Several studies showed the potential for the novel analgesic ziconotide in the chronic pain setting. Two studies examined the titration schedule, rapid or slow, as a component that may affect the efficacy and safety of the treatment. In one study by Fisher and colleagues, the investigators followed 27 patients who received ziconotide for 1 year after an initial rapid titration. The median time to stable dosing was 196.5 days, with a median maintenance dose of 0.34 mcg/hour. In the slow titration study, the same investigators followed 119 patients and found that the median time to dosing stability was 279 days, with a median dose of 0.24 mcg/hour. The investigators found that slow titration was feasible and may prevent some of the adverse effects associated with ziconotide, such as dizziness and confusion. Another investigator used the slow titration schedule and found it effective, but explained in an interview that patients need appropriate counseling so that they expect a slow change, with maximum benefits seen after 6 months of treatment. A meta-analysis showed that the treatment is effective in a variety of chronic pain settings and is effective in both cancer and non-cancer-related pain.
In another front in the quest to find effective nonopioid pain management strategies, Childers and associates have found that low doses of cyclobenzaprine, a muscle relaxant related to the tricyclic class of antidepressants, when given as monotherapy, is as effective as cyclobenzaprine and ibuprofen combined. In addition, the low dose — 5 mg 3 times daily — is as effective as a higher dose used in other research with cyclobenzaprine — 10 mg 3 times daily. In this 7-day study, Childers and colleagues randomized 867 patients with acute muscle spasm of the back or neck to 5 mg of cyclobenzaprine 3 times daily or 400 mg or 800 mg of ibuprofen. All 3 treatment groups had a significant improvement over baseline (P < .001). The findings led the investigators to conclude that for musculoskeletal pain with a spasmodic component, cyclobenzaprine monotherapy, even at a low dose, is as effective as combination therapy with ibuprofen, a finding that broadens the options for patients who cannot take ibuprofen.
Two studies involving the transdermal lidocaine 5% patch show that it may have a role in both musculoskeletal and neuropathic pain. In one study, Hobart and Nalamachu reviewed the charts of 14 patients, all of whom had pain secondary to entrapment, tendonitis, and bursitis. Of these patients, 82% reported significant improvement over baseline symptoms, with an average improvement of 44%. This led the investigators to consider that the lidocaine patch may allow such patients to take lower doses of systemic analgesics. In the study involving neuropathic pain, Gammaitoni and colleagues pooled data from 3 open-label studies involving 286 geriatric patients with neuropathic pain. The patients reported a significant reduction in the degree to which pain interfered with sleep, and treatment was linked to a significant reduction in pain intensity and an increase in pain relief (P < .001 for all). Of these patients, 144 (50.3%) had a decrease over baseline of at least 30% in average daily pain. Most of the adverse events were local in nature, such as rash. These findings led the investigators to conclude that the patch may have particular value for elderly patients who are at increased risk of toxicity from systemic medications.
In another study exploring nonsystemic treatment modalities, Jabbari B. found that patients with chronic low back pain may respond to injections of botulinum toxin A. In a prospective study involving 75 patients, patients received paraspinal intramuscular injections at baseline and then at recurrence of pain, typically at 4, 8, and 12 months after the initial therapy. Although a modest number of patients reported significant improvement, 56% at 3 weeks and 54% at 2 months, the investigators did note that among initial responders, 90% responded to subsequent treatments. Among the patients overall, there were 3 adverse events — 2 transient flulike reactions and 1 episode of acute root pain after the injection.
Two drugs typically used in the treatment of neurologic disease, memantine and tiagabine, show potential in 2 different pain settings — migraine and fibromyalgia, respectively. In the first study, Sorensen and Jenson explored memantine, which is approved for the treatment of Alzheimer’s disease, as a prophylactic agent for reducing the frequency of migraine. The 18 patients in the study had been refractory to a variety of other prophylactic agents and acute migraine therapies. However, 11 of the patients described their results as excellent and 4 as good. Sorensen also investigated the anticonvulsant tiagabine as a treatment for primary fibromyalgia syndrome. The short-form of the McGill Pain Questionnaire was used. Again, the 11 patients had not responded to a variety of standard treatments, including opiates, NSAIDs, tricyclic antidepressants, and another anticonvulsant — gabapentin. In this case, 6 patients reported an excellent result and 1 reported a good result, again with the McGill short form. One patient discontinued due to nausea and sedation, and 1 patient withdrew due to a poor response. Dr. Sorensen stressed that further investigation would be necessary with both therapies, although the initial results are promising.
Duloxetine and Diabetic Neuropathic Pain
Like several antidepressants in the selective serotonin reuptake inhibitor (SSRI) class, the serotonin and norepinephrine reuptake inhibitor (SNRI) duloxetine is showing promise in the setting of diabetic neuropathic pain. In 3 studies with overlapping investigators, it was found that patients who did not have symptoms of depression obtained significant relief from duloxetine. One study by Wernicke and associates found that 2 different doses, 60 mg daily and 60 mg twice daily, are effective, well tolerated, and do not impair control of diabetes. In an open-label study focused on safety and tolerability. Raskin and colleagues found that the treatment was well tolerated, although statistically significant but clinically unremarkable changes in blood pressure and heart rate were more likely to occur in patients receiving duloxetine. The remaining study also focused on safety and tolerability, and showed that several comorbid conditions common to diabetes, such as hypertension and hypercholesterolemia, did not adversely affect the patients’ ability to tolerate duloxetine.
Dr. Ian Gilron, an anesthesiologist at Queen’s University in Ontario studied using painkillers morphine and gabapentin in patients with diabetes or shingles-related pain. On their own, each drug reduced pain by about one-quarter or one-third. Used together, they worked simultaneously on different areas of the brain, and reduced neuropathic pain by 45 per cent.In addition, patients didn’t require as much medication to get an effect.
The results of Gilron’s study will be published on April 5, 2005 in the New England Journal of Medicine.