Efficacy of memantine premedication in alleviating postoperative pain- A systematic review and meta-analysis.

Many premedication agents with opioid-sparing properties have been used in patients undergoing various elective surgeries. Memantine is an N-methyl-D-aspartate (NMDA) receptor antagonist that has been used by many researchers as an opioid-sparing strategy. Various databases like PubMed, Scopus, Cochrane Library, and clinicaltrials.gov were searched after registering the review protocol in PROSPERO for randomized-controlled trials (RCTs) that investigated the efficacy and safety of memantine premedication in adult patients undergoing various elective surgeries. The risk of bias (RoB-2) scale was used to assess the quality of evidence. From the 225 articles that were identified after a database search, 3 studies were included for a qualitative systematic review and a quantitative meta-analysis. The pooled analysis revealed that the use of memantine provided better pain scores at 2nd (mean difference: -0.82, 95% CI: -1.60, -0.05, P = 0.04) with significant heterogeneity (P = 0.06; I² =71%), and 6 hours postoperatively (mean difference: -1.80, 95% CI: -2.23, -1.37, P < 0.00001), but not at 1 hour. The sedation scores at 1 hour were higher in the memantine group but comparable in the 2nd hour. The number of doses of rescue analgesia and nausea/vomiting in the postoperative period was comparable in both groups. The results of this review suggest that memantine premedication could provide better pain scores in the immediate postoperative period with acceptable adverse effects. However, the current evidence is insufficient to suggest the routine use of memantine as a premedication before elective surgeries.

Analgesic efficacy and safety of duloxetine premedication in patients undergoing hysterectomy - A systematic review.

Background and Aims: Patients undergoing hysterectomy by open or laparoscopic approach experience moderate to severe postoperative pain. A multimodal analgesic approach is recommended for these patients. This study reviews the analgesic efficacy of duloxetine, a selective serotonin and norepinephrine reuptake inhibitor used as an adjuvant for opioid-sparing postoperative analgesia. Methods: After registering the protocol in the international prospective register of systematic reviews (PROSPERO), databases like PubMed, Ovid, Scopus, Cochrane Library and clinicaltrials.gov were searched for randomised controlled trials using relevant keywords to find studies in which duloxetine premedication was compared to a placebo in patients undergoing hysterectomy. The revised Cochrane risk-of-bias tool for randomised trials (RoB 2) was used to assess the quality of evidence. Results: The qualitative systematic review included five of the 88 studies identified. The overall risk of bias in the included studies was very high. In all the studies, 60 mg oral duloxetine was used, and the control group was placebo. In two studies, duloxetine premedication was administered 2 h before and 24 h after surgery. In the other three studies, a single dose of 60 mg duloxetine was only administered 2 h before surgery. A pooled meta-analysis was not performed due to fewer studies that fulfilled the inclusion criteria and even fewer studies with consistent reporting of various outcomes. Conclusion: The evidence is insufficient to advocate routine duloxetine premedication in patients undergoing hysterectomy.

Efficacy and safety of avanafil as compared with sildenafil in the treatment of erectile dysfunction: A randomized, double blind, multicenter clinical trial.

OBJECTIVE: To compare the efficacy and safety of avanafil as compared with sildenafil in the management of patients with erectile dysfunction. METHODS: It was a prospective, randomized, double-blind, two-arm, active-controlled, parallel, multicenter, non-inferiority clinical study carried out in patients with erectile dysfunction for at least 3 months and International Index of Erectile Function - Erectile Function domain score of <26 at enrolment. RESULTS: A total of 220 patients were randomized to receive either avanafil tablets 100 mg or sildenafil tablets 50 mg in 1:1 ratio. After 4 weeks of treatment, 40.0% of patients in the avanafil group and 45.6% of patients in the sildenafil group required dose escalation to a high dose (avanafil 200 mg/sildenafil 100 mg). The difference in the mean change of International Index of Erectile Function - Erectile Function score from baseline in the two groups increased from week 4 (1.1, 95% confidence interval -0.2 to 2.5) to week 8 (1.4, 95% confidence interval 0.1-2.7) and week 12 (2.1, 95% confidence interval 0.8-3.5), showing non-inferiority at week 4, and superiority at week 8 and week 12. Avanafil showed a faster onset of action as shown by a significantly better response to modified Sexual Encounter Profile 1 in the avanafil group (84.8%) as compared with that in the sildenafil group (28.2%; P < 0.001). Both avanafil and sildenafil were well tolerated by all the patients in the study; the most common adverse event reported during the study was headache in both the groups. CONCLUSION: Avanafil is superior to sildenafil in improving the International Index of Erectile Function - Erectile Function domain score at the end of 12 weeks of treatment with the added advantage of faster onset of action.

Low-dose sodium valproate versus low-dose propranolol in prophylaxis of common migraine headache: A randomized, prospective, parallel, open-label study.

CONTEXT: Migraine is the second most common headache disorder. However, prophylactic therapy remains underutilized. AIMS: The objective of the study was to compare the efficacy and safety of low-dose sodium valproate and low-dose propranolol sustained release (SR) in the prophylaxis of common migraine headache. SETTINGS AND DESIGN: The study was conducted in a tertiary care teaching institute. It was a randomized, prospective, parallel, open-label, clinical study. SUBJECTS AND METHODS: The study included 60 patients with common migraine headaches (≥2 attacks/month) treated for 12 weeks. The patients were randomly divided into two treatment groups treated by sodium valproate 500 mg/day and propranolol SR 40 mg/day, respectively. The primary outcome measures were the percentage of responders (i.e., >50% decrease in mean headache frequency) at the end of 12 weeks and decrease in mean headache frequency (per 4 weeks) at the end of 12 weeks. The patients were assessed at 0, 4, 8, and 12 weeks of the study. STATISTICAL ANALYSIS USED: Intention-to-treat analysis was used for all the statistical analysis. RESULTS: Fifty-five patients completed the study. At the end of the treatment, both sodium valproate and propranolol caused a significant (P < 0.0001) reduction in frequency, severity, and duration of migraine headache. Propranolol caused significantly greater reduction in the severity of headache (P = 0.0410) than sodium valproate. The percentage of responders was 60% in sodium valproate group and 70% in propranolol group. Drowsiness was the most common adverse effect noted in both the groups. CONCLUSION: Both sodium valproate and propranolol significantly reduced frequency, severity, and duration of migraine headache, but propranolol caused significantly greater reduction in the severity of headache compared to sodium valproate. Both the medications were well tolerated and did not result in discontinuation.