Objective. To study the effect of fluoxetine (FL) and amitriptyline (AM), alone and in combination, in patients with fibromyalgia (FM).Methods. Nineteen patients with FM completed a randomized, double-blind crossover study, which consisted of 4 6-week trials of FL (20 mg), AM (25 mg), a combination of FL and AM, or placebo. Patients were evaluated on the first and last day of each trial period. Outcome measures included a tender point score, the Fibromyalgia Impact Questionnaire (FIQ), the Beck Depression Inventory (BDI) scale, and visual analog scales PAS) for global well-being (1 completed by the physican and 1 by the patient), pain, sleep trouble, fatigue, and feeling refreshed upon awakening.Results. Both FL and AM were associated with significantly improved scores on the FIQ and on the VAS €or pain, global well-being, and sleep disturbances. When combined, the 2 treatments worked better than either medication alone. Similar, but nonsignificant, improvement occurred in the BDI scale, the physician global VAS, and the VAS for fatigue and feeling refreshed upon awakening. Trends were less clear for the tender point score.Conclusion. Both FL and AM are effective treatments for FM, and they work better in combination than either medication alone.Clinical trials of medications for the treatment of fibromyalgia (FM) have demonstrated modest or little efficacy. Tricyclic and tetracyclic "antidepressant" drugs

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