Modafinil in Fibromyalgia Treatment

Reprinted with permission from the Journal of Clinical Neuroscience and APA

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 four 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, mood abnormalities.³ In addition, the American College of Rheumatology requires widespread pain for three months with tenderness in at least 11 of 18 specific trigger point sites.⁴

We excluded 2 patients for comorbid, secondary, Major Depression (MD) in two patients until they went into full remission on their antidepressants, confirmed by two MD research scales, to remove the variable of modafinil anti-depressant augmentation.⁵ All patients had physical exams and laboratory testing excluding Lyme disease, Ehrlichia equi and chaffeensis, Babesia microti, Rheumatoid or spinal arthritis, major sleep disorders, and abnormal cervical and brain MRI's.

After an average 18 months of medical care, they found minimal relief. None could stay awake 16 hours on three consecutive days, shop routinely, provide basic childcare, drive over an hour per day, balance a checkbook, maintain a 30-hour workweek nor cook routinely. Patient expectations for relief from this trial were very low because of past failures.

Two FM patients reported some beneficial effects on day one at 100 mg q am, which were nevertheless "incomplete." Weekly dose adjustments upward in 50 mg increments and the addition of an afternoon dose met with "highly significant" benefit in all patients. After titration adjustments were finalized over three weeks, all reported a sustained increase in functional capacity. Global Assessment of Functioning average improvement was movement from a 55 to a 70, i.e., moderate impairment moved to minimal impairment.

All patients had a strong desire to continue their treatment since they were now "Functional," "Able to work" or could now "Care for their children." Fatigue improved, with all four reporting "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 modafinil trial. Benefits persisted three continuous months at the same dose.

FM alertness benefits were lost if a breakfast modafinil dose was skipped. Benefits returned quickly the following day, if restarted. Each patient missed at least two days of medication, due to "forgetting" 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 potential gradual benefits.

The mean dose was 250 mg per day with a range of 150 to 300 mg. Patients took a 150-200 mg dose in the morning and half 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, for dropping out or being lost to follow up, e.g., relocating.

The fatigue of FM causes marked impairment and has no definitive single treatment. Modafinil is a potential treatment option, worthy of larger clinical trials.

James L. Schaller, M.D.
Chester County Research Center

David Behar, M.D.
Eastern Pennsylvania Psychiatric Institute
Philadelphia, PA

References

1. Rammohan KW, Rosenberg JH, Pollak CP, Lynn DY, Blumenfeld AM, Nagaraja HK. Provigil (modafinil): Efficacy for the treatment of fatigue in patients with multiple sclerosis. Neurology, 2000;54:A24. Also presented April, 2000 at the American Academy of Neurology.
2. Cochran JW. Effect of modafinil on fatigue associated with neurological illnesses. (In press). J Chronic Fatigue Syndrome. 2001;8:pages pending.
3. Matsumoto P. Fibromyalgia Syndrome. Nippon Rinsho, 1999;57:364-369; Cathebras P, Lauwers A, Rousset H. Fibromyalgia. A critical review. Ann Med Interne (Paris). 1998;149:406-414; White KP, Speechley M, Harth M, Ostbye T. The London fibromyalgia epidemiology study: the prevalence of fibromyalgia syndrome in London, Ontario. J Rheumatol, 1999;26:1570-1576.
4. Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenber DL, et. al.. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia: report of the multicenter criteria committee. Arthritis Rheum, 1990;33:160-172.
5. Menza MA, Kaufman KR, Castellanos A. Modafinil augmentation of antidepressant treatment in depression. J Clin Psychiatry, 2000;61:378-381; DeBattista C. Use of modafinil as an augmentation strategy in treatment resistant depression: prospective open label study of 20 patients. (In Press). 2001.