatric Association; 2010 Oct. 18. Goez H, Scott O, Nevo N et al. Using the test of variables of attention to determine the effectiveness of modafinil in children with attention-deficit hyperactivity disorder (ADHD): a prospective methylphenidate- controlled trial. J Child Neurol. 2012 Dec;27(12):1547-52 19. Greenhill L, Biederman J, Boellner S et al. A randomized, double-blind, placebo-controlled study of modafinil film-coated tablets in children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2006 May;45(5):503-11. 20. Hogl et al. Modafinil for the treatment of daytime sleepiness in Parkinson’s Disease: a double-blind, randomized, crossover, placebo-controlled polygraphic trial. Sleep 2002: 25(8): 905-9. 21. Jean-Pierre P, Morrow G, Roswe J et al. A phase 3 randomized, placebo-controlled, double-blind, clinical trial of the effect of modafinil on cancer-related fatigue among 631 patients receiving chemotherapy: a University of Rochester Cancer Center Community Clinical Oncology Program Research base study. Cancer. 2010 Jul 15;116(14):3513-20 22. Jha A, Weintraub A, Allshouse A, et al. A randomized trial of modafinil for the treatment of fatigue and excessive daytime sleepiness in individuals with chronic traumatic brain injury. J Head Trauma Rehabil. 2008;23(1):52-63. 23. Joos L, Goudriaan AE, Schmaal L, et al. Effect of modafinil on cognitive functions in alcohol dependent patients: a randomized, placebo-controlled trial. J Psychopharmacol. 2013 Nov;27(11):998-1006. 24. Lohr J, Liu L, Caligiuri M et al. Modafinil improves antipsychotic-induced parkinsonism but not excessive daytime sleepiness, psychiatric symptoms or cognition in and schizoaffective disorder: a randomized, double-blind, placebo-controlled study. Schizophr Res. 2013 Oct;150(1):289-96. 25. Lou JS, Dimitrova DM, Park BS, et al. Using modafinil to treat fatigue in Parkinson disease: a double-blind, placebo-controlled pilot study. Clin Neuropharmacol. 2009;32(6):305-310. 26. Mayer G, Benes H, Young P, et al. Modafinil in the treatment of idiopathic hypersomnia without long sleep time—a randomized, double-blind, placebo-controlled study. J Sleep Res. 2015 Feb;24(1):74-81. 27. McEvoy GK, ed. 2020. AHFS Drug Information® - 60th Ed. Bethesda, MD. American Society of Health- System Pharmacists. 28. Morgenthaler TI, Kapur VK, Brown T, et al; Standards of Practice Committee of the American Academy of Sleep Medicine. Practice parameters for the treatment of narcolepsy and other of central origin [published correction appears in Sleep. 2008;31(2): table of contents]. Sleep. 2007;30(12):1705-1711.

Page 7 of 8 Coverage Policy Number: 1501 29. Orlikowski D, Chevert S, Quera-Salva M et al. Modafinil for the treatment of hypersomnia associated with myotonic muscular dystrophy in adults: a multicenter, prospective, randomized, double-blind, placebo- controlled, 4-week trial. Clin Ther. 2009 Aug;31(8):1765-73 30. Rabkin JG, Gordon PH, McElhiney M, et al. Modafinil treatment of fatigue in patients with ALS: a placebo- controlled study. Muscle Nerve. 2009 Mar;39(3):297-303. 31. Rabkin JG, McElhiney MC, Rabkin R, et al. Modafinil treatment for fatigue in HIV/AIDS: a randomized placebo-controlled study. J Clin Psychiatry. 2010 Jun;71(6):707-15. 32. Swanson J, Greenhill L, Lopez F et al. Modafinil film-coated tablets in children and adolescents with attention-deficit/hyperactivity disorder: results of a randomized, double-blind, placebo-controlled, fixed-dose study followed by abrupt discontinuation. J Clin Psychiatry. 2006 Jan;67(1):137-47. 33. VA/DoD clinical practice guideline for the management of major depressive disorder. Management of Major Depressive Disorder Working Group. Washington (DC): Department of Veterans Affairs, Department of Defense; 2016 Apr. 173 p. 34. Young T, Skatrud J, Peppard PE. Risk factors for obstructive sleep apnea in adults. Jama. Apr 28 2004;291(16):2013-2016. 35. Zesiewicz TA, Sullivan KL, Arnulf I, et al; Quality Standards Subcommittee of the American Academy of Neurology. Practice Parameter: treatment of nonmotor symptoms of Parkinson disease: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2010;74(11):924-931.

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