Clinical depression does not respond to an antidepressant in more than 50% of older adults who have the condition, but when a second drug — an antipsychotic medication — is added to the treatment regimen, many times, the depression responds, according to the results of a multicenter clinical trial.

The findings, from a study of 468 people aged more than 60 years in whom depression had been diagnosed, have been published in The Lancet. They demonstrate that same strategy shown to relieve symptoms in younger people with depression — adding a low dose of the antipsychotic drug aripiprazole (Abilify, Otsuka America Pharmaceutical) to the treatment regimen — also works in older adults.

“The two-drug combination relieved depression in a significant number of patients and also reduced the likelihood that they would have suicidal thoughts,” according to the researchers.

“This is a rare study because it looks at depression specifically in older adults,” said Benoit Mulsant, M.D., a co-author of the study and senior scientist at Center for Addiction and Mental Health at the University of Toronto, one of the sites of the research. “It’s important to treat older adults effectively, especially given that adults with late-life depression are at an increased risk of developing dementia.”

In the study, each participant received an extended-release formulation of the antidepressant drug venlafaxine (Effexor XR, Pfizer) for 12 weeks. About half of these study participants still were clinically depressed after 12 weeks of treatment.

For the second phase of the study, participants whose depression initially did not respond to the venlafaxine continued to receive the drug along with aripiprazole or a placebo. Aripiprazole often is prescribed to treat schizophrenia and manic episodes associated with bipolar disorder. The two-drug combination led to a remission of depression in 44% of the treatment-resistant patients, compared with 29% of those who had received the placebo.

Some patients who took the two-drug combination experienced restlessness, and others developed mild Parkinsonism. The side effects tended to be mild and short-lived, however, and the researchers maintained that the potential benefits of the two-drug combination outweigh the side effects. Side effects that they expected to see, such as weight gain and metabolic problems, never occurred. 

The key remaining question, the researchers say, is which older patients with depression are likely to benefit from the two-drug combination. Learning the answer is a goal for future research, they said.

The study comes at a time when senior living and skilled nursing settings are trying to reduce the off-label use of antipsychotic medications for those with dementia in response to concerns from the federal government. In a report [PDF] made public in March, the Government Accounting Office recommended that the U.S. Department of Health and Human Services expand its efforts to reduce the use of antipsychotic medications in those with dementia beyond nursing homes to include assisted living communities, homes and other settings where those with dementia receive care. HHS agreed with the recommendation and said it would update its National Alzheimer’s Plan based on the recommendation.

In May, the National Center for Assisted Living extended its national quality initiatives through March 2018. One of those goals is to reduce the off-label use of antipsychotic medications by 15%.