To the Editor: Chronic fatigue syndrome is a medical condition only gradually being understood, with the criteria of a 6-month history of worsening fatigue with four of eight symptoms that include memory and sleep impairment as well as lymph node, joint, and muscular pain (1). Serotonin abnormalities, including antibodies to its presence, have been reported (2). Because of these findings, antidepressants have frequently been administered that may ease either its pain or its fatigue (2). A recent treatment option is nefazodone because of its positive effects on sleep by serotonergic pathways (3). Here we report on three patients with nefazodone-treated chronic fatigue syndrome, in which two of three showed positive results; none of these patients met the criteria for a major depressive disorder. The chronic fatigue syndrome scale employed below is an eight-symptom scale listing major criteria with a 1–4 level of severity.
Mr. A was a 58-year-old white man with a 2-year history of chronic fatigue syndrome symptoms. Previous treatment with paroxetine and fluoxetine had worsened his symptoms, particularly producing greater insomnia. He received a dose of 300 mg of nefazodone for most of 12 weeks; a dose of 500 mg led to dizziness. During his period of treatment, there was a minimum change in his Hamilton Depression Rating Scale score from 11 to 9. However, his sleep showed reduced early and middle insomnia, and he could go up to 4 days with decreased pain and increase in motivation and ability to work. His natural killer cell activity improved from 26.6% to 35.6%.
Ms. B was a 55-year-old white woman who was diagnosed with Epstein-Barr virus in 1991 but met criteria for chronic fatigue syndrome. She was able to sustain increases in her dose of nefazodone to 500 mg/day. Over 12 weeks, her chronic fatigue syndrome total score dropped by 15 points, with notable improvement in all areas, including fatigue, sore throat, muscle and joint pain, headaches, and sleep impairment. Simultaneously, her Hamilton rating scale score fell from 16 to 5; she was more able to reduce napping, increase leisure activity, and in particular, she was able to exercise without worsened fatigue. Her natural killer cell activity increased from 18.5% to 21%.
Ms. C was a 42-year-old white woman who met the criteria for chronic fatigue syndrome, not previously treated, who took a maximum dose of 400 mg/day of nefazodone for 12 weeks. During this time, she noted an overall improvement in chronic fatigue syndrome symptoms, with a reduction in score from 22 to 17 in joint and muscle pain, as well as headaches. Simultaneously, her Hamilton rating scale score fell from 12 to 5. She completed artwork, showed improved memory, more rapidly completed tasks, and had an increase in libido. In her case, however, the natural killer cell level dropped from 22.4% to 19.4%.
In all three patients treated with nefazodone, there were improvements in symptoms of chronic fatigue syndrome, particularly in the areas of pain and insomnia. Further, two of the three showed improvement in natural killer cell function. Of particular note is that one of the three had previously not responded and, in fact, reportedly had worsened on both fluoxetine and paroxetine. Thus, nefazodone may be one further option indicated for further investigation in chronic fatigue syndrome.