Clinical Briefs
By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville
Dr. Kuritzky is a retained consultant for Boehringer Ingelheim, Daiichi Sankyo, Forest Pharmaceuticals, Janssen, Lilly, Novo Nordisk, Pfizer, and Sanofi.
Treatment to Reduce Genital HSV Shedding
Source: Wald A, et al. N Engl J Med 2014;370:201-210.
Patients burdened with genital herpes often desire treatments to reduce the frequency of viral shedding, hoping to reduce the rate of transmission. Several antivirals are currently available to reduce viral shedding, each of which has demonstrated some efficacy, but none of which totally eliminates viral shedding.
Herpes simplex virus type 2 (HSV-2) comprises a substantial share of the causes of genital herpes infection. Although two decades ago HSV-2 was responsible for the vast majority of genital herpes infections, the prominent role of HSV-1 in genital herpes has been increasingly recognized since 2006. Clinically, outbreaks are indistinguishable, although nuances of difference between HSV-1 and HSV-2 do exist (e.g., frequency of outbreaks and severity of outbreaks being modestly less with the former).
Pritelivir (PRT) is the first member of a new class of antiviral agents active against both HSV-1 and HSV-2. The mechanism of action - inhibition of the viral helicase-primase complex - differs from currently available nucleosidase analogues.
Wald et al performed a double-blind, placebo-controlled trial among adults (n = 156) with a clinical history of genital herpes and confirmed HSV-2 seropositivity. Subjects performed daily self-swabbing for HSV PCR testing, as well as reporting on occurrences of HSV outbreaks (which had to be confirmed within 24 hours by clinic personnel).
Over the 28-day duration of the study, study subjects who received daily doses of PRT of 25-400 mg/day experienced a significant reduction in the number of days of viral shedding (43-87% reduction, depending on dose). Clinical outbreaks were also dramatically reduced (87% reduction). PRT was well tolerated, with no serious drug-attributable adverse effects. It is uncertain if and when PRT will find clinical utility because animal trials disclosed skin and hematologic abnormalities, albeit at much larger relative doses than used in humans.
The Continuing Saga of Vitamin D: Who, When, and Why Should We Use It
Source: Reid IR, et al. Lancet 2014;383: 146-155.
The greying of the population assures a continued prominence for osteoporosis and its consequences. The "story line" of vitamin D in relation to osteoporosis is fairly straightforward: As vitamin D levels decline to suboptimal levels (actual number of what constitutes "suboptimal" is still hotly debated), secondary hyperparathyroidism develops, resulting in accelerated bone loss. To date, clinical trials have not confirmed a fracture reduction benefit from vitamin D supplementation, and even the relationship between vitamin D status and bone mineral density (BMD) is plagued with inconsistencies. To further clarify the question of the relationship between vitamin D and BMD, Reid et al performed a meta-analysis of clinical trials that evaluated the effects of vitamin D on BMD.
The clinical trial results (23 studies, n = 4082) were quite mixed, with some showing BMD benefit, some detriment, and some neutral. In essence, the net small benefit suggested by some trial data was of dubious clinical significance. These results should be distinguished from data on vitamin D in combination with calcium supplementation; since many trials provide vitamin D in combination with calcium (calcium does increase BMD), it has been sometimes misconstrued that each component of the vitamin D/calcium combo contributed to better BMD. The authors suggest that vitamin D would be best suited for persons with vitamin D insufficiency, rather than for all persons at risk for osteoporosis.
Antidepressants and New Onset Diabetes
Source: Wu CS, et al. J Clin Psychiatry 2014;75:31-38.
The relationship between antipsychotic medication and diabetes has been well demonstrated and is widely recognized by clinicians. Unfortunately, the relatively limited selection of antipsychotics sometimes requires that in order to achieve symptom control, new-onset diabetes must be accepted as a consequence.
The population of individuals treated with antidepressants far eclipses those treated with antipsychotics. The earliest commonly used antidepressants, tricyclics, were associated with weight gain due to activity and the post-synaptic histamine receptor site, which of course could be diabetogenic.
Wu et al report on a case-control study based on the Taiwan National Health Insurance Research Database. Over the 1998-2009 interval, they compared use of antidepressants among patients with diabetes (n = 47,885) and controls (n = 95,770).
Overall, persons treated with antidepressants for at least 2 years were 20% more likely to develop diabetes. In particular, younger individuals were adversely affected: Persons < 44 years of age had more than a doubling of risk for new onset diabetes.
The mechanism(s) by which antidepressants impart increased risk for diabetes are not clear. For instance, the above-mentioned weight gain with tricyclic antidepressants was not reflected in a greater incidence of diabetes than that seen with newer antidepressants (e.g., SSRIs, SNRIs). Recent studies have shown that other commonly used medications are associated with increased risk for new onset diabetes, including statins and thiazide diuretics. The frequency of prescription of antidepressants merits enhanced clinician vigilance for the development of diabetes.
