title: Modafinil Moderates the Relationship Between Cancer-Related Fatigue and Depression in 541 Patients Receiving Chemotherapy.
abstract: The aim of this study was to examine the effect of modafinil on depression via a secondary data analysis of a randomized clinical trial of modafinil for fatigue in cancer patients. The primary aim is to elucidate factors that contributed to the effectiveness of modafinil in the parent trial.
  
  
  
  Five hundred forty-one cancer patients receiving chemotherapy and experiencing fatigue (Brief Fatigue Inventory [BFI] item 3 of ≥3) were randomized to receive 200 mg modafinil (n = 260) or placebo (n = 281) daily from baseline (cycle 2) to posttest (cycle 4). Patients completed the Center for Epidemiological Studies-Depression Scale (CES-D) and Profile of Mood States depression-dejection subscale at baseline and posttest. We used linear regression to address the hypothesis that modafinil would be associated with reduced depression, particularly in those experiencing severe fatigue (BFI ≥7).
  
  
  
  Modafinil did not have a significant effect on depression, even for those patients with severe fatigue. However, for subjects with severe fatigue (BFI ≥7), those receiving modafinil had lower depression scores than did control subjects. Modafinil significantly moderated the relationship between baseline fatigue and CES-D total scores (P = 0.04) and was marginally significant as a moderator for the relationship between baseline fatigue and Profile of Mood States depression-dejection subscale scores (P = 0.07). Modafinil also significantly moderated the relationship between baseline fatigue and CES-D positive affect subscale scores (P = 0.003), but not CES-D somatic, negative affect, or interpersonal subscale scores.
  
  
  
  Modafinil differentially impacts depression based on a patient's level of fatigue and reduced depressive symptoms only in those with extreme fatigue. This effect may be driven by increases in positive affective symptoms. These results have significant implications for intervention; in patients with high levels of fatigue, modafinil might also reduce depression. Future randomized clinical trials are needed to confirm these results.
authors.affiliation: From the *Department of Psychology, Ohio State University, Columbus, OH; †Cancer Control, Department of Surgery, University of Rochester Medical Center, Rochester, NY; and ‡Hematology/Oncology Associates of Central New York, Syracuse, NY; §Dayton Community Clinical Oncology Program, Dayton, OH; ∥Wichita Community Clinical Oncology Program, Wichita, KS; and ¶Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, CA.
authors.forename: Claire C
authors.initials: CC
authors.lastname: Conley
authors.forename: Charles S
authors.initials: CS
authors.lastname: Kamen
authors.forename: Charles E
authors.initials: CE
authors.lastname: Heckler
authors.forename: Michelle C
authors.initials: MC
authors.lastname: Janelsins
authors.forename: Gary R
authors.initials: GR
authors.lastname: Morrow
authors.forename: Luke J
authors.initials: LJ
authors.lastname: Peppone
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Scalzo
authors.forename: Howard
authors.initials: H
authors.lastname: Gross
authors.forename: Shaker
authors.initials: S
authors.lastname: Dakhil
authors.forename: Karen M
authors.initials: KM
authors.lastname: Mustian
authors.forename: Oxana G
authors.initials: OG
authors.lastname: Palesh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy* / Q000209:etiology; D004311:Double-Blind Method; D005221:Fatigue / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D009369:Neoplasms / Q000150:complications*; D011446:Prospective Studies; D064690:Wakefulness-Promoting Agents / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D001559:Benzhydryl Compounds; D064690:Wakefulness-Promoting Agents; D000077408:Modafinil