Modafinil treatment for fatigue in HIV/AIDS: a randomized placebo-controlled study.
OBJECTIVE
To evaluate the efficacy and safety of modafinil in the treatment of fatigue in patients with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and to assess effect on depressive symptoms.


METHODS
Patients who were HIV+ and had clinically significant fatigue (according to the Fatigue Severity Scale [FSS]) were included in a 4-week randomized, placebo-controlled, double-blind trial. This was followed by an additional 8 weeks of open-label treatment for modafinil responders and 12 weeks for placebo nonresponders. The primary outcome measure for fatigue and depression was the Clinical Global Impressions-Improvement scale, supplemented by the FSS, Hamilton Depression Rating Scale, and Beck Depression Inventory. Safety was assessed with assays of CD4 cell count and HIV ribonucleic acid (RNA) viral load. Visits were weekly for 4 weeks, then biweekly, with a follow-up visit at 6 months. Maximum trial dose of modafinil was 200 mg/d. Data for this study were collected between December 2004 and December 2008.


RESULTS
115 patients were randomly assigned. In intention-to-treat analyses, fatigue response rate to modafinil was 73% and to placebo, 28%. Attrition was 9%. Modafinil did not have an effect on mood alone in the absence of improved energy. At week 4, CD4 cell counts did not change significantly; HIV RNA viral load showed a trend decline for patients taking modafinil but not for those taking placebo. At 6 months, those still taking modafinil had more energy and fewer depressive symptoms than patients who were not taking modafinil, and only those still taking modafinil showed a significant decline from baseline in their HIV RNA viral load.


CONCLUSIONS
Modafinil appears to be effective and well tolerated in treating fatigue in HIV+ patients. Consideration of its use is warranted considering the high prevalence of fatigue in the HIV community, its minimal side effects, and overall patient acceptance.


BACKGROUND
clinicaltrials.gov Identifier: NCT00118378.
Rabkin
Judith G
JG
Department of Psychiatry, College of Physicians and Surgeons, Columbia University, and New York State Psychiatric Institute, New York, NY 10032, USA. jgr1@columbia.edu
McElhiney
Martin C
MC
Rabkin
Richard
R
McGrath
Patrick J
PJ
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000821:virology; D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count / Q000706:statistics & numerical data; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000188:drug therapy / Q000523:psychology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005221:Fatigue / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D006678:HIV / Q000187:drug effects / Q000302:isolation & purification; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D057194:Intention to Treat Analysis; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D010919:Placebos; D012720:Severity of Illness Index; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
D044966:Anti-Retroviral Agents; D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D010919:Placebos; D000077408:Modafinil