Science behind commonly used anti-depressants appears to be backwards, researchers say Posted on February 21, 2015, 0 Comments

Date:
February 17, 2015
Source:
McMaster University

The science behind many anti-depressant medications appears to be backwards, say the authors of a paper that challenges the prevailing ideas about the nature of depression and some of the world's most commonly prescribed medications.

The authors of the paper, posted by the journal Neuroscience & Biobehavioral Reviews, combed existing research for evidence to support the theory that has dominated nearly 50 years of depression research: that depression is related to low levels of serotonin in the gaps between cells in the brain.

The low-serotonin theory is the basis for commonly prescribed anti-depressant medications called selective serotonin re-uptake inhibitors, or SSRIs, which keep the neurotransmitter's levels high by blocking its re-absorption into the cells that release it.

Those serotonin-boosting medications actually make it harder for patients to recover, especially in the short term, says lead author Paul Andrews, an assistant professor of Psychology, Neuroscience & Behaviour at McMaster.

"It's time we rethink what we are doing," Andrews says. "We are taking people who are suffering from the most common forms of depression, and instead of helping them, it appears we are putting an obstacle in their path to recovery."

When depressed patients on SSRI medication do show improvement, it appears that their brains are actually overcoming the effects of anti-depressant medications, rather than being assisted directly by them. Instead of helping, the medications appear to be interfering with the brain's own mechanisms of recovery.

"We've seen that people report feeling worse, not better, for their first two weeks on anti-depressants," Andrews says. "This could explain why."

It is currently impossible to measure exactly how the brain is releasing and using serotonin, the researchers write, because there is no safe way to measure it in a living human brain. Instead, scientists must rely on measuring evidence about levels of serotonin that the brain has already metabolized, and by extrapolating from studies using animals.

The best available evidence appears to show that there is more serotonin being released and used during depressive episodes, not less, the authors say. The paper suggests that serotonin helps the brain adapt to depression by re-allocating its resources, giving more to conscious thought and less to areas such as growth, development, reproduction, immune function, and the stress response.

Andrews, an evolutionary psychologist, has argued in previous research that anti-depressants leave patients in worse shape after they stop using them, and that most forms of depression, though painful, are natural and beneficial adaptations to stress.

Story Source: http://www.sciencedaily.com/releases/2015/02/150217114119.htm

Abstract

The role of serotonin in depression and antidepressant treatment remains unresolved despite decades of research. In this paper, we make three major claims. First, serotonin transmission is elevated in multiple depressive phenotypes, including melancholia, a subtype associated with sustained cognition. The primary challenge to this first claim is that the direct pharmacological effect of most symptom-reducing medications, such as the selective serotonin reuptake inhibitors (SSRIs), is to increase synaptic serotonin. The second claim, which is crucial to resolving this paradox, is that the serotonergic system evolved to regulate energy. By increasing extracellular serotonin, SSRIs disrupt energy homeostasis and often worsen symptoms during acute treatment. Our third claim is that symptom reduction is not achieved by the direct pharmacological properties of SSRIs, but by the brain's compensatory responses that attempt to restore energy homeostasis. These responses take several weeks to develop, which explains why SSRIs have a therapeutic delay. We demonstrate the utility of our claims by examining what happens in animal models of melancholia and during acute and chronic SSRI treatment.

The above story is based on materials provided by McMaster University. Note: Materials may be edited for content and length.

Journal Reference:

  1. Paul W. Andrews, Aadil Bharwani, Kyuwon R. Lee, Molly Fox, J. Anderson Thomson. Is serotonin an upper or a downer? The evolution of the serotonergic system and its role in depression and the antidepressant response. Neuroscience & Biobehavioral Reviews, 2015; 51: 164 DOI: 10.1016/j.neubiorev.2015.01.018