Interventional Therapy: Intrathecal Therapy Trials With Ziconotide
by David Caraway, MD, PhD; Michael Saulino, MD, PhD; Robert Fisher, MD; Stuart
 The 2007 Polyanalgesic Consensus Panel recommends
ziconotide as one of three options for first-line intrathecal (IT) monotherapy. As we all
know, Medicare and most insurance companies require a trial of IT therapy before one can
proceed with implantation of a delivery system. Unlike opioids, which produce their effect
within hours of administration, ziconotide may require several days of administration to
demonstrate effectiveness. Ziconotide trials may require more rapid titration than would
otherwise be used for chronic administration. Unfortunately, rapid administration of IT
ziconotide can produce therapy-limiting side effects. The following article by Caraway et
al provides us with a practical way to address the trialing requirement for ziconotide.
Until the requirement for trialing is changed or eliminated, this guide should be very
helpful to those who want to use ziconotide as monotherapy.
— Lynn Webster, MD, FACPM, FASAM
Department Head
Intrathecal (IT) therapy is a well-established technique for the management of chronic,
severe pain. Intrathecal therapy trials provide an opportunity to assess both the positive
and negative aspects of a patient’s experience with IT therapy before committing to
long-term treatment with a fully implanted infusion system. Numerous protocols have been
used for trials of IT medications, and no protocol can be considered superior based on the
available literature. The choice of a trialing protocol is dependent on many factors
including (but not limited to) patient condition, available facilities and resources, and
practice environment.1,2 Ultimately, the protocol choice is determined by the
physician’s standard of care and comfort with the procedure,3 but
insurance companies may require specific trialing criteria for reimbursement. In the
United States, Medicare requires that a preliminary trial “be undertaken with a
temporary intrathecal/epidural catheter to substantiate adequately acceptable pain relief
and degree of side effects (including effects on the activities of daily living) and
patient acceptance.”4
In 2004, ziconotide became the first non-opioid IT analgesic agent approved by the U.S.
Food and Drug Administration for treatment of severe chronic pain. Ziconotide is the
synthetic equivalent of a neuroactive peptide isolated from the venom of the fish-eating
marine snail, Conus magus. Ziconotide can be considered for treatment of patients who are
intolerant of, or refractory to, systemic analgesics and adjunctive therapies or who are
intolerant of, or refractory to, other IT therapies such as IT morphine.5,6
Ziconotide has been evaluated for treatment of chronic pain caused by malignant or
nonmalignant conditions in three randomized, double-blind, placebo-controlled clinical
studies.7-9 In the two earlier studies,8,9 ziconotide administration
began with a dose of 9.6 mcg/d and titration occurred as often as twice daily. To mitigate
the frequency and severity of adverse events observed during the earlier studies, the
starting dose was lowered to 2.4 mcg/d while the studies were ongoing. In the more recent
study,7 ziconotide was initiated at 2.4 mcg/d with 1.2- to 2.4-mcg/d increases
occurring no more than once during a 24-hour period.
Please refer to the March 2008 issue for the complete text. In the event you need to order a back issue, please click here.
— March 2008
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