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The title of this week’s podcast is Depression and Antidepressants: opening Pandora’s box.

The term ‘Opening Pandora’s box’ is defined as ‘to start something that causes many new and unexpected problems’ ( As the articles I write are almost always focused on metabolic syndrome, which on the surface does not appear to include depression, you might justifiably ask: why discuss the topic now? Well, it turns out that there is a significant and reciprocal relationship between overweight or obesity and depression. It is also fair to say that many people who are diagnosed with some form of depression are also using 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 podcast .

A number of studies reveal that the likelihood of becoming depressed increases by about 55% over time for individuals who are obese when compared to similar individuals who are not obese. The converse also to appears hold true: people who are depressed have about a 27% increased risk of becoming obese. While the exact mechanisms involved in these reciprocal relationships are not clear, research clearly points to a significant relationship, as well as with other conditions of the metabolic syndrome such as insulin resistance and type 2 diabetes.

So as we have been able to establish that there appears to be a reciprocal and significant relationship between obesity and depression, then 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 so adding an antidepressant into the obesity -depression mix may likewise 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 recently reading an excellent research paper on antidepressants written 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). Dr Kirsch reviewed a great deal of the antidepressant literature, both published and unpublished. An important finding of his research is that the so-called serotonin theory or ‘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’. This is a very important finding, as I’m sure many will agree.

Dr Kirsch then goes on to open Pandora’s box a little further 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? In other words, it may be that the antidepressants themselves cause a ‘chemical imbalance in the brain’.

So 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 actions 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 have in 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 very ‘biological vulnerability’ that Professor Kirsch refers to.

I believe that this is a very important topic given that being overweight or obese, or having type 2 diabetes or insulin resistance –fellow travellers of the metabolic syndrome – are all associated with increased risk for depression, and because so many people today – especially women – use antidepressants. Furthermore, we know that being treated for depression with antidepressants is often associated with long-term weight gain, which in turn is a risk factor for diseases of the metabolic syndrome.

And so treatment of depression with antidepressants may be a bit like opening Pandora’s box. While these medicines may improve depressive symptoms – most often because of a placebo effect – they are also associated with a range of adverse effects, some of which are serious. Be informed and make informed decisions about your healthcare.

I’m Dr Peter Hill for UpforIt . Till next time be healthy and safe.