Gabapentin and Pregabalin Effective for Refractory Chronic Pruritus

SOURCE: Matsuda K, Sharma D, Schonfeld AR, Kwatra SG. Gabapentin and pregabalin for the treatment of chronic pruritus. J Am Acad Dermatol 2016;75:619-625.

Clinicians usually are successful when they treat pruritus with antihistamines. Some categories of pruritus prove somewhat refractory to intervention, such as uremic pruritus and neurogenic pruritus. When traditional antihistamines (e.g., diphenhydramine, hydroxyzine, cetirizine, loratadine) have failed, what else might work?

Gabapentin and pregabalin are analogues of gamma-aminobutyric acid, but do not actually interact with gamma-aminobutyric acid receptors. They generally are well tolerated, and although originally investigated for their antiepileptic potential, the authors addressed 37 different randomized, controlled trials of gabapentin, pregabalin, or the combination in a variety of different itch syndromes. Gabapentin and pregabalin were demonstrated to produce substantial clinical success in syndromes as far ranging as uremic pruritus, notalgia paresthetica, post-spinal cord pruritus, and cancer chemotherapy-related pruritus.

The tolerability of gabapentin and pregabalin was reflected in the modest discontinuation rates due to adverse effects (6-8%). Although most of the trials were small and lacked long-term follow-up, the promising results support consideration of gabapentin, pregabalin, or both for patients presenting with refractory pruritus.

Does Technology Accelerate Weight Loss?

SOURCE: Jakicic JM, Davis KK, Rogers RJ, et al. Effect of wearable technology combined with a lifestyle intervention on long-term weight loss: The IDEA randomized clinical trial. JAMA 2016;316:1161-1171.

For most patients, long-term weight loss is modest, whether they use diet, exercise, pharmacotherapy, or a combination. Only bariatric surgical interventions provide consistent and sustained substantial weight loss (> 20%) for the majority of patients. In this age of technological advances, will sophisticated tools lead our patients to enhanced weight loss?

Jakicic et al enrolled overweight and obese adults (n = 471) in a randomized trial comparing traditional interventions, such as education about diet, exercise, and counseling, with traditional interventions plus gadgetry, which included wearable devices to monitor physical activity and a web-based interface to monitor diet and activity. The authors analyzed the effect of the added gadgetry at 24 months.

Although both groups enjoyed weight loss at the conclusion of the 24-month intervention, the group randomized to add-on gadgetry actually experienced less weight loss than the group that simply received traditional diet and exercise advice (3.6% vs. 6.2%). Previous shorter-term studies have been more supportive of wearable devices, but perhaps the gloss wears off in longer-term studies such as this one.

The Importance of Low Uric Acid in Gout Patients

SOURCE: Ruoff G, Edwards NL. Overview of serum uric acid treatment targets in gout: Why less than 6 mg/dL? Postgrad Med 2016;128:706-715.

In addition to the burden caused by painful acute gout flares, inadequately managed gout can lead to substantial long-term disability and deformity. Not everyone presenting with hyperuricemia develops gout or requires treatment. Indeed, 10% of patients demonstrating marked elevation in serum uric acid (> 9.0 mg/dL) go on to develop gout annually. Once patients experience diathesis to deposit inflammatory urate crystals in joints (or other tissues) during a single attack of gout, 90% will suffer another attack within 10 years, suggesting that most sufferers will not be so lucky as to experience a one-time event.

In vitro, crystals tend to form when uric acid levels exceed about 6.8 mg/dL, reflecting saturation at that point. Various guidelines suggest clinicians treating gout should aim for a lowering to a minimum of 6.0 mg/dL, noting that sustained uric acid lowering ultimately is associated with a disappearance of flares as well as a dissolution of tissue deposits of uric acid (e.g., tophi). Indeed, the rate of tophus dissolution has been shown to be proportional to the degree of lowering of serum uric acid levels.

Although clinicians might be tempted to aim for a goal just below 6.8 mg/dL, it is probably unwise to do so. Dietary and physiologic changes may cause fluctuation substantially above 6.8 mg/dL unless a wide margin of safety is created. Tissue deposition of uric acid can cause chronic silent joint destruction at elevated levels of uric acid. Consistent abolition of acute flares has been confirmed only when uric acid levels < 6.0 mg/dL are maintained over the long term.