Tag: 5-HT3 receptor antagonists

Tryptophan depletion in chronic fatigue syndrome, a pilot cross-over study

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is still an enigmatic disorder. CFS can be regarded as a complex disorder with tremendous impact on lives of CFS-patients. Full recovery without treatment is rare. A somatic explanation for the fatigue is lacking. There is clinical and experimental evidence implicating enhanced serotonergic neurotransmission in CFS.

Genetic studies and imaging studies support the hypothesis of upregulated serotonin system in CFS. In line with the hypothesis of an increased serotonergic state in CFS, we performed a randomised clinical trial investigated the effect of 5-HT3 receptor antagonism in CFS. No benefit was found of the 5-HT3 receptor antagonist ondansetron compared to placebo.To further investigate the involvement of serotonin in CFS we performed a placebo controlled cross over pilot study investigating the effect of Acute Tryptophan Depletion.

FINDINGS: Five female CFS-patients who met the US Center for Disease Control and Prevention criteria for CFS were recruited. There were two test days, one week apart. Each participant received placebo and ATD. To evaluate the efficacy of the ATD procedure tryptophan and the large neutral amino acids were measured. The outcome measures were fatigue severity, concentration and mood states. ATD resulted in a significant plasma tryptophan to large neutral amino acid ratio reduction of 96%. There were no significant differences in fatigue-, depression and concentration between the placebo- and ATD condition.

CONCLUSIONS: These first five CFS-patients did not respond to the ATD procedure. However, a much larger sample size is needed to draw final conclusions on the hypothesis of an increased serotonergic state in the pathophysiology of CFS.

TRIAL REGISTRATION: ISRCTN07518149.

 

Source: The GK, Verkes RJ, Fekkes D, Bleijenberg G, van der Meer JW, Buitelaar JK. Tryptophan depletion in chronic fatigue syndrome, a pilot cross-over study. BMC Res Notes. 2014 Sep 16;7:650. doi: 10.1186/1756-0500-7-650. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176591/ (Full article)

 

Treatment of chronic fatigue syndrome with 5-HT3 receptor antagonists–preliminary results

Abstract:

OBJECTIVE: The serotonin system presumably is involved in the pathogenesis of chronic fatigue syndrome (CFS). Results from a few studies led to the hypothesis of a “postsynaptic hyperresponsiveness” in CFS. Therefore we intended to evaluate the efficacy of 5-HT3 receptor antagonists in the treatment of CFS.

PATIENTS AND METHODS: 2 patient groups (10 patients each; CFS according to the CDC classification criteria) received either oral tropisetron (5 mg once daily) or oral ondansetron (2 x 8 mg daily), open-labelled. Treatment duration was 15 days. Treatment response was evaluated by visual analog scales (VAS) for fatigue and capability.

RESULTS: 19 patients finished their respective study. In the tropisetron group 6/9 (VAS fatigue) and 7/9 (VAS capability) patients documented benefit, 8/10 rsp. 8/10 patients in the ondansetron group. The score changes (VAS before and after treatment) in case of response were more pronounced in the tropisetron group. The frequency of concomitant symptoms did not differ significantly in the treatment groups. The overall analysis of both studies showed a remarkable improvement (> or = 35%) of approximately one third of the patients in both VAS. Treatment was well tolerated.

CONCLUSION: Our preliminary results encourage to perform placebo-controlled, double-blind studies to further evaluate the efficacy of 5-HT3 receptor antagonists in the treatment of CFS.

Source: Späth M, Welzel D, Färber L. Treatment of chronic fatigue syndrome with 5-HT3 receptor antagonists–preliminary results. Scand J Rheumatol Suppl. 2000;113:72-7. http://www.ncbi.nlm.nih.gov/pubmed/11028837