Can Ziconotide Be Used to Replace Opioids? Exploratory Clinical Experience in 5 Patients Treated in the Pain Unit

Ziconotide and morphine are intrathecal (IT) drugs approved by the FDA and EMA for the treatment of chronic pain. The aim of this study was to determine whether opioid rescue can be achieved by gradually increasing doses of ziconotide, and to establish a practical protocol for its implementation.

Five patients unresponsive to IT morphine due to lack of efficacy or adverse events such as endocrine dysfunction, constipation and tolerance were selected. All had refractory, neuropathic or mixed pain. Ziconotide was gradually introduced while maintaining or reducing morphine doses in proportion to the ziconotide titration. Dose adjustments were made every 2 weeks, with a weekly ziconotide increase of 0.5 μg.

Of the five patients, three were female and two were male, with ages ranging from 53 to 75 years. Two had cancer (one with colon cancer and one with osteosarcoma), two had persistent spinal pain syndrome type 2, and one had spastic paraparesis. After 6 weeks of ziconotide treatment, all individuals showed a substantial reduction in daily morphine dosage (from 10 to 5.5 mg/day), which was associated with improved control of adverse events. Similarly, notable reductions were observed in pain intensity (from 8.0 to 2.5, measured by VAS) and neuropathic symptoms (from 6.0 to 2.0, measured by DN4). The most frequently improved neuropathic symptoms included tingling (4 patients), hypoesthesia to touch (3 patients), and pain evoked by brushing (3 patients). The duration of the rescue protocol ranged from 5 to 11 weeks.

Intrathecal opioid rescue with ziconotide emerges as a viable therapeutic option for patients with refractory pain and a neuropathic component, or for those who develop adverse events associated with IT morphine. Low doses and slow titration of ziconotide may help minimize adverse events while maintaining analgesic benefit.