Clinical Briefs
August 15, 2014 4 minutes read
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.
Exercise for Depression
Source: Cooney G, et al. JAMA 2014;311:2432-2433.
Common sense would predict that exercise might be beneficial for persons with depression, but since our simple intuitions have not always been confirmed by clinical data, it is nice to see data that say "Yes, your common sense was correct. Exercise is beneficial for depression."
Cooney et al reviewed clinical trials that compared exercise with either no treatment or a control for study subjects with depression. Because different clinical trials use different depression scales, results from different trials were converted to a single metric to standardize comparisons. To make the outcomes more clinically relevant, degree of change was quantified as small, moderate, or large.
Although not all trials found a favorable effect of exercise on depression — and one trial actually reported a detrimental effect — the meta-analysis of the data found an overall moderate, favorable effect of exercise compared to control, equivalent to an approximately 5-point reduction on the Beck Depression Inventory.
The data were not sufficient to distinguish a particular type (e.g., aerobic vs non-aerobic), intensity, or duration of exercise needed to achieve a favorable impact. Nonetheless, some national guidelines already include recommendations for exercise as a treatment for mild-to-moderate depression (NICE: National Institute for Health and Clinical Excellence Guideline from the United Kingdom). Patients might be more motivated to consider exercise as a respectable treatment if they understand that favorable results are supported by scientific data.
A Potential New Fix for Opioid-Induced Constipation
Source: Chey WD, et al. N Engl J Med 2014;370: 2387-2396.
Most of the commonplace adverse effects associated with opioid analgesia are transient. Constipation, unfortunately in addition to being one of the most common adverse effects of opioids, is also the most persistent. Mu receptors in the enteric nervous system (the colon has a brain, you say? Who knew!?) have a critical responsibility for controlling active propulsive activity of the colonic musculature: Activation of the mu receptor suppresses propulsive activity. Since all traditional opioids possess potent mu receptor agonist activity, suppression of colonic propulsive activity is routinely seen during opioid treatment, and the bowel does not appear to develop much tolerance to this effect.
Naloxegol is an oral mu receptor antagonist awaiting FDA approval in the United States. Because it is only effective at peripheral opioid receptor sites (e.g., colon) and not at central mu receptor sites (i.e., the CNS), it should not induce opioid withdrawal or reduce the efficacy of opioid analgesia. Data published from two randomized, double-blind, placebo-controlled clinical trials support the efficacy and tolerability of naloxegol. By intention-to-treat analysis, naloxegol provided a statistically significant and clinically meaningful sustained increase in frequency of bowel movements over a 12-week opioid treatment period compared to placebo. The drug was well tolerated. Although there are other mu receptor antagonists on the market — one is parenteral and the other is indicated only for postoperative ileus — it would be nice to have an orally active agent for patients treated with chronic opioids.
BP Lowering Effects of SGLT2 Inhibitors
Source: Oliva RV, Bakris GL. J Am Soc Hypertens 2014;8:330-339.
Sodium-glucose cotransporter type 2 (SGLT2) inhibitors are the newest class of agents available to treat diabetes. In the United States, only canagliflozin and dapagliflozin are FDA approved. SGLT2 inhibitors work by blocking the receptors in the proximal renal tubules from reabsorbing glucose back into circulation. As a result, glucose is excreted in the urine, calories are lost from the body, and we see not only reductions in plasma glucose and A1c, but reduced body weight and reduced blood pressure (BP).
BP reduction is critical in diabetics, who suffer a greater burden of cardiovascular (CV) disease than non-diabetics and worse outcomes when CV events occur. Currently, less than 50% of diabetics with hypertension have attained BP control.
A meta-analysis of placebo-controlled trials (n = 21 trials) with SGLT2 inhibitors found a mean change in systolic BP of approximately 4 mmHg. While at first glance this might seem small, remember that the patient populations selected for SGLT2 treatment were based on presence of diabetes, not hypertension, so the mean baseline BP levels in these trials would not reach the threshold for the diagnosis of hypertension.
SGLT2 inhibitors do not work to reduce glucose in persons with significant CKD (GFR < 45-60 mL/min) because they are dependent on good glomerular filtration rates to induce meaningful amounts of urinary glucose excretion. It is heartening to see a class of diabetic pharmacotherapy that not only produces improved glycemia, but also is associated with weight reduction and lower systolic BP.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content