Clinical Briefs
By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is a consultant for Sucampo Pharmaceuticals, Takeda, Boehringer Ingelheim; and is a consultant and on the speaker's bureau for Novo Nordisk, Lilly, Daiichi Sankyo, Forest Pharmaceuticals, Cephalon, Novartis, and Sanofi Aventis.
Long-term safety of ramelteon for insomnia
Source: Richardson GS, et al. Safety and subjective sleep effects of ramelteon administration in adults and older adults with chronic primary insomnia. J Clin Psychiatry 2009;70: 467-476.
A variety of highly effective agents for primary insomnia are currently available including benzodiazepines, benzodiazepine receptor agonists, and other classes. Agents that impact the benzodiazepine receptors (i.e., either benzodiazepines or benzodiazepine receptor agonists) are controlled substances and have occasional problematic issues such as misuse, diversion, cognitive clouding, and rebound upon withdrawal.
Ramelteon is a melanocortin receptor agonist (MT1 and MT2 receptors) that is not a controlled substance and has a clear safety profile, absent of next-day residual effects when used up to 5 weeks. To date, ramelteon has neither shown characteristics of substances of abuse, nor any street popularity as such.
Many literature resources suggest that soporific agents are best used over short-term periods (i.e., 2-3 weeks). Despite this assertion, many patients successfully use benzodiazepines and benzodiazepine receptor agonists for very long time periods without demonstrable toxicity. None-theless, concerns as mentioned above stimulate identification of safe agents for long-term use.
This large clinical trial (n = 1213) included a substantial subgroup of seniors (n = 248). Long-term administration of ramelteon (8 mg to seniors, 16 mg to younger adults) over 1 year was associated with improved sleep latency in both study groups, the efficacy of which did not diminish over time. Overall, there was excellent tolerability with no evidence of rebound. Ramelteon is a viable tool for long- term management of insomnia in adults.
Statins lower testosterone in diabetic men
Source: Stanworth RD, et al. Statin therapy is associated with lower total but not bioavailable or free testosterone in men with type 2 diabetes. Diabetes Care 2009;32:541-546.
Diabetic men have a dispropor-tionate incidence of comorbid hypogonadism. The acknowledged association might even be underestimated, since many experts believe that low-normal (not subnormal) testosterone levels, in concert with proto-typic symptoms of hypogonadism, merit consideration for testosterone supplementation.
There are few type 2 diabetics who do not qualify for statin therapy, since the presence of type 2 diabetes is considered a cardiovascular risk equivalent. Accordingly, most midlife type 2 diabetic males are appropriately receiving a statin. Because cholesterol is a building block of testosterone, and statin therapy impacts cholesterol production, it is sensible to look at whether statin therapy affects testosterone levels.
In a study of adult (mean age, 58 years) type 2 diabetic men (n = 250), measurements of total testosterone were compared in men on statins vs men not on statins. Patients on statins had lower total testosterone; however, the sex hormone binding globulin (the protein responsible for the bound, or unavailable, testosterone in plasma) levels were also lower, resulting in a net neutral effect on free testosterone. Since free testosterone is the component necessary for testosterone activity, these results are reassuring that statins should not cause decrements in testosterone activity. Clinicians should be reminded that reliance on total testosterone measurement is insuf-ficient to assess testosterone status: Free testosterone assessment is also necessary.
Rosuvastatin lowers DVT risk
Source: Glynn RJ, et al. A randomized trial of rosuvastatin in the prevention of venous thromboembolism. N Engl J Med 2009;360:1851-1861.
Clinicians attribute most, if not all, of the favorable outcomes in statin trials to LDL reduction. Some observational studies have suggested that statin use is associated with less venous thromboembolism (DVT), but observational data have been conflicting. The JUPITER trial, which demonstrated that rosuvastatin (ROV) reduced CV endpoints in persons with essentially normal LDL (< 130 mg/L) but elevated CRP (> 2.0 mg/L), also included a DVT endpoint.
The outcome measured was a composite of DVT or pulmonary embolus among 17,802 persons randomized to ROV or placebo and followed for up to 5 years (mean, 1.9 years).
The relative risk reduction in DVT was 43% (hazard ratio, 0.57). There was a trend toward favorable effects in persons with unprovoked DVT (i.e., absence of known precipitant factors), and a very strong 48% risk reduction in persons with provoked DVT (i.e., after trauma, in cancer patients, etc.). This risk reduction augments the already demonstrated benefits for CV endpoints. The mechanism(s) by which statins may benefit venous circulation are complex and incompletely understood. The consequences of DVT are significant; this additional benefit of statin therapy, in the absence of any signal of increased bleeding, is a welcome message.
A variety of highly effective agents for primary insomnia are currently available including benzodiazepines, benzodiazepine receptor agonists, and other classes. Agents that impact the benzodiazepine receptors (i.e., either benzodiazepines or benzodiazepine receptor agonists) are controlled substances and have occasional problematic issues such as misuse, diversion, cognitive clouding, and rebound upon withdrawal.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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