Randomised, double-blind, placebo-controlled study of fluoxetine in chronic fatigue syndrome

Lancet. 1996 Mar 30;347(9005):858-61. doi: 10.1016/s0140-6736(96)91345-8.


Background: No somatic treatment has been found to be effective for chronic fatigue syndrome (CFS). Antidepressant therapy is commonly used. Fluoxetine is recommended in preference to tricyclic agents because it has fewer sedative and autonomic nervous system effects. However, there have been no randomised, placebo-controlled, double-blind studies showing the effectiveness of antidepressant therapy in CFS. We have carried out such a study to assess the effect of fluoxetine in depressed and non-depressed CFS patients.

Methods: In this randomised, double-blind study, we recruited 44 patients to the depressed CFS group, and 52 to the non-depressed CFS group. In each group participants were randomly assigned to receive either fluoxetine (20 mg once daily) or placebo for 8 weeks. The effect of fluoxetine was assessed by questionnaires, self-observation lists, standard neuropsychological tests, and a motion-sensing device (Actometer), which were applied on the day treatment started and on the last day.

Findings: The two groups were well matched in terms of age, sex distribution, employment and marital status, and duration of CFS. There were no significant differences between the placebo and fluoxetine-treated groups in the change during the 8-week treatment period for any dimension of CFS. There was no change in subjective assessments of fatigue, severity of depression, functional impairment, sleep disturbances, neuropsychological function, cognitions, or physical activity in the depressed or the non-depressed subgroup.

Interpretation: Fluoxetine in a 20 mg daily dose does not have a beneficial effect on any characteristic of CFS. The lack of effect of fluoxetine on depressive symptoms in CFS suggests that processes underlying the presentation of depressive symptoms in CFS may differ from those in patients with major depressive disorder.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents, Second-Generation / therapeutic use*
  • Case-Control Studies
  • Depressive Disorder / complications*
  • Depressive Disorder / diagnosis
  • Depressive Disorder / drug therapy
  • Double-Blind Method
  • Fatigue Syndrome, Chronic / diagnosis
  • Fatigue Syndrome, Chronic / drug therapy*
  • Fatigue Syndrome, Chronic / psychology*
  • Female
  • Fluoxetine / therapeutic use*
  • Humans
  • Male
  • Psychological Tests
  • Time Factors
  • Treatment Outcome


  • Antidepressive Agents, Second-Generation
  • Fluoxetine