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According to ‘Opening Pandora’s box’ has been defined as ‘to start something that causes many new and unexpected problems’. It turns out that there is a significant and reciprocal relationship between depression and obesity. It is also fair to say that many people who have been diagnosed with some form of depression are also taking some form antidepressant. And so, I thought that it might be useful for me to discuss the relationship between obesity, the anchor tenant of the metabolic syndrome, depression and antidepressants in this blog post.

There appears to be a reciprocal relationship between being overweight or obese and being depressed. A number of studies have revealed that the likelihood of becoming depressed increases by about 55% overtime for individuals who are obese when compared to similar individuals who are not obese. The converse also to appears to hold true: people who are depressed have about a 27% increased risk of becoming obese. While the exact mechanisms are not clear, research clearly points to a significant relationship between obesity and depression, as well as with other conditions of the metabolic syndrome such as insulin resistance and type 2 diabetes.

Do antidepressants play a role?

Now it’s time to introduce a third party into the relationship, namely, antidepressants. As most of us realise, a third party can often complicate a bilateral relationship, and adding an antidepressant may complicate matters ,not least of all because many antidepressants are associated with weight gain. That’s right, people on antidepressants often report long term weight gain as an adverse effect of the medication.

Weight gain is not the only unwelcome guest to pop out of Pandora’s box. There are a large number of adverse effects associated with antidepressants. The most common adverse effects reported are those that may be classified under the banner of sexual dysfunction.

I spent some time this last week reading an excellent research paper about antidepressants by Dr Irving Kirsch an eminent professor of psychology at Harvard Medical School in the USA. The article is entitled Antidepressants and the Placebo Effect (Zeitschrift fϋr Psychologie 2014;222(3):128-134). Professor Kirsch reviewed a great deal of the antidepressant literature, both published and unpublished. An important finding of this research is that the so-called serotonin theory (‘chemical imbalance in the brain’ theory) is without foundation.

This is what he has to say: ‘The serotonin theory is as close as any theory in the history of science to having been proved wrong’. He then goes on to open Pandora’s box yet again, when he writes: ‘Instead of curing depression, popular antidepressants may induce a biological vulnerability making people more likely to become depressed in the future.’ Is this ‘biological vulnerability’ the true chemical imbalance of depression, and is it possible that it may be caused by the very medication people take to treat depression?

Do antidepressants work?

Yes, sometimes they do but sometimes they don’t. And here is what Professor Kirsch and his fellow researchers have to say about the effectiveness of this class of medication: ‘…we found that 82% of the drug response was duplicated by placebo.’ In other words, if antidepressants alleviate symptoms of depression they do so mostly not because of the active ingredients contained in the antidepressants but for some other reasons – the placebo effect. This is mind boggling (no pun intended), given the adverse effects associated with antidepressants, including weight gain, sexual dysfunction, insomnia, anxiety etc., as well as because of the very real difficulty many people having coming off these medicines. They experience withdrawal symptoms and an increased risk of relapse, which ‘depends on the degree to which the particular antidepressant used changes neurotransmission in the brain’ – the ‘biological vulnerability’ that Professor Kirsch refers to.

This is a very important topic given that being overweight or obese; having type 2 diabetes or insulin resistance – all fellow travelers of the metabolic syndrome – are all associated with increased risk for depression, and because many people use antidepressants. Furthermore, being treated for depression with antidepressants is associated with long-term weight gain, which in turn is a risk factor for diseases of the metabolic syndrome.

Treatment of depression with antidepressants may be like opening Pandora’s box. While these medicines may improve depressive symptoms (most often because of a placebo effect) , they are also associated with serious adverse effects.

If you have  any more questions, please don’t hesitate to email me on