An update on antidepressant pharmacotherapy in late-life depression

ABSTRACT

Introduction: Clinically important depressive symptoms that occur in adults over age 60 are often termed late-life depression (LLD). LLD poses challenges for treating clinicians in both detection and treatment. Antidepressants are the most common first-line treatment approach. Older adults are at an increased risk of adverse effects because of polypharmacy.

Areas covered: This article summarizes the challenges and approaches when using pharmacotherapy in LLD with a focus on newer data that have become available during the last five years. While no new antidepressants have become available during this period, a review of the literature summarizes advances in the knowledge of the adverse effects associated with various antidepressants and on the potential contribution of pharmacogenetic tools when prescribing antidepressants to older patients.

Expert opinion: During the past 5 years, most of the literature relevant to the pharmacotherapy of MDD in older patients has focused on adverse effects. In particular, the effects of antidepressants on cognition and bone are emerging as important areas for clinical attention and further investigation. There is also an emerging literature on the potential role of pharmacogenetic testing in patients with MDD, though recommendations for use in older adults await larger studies that demonstrate its efficacy and cost-effectiveness.

KEYWORDS:

• antidepressant
• depression
• major depressive disorder
• older adult
• elderly

Article highlights

• The treatment of late life depression (LLD) is challenging. Adherence and tolerability of pharmacologic interventions are influenced by a complex interplay of psychosocial factors and aging that lead to unique adverse effects of antidepressants in this population.

• The efficacy of antidepressants may be similar in adults and in older adults, but the risks of adverse effects is probably higher in late life. The increased risk of adverse effects is generally mitigated by the benefits of treating the depression.

• In the last 5 years, the majority of publications on antidepressant treatment of LLD published focused on adverse effects, especially related cognitive and bone effects, in the absence of any newly approved antidepressants. The causal relationship between these adverse effects has not been established and even if antidepressants play a causal role in cognitive decline or osteoporosis, this may be offset by the positive effect of treating the depression.

• Pharmacogenetic testing has been recognized as a helpful tool in general medicine and in the last 5 years several papers have evaluated the role of this approach in LLD treatment.

• Pharmacogenetic testing may become a useful tool in the pharmacologic management of LLD, helping to reduce the risks of adverse effects in this vulnerable population.

This box summarizes key points contained in the article.

Declaration of interest

B Mulsant receives financial support from the Labatt Family Chair in Biology of Depression in Late-Life Adults at the University of Toronto. He currently receives research support from Brain Canada, the Canadian Institutes of Health Research (CIHR), the Centre for Addiction and Mental Health (CAMH) Foundation, the Patient-Centered Outcomes Research Institute (PCORI), the US National Institutes of Health (NIH), Capital Solution Design LLC (software used in a study funded by CAMH Foundation), and HAPPYneuron (software used in a study founded by Brain Canada). Within the past five years, he has also received research support from Eli Lilly and Company (medications for an NIH-funded clinical trial) and Pfizer (medications for an NIH-funded clinical trial). He has also been an unpaid consultant to Myriad Neuroscience and directly owns stocks in General Electric (Less than $5,000). DM Blumberger has received research support from the CIHR, the NIH, Brain Canada and the Temerty Family through the CAMH Foundation and the Campbell Research Institute. He has received research support and in kind equipment support for an investigator-initiated study from Brainsway Ltd. and he is the site principal investigator for three sponsor-initiated studies for Brainsway Ltd. He also receives in-kind equipment support from Magventure for investigator-initiated studies. He also received medication supplies for an investigator-initiated trial from Indivior and has also participated in an advisory board meeting for Janssen Pharmaceuticals.

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.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript has not been funded.