Scientist discovers why antidepressants don't work for so many

"If the 'stress causes depression theory' was correct, there should have been a significant overlap between these two sets of genes," she said. "There weren't."

Out of a total of over 30,000 genes on the microarray, she discovered approximately 254 genes related to stress and 1275 genes related to depression, with an overlap of only five genes between the two.

"This overlap is insignificant, a very small percentage," Redei said. "This finding is clear evidence that at least in an animal model, chronic stress does not cause the same molecular changes as depression does."

Antidepressants Treat Stress Not Depression

Most animal models that are used by scientists to test antidepressants are based on the hypothesis that stress causes depression. "They stress the animals and look at their behavior," she said. "Then they manipulate the animals' behavior with drugs and say, 'OK, these are going to be good anti-depressants.' But they are not treating depression; they are treating stress."

That is one key reason why current antidepressants aren't doing a great job, Redei noted. She is now looking at the genes that differ in the depressed rat to narrow down targets for drug development.

She said another reason current antidepressants are often ineffective is that they aim to boost neurotransmitters based on the popular molecular explanation of depression, which is that it's the result of decreased levels of the neurotransmitters serotonin, norepinephrine and dopamine. But that's wrong, Redei said.

Drugs Aim at Wrong Molecular Target

In the second part of the study, Redei found strong indications that depression actually begins further up in the chain of events in the brain. The biochemical events that ultimately result in depression actually start in the development and functioning of neurons.

"The medications have been focusing on the effect, not the cause," she said. "That's why it takes so long for them to work and why they aren't effective for so many people."

via Why antidepressants don't work for so many.

Short term situational depression is something most people will experience. I think exercise, healthy food, relaxation, social connections, a hopeful outlook, planning good things for the future, etc. are the best ways to fight depression long term.

I was right about current antidepressants being primitive and often useless. This discovery means, I hope, that they can move forward and find things that really do work.

It is my philosophy that we are not intended to be happy all the time. If there was a 100% safe "happy pill", I would not want it.  Sadness, pain, anger ... these emotions exist to motivate us to make positive changes in our lives.