SIR: Modafinil has shown benefits in fatigue-related disorders such as multiple sclerosis and various forms of neurological fatigue.1,2 We report the successful use of modafinil for fibromyalgia (FM) fatigue in 4 patients in an open study with naturalistic on-off experiences. A rheumatologist and another physician confirmed each diagnosis of FM.
FM affects 2% of the population and is characterized by chronic musculoskeletal pain (especially at characteristic soft-tissue trigger sites); severe fatigue, typically lasting >24 h with minimal activity; nonrestorative sleep; and mood abnormalities.3—5 The American College of Rheumatology adds the criterion of widespread pain for 3 months with tenderness in at least 11 of 18 specific trigger-point sites.6
We excluded 2 patients for comorbid secondary major depression (MD) until they went into full remission on their antidepressants, confirmed by two MD research scales, to remove the variable of modafinil antidepressant augmentation.7,8All patients had physical exams and laboratory testing excluding Lyme disease, Ehrlichia equi and E. chaffeensis, Babesia microti, rheumatoid or spinal arthritis, major sleep disorders, and abnormal cervical and brain MRIs.
After an average 18 months of medical care, they found minimal relief. None could stay awake 16 hours on 3 consecutive days, shop routinely, provide basic childcare, drive over an hour per day, balance a checkbook, maintain a 30-hour work week, or cook routinely. Patient expectations for relief from this trial were very low because of past failures.
Two FM patients reported some beneficial effects of depression on day one at 100 mg q a.m., which were nevertheless incomplete. Weekly dose adjustments upward in 50-mg increments and the addition of an afternoon dose met with reports of highly significant benefit by all patients. After titration adjustments were finalized over 3 weeks, all reported a sustained increase in functional capacity. Global Assessment of Functioning average improvement was a change from 55 to 70; that is, from moderate impairment to minimal impairment.
All patients had a strong desire to continue their treatment because they now reported being "functional," able to work or to care for their children. Fatigue improved; all patients reported highly significant improvement in alertness and a reduced need for disruptive naps. They received unsolicited comments about their improvement from their children, spouses, employers, or parents, who were unaware of the modafinil trial. Benefits persisted over 3 continuous months at the same dose.
Alertness benefits were lost if a breakfast modafinil dose was skipped. Benefits returned quickly the following day if modafinil was restarted. Each patient missed at least 2 days of medication because of forgotten doses or a lost prescription. They reported a full return of fatigue and impairment that day. These mishaps represent naturalistic "on-off" experiments, supporting the immediate efficacy of modafinil. This immediate effect contrasts with our clinical expectations of gradual benefits.
The mean dose was 250 mg per day with a range of 150 to 300 mg. Patients took a dose of 150—200 mg in the morning, and half of them took an extra 50 mg or 100 mg in the early afternoon. One patient reported slight anxiety during week one, which resolved with a 50-mg dose reduction. We experienced inconclusive results in 3 patients, not included in our report, who dropped out or were lost to follow-up for reasons such as relocation.
The fatigue of FM causes marked impairment and has no definitive single treatment. Modafinil is a potential treatment option worthy of larger clinical trials.