COLUMBUS, Ohio--Recent clinical reports of nontraditional analgesics,
like calcitonin, gabapentin (Neurontin), and tramadol (Ultram),
suggest that these drugs may successfully control cancer pain in some
patients, said Mary Beth Shirk, PharmD, clinical assistant professor,
College of Pharmacy, Ohio State University. In some patients, the
drugs have been shown to be effective against neuropathic pain.
Although the analgesic pharmacology of these agents is still under
investigation, history has shown that drugs are often identified as
painkillers long before their mechanism of action is fully
understood. Dr. Shirk described the findings of nearly 20 recent
clinical reports conducted worldwide at a conference on narcotics and
pain management sponsored by Ohio State University .
Tramadol. A double-blind, placebo-controlled
study of 23 patients with diabetic neuropathy suggests that tramadol,
known to be effective against postoperative and acute pain, may also
be effective against neuropathic pain (Erdine: 8th World Congress on
Pain, 1996). However, its potential side effects are serious, Dr.
Shirk said. Nausea is common, as is dizziness. "Its
important to start with low doses and titrate up slowly," she
told Oncology News International. In the study reported by Erdine,
patients received 100 mg of tramadol every 12 hours.
Gabapentin. This agent, approved in 1994 as an
adjunctive agent for seizure control, has been shown to be effective
for neuropathic pain, Dr. Shirk said. A study of 82 patients with
chronic pain showed a "favorable response" with gabapentin
(Frinkel: American Pain Society Annual Meeting, 1995).
Side effects, which may include somnolence and dizziness, are minor.
Blood monitoring with gabapentin is unnecessary. The dose must be
adjusted for renal dysfunction, however, Dr. Shirk said. She also
pointed out that gabapentin is a very expensive medication.
Calcitonin. Salmon calcitonin has been studied
for its analgesic properties since the 1970s. The data suggest it is
effective as an analgesic for bone pain. "It may prevent the
development of problems for patients at high-risk for bone
metastasis," Dr. Shirk said. She anticipates continued research
in this area.
Another promising area for calcitonin is its use with phantom limb
pain. In one cross-over study, 21 patients were given an infusion of
salmon calcitonin. One week after treatment, 19 patients reported
pain relief of more than 50%, and 76% were pain free (Jaeger H, Maier
C: Pain 48:21-27, 1992).
Dextromethorphan. NMDA receptor antagonists,
like dextromethorphan, are new in pain management and have shown
promise. "This is an exciting area," Dr. Shirk said. Animal
studies suggest that dextromethorphan can prevent opioid tolerance
and can even reverse opioid tolerance once it develops.
Small studies have been conducted examining the use of
dextromethorphan to treat neuropathic pain. Although one such study
found no significant difference between dextromethorphan and placebo,
Dr. Shirk described the study design as "questionable"
(McQuay HJ et al: Pain 59:127-133, 1994). Another study
reported blurred vision, sedation, and dizziness as side effects
associated with dextromethorphan (Park: Annual Meeting of the
American Pain Society, 1995).
Ketamine. There has been an increase in interest
in ketamine (Ketalar), an anesthetic drug, in the past few years, Dr.
Shirk said. Ketamine, an NMDA receptor antagonist, has been studied
in cancer pain, neuropathic pain, phantom limb pain, postoperative
pain, and post-herpetic neuralgia. In a study of 18 patients with
cancer pain, ketamine was effective in 13 patients (Oshima E et al: Canad
J Anaesth 37:385-386, 1990). "We find it very effective for
resistant patients who are on high-dose opioids," Dr. Shirk told
Oncology News International.
The side effects of ketamine include hallucinations and out-of-body
experiences. Although ketamine is not a controlled substance, "it
should be," she said. It is very similar to the street drug
known as "angel dust" and is sold on the street as
Capsaicin. Capsaicin (Zostrix), an over-the-counter cream
derived from hot chili peppers, has been studied for use in
neuropathic pain. In one study, 13 of 19 patients with postmastectomy
pain syndrome reported a reduction in pain with use of topical
capsaicin. Two patients reported a complete disappearance of all
symptoms (Dini D et al: Pain 54:223-226, 1993).
"The potential toxicities of this product are tremendous,"
Dr. Shirk said, and may include burning, stinging, erythema, cough,
and respiratory irritation. Patients need to be taught how to use
this product, including avoiding contact with the eyes and using
caution when handling contact lens after application.
Paroxetine. The antidepressant paroxetine
(Paxil), a selective serotonin reuptake inhibitor, has been studied
for its effectiveness in diabetic neuropathy. Nineteen patients
completed a study comparing paroxetine with imipramine. The
researchers concluded that paroxe-tine significantly reduced the
symptoms of peripheral diabetic neuropathy (Sindrup SH et al: Pain 42:135-144,
These adjuvant drugs show individual variation from patient to
patient, Dr. Shirk said, and it is very important to monitor their
effectiveness, especially since they are quite expensive.
"Its really important to evaluate the drugs efficacy
and to discontinue the agent if its not improving quality of
life for your patient," she said.