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Why SSRI antidepressants work only half the time

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The SSRI (selective serotonin reuptake inhibitors) antidepressants, such as Prozac, are based on the theory that depression is the result of a chemical imbalance, and especially of serotonin, a neuro-transmitter that helps signalling in the brain.

But if the theory was right, every patient would have their depression lifted when they took an SSRI, but it’s effective only in between 30 per cent and 50 per cent of them, so researchers from the Instituto Superiore di Sanita in Rome decided to find out the reason for the high failure rate.

In an experiment with laboratory rats, the researchers discovered that the serotonin from the drug didn’t help ease depression – but instead it created a condition in the brain that made change possible. In other words, the chemical increased the brain’s plasticity. “In a certain way it seems that the SSRIs open the brain to being moved from a fixed state of unhappiness to a condition where circumstances can determine whether or not you recover,” said lead researcher Silvia Poggini.

And it’s the environment that really matters, and will determine whether or not your depression is lifted when you take an SSRI, they say.

To test the theory, half the rats given a SSRI were kept in a stressed environment, while the rest were placed in a more comfortable, and less stressful, environment. Those in the comfortable environment had much higher levels of markers in the blood that are related to depression than those kept in a stressed situation, even though both groups had exactly the same dose of the SSRI.

(Source: Brain, Behaviour and Immunity, 2016; doi: 10.1016/j.bbi.2016.07.155)

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