52 Pain Medicine C LINICAL P SYCHIATRY N EWS • July 2005 Patients Seek Natural Alternatives to NSAIDs

BY DOUG BRUNK phenolic glycosides, tannins, and fla- la, Fraxinus excelsior, and Solidago virgaurea. Complement. Altern. Med. 2004;4:13). San Diego Bureau vanoids. In a double-blind, placebo-con- Of the nine randomized, controlled trials Ǡ SAMe (S-adenosylmethionine). This trolled trial of 21 patients who took 240 involving phytodolor, those with a place- is an endogenous methyl donor that is a L A J OLLA, CALIF. — The recall of mg of salicin over a 2-week period, West- bo arm demonstrated superiority of naturally occurring product of the reac- Vioxx and safety warnings about Cele- ern Ontario and McMaster Universities phytodolor; six trials with a comparison tion between methionine and adenosine brex and Bextra created “a very insecure Osteoarthritis Index (WOMAC) pain group showed no benefit of phytodolor triphosphate (ATP). It is postulated to time for pain management,” Robert scores were reduced 40%, compared with over NSAIDs. have anti-inflammatory effects through Bonakdar, M.D., said at a meeting on nat- a 16% reduction among those on placebo. One trial found a dose response to dou- inhibition of tumor necrosis factor–α and ural supplements in evidence-based prac- At 2 weeks, the anal- ble-strength phytodo- upregulation of proteoglycan synthesis tice sponsored by the Scripps Clinic. gesic effect from wil- ‘People with higher pain lor vs. regular dosing and secretion into chondrocytes. SAMe But well before concern surfaced about low bark was as- at 2 weeks. also appears to have a serotonergic effect the safety of those drugs, patients with in- sessed to be about intensity and duration, and The typical dose in that may support its pain-modulating abil- flammatory disease increasingly began to 40% of that from those with a greater degree trials is 30 drops of ities. seek care from providers of complemen- high-dose NSAIDs. standardized extract In a metaanalysis of 11 osteoarthritis tri- tary and alternative medicine (CAM) be- “There is a dose- of self-care, are going to t.i.d. als, SAMe appeared to be as effective as cause they were dissatisfied with tradi- response relation- end up in more CAM Ǡ Devil’s claw NSAIDs in reducing pain and improving tional care results. ship,” Dr. Bonakdar (Harpagophytum functionality with fewer adverse effects “They thank their doctor for the said at the meeting, offices.’ procumbens). This than NSAIDS (J. Fam. Pract. 2002;51:425- NSAIDs, for the advice, for [the referral to] cosponsored by the South African plant is 30). SAMe is typically initiated in the 200- physical therapy, but they still have pain,” University of California, San Diego. A used for arthritis, myalgia, and as an ex- to 400-mg range and titrated to between said Dr. Bonakdar, director of pain man- randomized, double-blind placebo-con- ternal ointment for burns or sores. Its ac- 600 and 1,200 mg with caution regarding agement at the Scripps Center for Inte- trolled trial of 210 patients with low back tive ingredients are harpagoside and β- its serotonergic effects. grative Medicine, La Jolla, Calif. “Also, pain who took 120 mg or 240 mg salicin sitosterol. Other natural supplements such as gin- people with higher pain intensity and du- demonstrated complete relief from pain in There have been four double-blind, ger (Zingiber officinale), boswellia (Boswellia ration, and those with a greater degree of 21% and 39% of patients, respectively placebo-controlled trials involving 50-197 serrata), turmeric (Curcuma longa), and es- self-care, are going to end up in more (Am. J. Med. 2000;109:9-14). patients with osteoarthritis and low back sential fatty acids have also demonstrated CAM offices.” Only 6% of patients in the placebo pain. Patients were treated for 3-8 weeks anti-inflammatory activity in preliminary He discussed the following natural sup- group reported complete relief from pain. with 50-100 mg harpagosides/iridoid con- basic research or human trials. While these plements, which have been found useful in The dosage used in trials varies, but it is tent of 1.5%-3% (the typical dose in trials). and other natural supplements have been treating pain associated with inflammato- typically standardized to 240 g salicin/day. The treatments significantly improved documented for the treatment of pain, Dr. ry disease: Ǡ Phytodolor. Available since 1963, this the pain level and joint mobility in study Bonakdar emphasized that “further well- Ǡ Willow bark (Salix spp.). This agent patented supplement is from Germany. It participants. Side effects have included done trials are required to advance un- contains multiple constituents including contains 1 mg salicin/mL, Populus tremu- mild and infrequent GI symptoms (BMC derstanding.” ■ Low-Dose Combos Top High- Just 45% of Pain Patients Dose Monotherapy for Sciatica Take OxyContin as Prescribed

BY TIMOTHY F. KIRN more dose-finding studies are needed. BY BETSY BATES pliant if the level of OxyContin in his or Sacramento Bureau In a report on two combined studies in- Los Angeles Bureau her urine was within three standard de- volving 1,405 patients with low back or viations of the mean. Interestingly, about S NOWMASS, COLO. — Sciatica and neck pain, participants were randomly as- PALM S PRINGS, CALIF. — Just 45% 15% of patients prescribed OxyContin low back pain respond best to low doses signed to take the muscle relaxant cy- of prescriptions for the opiate OxyCon- had none of the drug in their urine. of medications used in combination as op- clobenzaprine or placebo. Dr. Borenstein tin (oxycodone HCl controlled release) At the same time, many patients being posed to high-dose monotherapy, David G. noted that the cyclobenzaprine outper- are taken as directed by patients being treated with alternative pain drugs in the Borenstein, M.D., said at a symposium formed placebo in three primary, patient- treated for nonmalignant pain, according clinics had OxyContin in their urine, sponsored by the American College of rated end points: relief from pain at the to a study of urine samples from ap- suggesting that “most of the diversion Rheumatology. start of the day, assessment of medication proximately 5% of the nation’s outpa- was patient to patient,” Dr. Kell said. There are no magic bullets. Instead, “it’s helpfulness, and clinical global impression tient pain clinics. “There is an incredible amount of di- trial and error and seeing what works with of change. Fully 40% of the drug was recycled version on the street [as well]. We tend a patient,” said Dr. Borenstein, a textbook Interestingly, when the researchers among other patients being treated for to be in denial,” he added. author and researcher who practices in a looked at three doses—2.5 mg, 5 mg, and pain in 264 clinics whose combined case- Funding for Dr. Kell’s study was pro- rheumatology group in Washington. 10 mg—each taken three times daily, they loads exceeded 33,000 patients, Michael vided by UD Testing Inc., a Marco Island, According to prescribing patterns, it ap- found that all the doses were more effec- Kell, M.D., of the Labyrinth Institute of Fla., company that uses Dr. Kell’s soft- pears that muscle relaxants are among tive than placebo. The 5-mg dose was no Smyrna, Ga., reported at the annual ware to monitor patient compliance with the most effective medications for back less effective than the 10-mg dose and was meeting of the American Academy of prescription medicine. pain, but they’re more effective when used less likely to cause sedation, Dr. Borenstein Pain Medicine. Another study presented at the meet- in combination with other medications. said (Clin. Ther. 2003;25:1056-73). Another 15% of OxyContin prescrip- ing described very preliminary results In a telephone survey of patients with Future strategies for treating low back tions were diverted to the black market, from a novel oxycodone drug formula- acute low back pain contacted 1 week af- pain may involve biologics such as inflix- said Dr. Kell, who was chosen to present tion called Remoxy. The formulation de- ter an office visit, the best outcomes ap- imab, Dr. Borenstein said. his poster in an oral format at the meet- livers a long-acting dose of the opiate in peared to be associated with a combina- Yet to be published open-label trials of ing. Dr. Kell, a toxicologist, collected his a gel cap designed to be impervious to ef- tion treatment using a muscle relaxant and infliximab, conducted in Finland, have data using software technology that in- forts to extract the full dose to achieve a an NSAID together. Other respondents shown significant efficacy within hours of terprets highly specific urinalysis results “spike” effect by crushing, freezing, heat- were taking no medication, or opioids, ac- patients’ receiving a single injection, com- that control for urine concentration and ing, or dissolving it in various substances. etaminophen, and muscle relaxants alone pared with controls that were given sham acidity and patient body mass index Current formulations of the drug can (Spine 1998;23:607-14). injections of saline. (BMI). be manipulated in this way, adding to Dr. Borenstein said the survey findings Yet the only double-blinded, controlled The urine from 55% of approximate- abuse and diversion. are consistent with his own clinical expe- trial reported to date found no benefit rel- ly 11,000 patients prescribed OxyContin Plasma concentrations were marked- rience using combination regimens, ative to placebo. The lack of efficacy either contained more of the drug, or ly lower in 20 subjects who took Remoxy which he said can minimize side effects seen in this unpublished trial may have less, than what would be expected based after it had been tampered with, com- and have a synergistic effect. He added been due to the high placebo response, on the amount prescribed to them. To al- pared with concentrations among people that providers could use a lot more guid- Dr. Borenstein said. Another trial is un- low for time of day and other varia- who had taken crushed controlled-re- ance on how to use drugs in combination; derway. ■ tions, Dr. Kell considered a patient com- lease formulations of oxycodone. ■