Eric J. Lenze, MD, consults with patient Daniel Viehmann. Lenze led a multicenter study that found that adding a second drug can relieve depression in many older adults whose symptoms don’t resolve after treatment with a standard antidepressant drug.
September 28, 2015, Newswise — More than half of older adults
with clinical depression don’t get better when treated with an antidepressant.
But results from a multicenter clinical trial that included Washington
University School of Medicine in St. Louis indicates that adding a second drug
— an antipsychotic medication — to the treatment regimen helps many of those
patients.
The
findings, from a study of 468 people over age 60 and diagnosed with depression,
are published in The Lancet. The study was sponsored by the National Institute
of Mental Health and is the largest of its kind ever undertaken in older people
with depression.
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.
“It’s
important to remember that older adults may not respond to medications in the
same way as younger adults,” said first author Eric J. Lenze, MD, a Washington
University professor of psychiatry.
“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.”
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.
The
consequences are costly: Elderly patients with clinical depression use more
health-care services, spending nearly twice as much on medical care as those
without the disorder.
Further, the suicide rate among people over 75 is higher
than in any other age group, and depression is a risk factor for dementia.
Lenze,
who directs the Healthy Mind Lab at Washington University School of Medicine,
was the principal investigator in St. Louis. Patients also were treated at the
University of Pittsburgh School of Medicine and at the Centre for Addiction and
Mental Health (CAMH) in Toronto.
“This
is a rare study because it looks at depression specifically in older adults,”
said Benoit H. Mulsant, MD, a co-author of the study and a senior scientist at
CAMH in Toronto. “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.”
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.
“We
know that in older adults with depression, about half will not respond to
medication,” Lenze said. “They may have a minimal response, but they’ll still
be depressed. The question we wanted to answer was whether there was anything
else we could do for them.”
So
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 with only 29 percent of those who had
received the placebo.
“This
study is a major advance in support of evidence-based care for older adults
with depression,” said Charles F. Reynolds III, MD, a 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.”
Some
patients who took the two-drug combination experienced restlessness. Others
developed some stiffness, called mild Parkinsonism. But the side effects tended
to be mild and short-lived.
“The
potential benefits outweighed the side effects,” Lenze said, adding that side
effects that investigators 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.”
The
key remaining question, Lenze explained, involves predicting which older
depressed patients with depression are likely to benefit from the two-drug
combination. Learning the answer is a goal for future research.
“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,” Lenze said.
This
work was funded by the National Institute of Mental Health and the National
Center for Advancing Translational Sciences of the National Institutes of
Health (NIH). Additional funding was provided by the University of Pittsburgh
Medical Center Endowment in Geriatric Psychiatry, the Taylor Family Institute
for Innovative Psychiatric Research at Washington University, the Washington
University Institute of Clinical and Translational Sciences, the Campbell
Family Mental Health Research Institute at the Centre for Addiction and Mental
Health, Toronto. Bristol-Meyers Squibb contributed aripiprazole and placebo
tablets, and Pfizer contributed venlafaxine extended-release capsules. NIH
grant numbers R01 MH083660, P30 MH90333, R01 MH083648, R01 MH083643 and UL1
TR000448.
Lenze
EJ, Mulsant BH, Blumberger DM, Karp JF, Newcomer JW, Anderson SJ, Dew MA,
Butters MA, Stack JA, Begley AE, Reynolds CF. Efficacy, safety, and
tolerability of augmentation pharmacotherapy with aripiprazole for
treatment-resistant depression in late life: a randomized placebo-controlled
trial. The Lancet, published online Sept. 28, 2015.
Washington
University School of Medicine’s 2,100 employed and volunteer faculty physicians
also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals.
The School of Medicine is one of the leading medical research, teaching and
patient-care institutions in the nation, currently ranked sixth in the nation
by U.S. News & World Report.
Through its affiliations with Barnes-Jewish
and St. Louis Children’s hospitals, the School of Medicine is linked to BJC
HealthCare.