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Modafinil Moderates the Relationship Between Cancer-Related Fatigue and Depression in 541 Patients Receiving Chemotherapy

Conley, Claire C. MA; Kamen, Charles S. PhD; Heckler, Charles E. PhD; Janelsins, Michelle C. PhD; Morrow, Gary R. PhD; Peppone, Luke J. PhD; Scalzo, Anthony J. MD; Gross, Howard MD; Dakhil, Shaker MD; Mustian, Karen M. PhD; Palesh, Oxana G. PhD

Journal of Clinical Psychopharmacology: February 2016 - Volume 36 - Issue 1 - p 82–85
doi: 10.1097/JCP.0000000000000442
Brief Reports

Objective 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.

Methods 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).

Results 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.

Conclusions 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.

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.

Received June 10, 2015; accepted after revision October 26, 2015.

Reprints: Claire C. Conley, MA, Stress and Immunity Cancer Projects, 159 Psychology Bldg, 1835 Neil Ave, Ohio State University, Columbus, OH 43215 (e-mail:

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