Clinical Briefs
With Comments from John La Puma, MD, FACP
Acupunture for HIV-Related Peripheral Neuropathy
March 1999; Volume 2: 35
Source: Shlay JC, et al. Acupuncture and amitriptyline for pain due to HIV-related peripheral neuropathy: A randomized controlled trial. JAMA 1998;280:1590-1595.
Peripheral neuropathy is common in persons infected with HIV but few data on symptomatic treatment are available. We conducted a randomized, placebo-controlled multicenter clinical trial to evaluate the efficacy of a standardized acupuncture regimen (SAR) and amitriptyline hydrochloride for the relief of pain due to HIV-related peripheral neuropathy. The interventions were SAR vs. control (sham acupuncture) points; amitriptyline 75 mg nightly vs. placebo, or both for 14 weeks. Of 250 patients enrolled, 125 were in a modified double-blind 2 x 2 factorial design of SAR, amitriptyline, or the combination compared with placebo; 114 were in SAR vs. control; and 11 were in amitriptyline vs. placebo.
Patients in all groups showed reduction in mean pain scores at six and 14 weeks compared with baseline values. For both the acupuncture/amitriptyline comparisons, changes in pain scores were not significantly different between the two groups. At six weeks, the estimated difference in pain reduction for patients in the SAR group compared with those in the control points group was 0.01 (P = 0.88, 95% CI -0.11 to 0.12) and for patients in the amitriptyline group vs. those in the placebo group was 0.07 (P = 0.38, CI -0.22 to 0.08). At 14 weeks the difference for those in the SAR group compared with those in the control points group was -0.08 (P = 0.26, CI -0.21 to 0.06) and for amitriptyline compared with placebo was 0 (P = 0.99, CI -0.8 to 0.19).
In this study, neither acupuncture nor amitriptyline was more effective than placebo in relieving pain caused by HIV-related peripheral neuropathy.
COMMENT
Supported in part by the National Institute of Allergy and Infectious Diseases, this well-designed multicenter national trial found a modest decline in pain scores in all groups. The investigators attributed their results to a placebo effect or time of entry in the trial.
The acupuncture treatments were administered twice weekly for six weeks, and once weekly for eight weeks thereafter. Exclusion criteria included taking a tricyclic or a MAOI two weeks before randomization. There were no statistically significant differences in adverse effects or discontinuations.
Consensus on the SAR was reached by nine acupuncturists before protocol implementation, but some believe that acupuncture of even "nonclassical points" may have analgesic effects. Studying standardized points allows a conclusion to be drawn about acupuncture as a whole, say the authors, but not individualized treatments. The control (sham) points chosen were three in a line on the back of the calf. The usefulness of sham acupuncture has been debated, even as a blinded research technique.
A statistically significant number of patients who reported moderate or more relief at 14 weeks tended to guess they were receiving SAR and not the control (sham) acupuncture. In contrast, regardless of their level of pain relief, those who took amitriptyline also correctly guessed the study treatment.
Latin for "I shall please," a placebo can be a powerful medicine. Here, two systems of pain control, representing two powerful belief systems, demonstrated no more effect than placebo. Whether placebos can improve symptoms by reducing stress, creating specific biochemical reactions, or playing on the brain’s conditioning and expectancy no one knows. But the idea that the mind and body are separate is probably false—some of the time, for some people, and some diseases.
Recommendation
This difficult-to-treat disease awaits effective medical therapy. Much lower dose amitriptyline (10 mg nightly) and off-label use of gabapentin for treatment of peripheral neuropathy are common in primary care.
Spinal Surgical Alternative: Exercise?
March 1999; Volume 2: 35-36
Source: Nelson BW, et al. Can spinal surgery be prevented by aggressive strengthening exercises? A prospective study of cervical and lumbar patients. Arch Phys Med Rehabil 1999;80:20-25.
To determine if patients recommended for spinal surgery can avoid it through an aggressive strengthening program, a privately owned medical clinic treated consecutive referred patients. Study entry criteria included a physician’s recommendation for lumbar or cervical surgery, no medical condition preventing exercise, and willingness to participate in an outpatient 10-week program.
Intensive, progressive resistance exercise of the isolated lumbar or cervical spine was practiced and continued to failure, and patients were encouraged to work through their pain. Forty-six of 60 participants completed the program; 38 were available for follow-up (average 16 months, range 12-30 months after discharge); three required surgery after completing the program.
COMMENT
Back pain hurts. It is the leading cause of disability in the United States, and a pile of frustration among practitioners and patients alike. It is also expensive—early 1990s data from the Worker’s Compensation Back Pain Claim Study show that "the average cost per industrial back injury in the U.S. is now more than $24,000." Here, the authors present surgical cost data of $60,000 for a cervical laminectomy and more than $168,000 for a lumbar fusion.
Of 651 patients referred for rehab, 62 with chronic pain (mean 28 months) met the inclusion criteria. Sixty began the outpatient program; 14 dropped out. Twenty-eight men and 18 women, mean age 42, completed the 10 weeks in an average of 21 visits, most to physical therapists. Nearly all patients—90%—had already tried and failed some type of exercise program.
The program emphasized progressive resistance, and used lumbar and cervical extension devices to isolate and strengthen lumbar extensors, cervical extensors and rotators, and thoracic rotators. A self-monitored maintenance program was also taught to maintain strength, vigor, self-care, and newly improved body mechanics.
Statistically significant gains in strength for lumbar and cervical extensor and rotator muscles in men and women were reported, and only three patients underwent surgery.
These Minneapolis area authors acknowledge their methodologic limitations—unblinded, no control group, no randomization, selection bias, variable follow-up, only regrets offered for the nearly one-quarter drop-out. Yet they observe that even patients recommended for spinal surgery can tolerate intensive, specific exercise. By specific they mean isolated musculature; by intensive they mean muscular exercise against dynamic resistance to volitional failure, through a full range of motion.
These bold investigators take a hands-on approach to patients famed for fragility, who "develop a keen sense of fear when it comes to spinal motion ... few understood that literally millions of people develop the same radiologic diagnoses with few or no symptoms." Provided there is no physical deterioration, emphasizing activity tolerance as a means to symptom relief is sensible, empowering, and precise.
Recommendation
Committed motivated patients who wish to avoid back or neck surgery may be able to do just that. This innovative program deserves better evaluation.
Calcium for PMS
March 1999; Volume 2: 36
Source: Thys-Jacobs S, et al. Calcium carbonate and the pre-menstrual syndrome: Effects on premenstrual and menstrual symptoms. Am J Obstet Gynecol 1988;179:444-452.
Previous reports have suggested that disturbances in calcium regulation may underlie the pathophysiologic characteristics of premenstrual syndrome (PMS) and that calcium supplementation may be an effective therapeutic approach. To evaluate the effect of calcium carbonate on the luteal and menstrual phases of the menstrual cycle in PMS, a prospective, double-blind, placebo-controlled, parallel group, mulitcenter randomized national clinical trial was conducted.
The study screened 720 healthy premenopausal women (ages 18-45) for moderate to severe, cyclically recurring premenstrual symptoms, prospectively documented over two menstrual cycles. Women were randomly assigned to either calcium supplements (1200 mg) or placebo for three menstrual cycles. Daily documentation of symptoms, adverse effects, and compliance with medications were monitored, with a resulting 17 parameter score.
Data were reported for 466 of the 497 women enrolled. The calcium treated group had a significantly lower premenstrual (luteal phase) symptom score for the second (P = 0.007) and third (P < 0.001) treatment cycles. By the third treatment cycle, the calcium group was associated with a 48% reduction in total symptom scores from baseline, compared with a 30% reduction in the placebo group.
COMMENT
This New York St. Luke’s-Roosevelt Hospital Center study found that irritability, depression, food craving, aches and pains, and water retention all improved with calcium carbonate supplementation. With the exception of aches and pains, however, the placebo group improved nearly as much in each category. The salutary effects were not apparent until the second month.
Why should calcium work in PMS? Evidence of secondary hyperparathyroidism in women with PMS has been demonstrated by the same principal investigator, who postulates serotonergic dysregulation in PMS.
Partially funded by SmithKline Beech-am, makers of TUMS®, questions of blinding (TUMS®’ texture and flavor are difficult to emulate) and adequacy of pain relief (analgesics were allowed but not tracked) mar this study’s methods. The strong placebo effect is comparable to that observed in trials of fluoxitene for premenstrual dysphoria and alprazolam for PMS.
Calcium carbonate is the least expensive form of supplemental calcium, and if not compounded from oyster shells, is unlikely to contain lead, as do some "natural" calcium supplements. Calcium supplements should be taken with food. Some of the best food sources of calcium include a cup of plain nonfat yogurt (450 mg), 3 ounces of sardines with bones (370 mg), a cup of calcium fortified orange juice (300-350 mg), and a cup of cooked turnip greens (200 mg).
Recommendation
A three-month therapeutic trial of 1200 mg of calcium daily for women with moderate or severe symptoms of premenstrual syndrome should be investigated more carefully. It also will, with weight-bearing exercise, reduce the chance of osteoporosis, especially in Caucasian women. Whether calcium acts as a placebo or changes biochemistry, it is an inexpensive and safe approach.
Editor’s Note
By January 21, when the U.S. FDA finally asked manufacturers to withdraw gamma butyrolactone (aka RenewTrient), reports of unconsciousness in 19 people had been filed. Seizures and bradycardia had also been reported, as had one death. Our Clinical Comments last November (1:131), after a New England Journal of Medicine letter the previous month, read in part "Gamma-butyrolactone is a dangerous dietary supplement’ that appears to induce coma. It is billed as a bodybuilding aid. Discourage its use."
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