1. 2009;12;E291-E296Intrathecal Ziconotide and Opioid Combination Therapy for Noncancer Pain: An Observational Study
   Observational Study
   Richard Bowman, MD, Diana Tolentino, , Christopher Kim, MD, Timothy R. Deer, MD, C Stewart, , and Wilfrido Tolentino, .

BACKGROUND: Intrathecal ziconotide is used to manage severe chronic pain. Although ziconotide is approved by the US Food and Drug Administration for monotherapy, it is sometimes used in combination with other intrathecal drugs for the management of intractable pain conditions in clinical practice.

OBJECTIVES: Evaluate the safety and tolerability of ziconotide combination therapy.

STUDY DESIGN: A retrospective, observational study.

SETTING: A single center.

METHODS: Patients with severe chronic pain of noncancer origin who were receiving inadequate analgesia with intrathecal opioid therapy (with or without intrathecal adjuvants) and who had ziconotide added to their intrathecal regimens were included. Patient characteristics, intrathecal ziconotide doses, concomitant intrathecal and systemic drug use, visual analog scale pain scores, Oswestry Disability Index scores, mini-mental status examination scores, neurological examination results, clinical observations (including adverse event reports), and equipment complications were reviewed for 12 weeks after ziconotide initiation.

RESULTS: Sixteen patients were identified. Ziconotide was initiated at a dose of 0.5 mcg/d and titrated to a mean dose of 2.64 mcg/d at week 12. Intrathecal opioids were hydromorphone (n=7), morphine (n=5), fentanyl (n=3), and sufentanil (n=1). Adverse events were noted in one patient, who reported increased depression and pain during combination therapy; ziconotide treatment was discontinued, and all adverse events resolved over a 4-week period. Substantial pain relief (≥4-point decrease in visual analog scale score) was reported in 3 of 15 patients (20.0%) and increased functional capacity was evident in 3 of 15 patients (20.0%).

LIMITATIONS: A retrospective study with a limited number of patients from a single center.

CONCLUSION: Results from this observational study suggest that combination intrathecal ziconotide and opioid therapy may be a safe and potentially effective treatment option for patients with refractory chronic pain. Controlled, prospective clinical trials to evaluate ziconotide combination therapy are needed.