A new clinical trial has demonstrated that combining an antidepressant with an antipsychotic drug could improve clinical depression in older adults who do not respond to regular treatment.

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Around half of older adults with diagnosed with clinical depression will not respond to standard medication.

The study, published in The Lancet, could bring hope to the millions of people with depression whose symptoms are not improved with taking an antidepressant.

“We know that in older adults with depression, about half will not respond to medication,” says first author Dr. Eric J. Lenze, professor of psychiatry at Washington University in St. Louis, MO. “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.”

A study conducted in 2007 revealed that of the 39 million older adults in the US, an estimated 7 million had clinical depression. Furthermore, 90% did not receive necessary care, with 78% believed to receive no treatment at all.

Untreated depression can be costly. Not only do older adults with depression spend nearly twice as much on health care services than those without the disease, but depression is associated with an increased risk of dementia.

Previous research had shown that prescribing a low dose of the antipsychotic drug aripiprazole alongside antidepressants was effective at relieving depression in a significant number of younger patients with depression whose symptoms were not relieved by an antidepressant on its own.

The combination also reduced the likelihood that the younger patients would have suicidal thoughts. This latter point is especially pertinent for older adults, given that the suicide rate among people over the age of 75 is higher than in any other age group.

However, Dr. Lenze states that it is important to remember older adults might not respond to medications in the same way as younger adults.

Fast facts about depression
  • Around 6.7% of adults in the US experience major depressive disorder
  • Women are around 70% more likely to experience depression than men
  • There are several different types of depressive disorders, including major depression, seasonal affective disorder and bipolar disorder.

Learn more about depression

“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,” he explains. “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.”

To investigate the efficacy of the new strategy in older patients, the researchers assessed 468 people over the age of 60 who had been diagnosed with depression. To begin with, each participant took the antidepressant drug venlafaxine for 12 weeks.

After 12 weeks, roughly half of the participants were still clinically depressed. The researchers then gave the participants who had not responded to the antidepressant either aripiprazole or a placebo to take alongside venlafaxine.

The researchers found that the two-drug combination led to improved symptoms in 44% of the patients who had not responded to venlafaxine alone. In comparison, 29% of the participants who received the placebo experienced remission of their depression.

Study co-author Dr. Charles F. Reynolds III, a geriatric psychiatrist at the University of Pittsburgh, PA, describes the study as a major advance in support of evidence-based care for older adults with depression. He adds:

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.”

Although one or two side effects were observed in some of the patients who received the two-drug combination – restlessness and stiffness – these were typically mild and short-lived. The researchers believe that the potential benefits of this novel treatment outweighed the side effects.

Following their discovery, the researchers now hope to find a way to discern which patients are likely to benefit from this new form of treatment.

“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,” Dr. Lenze concludes.

Combining different drugs can sometimes be a risky treatment strategy. Previously, Medical News Today reported on a study that suggested using antidepressants alongside nonsteroidal anti-inflammatory drugs – a common form of painkiller – could increase the risk of bleeding.