First Study on Hard-to-treat Depression in Older People

About half of older adults don’t respond to first-line medication for depression. A new study shows that adding a second drug to treatment with an antidepressant medication alone helps many of these patients.

John W. Newcomer, M.D., executive vice dean in FAU’s Charles E. Schmidt College of Medicine and co-author of the study published in 'The Lancet.'

By Gisele Galoustian | 9/30/2015

More than half of older adults with clinical depression don’t improve when treated with an antidepressant. A researcher from the Charles E. Schmidt College of Medicine at Florida Atlantic University is co-author on a paper just published in The Lancet reporting on the results of a study indicating that adding a second drug — an antipsychotic medication — to treatment with an antidepressant medication alone helps many of these patients.

The study was sponsored by the National Institutes of Health and involved 468 people aged 60 and older who were diagnosed with depression. It is the largest study of its kind ever undertaken in this patient population. Previous research in younger patients with depression showed that adding a low dose of the antipsychotic drug aripiprazole (brand name Abilify) helped relieve symptoms of depression when an antidepressant alone wasn’t effective. But the new study is the first to show that the same strategy 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.

“Medications work differently in younger and older adults and there are significant physiological and neurological differences in the way younger versus older individuals respond to treatment,” said John W. Newcomer, M.D., executive vice dean in FAU’s Charles E. Schmidt College of Medicine and co-author of the study. “There are a number of studies that have been done with younger adults and depression, but treatments need to be tested in older patients to establish effectiveness.”

A 2007 study estimated that about 7 million of the nation’s 39 million older Americans had clinical depression. Up to 90 percent did not receive necessary care, and 78 percent received no treatment at all. Elderly patients with clinical depression use more health-care services, spending nearly twice as much on medical care as those without the disorder. In addition, the suicide rate among people over 75 is higher than in any other age group, and depression is a risk factor for dementia.

“This study is unique because it examines depression treatment specifically in older adults and demonstrates that older patients can respond very well to effective treatment for depression,” said Newcomer.

Each study participant received an extended-release formulation of the antidepressant drug venlafaxine (brand name Effexor XR) for 12 weeks. About half of these patients still were clinically depressed after 12 weeks of treatment.

“Since we already know that about half of older adults don’t respond to first-line medication for depression we wanted to find out what we can do when the initial treatment approach is not effective,” said Newcomer.

For the second phase of the study, patients who 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 percent of the treatment-resistant patients, compared to only 29 percent of those who had received the placebo. “

“This study is a major advance that supports evidence-based care for older adults with depression," said Newcomer. “Our published findings may be beneficial to primary care physicians who provide most of the treatment needs for these geriatric patients.”

Some patients who took the two-drug combination experienced reversible side effects like restlessness. Others developed some stiffness, called mild Parkinsonism. But these side effects tended to be mild and short-lived, and the researchers say the potential benefits of the two-drug combination outweighed the potential risks of these side effects.

As well, side effects that the researchers expected to see, such as weight gain and metabolic problems like blood sugar or lipid (e.g. cholesterol) elevations, never occurred. Some antipsychotic medications can increase risk for weight gain and increased body fat, potentially increasing blood sugar and contributing to risk for diabetes. But aripiprazole was no more likely than the placebo to produce increases in body fat in these patients and had no effect on blood sugar or lipids.

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

Co-authors of the paper included faculty from Washington University School of Medicine in St. Louis, the Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, the University of Pittsburgh School of Medicine, and the University of Pittsburgh School of Public Health.


 Last Modified 11/8/16