Randomized, double blind, controlled placebo-phase in trial of low dose phenelzine in the chronic fatigue syndrome

Abstract

Because of the striking similarity of the clinical manifestations produced by use of the drug reserpine and seen in patients with the chronic fatigue syndrome (CFS), we theorized that CFS was a disorder of reduced central sympathetic drive. Because of the pharmacology of control of this central sympathetic system, we further postulated that CFS symptoms would respond quickly to low dose treatment with a monamine oxidase inhibitor. To test these hypotheses, we designed a randomized, double blind placebo controlled study using phenelzine. No patient in the trial had a diagnosis of lifetime or current psychiatric disorder and none had depressed mood in the range of clinically depressed patients on a paper and pencil test of depression. Patients in the placebo group received placebo for 6 weeks while those in the drug treatment group were treated in three 2-week segments-placebo, 15 mg phenelzine every other day, and then 15 mg daily. This treatment regimen produced a significant pattern of improvement compared to worsening in 20 self report vehicles of CFS symptoms, illness severity, mood or functional status. Thus the data support our hypothesis of reduced sympathetic drive, although an alternative hypothesis of pain alleviation is also possible. The study design also allowed us to evaluate patients for a placebo effect: no evidence for this was found, suggesting that CFS is not an illness due to patients' being overly suggestible.

Interventions for the Treatment and Management of Chronic Fatigue Syndrome

“…A mix of validated tools for different dimensions or domains is needed to take into consideration the wide and pervasive impact of this ill-* References 22,26,[29][30][31]33,35,37,43,45,51. ness on many domains. A comprehensive review of outcome measures currently used would be the first step in this process.…”

Single-Blind, Placebo Phase-in Trial of Two Escalating Doses of Selegiline in the Chronic Fatigue Syndrome

“…Evidence for the latter possibilities does exist in the literature on CFS clinical trials [18]. However, our own previous trial [5] plus another on fluoxetine [19] found no evidence for either spontaneous improvement or for a placebo effect. One explanation suggested for these results is that the study patients had a severe form of CSF which might be less responsive to treatment [20].…”

“…Of these, the pharmaceutical option is the weakest, and so current drug treatment is directed toward symptomatic relief. In a recent double-blind, placebo-controlled trial of low-dose phenelzine in a small number of patients, we reported a very small but statistically significant ameliorative effect which appeared independently of any antide-pressant effect [5]. To investigate further the effect of monoamine oxidase (MAO) blockade, we now report data from an open-label trial of selegiline where patients were told they would receive either active agent or placebo at some time during the trial.…”

Les syndromes de fatigue d'origine cérébrale

“…Quoiqu'il en soit, le manque de consensus entre les différentes études tout comme la diversité des étiologies avancées incitent à penser que le SFC n'est pas une entité pathologique distincte mais un syndrome multifactoriel qui doit être abordé sur les plans somatique, psychologique, et même social. En ce qui concerne les traitements, il semble que certains antidépresseurs (fluoxétine, phenelzine [inhibiteur de la monoamine oxydase]) puissent avoir une action bénéfique lorsque des symptômes tels que dépression, insomnie ou myalgies sont présents [18,19]. Le recouvrement qui existe entre le SFC et la dépression ne permet toutefois pas d'apprécier l'action précise des antidépresseurs.…”