Effect of nifedipine on urinary concentrating ability: a placebo controlled study

A placebo-controlled, randomized, crossover study was conducted to assess a possible effect of a dihydropyridine Ca-entry blocker, nifedipine, on urinary concentration ability in nine healthy men under a water-deprivated condition. Placebo and nifedipine (20 mg) were orally administered on two separate occasions, at least one week apart, after the urinary osmolarity was stabilized. Urinary osmolarity, osmolar clearance, negative free water clearance, urine volume, urinary solutes (Na, K and urea), creatinine clearance and plasma vasopressin (AVP) were measured during the postdose 3-hour period and compared with those during the respective predose (baseline) period. Urinary osmolarity decreased by nifedipine from 1047.2 +/- 34.4 to 873.0 +/- 38.3 mOsm/kg (mean +/- SEM) at 2 hours postdose (P less than 0.05). Mean % decrease in urinary osmolarity at 1 to 3 hours after nifedipine was significantly (P less than 0.01) greater than after placebo. Urine volume significantly (P less than 0.01) increased from the baseline of 0.49 +/- 0.06 to 1.1 +/- 0.15 ml/min at 2 hours after nifedipine. Relationship between osmolar clearance and negative free water clearance relative to glomerular filtration rate observed during the postnifedipine phase was significantly (P less than 0.01) shifted downward compared with that derived from the pooled data unrelated to nifedipine dosing. No significant drug effect was detected on plasma AVP. Both placebo and nifedipine dosed during the continued water deprivation and stabilized urinary osmolarity condition caused an increase in the urinary excretions of solutes. The results indicate that nifedipine inhibits urinary concentration. This does not appear to be due to the inhibition of AVP secretion from the hypophysis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Alcoholism and depression: a placebo controlled study with viloxazine

Depressive disorders are frequently associated with alcohol abuse. Though many studies have been carried out to clarify the role of antidepressant drugs in the management of alcoholic patients, the data are controversial. The present placebo-controlled study was planned to assess the antidepressant and attenuating drinking-behaviour efficacy of viloxazine (400 mg per os daily) versus a placebo in 30 dysthymic patients affected by alcohol dependence. The results significantly favour viloxazine treatment in alleviating depression and in reducing alcohol abuse. All patients showed baseline haematochemical evidence of liver dysfunction that did not change significantly during the treatment.     

Levetiracetam in social phobia: a placebo controlled pilot study

While serotonergic antidepressants are now established as first-line pharamcotherapy for generalized social anxiety disorder (SAD), other agents with different mechanisms have shown promise in treating SAD. The aim of this pilot study is to examine the efficacy and safety of levetiracetam (LEV), an anticonvulsant with calcium channel modulating properties, in treating SAD. Adult outpatients meeting DSM-IV criteria for SAD were randomly assigned (2:1) to double-blind treatment with either LEV (500-3000 mg/day) or placebo (PBO) for 7 weeks. The primary outcome measures were the change from baseline in the Brief Social Phobia Scale (BSPS) and response using the Clinical Global Impression of Improvement scale (CGI-I). The mean (SD) BSPS scores at baseline and endpoint were 45.4 (9.7) and 31.2 (19.7) for LEV (n=9), compared to 43.5 (8.4) and 37.8 (19.9) for PBO (n =7) (ITT; ns). Rates of response were 22% for LEV and 14% for PBO using the CGI-I. Using a BSPS response criterion (>30% reduction), response rates were 44% for LEV and 14% for PBO. The effect sizes of LEV relative to PBO were 0.33 for the BSPS and 0.50 for the LSAS. In summary, the results of this study, while negative on the pre-defined measures, suggest promise for LEV as a new treatment of SAD. Further work should be carried out with larger sample sizes and optimal dosing strategies of the drug.     

: a prospective, randomised, double-blind, controlled multicentre study

The efficacy and safety of etodolac and piroxicam were compared in patients with osteoarthritis of the hip (n = 111) or knee (n = 160). Special emphasis was placed on clinical gastrointestinal adverse effects. 271 patients participated in this 8-week prospective, multicentre, randomised, double-blind trial. Efficacy was measured by patient's and investigator's assessment of key parameters after 4 and 8 weeks of treatment compared with baseline. Tolerability was evaluated by patients' complaints at each visit (adverse events) and laboratory tests performed before and at the end of treatment. After 4 and 8 weeks of treatment and at the end of treatment, patients' and investigators' assessments were significantly improved from baseline in both groups. There were no statistically significant differences between the groups in any efficacy assessment at any observation. In the etodolac group 30% reported adverse events, compared with 46% in the piroxicam group (p < 0.01). In the study, 20% in the etodolac group and 29% in the piroxicam group reported gastrointestinal adverse events (not significant). Clinically significant falls in haemoglobin occurred in 22% of patients with no significant difference between the 2 groups. In conclusion, the study indicated that etodolac 600mg per day was as effective as piroxicam 20mg per day in the treatment of osteoarthritis. Etodolac produced adverse events in a significantly smaller number of patients than piroxicam. No significant differences were found between etodolac and piroxicam with respect to incidence of clinical gastrointestinal adverse events.     

Effects of enalapril in normotensive patients with stable effort angina: a double blind, placebo controlled study

To assess the anti-anginal and anti-ischaemic efficacy of the ACE-inhibitor enalapril in normotensive coronary patients, a double-blind, cross-over, placebo-controlled study was performed. Eight male patients, aged 45-68 years, with stable effort angina were given enalapril (10 mg) once a day or placebo for 7 days. Maximal exercise stress tests 10w/min in the upright position were performed at the end of each period. In comparison to placebo, enalapril increased significantly 1 mm of ST depression time and decreased significantly ST depression at maximal common work. Moreover, enalapril increased significantly the angina threshold and exercise duration. Three of the eight patients ended the exercise without pain. The rate-pressure product was not significantly modified at any time. Thus, the anti-ischaemic and anti-anginal activity may be due to an increase of coronary blood flow, rather than a reduction of MVO2 consumption.     

Effects of zolpidem on saccadic eye movements and psychomotor performance: a double-blind, placebo controlled study in healthy volunteers.

1. Peak saccade velocity provides a valuable means of assessing the sedative effect of drugs in humans. The present study investigated the effects of zolpidem, an imidazopyridine hypnotic, on saccade velocity in healthy volunteers after single and repeated administration. 2. Zolpidem 5 mg, 10 mg and 20 mg significantly and dose dependently depressed peak saccade velocity during the 1.5 h after a single administration. On the morning after zolpidem administration, peak saccade velocity had returned towards pretreatment levels. Nitrazepam 10 mg also significantly depressed peak saccade velocity but the effect was maintained the following morning. The saccade response to zolpidem (5 and 10 mg) was undiminished after the seven nightly doses. 3. Nightly administration of zolpidem improved subjective sleep quality and there was no evidence of rebound insomnia following cessation of drug treatment.     

Cost effectiveness of oral triptan therapy: a trans-national comparison based on a meta-analysis of randomised controlled trials

OBJECTIVE: The objective of this study was to appraise the relative cost effectiveness of oral triptan therapy in the management of acute migraine, comparing the results obtained using drug cost data from six different countries, USA, UK, Canada, Germany, Italy and The Netherlands. METHOD: A meta-analysis of randomised placebo controlled trials of single dose oral triptans was carried out in order to calculate aggregate Numbers Needed to Treat (NNT) for each triptan and dose. Cost effectiveness ratios were then derived for each treatment by applying mean drug acquisition costs for each country to these NNTs. Using a graphical plot for each country, incremental cost effectiveness comparisons were then made versus sumatriptan 100 mg, the most commonly used oral triptan. RESULTS: When analysed in terms of 2-h pain one country to another. When compared to free outcomes, rizatriptan 10 mg and eletriptan 40 and 80 mg were the most effective oral triptans. Rizatriptan 10mg has the most advantageous absolute cost effectiveness ratio in all six countries studied, although levels of statistical significance compared to other agents varied from sumatriptan 100mg, rizatriptan 10 mg and eletriptan 40 mg are most consistently the cost effective treatment choices, both being cost dominant in five out of six countries studied. CONCLUSIONS: There are systematic differences in triptan efficacy that have an impact on treatment choice. Differences in pricing structure between countries mean that hierarchies of cost effectiveness will vary. Country-specific data should therefore be examined before defining treatment strategies.     

Tonazocine mesylate in postoperative pain patients: a double-blind placebo controlled analgesic study

One hundred-fifty post-operative adult patients with moderate to severe pain were enrolled into this analgesic efficacy study comparing single doses of tonazocine mesylate, a new mixed agonist-antagonist opioid analgesic, with morphine. The patients were randomly assigned to five treatment groups: tonazocine mesylate 2, 4, 8 mg; morphine sulfate 10 mg and a placebo group. The results showed mean total pain relief scores for tonazocine 4 mg were nearly identical with that of morphine sulfate 10 mg while 8 mg of tonazocine were superior to 10 mg of morphine. All the active medication groups were superior to the placebo group (P less than 0.02) for both pain intensity and pain relief. Relative potency determined by the dose response indicates that 3.2 mg of tonazocine is equivalent to 10 mg of morphine. Drowsiness was the main adverse reaction seen in all active treatment groups. Tonazocine mesylate appears to be a potent analgesic with promising clinical usefulness and warrants further study.     

Cost effectiveness of oral triptan therapy: a trans-national comparison based on a meta-analysis of randomised controlled trials

Objective: The objective of this study was to appraise the relative cost effectiveness of oral triptan therapy in the management of acute migraine, comparing the results obtained using drug cost data from six different countries, USA, UK, Canada, Germany, Italy and The Netherlands.

Method: A meta-analysis of randomised placebo controlled trials of single dose oral triptans was carried out in order to calculate aggregate Numbers Needed to Treat (NNT) for each triptan and dose. Cost effectiveness ratios were then derived for each treatment by applying mean drug acquisition costs for each country to these NNTs. Using a graphical plot for each country, incremental cost effectiveness comparisons were then made versus sumatriptan 100mg, the most commonly used oral triptan.

Results: When analysed in terms of 2-h pain

free outcomes, rizatriptan 10mg and eletriptan 40 and 80?mg were the most effective oral triptans. Rizatriptan 10mg has the most advantageous absolute cost effectiveness ratio in all six countries studied, although levels of statistical significance compared to other agents varied from one country to another. When compared to sumatriptan 100mg, rizatriptan 10mg and eletriptan 40?mg are most consistently the cost effective treatment choices, both being cost dominant in five out of six countries studied.

Conclusions: There are systematic differences in triptan efficacy that have an impact on treatment choice. Differences in pricing structure between countries mean that hierarchies of cost effectiveness will vary. Country-specific data should therefore be examined before defining treatment strategies.     

Antihypertensive effect of once daily sustained release isradipine: a placebo controlled cross-over study

Summary To evaluate the magnitude and duration of the antihypertensive effect of sustained release (SRO) isradipine, 37 uncomplicated essential hypertensive patients (diastolic blood pressure 100–115 mm Hg after a one month run-in on placebo) were randomised to receive, according to a double-blind cross-over design, isradipine SRO 5 mg once daily and the corresponding placebo for 1 month. At the end of each treatment period, sitting blood pressure and heart rate were measured immediately before and every hour for 6 h after the last dose. Thirty-four patients [16 m, age 54 (7) y] completed the study.As compared to randomised placebo, isradipine SRO significantly reduced the systolic (SBP) and diastolic (DBP) blood pressure. Absolute DBP decrements versus placebo peaked 6 h after dosing (-8.8 mm Hg) and were not significantly lower (-8.2 mm Hg) at the end of the dose interval. At the same times, the absolute decrements in SBP were -9.8 mm Hg and -9.7 mm Hg, respectively.DBP was normalised in 19 patients (56%) at peak and in 17 (50%) at trough time. The trough to peak efficacy ratio in patients with peak DBP 90 mm Hg was 70%. Heart rate was slightly increased by isradipine SRO. Adverse effects monitored with a check-list occurred in 8/36 patients (22%) on isradipine SRO and in 4/35 (11%) on randomized placebo.The data suggest that isradipine SRO is an effective antihypertensive drug, with a trough to peak efficacy ratio supporting once daily administration in most mild to moderate essential hypertensives.