Antidepressants: the ongoing debate

What exactly is depression and how have we traditionally managed the symptoms? Hamish McAllister-Williams is a consultant psychiatrist and a professor of affective - or mood - disorders at Newcastle University. He spoke first about what we know about what’s going on inside someone’s head when they have a depressive episode…

Hamish  - Depression is probably a number of different conditions rather than just one disorder. One of the major features is feeling low or sad in mood, but there are different underlying abnormalities within the brain that may actually lead to those symptoms. What we do know is that if you look at a group of people with depression, you can see a number of changes in the structure and functioning of the brain compared to people who are currently, for example, we may see overactivity in circuits that are associated with ruminating about things. We also see changes, though, not just in the brain. We see alterations in markers of inflammation, alterations in the stress response system. So it's not just in the brain, but exactly how those precise changes lead to the various different symptoms. I don't think we have an absolute answer to it.

Chris  - And when it comes to treating the condition, how does a psychiatrist like yourself approach this?

Hamish  - So first of all, making a good assessment, really establishing whether the person does have depression rather than some other condition. And if depression, is this a depressive disorder as opposed to a bipolar depression, depression occurring in the context of bipolar disorder, what used to be referred to as manic depressive disorder. The way we treat depression is different and we use different psychotherapies and we use different medications. Then in terms of how we go about treating it, we have psychological treatments, talking therapists, we have medication and a range of different types of medication. And we're also now having an increasing number of what would be referred to as neuro stimulatory treatments. These are electrical or magnetic ways of being able to alter brain activity. These different treatments will suit different individuals at different times.

Chris  - Is there a threshold for which you decide this person has a major depressive disorder versus someone who they're feeling low this week, they're having a few knocks at work or in their family life and so on?

Hamish  - Ultimately, it is arbitrary and it is a challenge. We would look at the number of symptoms the patient has for an episode of major depression. We would normally be looking for a minimum of five symptoms out of a checklist of nine. But more importantly than that, we would be looking to see that the symptoms are persistent for at least a couple of weeks and that they are leading to significant impairment in the person's everyday life. Whether that's their ability to be able to go and function at school or at work or in their relationships or any other facet of their lives.

Chris  - And when a person embarks on treatment, what does it actually do? And how do these different therapies that you outlined compare in terms of how effective they are?

Hamish  - They do tend to have slightly different effects. Talking therapies will be targeting specific types of symptoms. They may be focused on the negative thoughts and memories that pop into people's minds when they're depressed. Medication can work in a number of different ways. We know that it can lead to an alteration in the way that we see the world around us, and stop seeing it in quite such a negative perspective.

Chris  - Do we know exactly what they're doing to the brain, these treatments? Is it just that they boost the levels of certain chemistries and certain neurochemicals and this immediately makes people feel better? Or do they change the way that the brain is wired? Because a number of years ago, people discovered that all through life we seem to be giving birth to new nerve cells in some areas of the brain. And then people made this leap and said, 'well, look, it's interesting. We also find that antidepressants make some of these newborn nerve cells live longer.' And so you put two and two together and say, well, are they working because they're basically helping the brain patch itself back together. Do we have any clear picture yet of what the drugs are doing?

Hamish  - Yes, to some extent. But what I would say is the thing that we know most convincingly is that the treatments work exactly how they work. There is uncertainty, but from all of those studies we do know that medications, for example, standard antidepressants, do lead to alterations in the functioning of some of the chemicals within the brain, some of the systems that those chemicals are involved in across treatments. We do see changes in the birth of new nerve cells that you mentioned. We see an increase in that. And it is interesting that we see that with medication. We see that with electroconvulsive therapy. We see that with exercise, which we also know can treat depression in animals. But perhaps even more importantly, the connections that are made between brain cells. These seem to be increased by all of these treatments. But the treatments then can be shown to have a range of other effects as well. We see a reduction in markers of inflammation. We see a normalisation in the way that stress response systems work as well. And precisely which of all of these different effects leads to the improvement in depression is a bit uncertain.

Chris  - And how long does one need to be treated? Is it a short course, it puts things right in the way you've outlined, and then people are back on the straight and narrow? Or is this something people should plan to be taking for the long term?

Hamish  - In the first instance, we would normally say that an episode of depression needs to be treated for six to 12 months. The reason for that is that if you stop treatment too early, there is an increased risk that the episode of depression will just come back again. Further to that, what we also know is that for many people, probably the majority unfortunately, of people who have depression, it is a recurrent disorder. That is that they have more than one episode. And what we know is that many treatments, particularly antidepressants, some psychotherapists, can be very good at helping to prevent recurrence of a new episode of depression in the future. So to start off with, when somebody has the first episode, we would treat it for six to 12 months, reducing the chance of that episode coming back. But for somebody who's had multiple episodes, we may recommend treatment for longer, maybe a couple of years, maybe even longer than that.

Antidepressants play a large role in a lot of medical settings. But they are not without their critics. Dr Joanna Moncrieff is one of Mark Horowitz’s colleagues at UCL and has some concerns about the widespread use of antidepressants.

Joanna - First of all, I just want to correct some things that Hamish McAllister Williams mentioned earlier. He gave the wrong impression that depression has been shown to be a brain disease, that abnormalities in the brain have been demonstrated in people with depression. That is simply not true. There are lots of theories about the biological basis of depression, and of course there are some studies that show some differences between people with depression and people without. But there are other ways of explaining those differences. And there really isn't convincing evidence that there is any sort of biological abnormality in people with depression. Just let me take one example, inflammation, that he mentioned. Yes, there are studies showing that people with depression have different inflammatory markers than people without depression, but we know that inflammatory markers are influenced by many things that can explain that difference. For example, the level of exercise that people get, people's weight, people's sleep, people's social class, stress, adverse life events, all these things can easily explain the abnormalities that are shown in inflammatory markers. So we don't have evidence that depression is caused by a brain abnormality.

Chris - It's very real though. To the people who suffer from it, it's very intrusive on their life. So they would argue that regardless of whether their brain is different, something is very different about the way their brain is working for them at that moment in time.

Joanna - People can be suffering. That doesn't mean that the cause of that suffering is in the brain. And the question we have to ask is, if there's nothing wrong with the brain, then what are antidepressants doing to the brain? If they're not correcting an underlying abnormality - it's not just a little bit uncertain - it is completely uncertain exactly what antidepressants are doing. They are actually creating an abnormality in the brain. They're changing the normal state of brain chemistry. And that is what leads to the sort of side effects that Mark Horowitz described. The lethargy, the tiredness, the memory problems and, of course, the withdrawal problems that people have when they're trying to get off these drugs because the body has adapted to the presence of this extraneous chemical and is trying to counteract its modifying effects.

Chris - So why do we carry on using them if this is the case?

Joanna - So there was a very concerted campaign starting in the 1990s to change people's common sense views about the nature of depression. And this was led by the pharmaceutical industry, but the medical profession jumped on board, and it basically set out to convince people that depression is a biological brain condition, that it's not some sort of understandable emotional reaction to life, but it's something that's biological in the brain and needs to be treated with medical treatments. Of course, drugs were the main thing that the pharmaceutical industry was pushing at that time, and that was a very deliberate campaign, and that's why many people have come to believe this idea that depression is a medical problem, that you need to take antidepressants, that antidepressants will rectify the underlying abnormality. It was the deliberate aim of these campaigns to make people think in this way.

Chris - Are there any exceptions to this situation? Are there any people for whom you would say that taking antidepressants is a good idea?

Joanna - First of all, I think we need to understand the effects of antidepressants differently. They are not reversing an underlying abnormality. They create an abnormal mental state in more or less subtle ways. Some of them have quite subtle effects on our mental activities. Some of them have more dramatic effects, make people drowsy and a bit foggy. And they all have this emotional numbing effect. And it may be the case that some people find that emotional numbing effect helpful when they're feeling very distressed. But I think it's really important to appreciate if that is useful, it's not because the drug is rectifying an underlying abnormality. It's because it is actually inducing an artificial state, which may temporarily relieve underlying feelings of distress. In the same way that if we had a drink of alcohol, we would feel different, and we might temporarily come out of our sadness. And, again, making the comparison to alcohol, it's not usually a good idea to do that on a long term basis. It may be okay. In the short term it may be helpful but, in the long term, it's not usually helpful either psychologically or physically.