|Ziconotide in Complex Regional Pain Syndrome
By Lynn R. Webster, MD, FACPM, FASAM
Ziconotide is a novel medication developed from marine life.
It is a synthesized peptide component of a neurotoxin secreted
by the cone shell snail, Conus magus, which is thought to
work by preventing the release of neurotransmitters involved
in the transmission of pain at the spinal cord level. Ziconotide
was recently approved by the U.S. Food and Drug Administration
(FDA) for the treatment of chronic severe pain in which intrathecal
(IT) therapy is warranted. In IT therapy, medication is delivered
by catheter to the spinal fluid by means of an internal pump
implanted in the abdomen.
Candidates for IT therapy are people with moderate-to-severe
pain who failed systemic medication therapy or experienced
intolerable side effects due to oral medications. To be considered
for ziconotide therapy, it is important that patients have
realistic expectations regarding treatment of their pain and
have complied with past treatments. Some therapeutic goals
of IT therapy include achieving greater than 50% pain relief,
reduction of side effects, and improvement in patient quality
of life and function.
Ziconotide has not been formally studied in patients only
with complex regional pain syndrome (CRPS); however, its
safety and efficacy have been evaluated in three double-blind,
placebo-controlled studies, and four long-term, open-label
studies. A review of these studies found 17 people who participated
in clinical trials had a diagnosis of CRPS; 11 patients
received ziconotide, and six received placebo. The mean change
in the Visual Analog Scale of Pain Intensity (VASPI) for this
subset of patients was 25.2% for patients who received ziconotide
and 2.8% for placebo.
Case Study Demonstrates Relief
In review of literature, one case report demonstrated the
benefit of ziconotide in a 16-year-old male with CRPS
involving bilateral lower extremities who had failed standard
care for CRPS. He received ziconotide in ranges from 2.5
mcg/day to 7.6 mcg/day for a reported duration of three years.
Initial response was improvement in pain reported at six weeks
on 5.5 mcg/day. The patient achieved normal gait at seven
months of therapy at a dose of 6.5 mcg/day. The dose was then
reduced to 2.8 mcg/day, and the patient reported complete
resolution of his pain after three years of therapy with ziconotide.
He experienced the side effects of urinary retention and depression
while treated with ziconotide.
Ziconotide is generally well tolerated if it is started at
a low dose of ? 1 mcg/day and titrated ? 0.5 mcg/day at no
greater then weekly intervals. Common side effects reported
in greater then 25% of patients in clinical studies include
dizziness, nausea, confusion, headache, nystagmus, and abnormal
sensations. It is important to note that the starting dose
and titration rate were greater than recommended above. Side
effects can be managed by dose reduction or cessation of therapy.
Ziconotide can be stopped abruptly without any signs of withdrawal.
Although ziconotide is FDA approved for monotherapy, the
treating physician may choose to use it in combination with
other medications in the pump. This would not deviate from
standard of practice. Ziconotide may prove additive or synergistic
when combined with other medications in pump.
Ziconotide is a novel medication in the armamentarium to
combat moderate-to-severe chronic pain. A review of clinical
trial data and scientific literature shows that ziconotide
may benefit patients with CRPS who have failed standard
therapies. Responsible use of ziconotide will ensure its success.
However, it is important to manage both physician and patient
expectations; at the recommended starting dose and titration,
it may take a few months to reach therapeutic benefit. As
demonstrated above in the case report, maximum benefit was
not achieved for several months, and immediate gratification
should not be expected.
Lynn R. Webster, MD, FACPM, FASAM, is Medical Director, Lifetree
Pain Clinic; Medical Director and CEO, Lifetree Clinical Research,
President, Utah Academy of Pain Medicine, and Chief of Anesthesiology
at the Health South Salt Lake Surgical Center. He is board
certified in anesthesiology and pain management and is also
certified in addiction medicine.
Updated October 7, 2005