A new study suggests most antidepressants do not target a key brain protein believed to be of importance in maintaining mood.
The protein is monoamine oxidase A (MAO-A), a substance that is highly elevated during clinical depression. The new study suggests this chemical is unaffected by treatment with commonly used antidepressants.
According to experts, the study has important implications for understanding why antidepressants don’t always work.
Researchers at the Centre for Addiction and Mental Health (CAMH) used an advanced brain imaging method to measure levels of the brain protein MAO-A. MAO-A digests multiple brain chemicals, including serotonin, that help maintain healthy mood.
High MAO-A levels excessively remove these brain chemicals.
Dr. Jeffrey Meyer, the lead investigator, explains, “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.”
Understanding the Problem of a Persistent Illness
Depression ranks as the fourth leading cause of disability and premature death worldwide, according to the World Health Organization. Recurrent illness is a major problem. Even under the most optimal treatment circumstances, recurrence rates for clinical depression are at least 20 percent over two years.
The new study also focused upon people who had fully recovered from past episodes of clinical depression. Some people who appeared to be in recovery actually had high levels of MAO-A. Those with high levels of MAO-A then had subsequent recurrence of their depressive episodes.
This new idea of high levels of MAO-A lowering brain chemicals (called monoamines), then falling into a clinical depression is consistent with the historical finding that medications which artificially lower monoamines can lead to clinical depression as a side effect.
In the 1950’s some medications to treat high blood pressure also lowered monoamines and people began to experience depressive episodes. When the medications were removed, people recovered.
From Technology to Treatment
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.”
According to Dr. Meyer, “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.”
Monoamine oxidase inhibitors (MAOIs) are an older class of antidepressants used for the treatment of depression. While more commonly prescribed in Europe and other places, they are not commonly prescribed in the U.S. due to the potential for serious dietary and drug interactions. People who take a MAOI antidepressant must eat a restricted diet to ensure they don’t suffer from serious side effects.
The study is found in the current issue of the Archives of General Psychiatry.