When opioid therapy does not relieve pain or when it leaves patients with intolerable side effects, a new option might be ziconotide (SNX-111, Pfizer/Elan/ Warner-Lambert/Partner Medtronic).
In experimental studies, the fact that intrathecal ziconotide cleared rapidly suggested that it would also metabolize through the cerebrospinal fluid rapidly. One study involved 24 patients who had chronic pain from cancer, acquired immunodeficiency syndrome (AIDS), and other conditions and who experienced pain control with opioids, even when they were given intrathecally. Of those 24 patients, 19 rated their pain on the Visual Analogue Scale of Pain Intensity as 43% lower in degree and 15 patients were able to reduce their concomitant use of opioids by at least 50%. Central nervous system effects were diminished or resolved when the infusion rate was reduced or stopped.
Encouraged by these preliminary findings, researchers conducted a double-blind, placebo-controlled trial of 111 patients at 32 study centers in the U.S., Australia, and the Netherlands. Intra-thecal ziconotide was titrated over five to six days, followed by a five-day maintenance phase for responders. Non-responders could cross over to the opposite treatment group.
For patients without previously implanted medication pumps, the researchers implanted an intrathecal catheter and used an external infusion system. Because of the known risk of infection with external systems, they limited the total time frame for drug infusion to two weeks. Even so, meningitis developed in seven patients, which the researchers attributed to poor physiological status and an external catheter, not to the drug.
Mean scores on the Visual Analogue Scale improved by 53% among the patients receiving ziconotide and by only 18% in the placebo group. The drug remained effective in the maintenance phase. Half of the ziconotide patients and 17.5% of the placebo patients experienced moderate to complete pain relief. Five patients taking ziconotide reported complete pain relief. Opioid use decreased in the ziconotide patients by 10% but increased in the placebo group by 5%.
Adverse drug events caused 12 zicon-otide patients and four placebo patients to stop the treatment. Twenty others withdrew from the study for reasons such as catheter complications. As in the earlier study, although ziconotide had significantly more vestibular effects, they were easily recognizable and reversible, the researchers say.