Combination Therapy for Elderly Patients with Depression

Study results indicate that adding aripiprazole to the treatment of adults aged 60 and older who do not achieve remission from depression with a first-line antidepressant appears to effectively achieve and sustain remission. The finding offers hope to the more than 50% of an estimated 7 million older adults with clinical depression who do not achieve remission on antidepressant therapy alone.

Published in the September 27, 2015 online issue of The Lancet, the multicenter clinical trial assessed 468 older adults diagnosed with depression, making it the largest of its kind to be undertaken in older people with depression to date. Whereas previous studies have shown that adding low-dose aripiprazole to the treatment of younger patients with depression helped relieve their symptoms when an antidepressant alone was not effective, the current study is the first to show that this approach is also successful in the elderly.

“It’s important to remember that older adults may not respond to medications in the same way as younger adults,” said lead author Eric J. Lenze, MD, professor of psychiatry at Washington University in St. Louis. “There are age-related changes in the brain and body that suggest certain treatments may work differently, in terms of benefits and side effects, in older adults. Even when a strategy works for patients in their 30s, it needs to be tested in patients in their 70s before it can be considered effective in older patients.”

Co-author Benoit H. Mulsant, MD, senior scientist at the Centre for Addiction and Mental Health in Toronto, Canada, added, “This is a rare study because it looks at depression specifically in older adults. It's important to treat older adults for depression, especially given that adults with late-life depression are at an increased risk of developing dementia. But this research demonstrates that older adults do respond to depression therapy.”

For the study, older adults who did not achieve remission during a pre-trial with venlafaxine extended-release (150 to 300 mg/day) were randomly assigned to the addition of aripiprazole with a target does of 10 mg daily or placebo for 12 weeks. The combination of venlafaxine and aripiprazole led to depression remission in 44% of the treatment-resistant patients, compared with a remission rate of 29% for those who received placebo.

“This study is a major advance in support of evidence-based care for older adults with depression,” said Charles F. Reynolds III, MD, geriatric psychiatrist at the University of Pittsburgh, the coordinating site for the study. “By publishing our findings in The Lancet, we hope particularly to reach primary care physicians, who provide most of the treatment for depressed older adults. The excellent safety and tolerability profile of aripiprazole, as well as its efficacy, should support its use in primary care, with appropriate medical monitoring.”

Side effects to the two-drug combination that were observed in the study included restlessness and mild Parkinsonism, but these side effects tended to be mild and short-lived. “The potential benefits outweighed the side effects,” said Lenze. He added that that the side effects that she and her colleagues expected to see, such as weight gain and metabolic problems, never occurred.

“Antipsychotic medications can cause increasing amounts of fat and thereby increase blood sugar, potentially contributing to diabetes,” Lenze said. “But compared with placebo, aripiprazole was no more likely to produce increased fat in these patients and had no effect on blood sugar, insulin or lipids.”

According to Lenze, future research in this area that will be most helpful will involve predicting which older patients with depression will likely benefit from the drug combination. “One of the things we see as critical to our future research will be trying to better understand the factors that make some people respond to specific forms of treatment that may not work for others,” he said.