Relief for treatment-resistant depression

by | Apr 7, 2023

The antipsychotic medication aripiprazole has been shown to help adults over 60 with treatment-resistant depression.
Plastic packaging containing two types of pills.

According the World Health Organization, depression affects more than 264 million people worldwide. It can negatively affect all areas of life, such as work performance and relationships and even physical health, because of symptoms like feeling excessively tired, changes in eating habits and weight, poor concentration, and feelings of hopelessness. Depression can, in some cases, lead to suicide.

The good news: there are many medications on the market these days to treat depression. The not-so-good news: some older adults (more than 60 years of age) have depression that does not improve with trials of at least two different types of antidepressants — a condition known as treatment-resistant depression. Treatment strategies include either adding another medication to patients’ standard regimen, or completely switching their medication for another one.

A different approach

While some studies have indicated that augmenting standard treatment regimens with an antidepressant called bupropion could help reduce treatment-resistant depression, others have shown that adding on the antipsychotic medication aripiprazole is an effective strategy.

Aripiprazole is a drug usually used to manage psychosis in patients with schizophrenia and for the treatment of bipolar disorder, as opposed to antidepressants that are usually prescribed to elevate mood, increase energy, and manage insomnia.

A recent study compared the effectiveness of an augmentation with bupropion or aripiprazole in older adults with treatment-resistant depression. Patients were randomly assigned to receive an augmentation of their current antidepressant medication with either bupropion or aripiprazole. A third group was assigned to switch their existing antidepressant medication to only bupropion.

The study involved a second step approach for participants who didn’t respond to bupropion. These participants were randomly assigned to one of two options: adding lithium (a mood stabilizer) to their current medication or switching to nortriptyline (an older antidepressant). Neither adding lithium nor switching to nortriptyline provided a significant advantage over the other in terms of improving overall well-being or achieving remission.

Measuring the road to recovery

To measure the effectiveness of the treatment strategies, the authors used a questionnaire that measured psychological well-being. The change in well-being scores from pre- to post-treatment was used as a primary outcome measure. Remission from the condition was another measure of effectiveness of the treatment strategies.

Remission, which is often a path to complete recovery from the condition, is defined as a level of depressive symptoms that is indistinguishable from someone who has never had depression. Remission or recovery are not indicators that a patient will never again experience depression in their lifetime.

“This study was designed with help from stakeholders — people with a stake in the treatment of depression. In this case, patients themselves — older adults who had battled depression — said that psychological well-being was an outcome that mattered to them. At the recommendation of these patients, we made it our primary measure,” said Eric Lenze, lead author of the study, in an email.

Over the span of 10 weeks, augmentation with the antipsychotic aripiprazole was found to significantly improve well-being in the study participants compared to adding on the antidepressant bupropion. Encouragingly, the former strategy also resulted in a greater percentage of patients achieving remission from the condition.

Falls and labels warrant further consideration

The study also compared potential risks of the two medications. Compared to the aripiprazole group, patients in the bupropion group had a higher incidence of falling. The authors suggest that this increased rate of falls may be clinically significant and would require more investigation in future studies because it included many falls that were injurious.

“It is the first study to compare aripiprazole augmentation to other strategies in a randomized controlled trial focused on older adults,” said Lenze. “This is important because both the benefits and risks of antidepressant medication strategies may be different in older adults.

“For example, we found an elevated risk of falls with augmentation with bupropion (compared to aripiprazole). I doubt this would be seen in young adults; it just shows how important it is to test these treatments in older adults.”

However, the study also had some limitations. For example, it was an open-label trial, meaning both the participants and the researchers knew which treatment option they received. This could have introduced some bias in the outcomes. Each step in the trial also lasted only 10 weeks, so the study cannot make any claims about longer-term effects of these drugs.

“As with any clinical trial, it can only answer the question you ask of it.  So in this case, there are many other treatment strategies,” added Lenze. “We can only say which treatment was best among the ones we tested. I think it would be best if health systems — academic medical centers and hospital systems — systematically tested the outcomes of treatments they provide. That would give us more answers.”

Reference: Lenze, E. J., et al., Antidepressant Augmentation versus Switch in Treatment-Resistant Geriatric Depression, New England Journal of Medicine (2023). DOI: 10.1056/NEJMoa2204462

Image credit: Simone van der Koelen on Unsplash.

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