title: Ziconotide combination intrathecal therapy: rationale and evidence.
abstract: BACKGROUND
  Ziconotide is a nonopioid intrathecal analgesic used to manage moderate to severe chronic pain. Although ziconotide is approved in the United States for intrathecal monotherapy only, it is often used in combination with other intrathecal drugs in clinical practice.
  
  
  OBJECTIVE
  The need exists for a critical assessment of the currently available published literature on ziconotide combination therapy. This review summarizes and evaluates the publications from preclinical and clinical peer-reviewed experiments that have investigated the safety and effectiveness of ziconotide in combination with a variety of other drugs.
  
  
  RESULTS
  Eleven relevant publications were identified through a systematic search of multiple databases.
  
  
  CONCLUSIONS
  In preclinical studies, additive or synergistic antinociceptive effects were discovered when ziconotide was used in combination with morphine, clonidine, or baclofen; however, no additional antinociceptive effects were observed when bupivacaine was added to ziconotide therapy. Safety data from animal studies revealed that ziconotide did not exacerbate morphine-induced respiratory depression, or clonidine-induced hypotension or bradycardia; however, ziconotide did potentiate morphine-induced hypotension and inhibition of gastrointestinal tract motility. Results from 2 open-label trials indicated that combination ziconotide and morphine therapy produced greater analgesia than was produced by the use of either drug alone. Preliminary support for the use of ziconotide in combination with morphine, baclofen, or hydromorphone was provided by case studies.
  
  
  CONCLUSIONS
  Although clinical and preclinical studies provide some support for the use of ziconotide in combination with morphine, hydromorphone, clonidine, or baclofen, strong evidence-based data are limited. Controlled, long-term clinical trials are warranted.
authors.affiliation: University of California, San Diego, School of Medicine, La Jolla, CA 92093, USA. mswallace@ucsd.edu
authors.forename: Mark S
authors.initials: MS
authors.lastname: Wallace
authors.forename: Richard L
authors.initials: RL
authors.lastname: Rauck
authors.forename: Timothy
authors.initials: T
authors.lastname: Deer
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000627:therapeutic use; D001418:Baclofen / Q000008:administration & dosage / Q000627:therapeutic use; D003000:Clonidine / Q000008:administration & dosage / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D006801:Humans; D007278:Injections, Spinal; D009020:Morphine / Q000008:administration & dosage / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy*; D016896:Treatment Outcome; D020960:omega-Conotoxins / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D000700:Analgesics; D020960:omega-Conotoxins; D009020:Morphine; C078452:ziconotide; D001418:Baclofen; D003000:Clonidine