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LETTER |

November 01, 2001

Modafinil in Fibromyalgia Treatment

James L. Schaller, M.D., M.A.R.; David Behar, M.D.

DisordersSleep Disorders
The Journal of Neuropsychiatry and Clinical Neurosciences 2001;13:530-531. doi:10.1176/appi.neuropsych.13.4.530
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 C ollege 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 ,8 All 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 150200 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.

References
1

Rammohan KW, Rosenberg JH, Pollak C P, et al: Provigil (modafinil): efficacy for the treatment of fatigue in patients
with multiple sclerosis. Neurology 2000; 54:A24

C ochran JW: Effect of modafinil on fatigue associated with neurological illnesses. J C hronic Fatigue Syndrome 2001;
8:65-70

Matsumoto P: Fibromyalgia syndrome. Nippon Rinsho 1999; 57:364-369

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C athebras P, Lauwers A, Rousset H: Fibromyalgia: a critical review. Ann Med Interne (Paris) 1998; 149:406-414
[PubMed]

White KP, Speechley M, Harth M, et al: The London fibromyalgia epidemiology study: the prevalence of fibromyalgia
syndrome in London, Ontario. J Rheumatol 1999; 26:1570-1576
[PubMed]

Wolfe F, Smythe HA, Yunus MB, et al: The American C ollege of Rheumatology 1990 criteria for the classification of
fibromyalgia: report of the multicenter criteria committee. Arthritis Rheumatol 1990; 33:160-172
[CrossRef]

Menza MA, Kaufman KR, C astellanos A: Modafinil augmentation of antidepressant treatment in depression. J C lin
Psychiatry 2000; 61:378-381
[CrossRef] | [PubMed]

DeBattista C , Solvason HB, Kendrick E, et al: Modafinil as an adjunctive agent in the treatment of fatigue and
hypersomnia associated with major depression. New Research Program and Abstracts, American Psychiatric
Association 154th Annual Meeting, May 9, 2001, New Orleans, LA. Abstract NR532:144

C opyright 2014 American Psychiatric Association

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