Safety and efficacy of intrathecal ziconotide: a literature review

Abstract

Intrathecal Ziconotide (ITZ) is a non-opioid analgesic used to control chronic pain in patients intolerant or refractory to oral and other intrathecal analgesics. A review of the literature was conducted to assess the safety and efficacy of this intrathecal agent in chronic pain patients. A search from 2006-2011 was conducted using PubMed, OVID, and Google Scholar. Four papers identified met inclusion (an implanted infusion system in chronic pain patients whose next step in therapy was intrathecal treatment) and exclusion criteria (no exposure to an investigational drug in thirty days). In a randomized double blind placebo controlled study (n=248), 112 patients were treated with ITZ and 108 randomized to placebo. Results showed significant reduction (>30%) in pain after one and three weeks of therapy, but greater frequency (p=0.023) of mild to moderate adverse effects (AE's) with ITZ versus placebo. Review of a retrospective cohort study yielded that despite reports of one mild to moderate AE by 63% of ITZ treated patients (n=104), statistically significant pain reduction (p<0.01) was still achieved after only one month of treatment. Analysis of multicenter open-label, long-term studies reveal that despite higher discontinuation rates over an extended time period, subjects tolerant of AE's from ITZ received prolonged and effective analgesic response when compared to alternative intrathecal therapies. Those with more severe pain treated with high doses of ITZ at longer duration (>90 days) exhibited more effective pain reduction (32% for VASPI score >50 mm versus 15% for VASPI score <50mm) without tolerance, respiratory depression, dependence, or withdrawal. In conclusion this first-line, non-opiod agent is both efficacious and safe for short-term management of refractory chronic pain once each patient's therapeutic window is identified. Slow dose titration yielded better patient retention and improved safety profile in long term treatment. Intrathecal Ziconotide (ITZ) is a non-opioid analgesic used to control chronic pain in patients intolerant or refractory to oral and other intrathecal analgesics. A review of the literature was conducted to assess the safety and efficacy of this intrathecal agent in chronic pain patients. A search from 2006-2011 was conducted using PubMed, OVID, and Google Scholar. Four papers identified met inclusion (an implanted infusion system in chronic pain patients whose next step in therapy was intrathecal treatment) and exclusion criteria (no exposure to an investigational drug in thirty days). In a randomized double blind placebo controlled study (n=248), 112 patients were treated with ITZ and 108 randomized to placebo. Results showed significant reduction (>30%) in pain after one and three weeks of therapy, but greater frequency (p=0.023) of mild to moderate adverse effects (AE's) with ITZ versus placebo. Review of a retrospective cohort study yielded that despite reports of one mild to moderate AE by 63% of ITZ treated patients (n=104), statistically significant pain reduction (p<0.01) was still achieved after only one month of treatment. Analysis of multicenter open-label, long-term studies reveal that despite higher discontinuation rates over an extended time period, subjects tolerant of AE's from ITZ received prolonged and effective analgesic response when compared to alternative intrathecal therapies. Those with more severe pain treated with high doses of ITZ at longer duration (>90 days) exhibited more effective pain reduction (32% for VASPI score >50 mm versus 15% for VASPI score <50mm) without tolerance, respiratory depression, dependence, or withdrawal. In conclusion this first-line, non-opiod agent is both efficacious and safe for short-term management of refractory chronic pain once each patient's therapeutic window is identified. Slow dose titration yielded better patient retention and improved safety profile in long term treatment.