Pharmacotherapy for Neuropathic Pain in Adults: A Systematic Review and Meta-Analysis

Abstract

et al. JAMA 2015;313:1133-42.Conclusions: Regular aspirin and/or NSAID use is associated with a lower risk of colorectal cancer and is tied to specific genetic variants.Summary: There is data that suggests that the use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a lower risk of colorectal neoplasms. (Chan AT, JAMA 2005; 294:914-923 and Friis S et al, Cancer Causes Control 2009; 20:731-740 and Rothwell PM et al, Lancet 2010; 376:1741-1750 Since virtually all vascular surgical patients are treated with aspirin or other antiplatelet agents with potential anti-inflammatory actions, the association of decreased colorectal cancer risks in such patients is of potential interest to those treating vascular surgical patients. The mechanisms, however, behind the association are not well understood. Chemo prevention of cancer is not currently recommended because of the uncertainty of risk benefit profile. The authors sought to identify genetic markers that characterize individuals who may obtain differential benefit from aspirin and NSAIDs. They conducted a discover-based, genome-wide analysis of gene X environment interactions between use of aspirin, NSAIDs or both and single nucleotide polymorphisms (SNPs) in relation to risk of colorectal cancer. This was a case controlled study using data from 5 case-control and 5 cohort studies initiated between 1976 and 2003 across the United States, Canada, Australia and Germany including colorectal cancer cases (N ¼ 8634) and matched controls (N ¼ 8553), ascertained between 1976 and 2011. All participants were of European descent. Overall regular use of aspirin and/or NSAIDs was associated with a lower risk of colorectal cancer (prevalence, 28% vs 38%; odd ratio [OR], 0.69 [95% CI, 0.64-0.74]; P ¼ 6.2 x 10 À28 ) compared with nonregular use. In the conventional logistic regression analysis, the SNP rs2965667 at chromosome 12p12.3 near the MGST1 gene showed a genome-wide significant interaction with aspirin and/or NSAID use (P ¼ 4.6 x 10 À9 for interaction). Aspirin and/or NSAID use was associated with a lower risk of colorectal cancer among individuals with re2965667-TT genotype (prevalence, 28% vs 38% OR, 0.66 [95% CI, 0.61-0.70]; P ¼ 7.7 x 10 À33 ) but with a higher rate risk among those with rare TA or AA genotypes (prevalence, 35% vs 29%; OR, 1.89 [95% CI, 1.27-2.81]; P ¼ .002). In case-only interaction analysis, the SNP re 16973225 at chromosome 15q25.2 near the IL16 gene showed a genome-wide significant interaction with use of aspirin and/or NSAIDs (P ¼ 8.2 x 10 À9 for interaction). Regular use was associated with a lower risk of colorectal cancer among individuals with rs16973225-AA genotype (prevalence, 28% vs 38%; OR, 0.66 [95% CI, 0.62-0.71]; P¼1.9 x 10 À30 ) but was not associated with risk of colorectal cancer among those with less common (9%) AC or CC genotypes (prevalence, 36% vs 39%; OR, 0.97 [95% CI, 0.78-1.20]; P ¼ .76).

Polyneuropathie im Alter

“…Zahlreiche Medikamente wurden in der Behandlung neuropathischer Schmerzen in randomisierten placebokontrollierten Studien untersucht [33]. Entsprechend der Pathophysiologie werden Antidepressiva, natriumkanal-und kalziumkanalblockierende Antiepileptika sowie Opiate mit zusätzlichen monoaminergen Wirkmechanismen verwendet.…”

“…Mehrheitlich wurde die Wirksamkeit dieser Substanzen bei schmerzhafter DPNP und bei postherpetischer Neuralgie untersucht. Einzelne Studien wurden bei Patienten mit schmerzhafter HIV-Neuropathie und unselektierten schmerzhaften Neuropathien durchgeführt [32,33]. Die im Folgenden genannten "numbers needed to treat" (NNT) beziehen sich auf eine Schmerzreduktion ≥50 %.…”

“…Sehr unterschiedliche Ergebnisse zur Wirksamkeit zeigten selektive Serotonin-Wiederaufnahmehemmer (SSRI); sie werden daher nicht zur Behandlung neuropathischer Schmerzen empfohlen [32,33]. Paroxetin ist mit einer NNT von 2,6 eine Ausnahme.…”

“…Die Hemmung von Zytochrom-P450(CYP)2D6 ist unter dem Aspekt einer Polypharmakotherapie zu beachten. Von den Antidepressiva mit Serotonin-und Noradrenalin-Wiederaufnahmehemmung (selektive Noradrenalin-Wiederaufnahmehemmer, SNRI) wurden Venlafaxin und Duloxetin untersucht; beide waren wirksam [32,33,35]: 4 Venlafaxin: NNT 5,2; 4 Duloxetin: NNT: 4,9-5,2.…”

“…Die natriumkanalblockierenden Antiepileptika Carbamazepin (NNT 3,3; 95 %-KI 2,5-9,4) und Phenytoin (NNT 2,1; 95 %-KI 1,5-3,6) zeigten ebenfalls positive Ergebnisse in der Behandlung neuropathischer Schmerzen [32,33,36] …”