[Treatment of systemic scleroderma with ketanserin. Randomized, double-blind 6-months study of 27 cases]. The effectiveness of ketanserin in patients with primary Raynaud's phenomenon. A randomized, double blind, placebo controlled study. Ketanserin in the treatment of systemic sclerosis: a double-blind controlled trial. A double-blind study of prazosin in the treatment of Raynaud's phenomenon in scleroderma. Controlled double-blind trial of dazoxiben and nifedipine in the treatment of Raynaud's phenomenon. Ketanserin versus nifedipine in secondary Raynaud's phenomenon. Infusion of iloprost, a prostacyclin analogue, for treatment of Raynaud's phenomenon in systemic sclerosis. Subjective and objective assessment of enalapril in primary Raynaud's phenomenon. Prazosin treatment of Raynaud's phenomenon: a double blind single crossover study.
Twenty-seven patients with systemic scleroderma and Raynaud's phenomenon underwent a randomised double blind therapeutic trial: monotherapy with Ketanserine (80 mg/day for 6 months) against Placebo. The secondary effects were comparable in both groups as were the withdrawals from the trial for aggravation of Raynaud's phenomenon (one in each group). No significant difference was observed between the two groups as regards the evolution of the Raynaud's phenomenon or skin changes. Dysphagia was improved in the Ketanserine group (p less than 0.05) but not in the Placebo group. Some patients in the Ketanserine group experienced an improvement in the Raynaud's phenomenon at the end of the trial period; there were no improvements in the Placebo group. Three haemorrheological parameters (total blood viscosity, plasma viscosity and thixotropism) were abnormal at the beginning of the trial and did not improve by the end in the Ketanserine group. The K infinity coefficient of Quemada's law was normal at the start of the trial and increased after treatment (p less than 0.05). In 41 patients with Primary Raynaud's Phenomenon (PRP) the effectiveness of the serotonin receptor blocker ketanserin has been studied in a double blind cross-over study. Subjective assessments included: frequency and duration of the attacks (both per se and combined to a severity score), cold sensation, numbness, paresthesia, pain, cold water and cold weather provocation and the appearance of spontaneous attacks. The objective measurements comprised Digital Skin Temperature (DST), Digital systolic Blood Pressure (DBP) and Doppler Spectral Analysis (DOSA) of the radial and ulnar arteries. All measurements were performed both at room temperature and after instant cold provocation. The severity score, the occurrence of numbness and paresthesia and cold weather provocation improved significantly on ketanserin treatment. All objective measurements with the exception of the end-diastolic blood flow velocity of DOSA did not show significant improvements. Neither blood chemistry nor systemic blood pressure showed any significant change during ketanserin treatment. However, in the 6 (15%) patients with hypertension both systolic and diastolic blood pressure normalized. Although in objective measurements hardly any significant effects of ketanserin could be demonstrated, the results of the study suggest that orally administered ketanserin is effective for minimizing subjective complaints in patients with PRP. Ketanserin did not show any side effects. In a randomized, double-blind study, the selective and specific S2-serotonergic receptor antagonist, ketanserin was compared with placebo in 24 patients with systemic sclerosis. Following a 6-week placebo washout period, patients were randomly allocated to receive ketanserin or placebo for 6 months. Ketanserin failed to produce a greater improvement than placebo in functional and objective clinical signs and symptoms as well as in most subjective assessments. However, in a global rating by the physician ketanserin was superior to placebo. No difference in the frequency or severity of side-effects was found. The results cast doubt on the hypothesis that serotonin may be a major contributing factor in the pathophysiology of systemic sclerosis. Nineteen patients with Raynaud's phenomenon in conjunction with progressive systemic sclerosis were given either prazosin hydrochloride (1 mg orally three times a day) or a placebo for eight weeks, after which the treatment procedure was reversed for four weeks. Prazosin was shown to be effective in reducing both the frequency and the severity of vasospasm reported by the patients. The prostaglandin thromboxane A2 causes platelet aggregation and vasoconstriction and may be important in the pathogenesis of Raynaud's phenomenon. Therefore, a randomized, double-blind, placebo-controlled trial was conducted to assess the effectiveness of dazoxiben, a selective thromboxane synthetase inhibitor, in the treatment of Raynaud's phenomenon and to compare it with nifedipine, a calcium channel blocker. Twenty-two subjects who had at least one episode of Raynaud's phenomenon per day entered the study. Three patients withdrew from the study because of side effects while taking nifedipine. There was no difference among the subjects' subjective evaluation of the three treatments. Seven of 19 (44 percent) reported a moderate to marked improvement while taking placebo compared with 12 of 19 (63 percent) taking nifedipine and five of 19 (26 percent) taking dazoxiben (p = NS). Similarly, there was no difference in the mean two-week episode rate among the three treatments: placebo 30.4 +/- 4.5, nifedipine 24.7 +/- 5.6, dazoxiben 32.0 +/- 4.9 (p = NS). Twelve of 22 subjects experienced side effects while taking nifedipine as compared with two of 21 taking placebo and eight of 21 taking dazoxiben (p less than 0.005). These data show that dazoxiben is not effective in the treatment of Raynaud's phenomenon and suggest that thromboxane does not cause the vasoconstriction that characterizes this disorder. nan Iloprost, a stable prostacyclin analogue, was given by intravenous infusion to 29 patients with severe Raynaud's phenomenon, 26 of whom had systemic sclerosis (SS), and compared with placebo infusion in a double blind crossover trial. Iloprost significantly lessened the number and the severity of attacks compared with placebo. Nine patients expressed a preference for effectiveness of treatment, eight of these in favour of Iloprost. Thermography failed to show any long term effect of Iloprost. Side effects of headache, flushing, nausea, and vomiting were common, and the inconvenience of intravenous administration may limit its routine use. 1. The efficacy and acceptability of enalapril were assessed in a double-blind, randomised, placebo controlled cross-over study in 21 patients with primary Raynaud's phenomenon. 2. Skin temperature was assessed by thermocouples in response to a 15 degrees C cold water challenge as an index of digital blood flow. 3. Following enalapril there were no significant changes in the number and severity of Raynaud's attacks, and no subjective benefit from treatment as measured by visual analogue scales, 5 point rating scales, and skin temperature response to cold challenge when compared with placebo. 4. Enalapril in a dose of 20 mg daily is ineffective in the management of primary Raynaud's phenomenon. The efficacy of prazosin (Minipress) for the treatment of Raynaud's phenomenon (RP) was assessed by patient diary data and by objective measurements of digital vessel patency before and after cold challenge. Nine of the 14 patients with complete data reported fewer RP episodes during the 2 weeks in which they received prazosin than with placebo. Eight of 9 patients in Group 1 (systemic lupus erythematosus, mixed connective tissue disease or idiopathic RP) reported improvement during prazosin therapy (p less than 0.05) while only one of 5 patients with progressive systemic sclerosis (PSS, Group 2) reported benefit. Objective measurements indicated a significant decrease (p less than 0.02) in digital artery resistance with prazosin only in Group 1. These data predict that prazosin may be beneficial in the treatment of RP for patients who do not also have PSS.
Ketanserin may have some efficacy in the treatment of Raynaud's phenomenon secondary to scleroderma. Overall, ketanserin is not significantly different from placebo for the treatment of Raynaud's phenomenon except for some decrease in the duration of attacks and more subjects improved on ketanserin compared to placebo. However, there were more side effects, and the frequency of attacks actually favored placebo. It can be concluded that ketanserin treatment in Raynaud's phenomenon secondary to scleroderma is not clinically beneficial.