Open-label, multicenter study of combined intrathecal morphine and ziconotide: addition of morphine in patients receiving ziconotide for severe chronic pain.

OBJECTIVE To assess the safety and efficacy of adding intrathecal morphine to intrathecal ziconotide in patients treated with stable ziconotide doses. DESIGN Multicenter, open-label study with a 4-week morphine titration phase during which ziconotide was held constant and an extension phase during which dosing of either drug could vary. SETTING Outpatient clinics. PATIENTS Patients with suboptimal pain relief receiving stable ziconotide doses (> or = 4.8 microg/day) in one of two ongoing ziconotide trials. INTERVENTIONS Ziconotide dosing remained constant during the titration phase; intrathecal morphine titration was based on each patient's daily systemic opioid dose at the study's start. During the extension phase, intrathecal ziconotide and morphine dosing were adjusted per investigator discretion. OUTCOME MEASURES Safety was assessed primarily via adverse events. Efficacy was analyzed via percentage change on the visual analog scale of pain intensity and in weekly systemic opioid consumption. RESULTS Twenty-five patients enrolled. The most common (> or = 10% of patients in either study phase) study drug-related (i.e., ziconotide/morphine combination [or ziconotide monotherapy in the extension phase only]) treatment-emergent adverse events included dizziness, peripheral edema, pruritus, and nausea. From the initial visit to week 4, visual analog scale of pain intensity scores improved by a mean of 26.3% (95% confidence interval: 15.6%-37.1%) but varied during the extension phase (mean percentage change from the initial visit ranged from -0.4% at week 16 to -35.0% at week 72). Mean percentage decrease in systemic opioid consumption from the initial visit was 49.1% at week 4 and 51.2% at week 56 of the extension phase. CONCLUSIONS Intrathecal morphine, combined with stable intrathecal ziconotide doses, reduced pain in patients with previously suboptimal pain relief on ziconotide monotherapy.