title: Cognitive behavioral therapy for insomnia, but not armodafinil, improves fatigue in cancer survivors with insomnia: a randomized placebo-controlled trial.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Surgery, University of Rochester James P. Wilmot Cancer Center, 265 Crittenden Blvd. CU 420658, Rochester, NY, 14642, USA. Charles_Heckler@urmc.rochester.edu.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Heckler
authors.affiliation: Department of Psychology, Memorial University of Newfoundland, St. John's, NL, Canada.
authors.forename: Sheila N
authors.initials: SN
authors.lastname: Garland
authors.affiliation: Department of Surgery, University of Rochester James P. Wilmot Cancer Center, 265 Crittenden Blvd. CU 420658, Rochester, NY, 14642, USA.
authors.forename: Anita R
authors.initials: AR
authors.lastname: Peoples
authors.affiliation: Department of Psychiatry, University of Pennsylvania, 3535 Market Street, Suite 670, Philadelphia, PA, 19104, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Perlis
authors.affiliation: Department of Surgery, University of Rochester James P. Wilmot Cancer Center, 265 Crittenden Blvd. CU 420658, Rochester, NY, 14642, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Shayne
authors.affiliation: Department of Surgery, University of Rochester James P. Wilmot Cancer Center, 265 Crittenden Blvd. CU 420658, Rochester, NY, 14642, USA.
authors.forename: Gary R
authors.initials: GR
authors.lastname: Morrow
authors.affiliation: Department of Surgery, University of Rochester James P. Wilmot Cancer Center, 265 Crittenden Blvd. CU 420658, Rochester, NY, 14642, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Kamen
authors.affiliation: Department of Surgery, University of Rochester James P. Wilmot Cancer Center, 265 Crittenden Blvd. CU 420658, Rochester, NY, 14642, USA.
authors.forename: Jenine
authors.initials: J
authors.lastname: Hoefler
authors.affiliation: Department of Surgery, University of Rochester James P. Wilmot Cancer Center, 265 Crittenden Blvd. CU 420658, Rochester, NY, 14642, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Roscoe
mesh_terms: D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D015928:Cognitive Behavioral Therapy; D003131:Combined Modality Therapy; D005221:Fatigue / Q000150:complications / Q000188:drug therapy / Q000209:etiology / Q000628:therapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D009369:Neoplasms / Q000150:complications* / Q000503:physiopathology; D012890:Sleep / Q000187:drug effects; D007319:Sleep Initiation and Maintenance Disorders / Q000150:complications* / Q000209:etiology; D017741:Survivors; D016896:Treatment Outcome; D064690:Wakefulness-Promoting Agents / Q000627:therapeutic use*
chemical_list: D001559:Benzhydryl Compounds; D064690:Wakefulness-Promoting Agents; D000077408:Modafinil
keywords: Armodafinil; CBT-I; Cancer; Cancer-related fatigue