Antipsychotic drug aripiprazole could aid antidepressant therapies in older adults

Elderly patients with depression who are not helped by a first-line antidepressant could benefit from the addition of an antipsychotic drug, finds a study published in The Lancet
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on 27 September 2015. 

Major depression that does not respond to treatment is common and potentially life threatening in elderly people.

More than half of all patients with depression will not gain sufficient benefit from a standard antidepressant like citalopram (Celexa), says lead author Eric Lenze, professor of psychiatry at Washington University School of Medicine in St Louis, Missouri. 

“There are many strategies to get people to full response or remission — often involving combination therapy — but as the population ages we need to make sure these medication combinations are safe and effective in older adults,” he says. “This was actually the first full-scale study of any augmentation medication in older adults with depression.” 

Lenze and colleagues recruited more than 450 treatment-resistant patients aged over 60 years for a randomised trial at three centres in the United States and Canada to test the efficacy and safety of adding the antipsychotic drug aripiprazole to the standard treatment for depression.

It was already established that the addition of a low dose of aripiprazole (Abilify) helped relieve symptoms of depression in younger patients when an antidepressant alone was not effective. But studies had not been carried out on older patients. 

An ageing population, coupled with insufficient numbers of mental health experts in ageing, highlights the need for new and effective treatments for older adults with late life depression, says Jovier Evans, program officer in the US National Institute of Mental Health (NIMH) Geriatrics and Aging Processes Research Branch. 

This study was important, say the authors, because older patients have been an overlooked group. Adults with late-life depression are at an increased risk of developing dementia, so discovering that older adults also respond favourably to this combined treatment was welcome. The two-drug combination relieved depression in a significant number of patients aged over 60 years and also reduced the likelihood that they would have suicidal thoughts. 

Although the drug combination was shown to be efficacious in both young and old patient groups, the side effects were slightly different. As expected, the researchers saw two known side effects — weight gain and restlessness — but they also saw a higher rate of Parkinsonism. 

“[This] was not entirely unexpected (after all, we were specifically examining participants for its emergence), but this is a little different than the findings in young adults, in whom aripiprazole does not seem to cause this side effect,” says Lenze. 

Overall though, he says, “given the generally mild and transient nature of the akathisia, and the generally mild Parkinsonism, in my opinion the benefits of aripiprazole will often outweigh the risks in older adults.”

The results suggest the drug is safe and effective in treating older adults with difficult treatment-resistant depression, says Evans at the NIMH, which co-funded the research. The results are “highly important”, he says, and now “more research is needed to examine the long-term effects of this particular treatment or its use in community contexts.” 

But the findings have been challenged by Toby Williamson, head of development and later life for the UK’s Mental Health Foundation. “It is concerning that people are receiving antipsychotics for a disorder that they don’t have. Less than half of the people in the study (44%) experienced a remission in their depression,” he says. 

“Medication may be effective for some people but not at the expense of exploring and trying to address the causes of depression among older people which may be to do with loss, poor physical health, changes in care dependencies, lack of meaningful activity, and loneliness,” says Williamson. 

He points to a recent study^[2]
published in the British Journal of Psychiatry, which showed that psychological treatments are effective in reducing symptoms of depression and anxiety for people with dementia. “Talking treatments that are widely available for younger adults have a very low referral rate for older adults, although older adults tend to benefit the most.” 

While some patients will benefit from the drug combination detailed in his study, Lenze agrees that this will not be best for everyone. “I would also put in a plug for non-medication options like psychotherapy or lifestyle changes — for example, exercise is a powerful antidepressant, and increasing evidence suggests that mindfulness training (as in meditation) has antidepressant properties as well.”