Study: Most Antidepressants Miss Target of Clinical Depression

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An important brain protein called monoamine oxidase A (MAO-A) is extremely elevated during clinical depression, however, it appears to be unaffected by treatment with commonly used antidepressants, according to an important study published in the Archives of General Psychiatry.

The study may shine some light as to why antidepressants don't always work. Researchers at the Centre for Addiction and Mental Health (CAMH) did the study using an advanced brain imaging method that assisted them in to measuring levels of the brain protein MAO-A which digests multiple brain chemicals, including serotonin that can help sustain a positive mood. High MAO-A levels excessively remove these brain chemicals.

Antidepressant medications are the most commonly prescribed treatments in North America, yet 50 per cent of people do not respond adequately to antidepressant treatment.
In fact, the U.S. Centers for Disease Control and Prevention looked at 2.4 billion drugs prescribed in visits to doctors and hospitals in 2005. Of those, 118 million were for antidepressants.

Dr. Jeffrey Meyer who was the lead investigator states, "Mismatches between treatment and disease are important for understanding why treatments don't always work. Rather than reversing the problem of MAO-A breaking down several chemicals, most antidepressants only raise serotonin."

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According to the World Health Organization, Depression ranks as the fourth leading cause of disability and premature death worldwide. Part of the problem is the recurrence of the illness and even with optimal treatment the recurrence rates for clinical depression are at least 20 per cent over two years.

The new study in addition looked at people who had seemed to fully recovered from past incidents of clinical depression. Some people who appeared to be in recovery had high levels of MAO-A. Those with high levels of MAO-A then had subsequent recurrence of their depressive episodes.

VP of Research Dr. Bruce Pollock highlights the study's use of advanced brain imaging technology. "CAMH has the only positron emission tomography (PET) centre in the world that is dedicated solely to mental health and addiction treatment and research. As a consequence, we were able to develop this new technology to measure MAO-A levels."

Virginia Wilson understands the struggle it can be to find medication that can actually work on depression. After being diagnosed with depression it took over eight years before she could find a medication that worked well for her. "During this time I was on every type of antidepressant available. This process was enormously frustrating, painful, and took a great toll on my personal life." This current research into depression offers people like Virginia hope for others who struggled as bad as she did and she states, "Understanding of the biochemical mechanisms behind depression is so important and can really improve the treatments that are available -- it can save lives."

Some early antidepressant medications did target MAO-A, but these MAO-A inhibitors were not favored too much in the 70s because of the adverse interactions with certain foods. There have been some advances that overcome these problems, but the vast majority of antidepressant development and use has overlooked the MAO-A target.

Dr. Meyer, a Canada Research Chair in the Neurochemistry of Depression and the Head of the Neurochemical Imaging Program in Mood Disorders says "Since most antidepressants miss MAO-A, we are counting on the brain to heal this process of making too much MAO-A, and that doesn't always happen. The future is to make treatments that tell the brain to make less MAO-A, even after the antidepressant treatment is over, to create better opportunities for sustained recovery."

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