Depression continues to be a challenging condition to treat despite the myriad treatment options available. Primary care providers are increasingly tasked with providing second- and third-line treatments for major depressive disorder, and thus, should be familiar with newer medication therapies that are available. In this article, we aim to provide the general internist and other providers who treat depression in their practice with a succinct review of recent developments in the treatment of depression.
BACKGROUND
Major depressive disorder is a common condition, affecting 6.7% of adults in the United States in 2015;1 16.2% of Americans will experience a depressive episode during their lifetime,2 and in 2010, depression resulted in 8 million ambulatory visits in the United States.3 Antidepressants are the second most commonly prescribed drug class, with a peak prevalence of 26% in women aged 50 to 64 years.4 Although a plethora of treatment options are available, most patients (56%-72.5%) will not respond to initial treatment with antidepressant monotherapy.5, 6Thus, additional treatment options are needed for patients with inadequate response to first-line medications. In this article, we aim to familiarize physicians with newer and adjunctive pharmacologic major depressive disorder treatments.
ANTIDEPRESSANTS APPROVED IN THE PAST 10 YEARS
Desvenlafaxine
Desvenlafaxine, the third serotonin-norepinephrine reuptake inhibitor (SNRI), was approved by the US Food and Drug Administration (FDA) in 2008 for major depressive disorder. Although it has been reported as safe and well tolerated in children,7, 8 it is not currently approved for use in pediatric patients. Desvenlafaxine is a salt of the major active metabolite of venlafaxine. It binds serotonin (5-HT) and norepinephrine (NE) receptors, with inhibition of 5-HT uptake being approximately 10 times more potent than NE uptake.9
Desvenlafaxine was studied in 3 randomized controlled trials at doses of 100 to 400 mg/d. The first 2 trials showed improvements in depression rating scales compared with placebo,10, 11 but the third study did not show a significant benefit of desvenlafaxine over placebo at 8 weeks.12 Because data from the initial studies showed increasing adverse effects with higher doses of desvenlafaxine, another study evaluated lower dosages and showed improvements in the primary end point, Hamilton Rating Scale for Depression score, with desvenlafaxine over placebo at the 50-mg but not the 100-mg dose.13
Despite the availability of 25-mg, 50-mg, and 100-mg desvenlafaxine tablets, 50 mg/d is the recommended starting and maintenance dosage, on the basis of the above trial data. Desvenlafaxine is generally safe and well tolerated at this dosage. Trial data indicate that doses higher than 50 mg offer no additional benefit14 and are associated with increased adverse effects and discontinuation rates.9, 15 Because metabolism of desvenlafaxine is through hepatic conjugation and urinary excretion, dosing should be adjusted for those with hepatic and renal impairment (Table).16 For discontinuation, tapering over 2 to 4 weeks is suggested; the 25-mg tablet should be used for this purpose.14 Desvenlafaxine is available only as extended-release tablets, which should not be split.
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-Tina H. Byun, MD, Swarna S. Chaliki, MD, MBBS, Kenneth G. Poole Jr, MD, MBA
This article originally appeared in the June 2019 issue of The American Journal of Medicine.
