Use of modafinil to moderate the relationship between cancer-related fatigue and depression in 541 patients receiving chemotherapy: A URCC CCOP study.

Abstract

9572 Background: Over 50% patients with cancer report symptoms of depression; 15% meet diagnostic criteria for Major Depressive Disorder. Depression is associated with increased insomnia, fatigue and reduced quality of life. We previously found that modafinil is effective for reducing high levels of fatigue among patients undergoing chemotherapy. This study aims to test whether modafinil can alleviate symptoms of depression by reducing fatigue. Methods: This study is a secondary analysis of 541 cancer patients receiving chemotherapy and experiencing fatigue (Brief Fatigue Inventory (BFI) >=3) that were randomized to receive either 200 mg of modafinil (N=260) or placebo (N=281) daily from baseline (Cycle 2) until post-test (Cycle 4). Depression was measured by the Center for Epidemiologic Studies Depression Scale (CES-D) at baseline and post-test. The CES-D total score and its subscales (Positive Affect, Negative Affect, Somatic Symptoms, and Interpersonal Symptoms) were analyzed. A linear model with CES-D post (outcome) and BFI baseline, Arm, and BFI*Arm interaction term (independent variables) was used to address the hypothesis; p<0.05 indicates significance. Results: We found no overall effect of modafinil on depression; however, the model demonstrated a significant moderating effect of modafinil on the relationship between baseline fatigue and CES-D total scores (p = 0.04). For subjects with severe fatigue (BFI ≥ 7), the drug reduced CES-D scores by 3-4. Modafinil also significantly moderated the relationship between baseline fatigue and Positive Affect subscale scores (p = 0.003), but not the relationship between baseline fatigue and Somatic, Negative Affect, or Interpersonal subscales. Conclusions: Modafinil differentially impacts depression based on a patient’s level of fatigue; reduced depressive symptoms occurred in those with extreme fatigue. This effect is 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 RCTs are needed to confirm these results. Funding: U10CA37420, K07CA120025, K07CA132916.