Serotonin norepinephrine reuptake inhibitors in managing neuropathic pain following spinal and non-spinal surgery: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: While serotonin norepinephrine reuptake inhibitors (SNRIs) offer promise in managing Post-surgical neuropathic pain (PSNP), uncertainties remain. This study aims to evaluate the effectiveness and adverse events of SNRIs in managing PSNP. METHODS: Systematic searches of PubMed, Embase, and Cochrane databases up to January 1st 2023 identified randomized controlled trials (RCTs) comparing SNRIs to placebo for PSNP. The primary outcome measures were pain at rest and adverse events post-surgery. Subgroup analyses were conducted based on surgical type and specific SNRIs. RESULTS: A total of 19 RCTs, encompassing 1440 participants (719 in the SNRI group vs 721 in the placebo group), met the inclusion criteria and were included. The pooled results demonstrated that pain scores were significantly lower in patients treated with SNRIs at 2 hours (MD:-0.26; 95%CI: -0.47 to -0.04; p=0.02), 6 hours (MD:-0.68; 95%CI: -1.01 to -0.34; p<0.0001), 24 hours (MD:-0.54; 95%CI: -0.99 to -0.09; p=0.02), and 48 hours (MD:-0.66; 95%CI: -1.23 to -0.10; p=0.02) post-surgery. In terms of adverse events, dizziness (OR:2.53; 95%CI: 1.34-4.78; p=0.004) and dry mouth (OR:2.21; 95%CI: 1.25-3.92; p=0.007) were significantly higher in the SNRIs group. Subgroup analysis showed that SNRI was found to significantly lower the 24-hour pain score after spinal surgery (MD:-0.45; 95%CI: -0.84 to -0.05; p=0.03). Duloxetine (MD:-0.63; 95%CI: -1.15 to -0.11; p=0.02) had a significant effect in lowering the 24-hour pain score at rest compared to placebo, whereas venlafaxine did not. CONCLUSIONS: SNRIs yielded considerable pain score reductions across multiple post-surgical intervals, although accompanied by an increased incidence of dizziness and dry mouth.

Influence of Solute Carrier Family 22 Member 1 (SLC22A1) Gene Polymorphism on Metformin Pharmacokinetics and HbA1c Levels: A Systematic Review.

BACKGROUND: Solute Carrier Family 22 Member 1 (SLC22A1, also known as OCT1) protein has a vital role in the metabolism of metformin, a first-line anti-diabetes medication. Genetic polymorphism in SLC22A1 influences individual response to metformin. OBJECTIVE: This review aims to compile the current knowledge about the effects of SLC22A1 genetic polymorphism on metformin pharmacokinetics and HbA1c levels. METHODS: We followed the PRISMA 2020 standards to conduct a systematic review. We searched the publications for all appropriate evidence on the effects of SLC22A1 genetic polymorphism on metformin pharmacokinetics and HbA1c from January 2002 to December 2022. RESULTS: Initial database searches identified 7,171 relevant studies. We reviewed 155 titles and abstracts after deleting duplicates. After applying inclusion and exclusion criteria, 23 studies remained. CONCLUSION: Three studies found that rs12208357, rs34059508, and G465R had a considerable impact (p < 0.05) on metformin pharmacokinetics, resulting in increased metformin plasma (Cmax), a higher active amount of drug in the blood (AUC), and lower volume of distribution (Vd) (p<0.05). SLC22A1 polymorphisms with effects on HbA1c include rs628031 (four of seven studies), rs622342 (four of six studies), rs594709 (one study), rs2297374, and rs1867351 (one of two studies), rs34130495 (one study), and rs11212617 (one study) (p < 0.05).