Late-Life Depression Can Be Slow to Respond to Treatment

Fran Lowry

September 07, 2015

Late-life depression can be difficult to treat, and in elderly patients, response to antidepressant therapy can vary considerably, new research suggests.

In a study that looked at longitudinal patterns of changes in depressive symptoms in older adults prescribed the antidepressant venlafaxine XR (Effexor XR, Wyeth Pharmaceuticals Inc), severe baseline depression tended to predict lack of response after 12 weeks of treatment.

However, some patients with severe pretreatment depression did respond, which led the investigators to conclude that high depression severity alone may not be a completely accurate predictor of treatment response.

The study was published online August 19 in JAMA Psychiatry.

"Elderly patients with late-life depression should get treated, that is the main take-home message from this study," lead author Stephen F. Smagula, PhD, from Western Psychiatric Institute and Clinic of the University of Pittsburgh Medical Center, in Pennsylvania, told Medscape Medical News.

"You should get treated, and you should stay with it. Some of these patients take 12 weeks or more to fully respond. Late-life depression is often difficult to treat, and solo venlafaxine is just not going to cut it for a lot of the patients out there. But get treated, stay with it, and also explore adjunctive care or alternatives, as indicated," Dr Smagula said.

Dr Stephen Smagula

"Looking at the trajectories in this paper, you can see that if the patient is not really changing, you need to monitor them early and often, and then try something different," he said.

Half Fail First-Line

More than 50% of older adults with late-life major depression fail to respond to initial treatment with first-line pharmacotherapy.

This prompted Dr Smagula and his group to look at typical patterns of response to venlafaxine XR, which is the antidepressant most prescribed for older adults, and also to evaluate which clinical factors are associated with response patterns.

They applied group-based trajectory modeling to examine the response to venlafaxine in the Incomplete Response in Late-Life Depression: Getting to Remission (IRLGREY) Study, a three-site open-label trial.

"IRLGREY is the largest open-label trial of solo pharmacotherapy conducted among older adults to date," Dr Smagula said.

"It afforded such a large sample that we thought it would allow us to describe the typical patterns of response in this elderly population over 12 weeks of treatment," he said.

IRLGREY participants included 453 adults aged 60 years or older diagnosed with major depressive disorder. The study was conducted between August 2009 and August 2014. Patients received venlafaxine XR, which was titrated up to 300 mg/day, for 12 weeks.

The researchers found that late-life depression was very difficult to treat and that there was a variety of different trajectories of response to venlafaxine XR.

Nearly half (44.59% of the participants) showed clear changes in symptom severity and were deemed responders.

Of these responders, 69 (15.23%) patients had the lowest baseline severity and were found to have a rapid response to venlafaxine treatment.

Distinct responses to treatment were also seen in patients who had moderate depression at baseline (n = 108; 23.84%) and in patients who had higher symptom levels at baseline (n = 25; 5.52%).

Within these groups, the number of weeks needed to achieve average symptom levels that were below typical remission criteria (MADRS score ≤10) differed, Dr Smagula said.

The researchers identified three subgroups of patients who had nonresponding trajectories to treatment with venlafaxine.

Of these subgroups, two had high baseline depression levels, and one had moderate baseline depression levels.

The researchers found that several factors were independently associated with having a nonresponsive trajectory, including greater baseline depression severity, longer episode duration, less subjective sleep loss, more guilt, and more work or activity impairment.

In addition, better performance on a delayed memory word list recognition test was associated with having a rapid response (adjusted odds ratio = 2.22; 95% confidence interval, 1.18 - 4.20).

"This finding suggests that despite older age and depressive illness, relative preservation of retention ability, which is associated with hippocampal function, may facilitate a rapid response," Dr Smagula said. "This hypothesis is consistent with prior evidence linking hippocampal volume to late-life depression treatment outcomes."

Most Late-Life Depression Does Not Respond

Commenting on this study for Medscape Medical News, Robert P. Roca, MD, MPH, vice president and medical director of Sheppard Pratt Health System, said: "The majority of patients with major depression do not fully recover in response to an initial course of antidepressant medication, and many do not even show a significant partial response."

Dr Roca, who is also chair of the American Psychiatric Association's Council on Geriatric Psychiatry, continued: "Although we are still not very good at predicting who will respond, there are data showing a relationship between severity of depression and likelihood of response, in that people with higher initial levels of symptomatology may be less likely to show a significant response to antidepressant medications."

The problem of late-life depression in the elderly has not been well studied, Dr Roca said.

"In this study published in JAMA Psychiatry, the authors apply a novel approach to the analysis of patterns of antidepressant response among older adults in an effort to identify predictors of response. They found three distinct trajectories of response among patients who improved and three distinct trajectories of response among those who did not," he said.

The finding that patients who did not improve had high initial levels of depressive symptomatology is consistent with findings from other studies.

However, the fact that one of the groups that had a good response to treatment had high initial symptom levels demonstrates that "a subset of patients with severe depression may indeed respond to initial monotherapy with venlafaxine. It is clear that depression severity by itself does not reliably predict antidepressant response among older adults. Much work remains to be done. We may ultimately be disappointed in our quest to discover robust clinical predictors of response and in the end may need to look to biomarkers for guidance," Dr Roca said.

The study was supported by grants from the University of Pittsburgh, Washington University in St. Louis, the Center for Addiction and Mental Health, the University of Toronto, and the Natitional Institute of Mental Health. Dr Smagula and Dr Roca report no relevant financial relationships.

JAMA Psychiatry. Published online August 19, 2015. Abstract

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