The largest study of treatment-resistant depression in older adults has found that augmenting commonly used antidepressants with the antipsychotic drug aripiprazole can induce remission of depressive symptoms in 30 per cent of patients.

The results of the Optimizing Outcomes of Treatment-Resistant Depression in Older Adults (OPTIMUM) clinical trial have just been published in the New England Journal of Medicine.

CAMH and the University of Toronto collaborated with leading institution the Washington University School of Medicine and several other research centres on the study, which included 742 participants over the age of 60 with treatment-resistant depression, meaning that at least two courses of treatment had been unsuccessful in improving symptoms. Up to one in three people diagnosed with depression are considered treatment resistant.

“There are a lot of myths about depression in older people.  It is a myth that older people have higher rates of depression and it is a myth that depression in older people is more resistant to treatment,” said study co-author Dr. Benoit Mulsant, Clinician Scientist at CAMH. “This study shows that there are effective treatments for older people and they can recover and live happier, healthier lives.”

The study compared the efficacy of different medications: One group had aripiprazole (brand name Abilify) added to their existing anti-depressant. Another group had the drug bupropion (brand names Wellbutrin and Zyban) added instead. A third group had lithium added while a fourth and fifth group tapered off the anti-depressant they were using and switched to bupropion or nortriptyline.

Participants in each group reported improvement in their mental health over the 10-week course of treatment, but those who were given aripiprazole improved the most, with 30 per cent of participants showing remission in symptoms, compared to 20 per cent who improved when switched to bupropion.

Typically, when patients do not respond positively to a first course of treatment for mental illness, physicians will try one treatment after another until they find something that works and does not have debilitating side-effects. For example, problems with balance can be a risk factor for some anti-depressants that increase the risk of falls and injury and have a devastating impact on older patients.  The OPTIMUM study found that while patients who received aripiprazole or bupropion both showed similar improvements in mental health, those taking bupropion were at greater risk for serious injury due to falls.

“By establishing the likelihood that different treatment options will be effective, and the risks attached to each treatment, we can ensure that we are choosing the best option to help patients with treatment-resistant depression,” said co-author Dr. Daniel Blumberger, Clinician Scientist at CAMH and Director of the Temerty Centre for Therapeutic Brain Intervention. “We may not know for certain which treatments will work, but we know which ones are most likely to. In this way, we can quantify that we are making the best choices for our patients.”

Dr. Mulsant says that research into mental illness treatments for older adults has been lacking compared to other age groups. He and Dr. Blumberger are two of a small number of senior scientists in the world specializing in treatment-resistant depression in late life.

“Over the past 15 years CAMH has become a leader in North America in research into geriatric depression,” said Dr. Mulsant. “That is why colleagues from places like Columbia University and UCLA want to work with us.”

About The Centre for Addiction and Mental Health (CAMH)

CAMH is Canada’s largest mental health and addiction teaching hospital and a world leading research centre in this field. CAMH combines clinical care, research, education, policy development and health promotion to help transform the lives of people affected by mental illness and addiction. CAMH is fully affiliated with the University of Toronto, and is a Pan American Health Organization/World Health Organization Collaborating Centre. For more information, please visit or follow @CAMHnews on Twitter.


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