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Cognitive behavioral therapy for insomnia, but not armodafinil, improves fatigue in cancer survivors with insomnia: a randomized placebo-controlled trial

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Abstract

Purpose

Fatigue is a prevalent, distressing side effect of cancer and cancer treatment which commonly coexists with insomnia. Cognitive behavioral therapy for insomnia (CBT-I) has been shown to improve insomnia in cancer patients, but less is known about its ability to impact fatigue. This work is the analysis for a secondary aim of a four-arm randomized controlled trial (RCT) study assessing the combined and comparative effect of CBT-I and a wakefulness-promoting agent, armodafinil (A), to improve sleep and daytime functioning in cancer survivors. Herein, we examine the effect of CBT-I, with and without A, on fatigue in cancer survivors.

Patients and methods

This study was a four-arm factorial study with CBTI-I (yes/no) versus A (yes/no). It consisted of 96 cancer survivors (average age 56 years; 88 % female; 68 % breast cancer). Fatigue was assessed by the brief fatigue inventory (BFI) and the FACIT-Fatigue scale. The analysis assessed the additive effects of CBT-I and A and possible non-additive effects where the effect of CBT-I changes depending on the presence or absence of A.

Results

Analyses adjusting for baseline differences showed that CBT-I improved fatigue as measured by two separate scales (BFI: P = 0.002, Std. error = 0.32, effect size (ES) = 0.46; FACIT-Fatigue: P < 0.001, Std. error = 1.74, ES = 0.64). Armodafinil alone did not show a statistically significant effect on fatigue levels (all Ps > 0.40) nor did the drug influence the efficacy of CBT-I. Structural equation analysis revealed that reductions in insomnia severity were directly responsible for improving cancer-related fatigue.

Conclusions

CBT-I with and without armodafinil resulted in a clinically and statistically significant reduction of subjective daytime fatigue in cancer survivors with chronic insomnia. Armodafinil did not improve cancer-related fatigue (CRF) and did not change the efficacy of CBT-I. Patients reporting CRF should be screened and, if indicated, treated for insomnia as part of a comprehensive fatigue management program.

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Acknowledgments

This study is supported by NCI grants 5 R01 CA126968, R25 CA102618 and UG1 CA18961. Study medication was provided by Teva Pharmaceuticals USA.

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Authors and Affiliations

  1. Department of Surgery, University of Rochester James P. Wilmot Cancer Center, 265 Crittenden Blvd. CU 420658, Rochester, NY, 14642, USA

    Charles E. Heckler, Anita R. Peoples, Michelle Shayne, Gary R. Morrow, Charles Kamen, Jenine Hoefler & Joseph A. Roscoe

  2. Department of Psychology, Memorial University of Newfoundland, St. John’s, NL, Canada

    Sheila N. Garland

  3. Department of Psychiatry, University of Pennsylvania, 3535 Market Street, Suite 670, Philadelphia, PA, 19104, USA

    Michael L. Perlis

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  1. Charles E. Heckler
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  2. Sheila N. Garland
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  4. Michael L. Perlis
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  5. Michelle Shayne
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Corresponding author

Correspondence to Charles E. Heckler.

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Conflict of interest

Dr. Perlis receives royalties for a CBT-I manual and demonstration DVD and research funding from Teva Pharmaceuticals and served as an advisor to InsomniSolv. He has also provided expert testimony to Cantor Colburn, LLP. None of the remaining authors have disclosures to report.

Drs. Heckler and Roscoe have full control of the primary data and agree to allow the journal to review it on request.

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Heckler, C.E., Garland, S.N., Peoples, A.R. et al. Cognitive behavioral therapy for insomnia, but not armodafinil, improves fatigue in cancer survivors with insomnia: a randomized placebo-controlled trial. Support Care Cancer 24, 2059–2066 (2016). https://doi.org/10.1007/s00520-015-2996-y

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