5 Treatments for depression

Dr Danny Penman:

Hello and welcome to the ‘New Psychology of Depression’, a series of programmes with me, Dr Danny Penman and Professor Mark Williams of Oxford University. In this episode, we’ll be looking at the treatment of depression, and how it has changed over the last few decades or so.

Mark, at the moment, what are the main ways of treating depression?

Professor Mark Williams:

Well there’s two big approaches, physical treatments and psychological treatments. Those are the main two approaches, but there are many psychological treatments. I’ll come to those in a moment. Of the physical treatments, there are some that are fairly rarely used nowadays that used to be used a few decades ago like ECT ‘electro-convulsive therapy’ treatment. But the main physical treatment is antidepressant medication. They’re very, very widely used now all over the world, and they work pretty well.

Dr Danny Penman:

So, anti-depressant medication. They obviously affect brain chemistry. How in detail do they work?

Professor Mark Williams:

Well, in the brain there are many, many different receptor sites, for example, the way in which nerve cells work is an electrical impulse running down the nerve cell, but then it comes to a junction. And then the current, as it were, the impulse has to be transferred from one nerve cell to another and that’s called the synapse, the junction of these two things. And that’s the point where chemicals come in, because those neurotransmitters are released from one end and are picked up at the receptor sites of the other one, and then the transmission continues.

Now there are millions and millions of these in the brain, and so much of our functioning, our eating, our sleeping, our mood, everything is governed by the action of neurotransmitters in the brain. And what we know is that when they get unbalanced, then, depression can result.

There are many neurotransmitters. The ones that are most thoroughly studied are noradrenaline and serotonin. And what we know is that the antidepressants that work, are often antidepressants that effectively increase the availability of these substances in the brain. They usually do so by blocking reuptake. What that means is that usually when the neurotransmitter is released, if that synapse is going to be effective it can’t linger for very long, so there’s got to be a mechanism for as it were, ‘gobbling up’ the neurotransmitter. So when the next impulse comes, you know, it can release. So that’s called ‘reuptake’.

Now if you have a reuptake blocker that means that when a neurotransmitter has been released it stays around for longer. That’s one of the ways in which it works. Now we know that it takes some time, it takes a few days for most antidepressants to, as it were, kick in and affect your mood in a noticed and significant way that you actually notice it. Although they start working straightaway the fact that it takes a little time suggests that it’s not just more neurotransmitter that’s the critical thing, but it’s actually changing the balance. The sort of change in the balance of sensitivity in the cells at the, sort of, sending and receiving sites.

Dr Danny Penman:

So is depression caused by low levels of these chemicals in the brain such things as serotonin, or is it more complex than that?

Professor Mark Williams:

It’s probably more complex than that because if it was, you could just give things to increase the levels and people would be instantly happier. That doesn’t happen. So what people think is that there might be something in some of the receptor sites. For example, they might be just insensitive. Now if you get a receptor site insensitive, just increasing the amount of available neurotransmitter isn’t going to work instantly, so that might be something.

We also know that the transporter gene, that’s the genetic, as it were, messenger, mechanics of getting the stuff available to the brain, that might also be effective. And there’s quite a lot of interesting work now at the frontier of this science looking at serotonin transporter genes, for example.

Dr Danny Penman:

How effective are these drugs? Are they are all similarly effective?

Professor Mark Williams:

Well, they seem to be. I mean the drugs that were introduced in the 1950s and 60s−what are called ‘tricyclic’ antidepressants−are pretty effective. The new generation of antidepressants are about as effective. The major aspect of them is they’re less toxic in overdose, for example. They’re safer, they don’t have so many side effects. Of course, side-effects are always an individual interaction between the profile, the biological profile of the individual taking them and the biological profile of the medication. And therefore it’s impossible to predict exactly what side-effects come with each antidepressant.

So, very often a physician will try a person on one antidepressant, and then say 'Come back and tell me if this suits you' and 'Try another one of the same or a different class', if it doesn’t. So there is a part of this which is experimental and it’s always of discovery for the physician and the person themselves in discussion, to decide what works for them. But if you ask whether they work? Well, it’s pretty controversial. It looks as if about 60% of people in most studies, you know, if you go on for a year you’ll get remission or recovery. That’s depression really going down to bearable levels. and maybe there’s only one or two symptoms around in any one week instead of these crushing, weighted depression. About 60% will recover.

Later data from things like the big STAR*D Trial I was referring to in episode one, that suggests that after twelve weeks on one form of medication, then about 30% will respond to that. If you then change to another antidepressant, a further 19% will respond to that. If you then change to another in those who haven’t actually responded to either of those first two, then another 14% will respond to a third.

Now that cumulative rate of about 47% over one year is slightly more pessimistic than many would have hoped. And there’s new evidence all the time on the effectiveness of antidepressants, and some of the big meta-analyses, that’s when people get all the data, all the studies together, are beginning to suggest that from ‘mild’ depression, or perhaps even some ‘moderate’ depression, antidepressants don’t work much better than a placebo, a sort of sugar pill. But for ‘severe’ depression, which cause the greatest amount of problem, then you do see clear blue water between the antidepressant and a placebo.

Now, having said all that, of course, your doctor, if you go to the doctor, will never give you a sugar pill, as it were, if you’re not part of the research trial where you’ve got consent to do that. And therefore the fact that you get both a placebo effect and a therapeutic effect can be for many people a life saver, as it were. It does change lives. It does change moods. So nothing about the psychology or the ‘new psychology’ of depression means that these are now irrelevant, or should be substituted for psychology. For many people they’re a life saver, but probably the best estimate is 50 to 60% of people responding.

And, of course, one of the things that emerges from that is, well, what about the other 40%? And also what about the people who don’t respond to one or the other? And, of course, some people don’t want to stay on antidepressants for a long time. The major problem with antidepressants is this, that when you stop taking them, let’s say you take them for six to nine months or a year, and it deals with the depression and then you feel stable. If you then come off antidepressants then your risk of getting depressed again returns to the risk that you had before you started taking them.

That means if you’ve had three episodes of depression, and your risk was 60 to 70% you can deal with that with antidepressants for, say, a year, two years. When you come off them your risk goes back to 60 to 70%. If you’ve had five depressions in the past and your risk is 90%, when you come off antidepressants your risk goes back. Now you might not become depressed immediately, but a recurrence is, of course, a very, very damaging and disappointing thing to happen when you thought you’d coped with it.

And therefore many physicians are saying 'Well, why not go on antidepressants and stay on them?' If they suit you, treat it like diabetes, you know, like it’s a permanent lifetime thing you’ve got, treatment of the diabetes. But the trouble is that many people don’t want to be on drugs for the rest of their life. Some people naturally come off.

So in that long-term study from what I was telling you that started in the 1970s, virtually everybody after a year had spontaneously come off their antidepressants. We know from recent data that 30% of people don’t even go back for their repeat prescription. So there’s a large, sort of, weight of evidence that people naturally come off despite their doctor’s advice, they come off antidepressants. And then of course they are at risk of getting depressed again.

Dr Danny Penman:

Is that risk a withdrawal symptom or is it just they’re returning back to normality and, you know, the world hasn’t changed?

Professor Mark Williams:

It’s a good question. If it was just a withdrawal system then you’d expect the depression to come back quite quickly and that does indeed happen when you come off your antidepressants, say, within three months, four months, five months, six months. And when you think about it imagine that a depression was going to last four, five, six months naturally. We know that depression naturally gets better if you don’t do anything with it. It tends to be episodic. That means it comes, it’s crushing when it happens, but then you get over it.

Now if you take antidepressants for an episode of depression, then if you take your antidepressants for a few weeks, the depression,as it were, is still there underneath, the biological process is still at work. If you come off prematurely the depression comes back pretty quickly. That’s what’s called a ‘relapse’. And that’s where you get this sort of kick-back effect. However, if you’ve taken antidepressants for six, nine months, a year, that has covered that episode of depression. And when you come off, you’ll be OK for a while probably. But then there’s what we call a ‘recurrence’ as opposed to ‘relapse’, which is that within a year or two the depression tends to start again.

So it’s probably not just a kick-back effect, a withdrawal, although some of antidepressants are harder to come off than others and some, I mean and you always of course need your doctor’s advice. If you’re thinking of coming off antidepressants you always go and see the physician who has given you them or has prescribed them and ask their advice and they’ll help you. Because some are easy to come off, others are much more difficult and you can get a lot of other symptoms, a lot of flu-like symptoms from some, for example. And you need to have a doctor’s reassurance that these are recognisable and to help you get through that, so you can get out to the other side.

Dr Danny Penman:

So does this mean the only long-term solution to depression is a psychological approach?

Professor Mark Williams:

Well, yes, in sense it is. Now if it’s true that just by carrying on taking your antidepressants you can reduce the risk of depression, that will work for some people. And for those who’ve been advised by their doctor that’s what to do and if they’re happy with that, and it doesn’t cause great side-effects, then there’s no reason why they should suddenly stop their antidepressants.

Of course, there’s still a bit of a risk of relapse coming, even if you carry on with the antidepressants and that’s where you can supplement them with psychological skills and psychological therapies as well. But we do know, and this is in a sense turning to our second major strategy, that there are psychological approaches that help, and that when they help they actually also protect against relapse and recurrence.

Dr Danny Penman:

So let’s come to psychological treatments. What are the main psychological treatments at the moment?

Professor Mark Williams:

There are five or six psychological treatments that work well in dealing with acute episodes of depression. The one that’s got most evidence for it is cognitive therapy. So I’ll come back to that. But it’s true to say that there’s something called ‘behavioural activation’, which is getting people moving as it were, in their behaviour. There’s something called ‘interpersonal psychotherapy’, which is as effective as cognitive therapy in trials which deal with things that happen in your interpersonal life. I mean, it’s an individual therapy that deals with things like guilt, with role transitions, with interpersonal effectiveness, these sort of things.

In the early days people thought that ‘psychodynamic psychotherapy’, sort of Freudian and more analytic psychotherapies would be good. And there wasn’t much evidence for that, but then there wasn’t much evidence collected so there weren’t many scientific studies. And indeed, as people began to make those approaches, more psychoanalytic approaches,more structured and shorter, then, for example, there’s something called ‘psychodynamic interpersonal psychotherapy’ which they got it down to 15 sessions just like other psychotherapies and they found that it worked pretty well.

There’s ‘problem solving therapy’ which works pretty well, there’s, for milder depression certainly, and exercise. We know that exercise works pretty well for milder depressions.

So there’s a whole range of things that we can do to deal with acute depression, but probably the main one is, and the one with the biggest evidence base is cognitive therapy. And the history of cognitive therapy is really interesting.

One of the puzzles about the psychology of depression was that in the 1970s, people didn’t actually think that depression was treatable with psychological means. They thought perhaps the new antidepressants work one way because it was a biological thing, and there were people with the analytic side talking about psychoanalysis, but without much evidence. But certainly there was accumulating evidence that depression could be treated with antidepressant medication. And that although in the 1950s and 60s people had many psychological treatments for anxiety and phobias, nobody thought that depression was the sort of thing that you could treat with this approach.

Dr Danny Penman:

So did people once think that you could treat depression by correcting irrational ways of thinking?

Professor Mark Williams:

Well it seems obvious now, but actually no they didn’t. I mean, obviously, in history, throughout history people had a go at that. It’s obvious that irrational thoughts and negative thinking is a very important part of depression. But people thought that it was a symptom of depression, that you had to cure the underlying thing. If you think about what antidepressants are doing you’re treating the underlying biological problem, and you expect the thoughts to clear up by themselves.

In psychodynamic psychology, you’re in a sense doing a similar thing. You’re going for the underlying, say, intrapsychic conflict, whatever it is, and hoping that the thoughts themselves would sort themselves out when you got to the underlying problem. Both biological and dynamic models have this in common. Go for the underlying source of the problem and negative thinking, and so on, would naturally just dissolve.

It wasn’t until two major things happened in the late 60s and early 70s that we changed our mind as psychologists about this. First of all, there was a big emphasis within animal learning theory on what is called ‘learned helplessness’. There is a professor in the United States called Martin Seligman who found almost by accident, that when he had animals in experiments that had been subject to uncontrollable stresses, electric shocks, noise, this sort of thing, that if they were then put, used in another experiment in the days when you did this sort of animal experimentation, in another experiment where they could actually escape the stress they were going to be put under. He found that two-thirds of them didn’t escape. It was almost they’d learnt to be, as he described it, helpless. That they learned there was nothing they can do. He called it ‘response outcome independence’, and they would learn that, well there’s nothing I can do. And he said, you know, this could be a model for depression.

And he started to look at human laboratory experiments and invited ordinary people, well students anyway, to come to the laboratory and to be subject to stress that they couldn’t control or anagrams they couldn’t do. Or little problem solving they couldn’t do. And then he began to wonder if they can’t do one, what’s their effect on the next thing they do?

That’s where I started my PhD studies. I mean my interest in depression started in 1975, 1976 when I started to research why do some people who fail then expect to fail on the next task, whereas other people who expect to fail, it galvanises them for the next task? And that'd been what Seligman was interested in. It was what my colleague, John Teasdale who was my PhD supervisor, originally was interested in. And so that’s what I worked on for my doctoral studies.

Now the interesting thing about learned helplessness is that it works right through the animal kingdom, and it suggested that when you have human depression you have to discover what it is that makes humans begin to, as it were, learn from one event something which may not be true of the next event. You know, 'I’ve just failed, does it mean I’m going to be a failure in the future?' In as much as you believe that, then you’re going to have problems. You know, if you think 'I’m not going to enjoy this party, therefore there’s no point in going', you’re making an inference about the next event based on your experience. And therefore you begin to reduce what you do in your life.

But Seligman didn’t have any treatment. He had a great theory which then started to be picked up by undergraduates and graduate students all over the world. Taught in medical schools all over the world, a very famous theory of depression, but no treatment. So people started to come out of medical school, come out of psychology, come out of clinical psychology training saying 'Well we’ve got a theory, but what can we actually do and offer to our patients'. And then there was somebody called Tim Beck, Aaron Beck who had been working in Pennsylvania on something that he called ‘cognitive therapy’.

Now this, of course, elicits a great deal of interest, because cognitive psychology was the Zeitgeist within experimental psychology. The term had been coined by Dick Neisser in 1967. By 1970,72 the world was abuzz in psychology about cognition, about thinking, about memory, about attention, how it’s deployed. He was a psychiatrist, Tim Beck, trained as a psychoanalyst. He’d worked with Korean veterans coming back from the Korean War. He’d noticed how they were often depressed as a result of the trauma they’d been through, and how often thoughts about worthlessness, helplessness, about not being good enough, how much their thoughts were going round and round and round. As an analyst he’d thought 'Right I need to get underneath this to find out what it’s about'.

As a biological psychiatrist, because he was a psychiatrist, he could treat it with antidepressants. But his amazing insight was to say 'What would it be like, what would a theory look like if the thinking that’s going on in their mind was actually part of the cause of their depression? And if not the cause, part of what was maintaining the depression?'

And that one insight led him to start asking his patients 'Why don’t every time you feel down, just catch what went through your mind just the moment before?' And he started to notice that people began to be able to catch their negative thinking. That there was often a flash. It might be very fast, it might be slow, of a negative thought. And he started to get people to write them down and then say 'Look, what if this is the depression speaking? What about seeing whether the depression is telling the truth or not? Let’s take these ideas of how useless you are, how much you’ve always failed and so on. Let’s write them down, and let’s actually be a bit of a scientist here. Let’s look at them, look at the evidence for, the evidence against.'

And soon he began to find that this was liberating huge swathes of his patients without having to do long psychoanalysis, and without having to do biological treatments. And in 1977 he and his colleagues, Gary Emery, Brian Shaw, John Rush and him, published the first randomised clinical trial where they compared antidepressants for properly diagnosed depressed patients with this new what called ‘cognitive therapy.’ And it was astonishing. Not only did it do as well, there was some suggestion that he could do better, with this ability to test out your thoughts and change your behaviour in these interesting ways. And that was the major, major change in depression in the last 50 years, I think.

Dr Danny Penman:

Presumably this insight was revolutionary?

Professor Mark Williams:

It was and like most revolutionary insights, after the fact, it just seemed so obvious. I remember in the mid-70s when I started to read Beck’s work thinking that it was trivial and I don’t really even need to read very much because it’s so obvious that when people are depressed they get negative thoughts. We need to go underneath the problem. Just to deal with negative thoughts was a trivial way of approaching a really hard problem. But now when you look at the work by Chris Padesky and Dennis Greenberger their book, Mind Over Mood is an incredible best-seller for obvious reasons, because people can do this by themselves. David Burns, The Feeling Good: The New Mood Therapy. Work that Beck himself has continued to do and his colleagues, has revolutionised the study of depression.

I mean, one of the other indications is that my colleague John Teasdale, when he was a psychologist and due to move to Oxford to start off one of the first laboratory programmes in the Psychology of Depression anywhere in the world in 1975, that he was advised by his colleagues there that this would be a waste of time. Everybody knew, they said, that depression was a biological problem or needed some long-term analysis. But as a biological problem, what’s the point in dealing with psychology. Psychology is ‘epiphenomenon’. Psychology is the epiphenomenon. You can’t treat depression by dealing with something which is just a surface epiphenomenon. And how wrong they were, because Teasdale’s work has turned out to be the most influential work together with Tim Beck, I think,in the last 40 or 50 years.

Dr Danny Penman:

And you were his student.

Professor Mark Williams:

And I was his student. I was very lucky to be his student.

Dr Danny Penman:

Just a point of terminology really. What’s the difference between CBT ‘cognitive behavioural therapy’, and CT ‘cognitive therapy’?

Professor Mark Williams:

There’s actually no difference at all. CT tends to be used in the United States, cognitive therapy. But there was a long history of behaviour therapy in Britain and Europe, before cognitive therapy came along and therefore cognitive therapy was sort of seen as an add-on to behaviour therapy. And therefore cognitive behaviour therapy is the word coined in Britain and Europe. But actually it refers to the same set of procedures.

Dr Danny Penman:

So is it possible to tell which patients are going to respond most favourably to the likes of anti-depressant medication or CT?

Professor Mark Williams:

It’s really interesting that you ask that question because one of the earliest studies asked exactly that question. And what they did was they gave people a scale which they called ‘learned resourcefulness scale’, and it measured basically how much you tend to take an active approach to your problem-solving or how much you prefer a passive approach where people do something for you and to you rather than you taking an active approach.

And what these early studies found was that people that tend to like to take an active approach to their problem really responded to cognitive therapy, but don’t do too well with antidepressants. Whereas people that tend to be passive do pretty well with antidepressants, but actually they don’t do too well with cognitive therapy.

Now how can we check that out? Well, one way of checking it out is giving people, like, say, if somebody comes for cognitive therapy. It’s been found that if you give people a little leaflet, six page long, at the first session and you say to people, in fact this is one of the first things that John Teasdale did with my colleague Melanie Fennell who still works with us here in Oxford. And then you say 'Part of your homework for this week is to read this and see whether you like it or not, you know, tell me what you think of it. This is what we’re going to be doing together and I’d be interested in your response.'

Well, they came back in Session 2, and 'How did you get on with this leaflet?' And some people said, 'Ah. It was just describing me. I felt I was the person referred to there, and it was exactly what I think I need. 'And other people said “'Oh you know, I didn’t get on with all this business about taking an active approach, you know. I’ve got a biological depression. I’m not sure about this at all.'

Now if you transcribe that and put it on a seven-point scale from plus 3, through 0, to minus 3 they found that that scale predicted outcomes after twelve weeks just about as well as anything else. And the people who took to it in those early days actually worked hard, did the homework that they had to do, they got a lot of benefit. Those people that were saying' Ah, I don’t know', they didn’t make very much progress in the first few weeks. They didn’t make very much progress in the last few weeks either.

So there are ways of telling. It’s a matching process between what people think is plausible for them, you know, what they think the model of their illness is. And if you get a meshing between people’s own feelings about what’s going wrong and what you’re offering to help do about it, then you get that sort of gelling. You get that enthusiasm, and you get a lot of progress.

Dr Danny Penman:

Are these underlying character traits that determine this or is it a character of the depression that they’re suffering from?

Professor Mark Williams:

It’s quite possibly both. Actually the truth is we don’t know. So that there are underlying traits in how passive or active people are. Whether it’s a character trait, as it were, like, there from birth we don’t know. It may just be your experiences over life-time, your learning history, as it were, has set you up to be passive or to be active. So it’s not necessarily a character trait in a sense of, you know, biologically determined.

However, you’re quite right that there are different sorts of depressions as well. And that some people do respond, some sort of depressions do respond better than others. And when we come later, in later episodes to talk about mindfulness and mindfulness-based cognitive therapy we’ll be able to describe ways in which we can begin to learn who’s responsive to what aspect of treatment, because that turns out to be very important.

Dr Danny Penman:

Well thank you very much for that. In this programme we were looking at the treatment of depression. And in the next episode we’ll be looking at why people relapse despite their best efforts and the best drugs available.

For further information about the issues raised in this programme you can read The Mindful Way through Depression by Professor Mark Williams and his co-workers or you can read our book Mindfulness: Finding Peace in a Frantic World by Mark Williams and me, Danny Penman or you can visit our website: franticworld.com

If you’d like to support further research in this area you could visit:oxfordmindfulness.org and follow the links to the development campaign.