CARDIOVASCULAR DRUGS
No link between beta-blockers and depression
Widely prescribed to treat cardiovascular disease, beta-adrenergic antagonists (beta-blockers) such as metoprolol or propranolol have been linked to adverse reactions such as depression, anxiety, and sleep disturbances. A comprehensive meta-analysis was conducted to explore this association. Involving data on over 53,000 patients, it was the first study designed to examine the full range of psychiatric adverse reactions linked to beta-blockers. Only data from double-blind, randomized, controlled trials were included in the analysis, which examined 285 individual studies and 24 different beta-blockers.
No causal association was found between beta-blockers and most psychiatric adverse reactions, including depression, with the possible exception of sleep disturbances. However, the researchers noted that patients with chronic cardiovascular disorders are prone to mental health complications and should be closely monitored for these throughout therapy.
Sources: Riemer TG, Villagomez Fuentes LE, Algharably EAE, et al. Do [beta]-blockers cause depression? Systematic review and meta-analysis of psychiatric adverse events during [beta]-blocker therapy. Hypertension. [e-pub March 15, 2021] Beta blockers not associated with risk of depression. Charite - Universitatsmedizin Berlin. News release. March 15, 2021.
NULIBRY
FDA approves first drug for fatal genetic disorder
Molybdenum cofactor deficiency type A is a rare genetic metabolic disorder that typically presents in the first few days of life, causing intractable seizures, brain injury, muscle weakness, and feeding difficulties. Most patients die in early childhood from infections.
The FDA has approved Nulibry (fosdenopterin), the first medication indicated to reduce the risk of death from this disorder. Administered I.V., Nulibry replaces cyclic pyranopterin monophosphate, an enzyme that affected patients cannot produce. Previously, the only treatments available for these patients were supportive measures for managing complications.
The new drug's effectiveness was demonstrated in a trial comparing 13 treated patients with 18 matched, untreated patients. The patients treated with Nulibry had a survival rate of 84% at 3 years compared with 55% for the untreated patients. The most common adverse reactions were catheter-related complications, pyrexia, viral infection, pneumonia, otitis media, vomiting, cough and sneezing, viral upper respiratory infection, gastroenteritis, bacteremia, and diarrhea.
Because the drug causes photosensitivity, advise patients and/or parents to avoid patient exposure to sunlight if possible and have the patient wear sunscreen, protective clothing, and sunglasses whenever sun exposure occurs.
Source: US Food and Drug Administration. FDA approves first treatment for molybdenum cofactor deficiency type A. News release. February 26, 2021.
HEART FAILURE
Some BPH medications raise cardiac risk
Prior research suggests an increased risk of heart failure in patients treated with alpha-adrenergic receptor antagonists or alpha-blockers (such as prazosin) for hypertension and those treated with 5-alpha reductase inhibitors (such as finasteride) for benign prostatic hyperplasia (BPH). A study was conducted to determine if these medications are associated with an increased risk of heart failure when used for routine treatment of BPH. This population-based study included 175,201 men over age 66 with a BPH diagnosis between 2005 and 2015. Men were categorized based on 5-alpha reductase inhibitor exposure and/or alpha-blocker exposure with a primary outcome of new heart failure.
The results showed that men treated with a 5-alpha reductase inhibitor and an alpha-blocker, alone or in combination, had a statistically higher risk of heart failure compared with men not taking medication. Heart failure risk was highest for alpha-blockers alone, intermediate for a combination of alpha-blockers and 5-alpha reductase inhibitors, and lowest for 5-alpha reductase inhibitors alone. The risk of heart failure was higher with the use of nonselective alpha-blockers compared with selective alpha-blockers. However, the authors emphasize that the absolute risk of developing heart failure was relatively low. Risk factors common among older men, such as preexisting heart disease, high BP, and diabetes, have a greater impact on heart failure risk than drugs prescribed to treat BPH.
Sources: Lusty A, Siemens DR, Tohidi M, Whitehead M, Tranmer J, Nickel JC. Cardiac failure associated with medical therapy of benign prostatic hyperplasia: a population based study. J Urol. [e-pub February 22, 2021] Medications for enlarged prostate increase heart failure risk. Wolters Kluwer. News release. February 22, 2021.
DRUGS FOR OSTEOPOROSIS
Many clinicians do not follow guidelines
Hip fracture is a major complication of osteoporosis, yet less than 1 in 10 patients in the US receives any osteoporosis medical treatment within two calendar quarters of a hip fracture, according to a study reviewing more than 15 million prescription claims in a large private insurance database. In addition, rates of treatment with osteoporosis drugs such as bisphosphonates dropped dramatically over the past decade, from 15% to 8%.
One reason could be concerns about adverse reactions to some drugs, such as the risk of jaw or thigh osteonecrosis associated with bisphosphonates. However, the Endocrine Society's clinical practice guideline on osteoporosis treatment in postmenopausal women states that the benefits of bone-directed medications outweigh their risk for women at high risk of bone fracture, especially those who recently experienced a fracture.
Another worrisome trend is the rapid increase in use of denosumab, a monoclonal antibody given twice a year by injection. By 2017, use of denosumab surpassed that of all other bone-directed drugs except the bisphosphonate alendronate for treatment of osteoporosis. However, the guideline recommends denosumab as an alternative to bisphosphonates for the initial treatment of osteoporosis in patients who cannot take bisphosphonates or are at high risk of osteoporotic fractures.
Although denosumab is highly effective at improving bone density and preventing fractures, lead study author Sara Cromer, MD, notes that it is also associated with an increase in spinal fractures, especially if it is discontinued without follow-up treatment. "This safety concern does not seem to be reflected in medication use as of early 2020, the end of our study," she said.
According to the CDC, more than 300,000 older adults sustain a hip fracture requiring hospitalization every year. The study was presented at ENDO 21, the Endocrine Society's annual meeting.
Source: The Endocrine Society. Osteoporosis drug prescribing often does not follow guidelines. News release. March 18, 2021. Eastell R, Rosen CJ, Black DM, Cheung AM, Murad MH, Shoback D. Pharmacological management of osteoporosis in postmenopausal women: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2019;104(5):1595-1622.