Combining Aripiprazole, Venlafaxine Reduces Depressive Symptoms in Older Adults

A recently published study in The Lancet suggests that adding a low dose of the antipsychotic aripiprazole to an antidepressant regimen in older adults with treatment-resistant depression may help them achieve and sustain remission.

University of Pittsburgh School of Medicine

The multisite study coordinated by Charles Reynolds III, M.D., an endowed professor of geriatric psychiatry at the University of Pittsburgh School of Medicine, tested the effectiveness and safety of aripiprazole as an adjunctive therapy to the antidepressant venlafaxine in 468 adults aged 60 to 75.

“About half of older adults with major depression show incomplete response to antidepressant pharmacotherapy, in particular to selective serotonin reuptake inhibitors [SSRIs] or serotonin-norepinephrine reuptake inhibitors [SNRIs], with or without psychotherapy,” Reynolds told Psychiatric News. “Yet there are few data from controlled clinical trials [involving this population and second-line pharmacotherapy] to guide decision making by patients and clinicians.”

Prior research in younger patients—averaging 30 years of age—with major depressive disorder showed that adding aripiprazole to an antidepressant regimen helped relieve symptoms of depression when an antidepressant alone was not effective. However, data concerning a combination of aripiprazole and antidepressants in older adults were lacking.

“It’s important to remember that older adults may not respond to medications in the same way as younger adults,” Eric Lenze, M.D., a professor of psychiatry at Washington University in St. Louis and lead author of the Lancet paper, said in a press release. “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.”

This was of particular concern with aripiprazole after studies evaluating the medication in younger adults with major depressive disorder suggested it increased risk of neurological and cardiometabolic adverse effects.

To test the effectiveness and safety of aripiprazole in older patients with major depressive disorder and no history of cognitive decline, each study participant received an extended-release formulation of venlafaxine—ranging from 150 mg a day to 300 mg a day—for 12 weeks. Of the 181 patients whose symptoms did not remit after 12 weeks of treatment, 91 were randomly assigned to receive venlafaxine for another 12 weeks with the addition of 10 mg to 15 mg of aripiprazole and 90 received placebo in addition to venlafaxine each day. Remission was defined as a Montgomery Asberg Depression Rating Scale score of 10 or less (and at least 2 points below the score at the start of the randomized phase) at both of the final two consecutive visits. The researchers chose venlafaxine as a lead-in antidepressant, in part, to avoid adverse drug interactions that have been known to occur between aripiprazole and some widely prescribed antidepressants (such as paroxetine and duloxetine).

The results showed that combined venlafaxine and aripiprazole therapy led to remission of depressive symptoms in 44 percent of treatment-resistant patients compared with 29 percent of participants who received venlafaxine and placebo.

Akathisia and Parkinsonism were the most common adverse events reported by participants in the aripiprazole adjunctive therapy group, occurring respectively in 26 percent and 17 percent of those patients. The groups showed no differences in changes in percentage of body fat, total cholesterol, HDL, LDL, triglycerides, glucose, or insulin concentrations.

“This study is a major advance in support of evidence-based care for older adults with depression,” said Reynolds. “By publishing our findings, … 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.”

Reynolds told Psychiatric News that although the study provided evidence for aripiprazole to be safe and effective in adults aged 60 to 75, further research into augmentation strategies in adults above the age of 75 is needed.

The study was funded by the National Institute of Mental Health. ■