Pharmacotherapy of major depression in late life: what is the role of new agents?

ABSTRACT

Introduction: Evidence on the pharmacotherapy of late-life major depressive disorder (LLD) is scant. Most of the recommendations in existing clinical guidelines are based on expert opinions, extrapolations from data obtained in younger patients, or theoretical considerations.

Areas covered: This article summarizes the recommendations from existing clinical guidelines and recent reviews on the treatment of LLD. Next, it discusses the potential role of newer antidepressants – vilazodone, levomilnacipran, and vortioxetine – based on a systematic search of the literature published during the past five years. Then, it presents evidence pertaining to the use of ketamine, aripiprazole, brexpiprazole, quetiapine, and methylphenidate in the treatment of LLD.

Expert opinion: Very few recent publications directly relevant to the pharmacotherapy of LLD were identified: there are no published data supporting the use of vilazodone, levomilnacipran, ketamine, or brexpiprazole in older patients. Recent placebo-controlled randomized controlled trials (RCTs) support the use of vortioxetine, quetiapine monotherapy, aripiprazole augmentation, or methylphenidate augmentation (with one RCT for each). Thus, overall, there have been few innovations in the pharmacotherapy of LLD over the past decade and the stepwise approach recommended in older guidelines remains relevant today. More studies addressing the relative efficacy, tolerability, and safety of psychotropic medications are needed.

KEYWORDS:

• Aging
• antidepressant
• clinical trials
• depression
• pharmacotherapy
• review
• vortioxetine
• aripiprazole
• quetiapine

Article highlights

• The overall efficacy and tolerability of antidepressants in older patients with Major Depressive Disorder (MDD) is well established. However, most of these patients do not benefit fully from them when treated under usual care conditions. Many studies have shown that the way an antidepressant is used is more important to treatment outcome than the specific antidepressant that is selected

• As of January 2017, there are no published randomized controlled trials (RCTs) of vilazodone, levomilnacipran, ketamine, or esketamine in older patients. In a single RCT, the remission rate of in older patients with MDD was higher with vortioxetine than with placebo; tolerability was comparable but those randomized to vortioxetine improved more than those randomized to placebo on two cognitive tests. Similarly, one recent placebo-controlled trial supports the use of quetiapine monotherapy in older patients with MDD.

• Clinicians should favor monotherapy because it is simpler, safer, and more cost-effective. However, augmenting an antidepressant is favored when there is a risk of worsening upon stopping a first-line antidepressant. Two relatively large recent RCTs support the potential benefits of augmenting antidepressants with either aripiprazole or methylphenidate in older patients with MDD.

• An extensive literature search identified only three geriatric placebo-controlled RCTs published over the past five years assessing newer antidepressants or a novel role for older psychotropic medications. Until the efficacy and safety of newer agents are better established in geriatric patients, older patients with MDD should be treated following a stepwise use of a few true and proven antidepressants.

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Declaration of interest

B H Mulsant currently receives research financial support from Brain Canada, the CAMH Foundation, the Canadian Institutes of Health Research (CIHR), the US Patient-Centered Outcomes Research Institute (PCORI), and the US National Institute of Health (NIH); and in kind support from Capital Solution Design LLC (software used in a study founded by CAMH Foundation), Eli Lilly (medications for a NIH-funded clinical trial), Capital Solution Design LLC (software used in a study founded by CAMH Foundation), HAPPYneuron (software used in a study founded by Brain Canada), and Pfizer (medications for a NIH-funded clinical trial). Within the past five years he has also received research support from Bristol-Myers Squibb (medications for a NIH-funded clinical trial). He directly own stocks of General Electric (less than $5,000). During the past five years, T K Rajji has received research support from Brain Canada, Brain and Behavior Research Foundation, Canada Foundation for Innovation, Canada Research Chair, Canadian Institutes of Health Research (CIHR), Ontario Ministry of Health and Long-Term Care, Ontario Ministry of Research and Innovation, the US National Institute of Health (NIH), and the W. Garfield Weston Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed

Additional information

Funding

This paper is not funded