Efficacy and Safety of Intrathecal Ziconotide for the Management of Chronic Pain. A Systematic Review of the Literature and Meta-Analysis of Randomized, Placebo-Controlled Trials

Background: Chronic pain is a frequent condition that leads to a significant decline in the quality of life and most patients do not respond to medical treatment. New molecules, such as ziconotide, arise as alternatives in the management of these patients. We meant to determine the efficacy of intrathecal ziconotide in the treatment of refractory chronic pain. Databases and Data Treatment: As of February 2015, a systematic search of the literature in PubMed/MEDLINE, EMBASE, LILACS, Cochrane (Ovid), American Academy of Pain Medicine, North American Neuromodulation Society, American Pain Society and grey literature was made. We included Clinical Randomized Controlled Trials, which used ziconotide as monotherapy or combined therapy for the treatment of chronic pain. This study follows the Cochrane Collaboration methodology. The main measured outcome is the improvement of pain according to a decrease in the Visual Analogue Scale of Pain Intensity (VASPI) score. Information for other critical outcomes was assessed (improvement of pain in the Category Pain Relief Score [CPRS], Response to Treatment, Safety) with the fixed effects Mantel-Haenzhel model. Subgroup analysis was performed when increased heterogeneity demanded it. The quality of evidence for each study and each outcome was estimated with the GRADE tool of assessment. Results: The search yielded 666 results, only three of these studies were selected for analysis. All three were double blind, randomized, placebo-controlled trials. The use of ziconotide resulted in adequate pain relieve with VASPI score reduction of over 30% compared to baseline (3 studies, 595 patients, RR 2.04 [CI 95% 1.55-2.7]; p<0.00001) and CPRS improvement (3 studies, 595 patients, RR 4.2 [CI 95% 2.52-7.01]; p<0.00001). The GRADE quality of evidence was moderate due to the risk of blinding bias and indirect comparisons between studies. Conclusions: Our analysis suggests that intrathecal ziconotide is superior to placebo in the management of refractory chronic pain. The quality of evidence for this outcome was low, and further clarifying research is needed.