To compare fluoxetine, a selective serotonin reuptake inhibitor, with nifedipine as treatment for primary or secondary Raynaud's phenomenon.
Twenty-six patients with primary and 27 patients with secondary Raynaud's phenomenon were assigned randomly to receive 6 weeks of treatment with fluoxetine (20 mg daily) or nifedipine (40 mg daily). Following a 2-week washout period, each group was crossed over to the other treatment arm. The primary outcome variable was the frequency of attacks of Raynaud's phenomenon. Self-reported attack severity, thermographic recovery from cold challenge and plasma levels of von Willebrand factor and soluble P-selectin were also measured.
There was a reduction in attack frequency and severity of Raynaud's phenomenon in patients treated with either fluoxetine or nifedipine, but the effect was statistically significant only in the fluoxetine-treated group (P=0.0002 for attack severity and P=0.003 for attack frequency). Subgroup analysis showed that the greatest response was seen in females and in patients with primary Raynaud's phenomenon. A significant improvement in the thermographic response to cold challenge was also seen in female patients with primary Raynaud's phenomenon treated with fluoxetine but not in those treated with nifedipine. There was no significant treatment effect on von Willebrand factor or soluble P-selectin. No significant adverse effects occurred in the fluoxetine-treated group.
This pilot study confirms the tolerability of fluoxetine and suggests that it would be effective as a novel treatment for Raynaud's phenomenon. Larger and placebo-controlled trials are warranted to assess fluoxetine's therapeutic potential further in this vasospastic condition.
"An integrated clinical and molecular view presence of extensive fibrogenic activity and vasoconstriction as well as increased incidence of mood disorders in SSc (Coleiro et al., 2001; Garcia-Porrua et al., 2004). An imbalance between endothelial prostacyclin (PGI2) and platelet-derived thromboxane (TXA2) has long been recognized as a key factor in determining the risk of ischemia by means of platelet aggregation and vessel vasoconstriction (and it constitutes the main rationale for the use of low-dose aspirin for anti-thrombotic prevention). "
[Show abstract][Hide abstract] ABSTRACT: Systemic sclerosis (SSc) is an inflammatory disease of unknown etiology characterized by widespread organ dysfunction due to fibrosis and ischemia. Its nebulous pathogenic background and the consequent absence of an etiological therapy prevent the adoption of satisfying treatment strategies, able to improve patients' quality of life and survival and stimulate researchers to identify a unifying pathogenic target. Platelets show a unique biological behavior, lying at the crossroads between vascular function, innate and adaptive immunity, and regulation of cell proliferation. Consequently they are also emerging players in the pathogenesis of many inflammatory diseases, including SSc. In the setting of SSc platelets are detectable in a persistent activated state, which is intimately linked to the concomitant presence of an injured endothelium and to the widespread activation of the innate and adaptive immune system. As a consistent circulating source of bioactive compounds platelets contribute to the development of many characteristic phenomena of SSc, such as fibrosis and impaired vascular tone.
Frontiers in Immunology 06/2012; 3:160. DOI:10.3389/fimmu.2012.00160
"SJW was not superior to placebo, and in fact, placebo was numerically but not significantly better than SJW on some outcomes. It is likely that shared properties between SSRIs and SJW in the treatment of depression are not similar in RP treatment at the dose studied . SJW should not be pursued for the treatment of RP in a larger trial as there was no biomarker or clinical change that was superior to the placebo group. "
[Show abstract][Hide abstract] ABSTRACT: Objectives.To perform a 6-week double-blind RCT in Raynaud's phenomenon (RP) comparing the plant extract St. John's Wort (SJW) to placebo. Methods. RP patients having at least 7 attacks per week were stratified by primary and secondary RP and within secondary by systemic sclerosis or other connective tissue disease. Subjects completed a daily standardized diary recording all RP attacks (frequency, duration and severity). Serum levels of 18 inflammatory and angiogenic cytokines were measured pre- and post-treatment. Results. Eighteen patients completed the study; 8 received SJW and 10 placebo. The decrease in mean number of attacks per day was 0.75 with SJW and 1.01 with placebo, P = 0.06. Attack duration and severity were not different between groups. Cytokine analyses demonstrated no between-groups differences. Combining treatment groups, those with >50% improvement in frequency of attacks yielded a significant increase in E-selectin (P = 0.049), MMP-9 (P = 0.011), G-CSF (P = 0.02), and VEGF (P = 0.012) pre- versus post-treatment. A ≥50% improvement in severity of attacks corresponded to a significant increase in levels of sVCAM-1 (P = 0.003), sICAM-1 (P = 0.007), and MCP-1 (P = 0.004). Conclusions. There were no clinical or biomarker benefit of SJW versus placebo in RP. However, combining all patients, there were changes in some cytokines that may be further investigated.
"Moreover, serotonin reuptake may interfere with platelets, but the overall role in Raynaud’s phenomenon remains uncertain. In patients with primary Raynaud’s disease, 6 weeks’ treatment with the selective serotonin reuptake inhibitor fluoxetine (20 mg) improved severity and frequency of attacks compared to nifedipine (40 mg) significantly (P < 0.001), but effects were less pronounced in secondary Raynaud’s phenomenon.52 Consistently, a metaanalysis of the serotonin-reuptake inhibitor ketanserin demonstrated no beneficial effects in secondary Raynaud’s phenomenon due to systemic sclerosis.53 "
[Show abstract][Hide abstract] ABSTRACT: Raynaud's phenomenon is a clinical disorder with episodic digital ischemic vasospasm triggered by cold- or emotional-stress. It was first mentioned by Maurice Raynaud in 1862 describing "a local asphyxia of the extremities" and was further divided into primary Raynaud's disease and secondary Raynaud's phenomenon, which is often related to connective tissue diseases, but also physical or chemical strain. Though pathophysiology of Raynaud's phenomenon is still poorly understood, systemic and local vascular effects are most likely to be involved in primary Raynaud's disease. In secondary Raynaud's phenomenon additional abnormalities in vascular structure and function may play the major role. Thus, medical treatment of Raynaud's phenomenon remains unsatisfactory, due to limited understanding of pathophysiological mechanisms. This review addresses current evidence for medical treatment of primary and secondary Raynaud's phenomenon with regard to pathophysiological mechanisms as well as future perspectives.
Vascular Health and Risk Management 04/2010; 6(1):207-14. DOI:10.2147/VHRM.S5255
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