and will be presented later that day at the American Geriatric Psychiatric Association annual meeting in New Orleans by Eric J. Lenze, MD, principal investigator and head of the Department of Psychiatry at the University of Washington, and colleagues.
Many people with clinical depression do not respond to medications used to treat the condition. As a result, some doctors switch to different antidepressants to find one that works for these patients, while other doctors may prescribe another class of medication to see if a combination of drugs helps.
Both strategies have been recommended by experts as options for older adults with treatment-resistant depression. However, the new study was designed to determine which strategy was most effective.
“Often, if a patient doesn’t respond to the first treatment prescribed for depression, doctors follow a pattern of trying one treatment after another until they find an effective medication,” says Lenze, the Wallace and Lucille Renard Professor and corresponding author of the study. “It would be useful to have an evidence-based strategy that we can rely on to help patients feel better as quickly as possible. We found that the addition of aripiprazole led to higher rates of depression remission and greater improvement in psychological well-being – how positive is that?” and satisfied patients – and that’s good news. However, even this approach helped only about 30% of people with treatment-resistant depression in the study, highlighting the need to find and develop more effective treatments that could help more people.”
Treatment-resistant depression is no more or less common in older people than in younger people, but because it accelerates cognitive decline, identifying more effective ways to treat it is critical.
Lenze, along with colleagues at Columbia University, UCLA, the University of Pittsburgh and the University of Toronto, studied 742 people aged 60 and older with treatment-resistant depression, which means their depression has not responded to at least two different antidepressant medications.
The researchers evaluated strategies commonly used in clinical practice to help reduce treatment-resistant depression in older patients and designed the study to consist of two distinct phases. In the first phase, 619 patients were randomly divided into three groups, each taking an antidepressant such as Prozac, Lexapro or Zoloft. In the first group, if patients were taking any antidepressant medication, they were also taking aripiprazole (Abilify). The second group also continued to take their antidepressants but added bupropion (brand names Wellbutrin or Zyban), while the third group each reduced their antidepressants and switched to bupropion entirely.
Treatment-resistant depression: new findings
For 10 weeks, participants received biweekly phone calls or in-person meetings with study clinicians. At these visits, medications are adjusted according to the individual patient’s response and side effects. The researchers found that the group with the best overall results was the group in which patients continued their original antidepressant but added aripiprazole.
The researchers also expected that some people in the study would not respond to the different treatments, so they added a second phase that included 248 participants. At this stage, patients taking antidepressants such as Prozac, Lexapro, and Zoloft were treated with lithium or nortriptyline—drugs that were widely used before other, newer antidepressants were approved more than two decades ago. In the second phase of the study, depression reduction rates were lower, at about 15%. There was no clear winner when comparing augmentation with lithium versus switching to nortriptyline.
“The use of these older drugs is a little more complicated than the newer treatments,” Lenze said. “For example, blood testing is required to ensure the safety of lithium, and patients taking nortriptyline are advised to have periodic electrocardiograms to monitor the heart’s electrical activity. Because neither lithium nor nortriptyline shows promise against treatment-resistant depression in older adults, these drugs are often useful can not be”.
“This really highlights an ongoing problem in our field,” said lead author Jordan F. Karp, MD, professor and chair of the Department of Psychiatry at the University of Arizona College of Medicine – Tuscon. “Any treatment is likely to help only a subset of people, and ideally we would like to know in advance who will be most helped, but we still don’t know how to determine that.”
Lenze emphasized that in general, antidepressants are very helpful for most people with clinical depression. At least half of people with depression feel better after taking the first drug they try. Almost half of the rest do not improve when switched from the first drug to the second drug, but this leaves a large group with clinical depression that does not respond to two treatments.
The problem is especially difficult in older adults, many of whom already take multiple medications for other conditions, such as high blood pressure, heart problems or diabetes. “Thus, switching to new antidepressants every few weeks or adding other psychiatric medications can be complicated. Furthermore, since depression and anxiety can accelerate cognitive decline in older adults, there is an urgent need to find more effective treatment strategies.
“There’s definitely something in this population that makes depression more difficult to treat, something that’s only going to get bigger as our population ages,” he said.