• Gladstone C McDowell and Jason E Pope.
• Integrated Pain Solutions, Columbus, OH, USA.
• Neuromodulation. 2016 Jul 1; 19 (5): 522-32.

IntroductionZiconotide is a non-opioid analgesic for intrathecal (IT) administration. The aim of this review is to provide a comprehensive and clinically relevant summary of the literature on dosing and administration with IT ziconotide in the management of refractory chronic pain, and to describe novel dosing strategies intended to improve clinical outcomes.Materials And MethodsA Medline search was conducted for "ziconotide," supplemented by manual searching of published bibliographies and abstracts from conferences.ResultsEarly experience with IT ziconotide in clinical trials combined with improved understanding of drug pharmacokinetics in the cerebrospinal fluid have led to a reappraisal of approaches to trialing and initiation of continuous-infusion therapy in an effort to improve tolerability. The traditional paradigm of trialing by inpatient continuous infusion may be shifting toward outpatient trialing by IT bolus, although definitions of success and specific protocols remain to be agreed upon. Expert consensus on IT continuous infusion with ziconotide suggests a starting dose of 0.5 to 1.2 mcg/day followed by dose titration of ≤0.5 mcg/day on a no more than weekly basis, according to individual patients' pain reductions and regimen tolerability.DiscussionNewer modalities that include patient-controlled analgesia and nocturnal flex dosing have been shown to hold promise of further improvements in ziconotide efficacy and tolerability.ConclusionsClinical trials and experience confirm the feasibility and usefulness of IT ziconotide in the management of refractory chronic pain. Emerging evidence suggests that additional IT delivery options may further expand the usefulness and benefits of ziconotide.© 2016 The Authors. Neuromodulation: Technology at the Neural Interface.

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