Adding meds to an antidepressant may help older adults with treatment-resistant depression

For some patients, two different medications are better than antidepressants alone.


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According to a recent multicenter study conducted by Washington University School of Medicine in St. Louis, giving older adults with clinical depression- who haven’t responded to standard treatments- the drug aripiprazole and an antidepressant they’re already taking are more effective.

 The study was designed to help determine which strategy is most effective for helping patients feel better as quickly as possible.

The drug aripiprazole was approved by the FDA in 2002 as a treatment for schizophrenia and has been used in lower doses as an add-on treatment for clinical depression in younger patients who do not respond to antidepressants alone. 

The study was divided into two independent phases. Researchers investigated treatments for older patients’ treatment-resistant depression that are often used in clinical practice. Six hundred nineteen individuals taking an antidepressant such as Prozac, Lexapro, or Zoloft were randomized into three groups in the first phase. Patients in the first group received the medication aripiprazole along with whichever antidepressant they were previously taking.

A third group gradually went off the antidepressant each was taking and switched totally to bupropion, while a second group maintained taking antidepressants while additionally adding bupropion (brand names Wellbutrin or Zyban).

These approaches have been suggested by experts as potential treatments for older persons with depression that has resisted therapy. The goal of the new study was to identify the most successful method. According to the study, adding aripiprazole to an antidepressant improved the condition of 30% of patients with treatment-resistant depression compared to just 20% of those who switched to another antidepressant alone.

 Eric J. Lenze, MD — principal investigator and head of the Department of Psychiatry at Washington University, said, “Often unless a patient responds to the first treatment prescribed for depression, physicians follow a pattern in which they try one treatment after another until they land on an effective medication. The Wallace and Lucille Renard Professor, and the study’s corresponding author. It would be beneficial to have an evidence-based strategy we can rely on to help patients feel better as quickly as possible. We found that adding aripiprazole led to higher rates of depression remission and greater improvements in psychological well-being — which means how positive and satisfied patients felt — and this is good news. However, even that approach helped only about 30% of people in the study with treatment-resistant depression, underscoring the need to find and develop more effective treatments that can help more people.”

Scientists and his colleagues from Columbia University, UCLA, the University of Pittsburgh, and the University of Toronto evaluated 742 persons aged 60 and above with treatment-resistant depression.

The researchers found that the group that experienced the best overall outcomes was the one that continued with their original antidepressants but added aripiprazole. They also found that some people in the study wouldn’t respond to the various treatments, so they added a second phase with 248 participants. In this phase, patients taking antidepressants such as Prozac, Lexapro, and Zoloft were treated with Lithium or nortriptyline. Rates of alleviating depression in the study’s second phase were low, about 15%. There was no clear winner when augmentation with Lithium was compared with switching to nortriptyline.

He explained, “Those older drugs also are a bit more complicated to use than newer treatments. Lithium, for example, requires blood testing to ensure its safety, and it’s recommended that patients taking nortriptyline receive electrocardiograms periodically to monitor the heart’s electrical activity. Since neither Lithium nor nortriptyline was promising against treatment-resistant depression in older adults, those medications are unlikely to be helpful in most cases.”

He also added, “There definitely is something that makes depression harder to treat in this population, a population that’s only going to keep getting larger as our society gets older.” 

Senior author Jordan F. Karp, MD, professor and chair of the Department of Psychiatry at the University of Arizona College of Medicine – Tuscon said, “This really highlights a continuing problem in our field. Any given treatment is likely to help only a subset of people, and ideally, we would like to know, in advance, who is most likely to be helped, but we still don’t know how to determine that.”

Scientists highlighted that, overall, antidepressants are beneficial for the majority of people suffering from clinical depression. Antidepressants benefit most people with clinical depression, with at least half feeling better after taking the first medication and almost half improving when switched to a second. However, some people do not respond to two treatments.

The issue is particularly challenging for older adults because many are already taking medications for other conditions, including high blood pressure, heart problems, or diabetes, according to Lenze. Thus it can be challenging to add new mental drugs or switch to new antidepressants every few weeks. Furthermore, it is critical to identify more efficient treatment approaches because depression and anxiety in older persons may hasten cognitive deterioration.

The drugs prescribed to treat clinical depression are often ineffective in these patients. As a result, some doctors change these patients’ antidepressants to discover one that works, while others may prescribe another class of pharmaceuticals to test whether a combination of meds helps.

The results showed that augmenting an antidepressant with the drug led to higher rates of depression remission and more significant improvements in psychological well-being. However, only about 30% of the people in the study helped. 

Aripiprazole augmentation of existing antidepressants improved well-being significantly more over 10 weeks than a switch to bupropion. It was associated with a numerically higher incidence of remission in older adults with treatment-resistant depression.  

Journal Reference:

  1. Eric J. Lenze, M.D., Benoit H. Mulsant etal.Antidepressant Augmentation versus Switch in Treatment-Resistant Geriatric Depression.The New England Journal of Medicine.DOI: 10.1056/NEJMoa2204462


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