Cognitive behavioral therapy for insomnia in veterans with gulf war illness: Results from a randomized controlled trial

Linda L Chao, Jennifer C Kanady, Nicole Crocker, Laura D Straus, Jennifer Hlavin, Thomas J Metzler, Shira Maguen, Thomas C Neylan, Linda L Chao, Jennifer C Kanady, Nicole Crocker, Laura D Straus, Jennifer Hlavin, Thomas J Metzler, Shira Maguen, Thomas C Neylan

Abstract

Aims: To examine whether cognitive behavioral therapy for insomnia (CBT-I), delivered by telephone, improves sleep and non-sleep symptoms of Gulf War Illness (GWI).

Main methods: Eighty-five Gulf War veterans (21 women, mean age: 54 years, range 46-72 years) who met the Kansas GWI case definition, the Centers for Disease Control and Prevention (CDC) case definition for Chronic Multisymptom Illness (CMI), and research diagnostic criteria for insomnia disorder were randomly assigned to CBT-I or monitor-only wait list control. Eight weekly sessions of individual CBT-I were administered via telephone by Ph.D. level psychologists to study participants. Outcome measures included pre-, mid-, and post-treatment assessments of GWI and insomnia symptoms, subjective sleep quality, and continuous sleep monitoring with diary. Outcomes were re-assessed 6-months post-treatment in participants randomized to CBT-I.

Key findings: Compared to wait list, CBT-I produced significant improvements in overall GWI symptom severity, individual measures of fatigue, cognitive dysfunction, depression and anxiety, insomnia severity, subjective sleep quality, and sleep diary outcome measures. The beneficial effects of CBT-I on overall GWI symptom severity and most individual GWI symptom measures were maintained 6-months after treatment.

Significance: GWI symptoms have historically been difficult to treat. Because CBT-I, which is associated with low stigma and is increasingly readily available to veterans, improved both sleep and non-sleep symptoms of GWI, these results suggest that a comprehensive approach to the treatment of GWI should include behavioral sleep interventions.

Keywords: Chronic multisymptom illness; Cognitive behavioral therapy; Gulf war illness; Insomnia; Telehealth; Veteran.

Conflict of interest statement

Declaration of competing interest

The authors have no competing interests.

Published by Elsevier Inc.

Figures

Fig. 1.
Fig. 1.
Consort diagram. Flowchart of participant numbers through the trial; Cognitive Behavioral Therapy for Insomnia (CBT-I); Gulf War Illness (GWI); Obstructive Sleep Apnea (OSA); Restless Legs Syndrome (RLS); Diagnostic and Statistical Manual for Mental Disorders (DSM-5); Traumatic Brain Injury (TBI); Obsessive Compulsive Disorder (OCD).
Fig. 2.
Fig. 2.
Primary outcome measures in CBT-I (red triangle) and Wait List (blue circle) groups showing means and standard deviations for scores on the Gulf War Illness Severity Index (A) and Insomnia Severity Index (B). Higher scores on both measures indicate more severe symptoms.
Fig. 3.
Fig. 3.
Secondary outcome measures for CBT-I (red triangle) and Wait list (blue circle) groups. The graphs show means and standard deviations intervals for the Fatigue Severity Scale, FSS (A); Brief Pain Inventory, BPI - pain severity index (B); BPI pain interference index (C); Multiple Abilities Self-report Questionnaire, MSAQ (D); Hospital Anxiety and Depression Scale, HADS – anxiety index (E); HADS – depression index (F); Pittsburgh Sleep Quality Index, PSQI (G). Higher scores on all measures indicate more severe or worse symptoms.
Fig. 4.
Fig. 4.
Sleep diary measures for CBT-I (red triangle) and Wait list (blue circle) groups. (A) Sleep Efficiency (SE), higher values are better; (B) Sleep Latency (SL), lower values are better; (C) Wake After Sleep Onset (WASO), lower values are better; (D) Total Sleep Time (TST), higher values are better. SE and SL data were non-normally distributed and transformed for analyses. The graphs show medians and inter-quartile range, converted back to percent and minutes. WASO and TST data were normally distributed; the graphs show means and standard deviations.

References

    1. Institute of Medicine, Gulf War and Health: Volume 8 - Health Effects of Serving in the Gulf War, 2010. (Washington, D.C.).
    1. Kang HK, Li B, Mahan CM, Eisen SA, Engel CC, Health of US veterans of 1991 Gulf War: a follow-up survey in 10 years, J Occup Environ Med. 51 (2009) 401–410.
    1. Research Advisory Committee on Gulf War Veterans’ Illnesses (RAC-GWVI). Gulf War Illness and the Health of Gulf War Veterans. Washington, D.C., 2008.
    1. Fukuda K, Niesenbaum R, Stewart G, et al., Chronic multisymptom illness affecting Air Force veterans of the Gulf War, JAMA. 280 (1998) 981–988.
    1. Goss Gilroy Inc. Health Study of Canadian Forces Personnel Involved in the 1991 Conflict in the Persian Gulf. Ottawa, Canada: Gulf War Illness Advisory Committee; 1998.
    1. Kang HK, Mahan CM, Lee KY, Magee CA, Murphy FM, Illnesses among United States veterans of the Gulf War: a population-based survey of 30,000 veterans, J Occup Environ Med. 42 (2000) 491–501.
    1. Unwin C, Blatchley N, Coker W, et al., Health of UK servicemen who served in Persian Gulf War, Lancet. 353 (1999) 169–178.
    1. Chester JE, Rowneki M, Van Doren W, Helmer DA, Progression of intervention-focused research for Gulf War illness, Mil Med Res. 6 (1) (2019) 31.
    1. Committee on the Development of a Consensus Case Definition for Chronic Multisymptom Illness in 1990–1991 Gulf War Veterans. Chronic Multisymptom Illness in Gulf War Veterans: Case Definitions Reexamined. Washington, D.C.: Institute of Medicine, 2014.
    1. Theadom A, Cropley M, Humphrey KL, Exploring the role of sleep and coping in quality of life in fibromyalgia, J Psychosom Res. 62 (2) (2007) 145–151.
    1. Fernandez-Mendoza J, Vgontzas AN, Insomnia and its impact on physical and mental health, Curr Psychiatry Rep. 15 (12) (2013) 418.
    1. Buenaver LF, Townsend D, Ong JC, Delivering cognitive behavioral therapy for insomnia in the real world: considerations and controversies, Sleep Med Clin. 14 (2) (2019) 175–181.
    1. Smith MT, Huang MI, Manber R, Cognitive behavior therapy for chronic insomnia occurring within the context of medical and psychiatric disorders, Clin Psychol Rev. 25 (5) (2005) 559–592.
    1. Wu JQ, Appleman ER, Salazar RD, Ong JC, Cognitive behavioral therapy for insomnia comorbid with psychiatric and medical conditions: a meta-analysis, JAMA Internal Med. 175 (9) (2015) 1461–1472.
    1. Wolfe F, Clauw DJ, Fitzcharles MA, et al., The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity, Arthritis Care Res (Hoboken). 62 (5) (2010) 600–610.
    1. Shah MA, Feinberg S, Krishnan E, Sleep-disordered breathing among women with fibromyalgia syndrome, J Clin Rheumatol. 12 (6) (2006) 277–281.
    1. Roizenblatt S, Neto NS, Tufik S, Sleep disorders and fibromyalgia, Curr Pain Headache Rep. 15 (5) (2011) 347–357.
    1. Meresh ES, Artin H, Joyce C, et al., Obstructive sleep apnea co-morbidity in patients with fibromyalgia: a single-center retrospective analysis and literature review, Open Access Rheumatol. 11 (2019) 103–109.
    1. Lami MJ, Martinez MP, Sanchez AI, et al., Gender differences in patients with fibromyalgia undergoing cognitive-behavioral therapy for insomnia: preliminary data, Pain Pract. 16 (2) (2016) E23–E34.
    1. Sanchez AI, Diaz-Piedra C, Miro E, Martinez MP, Galvez R, Buela-Casal G, Effects of cognitive-behavioral therapy for insomnia on polysomnographic parameters in fibromyalgia patients, Int J Clin Health Psychol. 12 (2012) 39–53.
    1. Edinger JD, Wohlgemuth WK, Krystal AD, Rice JR, Behavioral insomnia therapy for fibromyalgia patients: a randomized clinical trial, Arch Intern Med. 165 (2005) 2527–2535.
    1. Martinez MP, Miro E, Sanchez AI, et al., Cognitive-behavioral therapy for insomnia and sleep hygiene in fibromyalgia: a randomized controlled trial, J Behav Med. 37 (4) (2014) 683–697.
    1. Larun L, Brurberg KG, Odgaard-Jensen J, Price JR, Exercise therapy for chronic fatigue syndrome, Cochrane Database Syst Rev. 2017 (4) (2017), CD003200.
    1. Kallestad H, Jacobsen HB, Landro NI, Borchgrevink PC, Stiles TC, The role of insomnia in the treatment of chronic fatigue, J Psychosom Res. 78 (5) (2015) 427–432.
    1. Vethe D, Kallestad H, Jacobsen HB, Landro NI, Borchgrevink PC, Stiles TC. The relationship between improvement in insomnia severity and long-term outcomes in the treatment of chronic fatigue. Front Psychol. 2018;9:1764.:1764.
    1. Karlin BE, Trockel M, Taylor CB, Gimeno J, Manber R. National dissemination of cognitive behavioral therapy for insomnia in veterans: therapist- and patient-level outcomes. J Consult Clin Psychol. 2013;April 15.
    1. Karlin BE, Trockel M, Spira AP, Taylor CB, Manber R, National evaluation of the effectiveness of cognitive behavioral therapy for insomnia among older versus younger veterans, Int J Geriatr Psychiatry. 30 (3) (2015) 308–315.
    1. Arnedt JT, Cuddihy L, Swanson LM, Pickett S, Aikens J, Chervin RD, Randomized controlled trial of telephone-delivered cognitive behavioral therapy for chronic insomnia, Sleep. 36 (2013) 353–362.
    1. McCurry SM, Guthrie KA, Morin CM, et al., Telephone-based cognitive behavioral therapy for insomnia in perimenopausal and postmenopausal women with vasomotor symptoms: a MsFLASH randomized clinical trial, JAMA Internal Med. 176 (7) (2016) 913–920.
    1. Pepin R, Segal DL, Coolidge FL, Intrinsic and extrinsic barriers to mental health care among community-dwelling younger and older adults, Aging Ment Health. 13 (5) (2009) 769–777.
    1. Sarmiento KF. VA’s TeleSleep Program: Understanding Disparities in Rural Sleep Care. Seminar Presented at the San Francisco VA Health Care System; San Francisco, CA, March 14, 2019.
    1. U.S. Department of Veterans Affairs, Gulf War (including operation Iraqi freedom) registry (GWR) program (formerly Persian Gulf registry program). , 2007.
    1. Steele L, Prevalence and patterns of Gulf War illness in Kansas veterans: association of symptoms with characteristics of person, place, and time of military service, Am J Epidemiol. 152 (2000) 992–1002.
    1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: Diagnostic and Statistical Manual of Mental Disorders. Vol 5. Arlington, VA: American Psychiatric Association; 2013.
    1. Chung F, Yegneswaran B, Liao P, et al., STOP questionnaire: a tool to screen patients for obstructive sleep apnea, Anesthesiology. 108 (2008) 812–821.
    1. Weaver TE, Grunstein RR, Adherence to continuous positive airway pressure therapy the challenge to effective treatment, Proc Am Thorac Soc. 5 (2) (2008) 173–178.
    1. Stiasny-Roister K, Möller JC, Heinzel-Gutenbrunner M, Baum E, Ries V, Oertel WH, Validation of the Restless Legs Syndrome Screening Questionnaire (RLSSQ), Somnologie - Schlafforschung und Schlaftnedizin. 13 (1) (2009) 37–42.
    1. Corrigan JD, Bogner JA, Initial reliability and validity of the OSU TBI Identification Method, J Head Trauma Rehabil. 22 (2007) 318–329.
    1. Blake DD, Weathers FW, Nagy LM, et al., The development of a clinican-administered PTSD scale, J Trauma Stress. 8 (1995) 75–90.
    1. Skinner HA, Sheu WJ, Reliability of alcohol use indices: the Lifetime Drinking History and the MAST, Journal of Studies on Alcohol. 43 (1982) 1157–1170.
    1. Bastien CH, Vallieres A, Morin CM, Validation of the Insomnia Severity Index as an outcome measure for insomnia research, Sleep Medicine. 2 (2001) 297–307.
    1. Morin CM, Belleville G, Belanger L, Ivers H, The insomnia severity index: psychometric indicators to detect insomnia cases and evaluate treatment response, Sleep 34 (2011) 601–608.
    1. Steele L, Sastre A, Gerkovich MM, Cook MR, Complex factors in the etiology of Gulf War Illness: wartime exposures and risk factors in veteran subgroups, Environ Health Perspect. 120 (2012) 112–118.
    1. Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD, The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus, Arch Neurol. 46 (1989) 1121–1123.
    1. Cleeland CS, Ryan KM, Pain assessment: global use of the Brief Pain Inventory, Ann Acad Med Singapore. 23 (1994) 129–138.
    1. Seidenberg M, Haltiner A, Taylor MA, Hermann BB, Wyler A, Development and validation of a Multiple Ability Self-Report Questionnaire, J Clin Exp Neuropsychol. 16 (1994) 93–104.
    1. Zigmond AS, Snaith RP, The hospital anxiety and depression scale, Acta Psychiatr Scand. 67 (1983) 361–370.
    1. Buysse DJ, Renolyds CF 3rd., Monk TH, Berman SR, Kupfer DJ, The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research, Psychiatry Research. 28 (1989) 193–213.
    1. R: A Language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing, 2020.
    1. Bates D, Maechler M, Bolker B, Walker S, Fitting linear mixed-effects models using lme4, J Stat Softw. 67 (1) (2015) 1–48.
    1. Halekoh U, Hojsgaard S, A Kenward-Roger approximation and parametric bootstrap methods for tests in linear mixed models - the R package pbkrtest, J Stat Softw. 59 (9) (2014) 1–30.
    1. Morin CM, Beaulieu-Bonneau S, Belanger L, et al., Cognitive-behavior therapy singly and combined with medication for persistent insomnia: impact on psychological and daytime functioning, Behav Res Ther. 87 (2016) 109–116.
    1. Manber R, Edinger JD, Gress JL, et al., Cognitive behavioral therapy for insomnia enhances depression outcome in patients with comorbid major depressive disorder and insomnia, Sleep. 31 (2008) 489–495.
    1. Taylor DJ, Lichstein KL, Weinstock J, Sanford S, Temple JR, A pilot study of cognitive-behavioral therapy of insomnia in people with mild depression, Behav Ther. 38 (1) (2007) 49–57.
    1. Fleming L, Randall K, Harvey CJ, Espie CA, Does cognitive behaviour therapy for insomnia reduce clinical levels of fatigue, anxiety and depression in cancer patients? Psychooncology. 23 (6) (2014) 679–684.
    1. Talbot LS, Maguen S, Metzler TJ, et al., Cognitive behavioral therapy for insomnia in posttraumatic stress disorder: a randomized controlled trial, Sleep. 37 (2014) 327–341.
    1. Gotts Z, Deary V, Newton JL, Ellis J, Treatment of insomnia reduces fatigue in chronic fatigue syndrome in those able to comply with the intervention, Fatigue: Biomedicine, Health & Behavior. 4 (4) (2016) 208–216.
    1. Amin MM, Gold MS, Broderick JE, Gold AR, The effects of nasal continuous positive airway pressure on the symptoms of Gulf War illness, Sleep Breath. 15 (2011) 579–587.
    1. Nakamura Y, D.L. L, Kanarowski E, McCormick T, Sutherland D, Melow-Murchie M. Investigating impacts of incorporating an adjuvant mind-body intervention method into treatment as usual at a community-based substance abuse treatment facility: a pilot randomized controlled study. SAGE Open. 2015;5(1).
    1. Nakamura Y, Lipschitz DL, Donaldson GW, et al., Investigating clinical benefits of a novel sleep-focused mind-body program on gulf war illness symptoms: a randomized controlled trial, Psychosom Med. 79 (6) (2017) 706–718.
    1. Donta ST, Clauw DJ, Engel CC Jr., et al., Cognitive behavioral therapy and aerobic exercise for Gulf War Veterans’ illnesses: a randomized controlled trial, JAMA. 289 (2003) 1396–1404.
    1. Bastawrous A, Hennig B, Livingstone I, mHealth possibilities in a changing world. Distribution of global cell phone subscriptions, Journal of Mobile Technology in Medicine. 2 (1) (2013) 22–25.
    1. Watzke B, Haller E, Steinmann M, et al., Effectiveness and cost-effectiveness of telephone-based cognitive-behavioural therapy in primary care: study protocol of TIDe – telephone intervention for depression, BMC Psychiatry. 17 (1) (2017) 263.
    1. Bastien CH, Morin CM, Ouellet MC, Blais FC, Bourchard S, Cognitive behavioral therapy for insomnia: comparison of individual therapy, group therapy, and telephone consultations, J Consult Clin Psychol. 72 (2004) 653–659.
    1. Brenes GA, Miller ME, Williamson JD, McCall WV, Knudson M, Stanley MA, A randomized controlled trial of telephone-delivered cognitive-behavioral therapy for late-life anxiety disorders, Am J Geriatr Psychiatry. 20 (8) (2012) 707–716.
    1. Brenes GA, Danhauser SC, Lyles MF, Anderson A, Miller ME, Effects of telephone-delivered cognitive-behavioral therapy and nondirective supportive therapy on sleep, health-related quality of life, and disability, Am J Geriatr Psychiatry. 24 (10) (2016) 846–854.
    1. Hammond GC, Croudace TJ, Radhakrishnan M, et al., Comparative effectiveness of cognitive therapies delivered face-to-face or over the telephone: an observational study using propensity methods, PLoS One. 7 (9) (2012), e42916.
    1. Butterick TA, Trembley JH, Hocum Stone LL, Muller CJ, Rudquist RR, Bach RR, Gulf War Illness-associated increases in blood levels of interleukin 6 and C-reactive protein: biomarker evidence of inflammation, BMC Research Notes. 12 (2019) 816.
    1. Johnson GJ, Slater BC, Leis LA, Rector TS, Bach RR, Blood biomarkers of chronic inflammation in Gulf War illness, PLoS One. 11 (6) (2016), e0157855.
    1. Del Giudice M, Gangestad SW, Rethinking IL-6 and CRP: why they are more than inflammatory biomarkers, and why it matters, Brain Behav Immun. 70 (2018) 61–75.
    1. Sproston NR, Ashworth JJ, Role of C-reactive protein at sites of inflammation and infection, Front Immunol. 9 (2018) 754.
    1. Suyasa IK, Kawiyana IKS, Bakta IM, Widiana IGR, Interleukin-6 and ratio of plasma interleukin-6/interleukin-10 as risk factors of symptomatic lumbar osteoarthritis, World J Orthop. 8 (2) (2017) 149–155.
    1. Irwin MR, Olmstead R, Carrillo C, et al., Cognitive behavioral therapy vs. Tai Chi for late life insomnia and inflammatory risk: a randomized controlled comparative efficacy trial, Sleep. 37 (9) (2014) 1543–1552.
    1. Edinger JD, Wohlgemuth WK, Radtke RA, Marsh GR, Quillian RE, Cognitive behavioral therapy for treatment of chronic primary insomnia: a randomized controlled trial, JAMA. 285 (2001) 1856–1864.
    1. Espie CA, Inglis SJ, Tessier S, Harvey L, The clinical effectiveness of cognitive behaviour therapy for chronic insomnia: implementation and evaluation of a sleep clinic in general medical practice, Behav Brain Res. 39 (2001) 45–60.
    1. Morin CM, Colecchi C, Stone J, Sood R, Brink D, Behavioral and pharmacological therapies for late-life insomnia: a randomized controlled trial, JAMA. 281 (1999) 991–999.
    1. Verbeek I, Schreuder K, Dederck G, Evaluation of short-term nonpharmacological treatment of insomnia in a clinical setting, J Psychosom Res. 47 (1999) 369–383.
    1. Cervena K, Dauvilliers Y, Espa F, et al., Effect of cognitive behavioural therapy for insomnia on sleep architecture and sleep EEG power spectra in psychophysiological insomnia, J Sleep Res. 13 (2004) 385–393.
    1. Iacovides S, George K, Kamerman P, Baker FC, Sleep fragmentation hypersensitizes healthy young women to deep and superficial experimental pain, J Pain. 18 (7) (2017) 844–854.
    1. Yue HJ, Bardwell W, Ancoli-Israel S, Loredo JS, Dimsdale JE, Arousal frequency is associated with increased fatigue in obstructive sleep apnea, Sleep Breath. 13 (2009) 331–339.
    1. Hursel R, Rutters F, Gonnissen HKJ, Martens EAP, Westerterp-Plantenga MS, Effects of sleep fragmentation in healthy men on energy expenditure, substrate oxidation, physical activity, and exhaustion measured over 48 h in a respiratory chamber, Am J Clin Nutr. 94 (3) (2011) 804–808.
    1. Martin SE, Brander PE, Deary IJ, Douglas NJ, The effect of clustered versus regular sleep fragmentation on daytime function, J Sleep Res. 8 (4) (1999) 305–311.
    1. Blackwell T, Yaffe K, Ancoli-Israel S, et al., Poor sleep is associated with impaired cognitive function in older women: the study of osteoporotic fractures, J Gerontol A Biol Sci Med Sci. 61 (4) (2006) 405–410.
    1. Spira AP, Stone KL, Redline S, et al. Actigraphic sleep duration and fragmentation in older women: associations with performance across cognitive domains. Sleep. 2017;40(8):zsx073.
    1. Bender R, Lange S, Adjusting for multiple testing — when and how? J Clin Epidemiol. 54 (2001) 343–349.
    1. Luyster FS, Buysse DJ, Strollo PJ Jr., Comorbid insomnia and obstructive sleep apnea: challenges for clinical practice and research, J Clin Sleep Med. 6 (2010) 196–204.
    1. Cho YW, Kim KT, Moon HJ, Korostyshevskly VR, Motamedi GK, Yang KI, Comorbid insomnia with obstructive sleep apnea: clinical characteristics and risk factors, J Clin Sleep Med. 14 (3) (2018) 409–417.
    1. Sweetman A, Lack L, Bastien C. Co-Morbid Insomnia and Sleep Apnea (COMISA): prevalence, consequences, methodological considerations, and recent randomized controlled trials. Brain Sci. 2019;9(12):371.
    1. Chao LL, Abadjian L, Esparza IL, Reeb R, Insomnia severity, subjective sleep quality, and risk for obstructive sleep apnea in veterans with Gulf War illness, Mil Med. 181 (9) (2016) 1127–1134.
    1. Sweetman A, Lack L, Lambert S, Gradisar M, Harris J, Does comorbid obstructive sleep apnea impair the effectiveness of cognitive and behavioral therapy for insomnia? Sleep Med. 39 (2017) 38–46.
    1. Espie CA, Emsley R, Kyle SD, et al., Effect of digital cognitive behavioral therapy for insomnia on health, psychological well-being, and sleep-related quality of life: a randomized clinical trial, JAMA Psychiatry. 76 (2018) 21–30.
    1. Koffel E, Kuhn E, Petsoulis N, et al., A randomized controlled pilot study of CBT-I Coach: feasibility, acceptability, and potential impact of a mobile phone application for patients in cognitive behavioral therapy for insomnia, Health Informatics J. 24 (1) (2018) 3–13.
    1. Peter L, Reindl R, Zauter S, Hillemacher T, Richter K, Effectiveness of an online CBT-I intervention and a face-to-face treatment for shift work sleep disorder: a comparison of sleep diary data, Int J Environ Res Public Health. 16 (17) (2019) 3081.

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever