Why medication fails to address mood disorders

The majority of people with mood and anxiety disorders who receive the most commonly prescribed anti-depressants -- called SSRIs -- are not helped by these medications.

A new research sheds light on why Selective Serotonin Reuptake Inhibitors or SSRIs fail to work in most patients.

SSRIs are designed to increase serotonin, a neurotransmitter in the brain that is key to maintenance of mood.

"We have shown that serotonin is too high near the serotonin brain cells, reducing firing of the serotonin nerve cells through a well-documented negative feedback mechanism in the raphe nucleus.

"The result is that the hippocampus and other critical brain structures needed for mood maintenance do not get enough serotonin," explained lead researcher Jeremy D. Coplan.

"We have hypothesised in an earlier paper that this is a plausible reason why SSRIs may not work in a majority of people, because SSRIs will tend to make the high serotonin even higher in the raphe nucleus.

"The serotonin neuron may not be able to adapt and restore its firing, inducing a presumed serotonin deficit in terminal fields, evidenced by shrinkage of the hippocampus," added Coplan, a professor of psychiatry at SUNY Downstate Medical Center, in the US.

The researchers advocate that additional studies should be performed as better understanding of the serotonin system will significantly improve future treatment options.

Coplan noted that a recent large-scale study showed only a minority of patients do well on SSRIs, and of those, many lose response in a year or two.

"There is an epidemic of inadequately treated depression and psychiatrists are not well trained to deal with this challenge," he observed.

"What they often do is change from one anti-depressant to another when there is a lack of response. Eventually the patient becomes non-compliant and the patient, rather than the treatment, is blamed for the non-efficacy," he rued.

The research was published in Frontiers in Behavioural Neuroscience.