Have we been treating depression all wrong? The case against serotonin.

Anyone who has ever suffered from depression can tell you that it feels like nothing is right. You don’t want to do anything, say anything, be anything or flat out exist if that were possible. You don’t know why you feel that way, and often times there may not be a tangible reason. Depression is a hard thing to define and often definitions fall short of describing exactly what the problem is. Symptoms listed as restlessness, irritability, feelings of guilt or worthlessness and persistent sadness don’t really nail home the true feelings of depression, the feeling of a black hole in your gut. Depression affects that nearly 40 million adults in the US and while there are treatments available, many of the ones targeting serotonin have been shown to only improve depression symptoms by a small margin over placebos.

So what causes depression? Depression originally was suspected to be caused by low serotonin levels in the brain because early treatment of people who had depression with Prozac caused a slight improvement in their symptoms. Recently however, the medical community has been shifting away from the low serotonin explanation for depression to one that is much more complex and involves genetics, problems with mood regulation, and other potential defects.

Did we get depression all wrong to begin with? The problem with the serotonin theory is that when it was developed no one knew how to treat depression. Then Prozac came along. Prozac seemed to help a subset of patients with depression and so everyone came to agree that serotonin was the culprit. Problem is, most of the serotonin boosting treatments have modest effects at best. Randomized control trials (the gold standard for testing the efficacy of drugs) have shown that selective serotonin re-uptake inhibitors (SSRI) are no more effective than any other treatment, including St. John’s Wort or placebo.

The case against serotonin and depression takes another hit thanks to a recent study in the journal ACS Chemical Neuroscience showing that mice that completely lack serotonin do not show behaviours indicative of depression. While the study was done on a mouse model, it does provide some useful insight into whether there is a connection between serotonin and depression. The research suggests that the complete lack of serotonin in the brains of these mice does not confer risk to depression. Interestingly, when the mice that completely lacked serotonin where given an SSRI, some of them showed improvements in measures of depression to the same level as those mice that still had serotonin in their brains. This lends more evidence that the link between SSRI’s (like Prozac) and depression is more likely a placebo effect. Hopefully this mouse study will lead to some more definitive studies in humans about serotonin and depression.

The conversation going on currently in the research field promises to find the true causes of depression and hopefully find better medication than SSRI and other serotonin based medications. Some patients on SSRI’s do see meaningful improvements in their symptoms; unfortunately there are an equal (or greater) number of patients who do not respond to their medication. Some people with depression may have decreased serotonin in their brains, but this could be a result of the depression rather than the cause. In this case, SSRI’s will help to return the serotonin back to normal levels but will not treat the underlying cause of depression that could explain why many patients continue to have problems while still on antidepressant’s. Similar to the way people who suffer from migraines get relief from aspirin but can still continue to suffer from them even while taking aspirin. The aspirin doesn’t treat the underlying cause.  If you are someone else you know if struggling with depression, visit this website to learn more about other treatment options. We need to start the conversation on depression to find the underlying cause and help those who are suffering in silence.

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2 thoughts on “Have we been treating depression all wrong? The case against serotonin.

  1. Pingback: Mental health and inflammation: new idea for fighting depression. | Science Translation

  2. Pingback: Who is affected by mental illness? | Science Translation

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