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Hello and welcome to the new psychology of Depression.

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A series of programmes with me, Dr. Danny Penman and Professor Mark Williams of Oxford University.

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In this episode, we'll be looking at the treatment of depression and how it has changed over the last few decades or so.

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Mark, at the moment, one of the main ways of treating depression, well, there's two big approaches, physical treatments and psychological treatments.

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Those are the main two approaches. But there are many psychological treatments are come to those in a moment of the physical treatments.

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There are some that are fairly rarely used nowadays that used to be used a few decades ago, like ECD Electroconvulsive Therapy treatment.

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But the main physical treatment is antidepressant medication. They're very, very widely used now all over the world and they work pretty well.

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So antidepressant medication. They obviously affect brain chemistry.

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How in detail do they work? Well, in the brain there are many, many different receptors sites.

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For example, the way in which nerve cells work is an electrical impulse running down a nerve cell.

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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.

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And that's called the sign ups, the junction of these two things. And that's the point where chemicals come in because those neurotransmitters are

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released from one end and are picked up at the receptor site of the other one.

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And then they the transmission continues.

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Now, there are millions and billions of these in the brain and so much of our functioning are eating our sleeping mood.

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Everything is governed by the action of neurotransmitters in the brain.

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And what we know is that when they get unbalanced, then depression can result.

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There are many neurotransmitters, the two ones that are most thoroughly studied, noradrenaline and serotonin.

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And what we know is that the antidepressants that work are often antidepressants

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that effectively increase the availability of these substance in the brain.

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They usually do so by blocking re uptake.

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What that means is that usually when the neurotransmitter is released, if that sign up is going to be effective, it can't linger for very long.

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So there's got to be mechanism for, as it were, gobbling up the neurotransmitter. So when the next impulse comes, you know, it can release.

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And so that's called re uptake.

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Now, if you have a really uptake blocker, that means that when neurotransmitter has been released, it stays around for longer.

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That's one of the ways in which it works. Now, we know that it takes some time.

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It takes a few days for most anti-depressants to, as it were, kick in and affect your mood.

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In a notice and significant way that you actually notice it, although they start working straight away.

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The fact that it takes a little time suggests that it's not just more neurotransmitter.

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That's the critical thing, but it's actually changing the balance,

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the the sort of changing the balance of sensitivity in the cells, the sort of sending and receiving sites.

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

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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.

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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.

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Now, if you get a receptor sites insensitive, just increasing the amount of available neurotransmitter isn't going to work instantly.

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So that might be something. We also know that the transporter gene, that's the the genetic, as it were,

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messenger mechanics of getting the stuff available to the brain that might also be effective.

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And there's quite a lot of interesting work now at the frontier of this science, looking at serotonin transporter genes, for example.

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How effective are these drugs? Are they all similarly effective? Well, they seem to be.

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I mean, the drugs that were introduced in 1950s and 60s, what called tricyclic antidepressants, are pretty effective.

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The new generation of antidepressants are about as effective.

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The major aspect of them is they're less toxic in overdose, for example.

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They're safer. They don't have so many side effects. And, of course, side effects are always an individual interaction between the profile,

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the biological profile of the individual taking them and the biological profile of the medication.

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And therefore, it's impossible to predict exactly what side effects come with each antidepressant.

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So very often a physician will will try a personal one antidepressant and then say,

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come back and tell me if this suits you and try another one of the same or a different class.

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If it doesn't. So there is a part of of this which is experimental and it's always a of discovery for

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the physician and the person themselves in discussion to decide what works for them.

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But if you ask whether they work well, it's pretty controversial.

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It looks as if about 60 percent of people in most studies after you know, if you go on for a year, you'll get remission or recovery.

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That's depression really going down to bearable levels and a premature babies, only one or two symptoms around any in any one week.

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Instead of these crushing weight depression,

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about 60 percent will or recover later data from things like the Big Star D trial I was referring to in Episode

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one that suggested after 12 weeks on one form of medication and then about 30 percent respond to that.

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If he then changed to another antidepressant, a further 19 percent will respond to that.

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If you then change to another of those who haven't actually responded to either of those first two, then another 14 percent will respond to a third.

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Now, that cumulative rate of about 47 percent over one year is slightly more pessimistic than than many would have hoped.

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And there's new evidence all the time on the effectiveness of antidepressants and some of the big meta analysis.

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That's when people get all the data.

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All the studies together are beginning to suggest that for mild depression or perhaps even some moderate depression,

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antidepressants don't work much better than the placebo, a sugar pill. But for this as vier depression, which caused the greatest amount of problem,

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then you do see clear blue water between the antidepressant and a placebo.

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Now, having said all that, of course, your doctor, if you go to the doctor, will never give you a sugar pill.

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Well, if you're not part of a research trial where you've got consent to do that,

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and therefore the fact that you get both a placebo effect and a therapeutic effect can be, for many people, a lifesaver, as it were.

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It does change lives. It does change moods.

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And so nothing about the psychology or the new psychology or depression means that these are now irrelevant or should be substituted for psychology.

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For many people, they're a lifesaver. But probably the best estimate is 50 to 60 percent of people responding.

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And of course, one of the things that emerges from that is, well, what about the other 40 percent?

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And also, what about the people who are respond to one or the other? And of course, some people don't want to stay on antidepressants for a long time.

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The major problem with antidepressants is this, that when you stop taking them,

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let's say you take them for six to nine months or a year and it deals with depression and then you feel stable.

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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.

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That means if you've had three episodes of depression, then your risk was 60 to 70 percent.

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You can deal with that with antidepressants for, say, a year, two years.

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When you come off them, your risk goes back to 60 to 70 percent. If you've had five depressions in the past, then your risk is 90 percent.

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When you come off antidepressants, your risk goes back. Now, you might not become depressed immediately.

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But a recurrence is. Of course, a very, very damaging and disappointing thing to happen when you thought you'd coped with it.

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And therefore, many physicians are saying, well, why not go on antidepressants and stay on them if they suit you?

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Treat it like diabetes, you know, like it's a permanent lifetime thing.

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You've got free with diabetes. But the trouble is that many people don't want to be on drugs for the rest of their life.

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Some people naturally come off. So in that long term study from I was telling you that started 1970s,

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virtually everybody after a year had spontaneously come off their antidepressant.

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We know from recent data that 30 percent of people don't even go back for their repeat prescription.

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So there's a large sort of weight of evidence that people naturally come off despite their doctor's advice.

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They come off antidepressants and then, of course, they are at risk of getting depressed again.

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

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It's a good question. If it was just a withdrawal system, then you'd expect the Depression to come back quite quickly.

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And that does indeed happen. When you come off your antidepressants, say, within three months, four months, five and six months.

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And when you think about it, imagine that a depression is going to last for five or six months.

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Naturally, we know that depression naturally gets better if you don't do anything with it.

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It tends to be episodic. That means it comes it's crushing when it happens, but then you get over it.

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Now, if you take antidepressants for an episode of depression, then if you take your antidepressants for a few weeks,

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the depression is, as it were, still there underneath the biological processes, still at work.

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If you come off prematurely, the depression comes back pretty quickly.

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That's what's called a relapse. And that's where you get these sort of a kick back effect.

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However, if you've taken antidepressants for six, nine months a year, that has covered that episode of depression.

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And when you come off, you'll be OK for a while, probably.

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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.

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So it's probably not just a kick back effect, a withdrawal, although scientist patients are harder to come off than others.

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And and some I mean, you always, of course, need your doctor's advice.

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If you think you're coming off antidepressants, you always go and see the physician who's given you them,

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who is prescribed them and ask their advice and they'll help you because some are easy to come off.

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Others are much more difficult than you can get a lot of other symptoms of flu like symptoms from some, for example.

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And you need to have a doctor's reassurance that these are recognisable and that to help you get through that so you can get out to the other side.

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

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Well, yes, in a sense it is. Now, if it's true that just by carrying on taking your antidepressants, you can reduce the risk of depression,

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that will work for some people and for those who've been advised by their doctor, that's to do that.

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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.

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Of course, there's still a bit of a risk of relapse coming,

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even if you carry on with antidepressants and that's where you can supplement them with psychological skills and psychological therapies as well.

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But we do know and this is in a sense turning to our second major strategy, that there are psychological.

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There are psychological approaches that help and that when they help, they actually also protect against relapse and recurrence.

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

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There are five or six psychological treatments that work well in dealing with acute episodes of depression.

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The one that's got most evidence for it is cognitive therapy. So I come back to that.

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But it's true to say that there's something called behavioural activation, which is getting people moving, as it were, in their behaviour.

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There's something called interpersonal psychotherapy,

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which is as effective as cognitive therapy in trials which deal with the things that happen, you know, interpersonal life.

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I mean, it's an individual therapy. It deals with things like guilt, with real transitions, with interpersonal effectiveness, these sort of things.

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In the early days, people thought that psychodynamic psychotherapy, sort of Freudian, more analytic psychotherapies would be good.

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And there wasn't much evidence for that. But then there wasn't much evidence collected.

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So there wasn't there weren't many scientific studies.

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And indeed, as people began to make those approaches, more psychoanalytic approaches, more structured and shorter, then, for example,

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there's something called psychodynamic interpersonal psychotherapy, which they got it down to 15 sessions, just like other psychotherapies.

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And they found. It worked pretty well. This problem solving therapy, which works, works pretty well.

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That's for mild depression, certainly an exercise. We know exercise works pretty well for milder depressions.

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So there's a whole range of things that we can do to to deal with acute depression.

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But probably the main one is the one with the biggest evidence base is cognitive therapy.

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And the history of cognitive therapy is really interesting. One of the puzzles about the psychology of depression was that in the 1970s,

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people didn't actually think that depression was treatable with psychological means.

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They thought perhaps the new antidepressants were one way because it was a biological thing.

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And there were people on the analytic side talking about psychoanalysis, but without any much evidence.

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But certainly there was accumulating evidence that depression could be treated with antidepressant medication and that although in the 1950s and 60s,

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people had many psychological treatments for anxiety and phobias.

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Nobody thought that depression was the sort of thing that you could treat with with this approach.

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

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Well, it seems obvious now, but actually, no, they didn't. I mean, obviously in history, throughout history, people had a go at night.

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It's obvious that irrational thoughts and negative thinking is a very important part of depression.

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But people thought that it was a symptom of depression, that you had to cure the underlying thing.

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If you think about what antidepressants are doing,

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you're treating the underlying biological problem and you expect the thoughts to clear up by themselves.

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And in psychodynamic psychology, you're in a sense doing a similar thing.

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You're going for the underlying, say, interest, psychic conflict, whatever it is,

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and hoping that the thoughts themselves would sort themselves out when you got to the underlying problem,

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both biological and dynamic models have this in common.

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Go for the underlying source of the problem and negative thinking and so on would would naturally just dissolve.

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It wasn't until two major things happened in the late 60s and early 70s that we changed our mind.

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A psychologist about this. First of all, there was a big emphasis within animal learning theory on what was called learnt helplessness.

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There was a professor in the United States called Martin Seligman,

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who found almost by accident that when he had animals and experiments that had been subject to uncontrollable stresses,

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electric shocks, noise, this sort of thing,

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that if they were then put used in another experiment in the days when you did this sort of animal experimentation

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in another experiment where they could actually escape the stress they were going to be put under.

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He found that two thirds of them didn't escape.

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It was almost they learnt to be, as he described it, helpless that they learnt there was nothing they can do.

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He called it response, outcome, independence. And they will learn that, well, there's nothing I can do.

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And he said, you know, this could be it a model for depression. And he started to look at human laboratory experiments and invited ordinary people.

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Well, students, anyway, to come to the laboratory and to be subject to stress that they couldn't control

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or anagrams they couldn't do or little Problem-Solving they couldn't do.

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And then he began to wonder if they can't do one, what's their effect on the next thing they do?

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That's where I started my HD studies. I mean, my interest in depression started in 1975, 1976, when I started to research.

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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.

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And that had been what Seligman was interested. It was what my colleague John Teesdale, who is my Ph.D. supervisor, originally was interested in.

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And so that's what I worked on for my doctoral studies.

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Now, the interesting thing about learnt helplessness is that it works right through the animal kingdom.

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And it suggested that when you have human depression, you have to discover what it is that makes humans begin to,

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as it were, learnt from one event, something which may not be true of the next event.

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You know, I've just failed. Does it mean I'm going to be a failure in the future? Inasmuch as you believe that then you're going to have problems.

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You know, you're not going to know if you think I'm not going to enjoy this party. Therefore, there's no point in going.

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You're making an inference about the next event based on your experience.

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And therefore, you begin to reduce what you do in your life. But Seligman didn't have any treatment.

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He had a great theory which then started to be picked up by undergraduates and graduate students all over the world taught in.

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Medical schools all over the world, very famous theory of depression, but no treatment.

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So people started to come out of medical school, come out of psychology, come out of clinical psychology training,

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say we've got a theory, but what can we actually do and offer to our patients?

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And then there was somebody called Tim Beck, Aaron Beck, who'd been working in Pennsylvania on something he called cognitive therapy.

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Now, this of course, this is a great deal of interest because cognitive psychology was the designed guised within experimental psychology.

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The term had been coined by Dick Neisser in 1967, by 1970, 72.

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Every the world was abuzz in psychology about cognition, about thinking, about memory, about attention.

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How is deployed? Here was a psychiatrist, Tim Beck, trained as a psychoanalyst.

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He'd worked with Korean veterans coming back from the Korean War.

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He'd noticed how they were often depressed as a result of the trauma they'd been through and how often thoughts about worthlessness,

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helplessness, about not being good enough, how how much their thoughts were going round and round and round.

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As an analyst, he'd thought, right. I need to get underneath this to find out what's it about as a biological psychiatrist,

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because he is a psychiatrist who could treat it with antidepressants. But his amazing insight was to say, what would it be like?

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What would a theory look like if the thinking that's going on in their mind was actually part of the cause of the depression?

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And if not, the cause? Part of what was maintaining the depression.

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And that one insight led him to start asking his patients, why did every time you feel down.

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Just catch. What went through your mind just the moment before?

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And he started to notice that people began to be able to catch their negative thinking that there was often a flash.

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It might be very fast. It might be slow of a negative thought.

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And he started to get people to write them down and then say, look, what if this is the depression speaking?

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What about seeing whether depression is telling the truth or not?

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Let's take these ideas about how useless you are, how much you've always failed and so on.

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Let's write them down and let's actually be a bit of a scientist here.

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Let's look at them. Look at the evidence for the evidence against. And soon he began to find this was liberating huge swathes of his patients without

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having to do long psychoanalysis and without having to do biological treatments.

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And in 1977, he and his colleagues, Gary Emery, Brian Shaw,

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John Rush and him published the first randomised clinical trial where they compared antidepressants for properly diagnosed,

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depressed patients with this new what called cognitive therapy.

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And it was astonishing. Not only did it as well.

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There was some suggesting it could do better with this ability to test out your thoughts and change your behaviour in these interesting ways.

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And that was the major, major change in depression in the last 50 years.

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I think presumably this insight was revolutionary. It was.

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And like most revolutionary insights after the fact, it just seems so obvious.

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I remember in the mid 70s when I started to read Beck's work thinking that it was trivial and I

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don't really even need to read very much because it's so obvious that when people are depressed,

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they get negative thoughts.

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We need to go underneath the problem just to deal with negative thoughts was was was a trivial way of approaching a really hard problem.

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But now when you look at the work by Chris Diski and Dennis Greenberger that their book,

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Mind Over Mood is an incredible bestseller for obvious reasons because people can do this by themselves.

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David Berns, the feeling good,

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the new mood therapy and work that Beck himself has continued to do and his colleagues has revolutionised the study of depression.

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I mean, one of the other indications is that my colleague, John Teesdale,

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when he was a psychologist and due to move to Oxford to start off one of the first

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laboratory programmes in the psychology depression anywhere in the world in 1975,

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that he was advised by his colleagues there that this would be a waste of time.

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Everybody knew, they said that depression was a biological problem or needed some long term analysis.

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But as a biological problem, what's the point in dealing with psychology? Psychology is epiphenomenon.

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Psychology is the epiphenomenon.

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You can't treat depression by dealing with something which is just a surface happy phenomenon and how wrong they were,

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because today's work has turned out to be the most influential work together with Tim Beck, I think, in the last 40 or 50 years.

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You are a student and I was his student. I was very lucky to be his student.

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Just to put your terminology, really. What's the difference between CBT, cognitive behavioural therapy and CTE?

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Mesotherapy that actually no difference at all. S.T. tends to be used in the United States cognitive therapy.

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But there was a long history of behaviour therapy in Britain and Europe before cognitive therapy came along.

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And therefore, cognitive therapy was sort of seen as an add on to behaviour therapy.

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And therefore, cognitive behaviour therapy is the word coined in Britain and Europe.

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But actually, it refers to the same set of procedures.

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So it's impossible to tell which patients are going to respond most favourably to the likes of antidepressant medication or S.T.

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It's really interesting that you ask that question because one of the earliest studies asked exactly that question.

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And what they did was they gave people a scale which they call learnt, resourceful, the scale.

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And it measured basically how much you tend to take an active approach to your Problem-Solving or how much you

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prefer a passive approach where people do something for you and to you rather than you take an active approach.

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And what these early studies found was that people that tend to like to take an active approach, their problem, really respond to cognitive therapy,

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but don't do too well with antidepressants, whereas people that tend to be passive do pretty well with antidepressants.

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But actually they don't do too well with cognitive therapy. Now, how do we how can we cheque that out?

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Well, one way of checking it out is giving people safe.

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If somebody comes for cognitive therapy,

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it's been found that if you give people a little leaflet six page log at the first session and you say to people,

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in fact, it's one of the first things that John Teesdale did with with my colleague Melanie Fennell, who's still workless here in Oxford.

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And then you say part of your homework for this week is to read this and see whether you like it or not.

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You know, tick down the what you think of it. This is what we're going to be doing together.

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And I'd be interested in your response when they came back in session, too.

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And how did you get on this question with this with this leaflet? And some people said, oh, it's it was just describing me.

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I felt I was the person referred to there. And it was exactly what I think I need.

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And other people said are, you know, I didn't I didn't get on with all this business about taking an active approach,

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you know, is it I've got a biological depression or, you know, I'm not sure about this at all.

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Now, if you transcribe that and put it on a seven point scale from plus three through zero to minus three,

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they found that that scale predicted outcomes after twelve weeks.

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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.

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They got a lot of benefit. Those people were saying, I don't know. They were they they didn't make very much progress in the first few weeks.

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They didn't make very much progress in the last few weeks either. So there are ways of telling.

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It's a matching process between what people think is plausible for them.

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You know what they think they by the model of their illnesses.

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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,

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then you get that sort of gelling, you get that enthusiasm and you get a lot of progress.

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

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It's quite possibly both so that we don't.

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And actually, the truth is we don't know. So that there are underlying traits in how passive and active people are.

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Whether it's a character trait, as it were, like there from birth, we don't know.

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It may just be your experiences over a lifetime. You're learning history, as it were, has set you up to be passive or to be active.

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So it's not really a character trait in the sense of biologically determined.

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However, you're quite right that there are different sorts of depressions as well,

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and that some people do respond some sort of depression to respond better than others.

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And when we come later, in later episodes to talk about mindfulness and mindless based cognitive therapy,

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we'll be able to describe ways in which we can begin to learn who is responsive to what aspect of treatment,

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because that turns out to be very important. Well, thank you very much for that.

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In this programme, we were looking at the treatment of depression,

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and in the next episode we'll be looking at why people relapse despite their best efforts and

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the best drugs available for further information about the issues raised in this programme.

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You can read The Mind four Way Through Depression by Professor Mark Williams and his co-workers.

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Well, you could read our book, Mindfulness Finding Peace in a Frantic World by Mark Williams and me, Danny Penman, where you could visit our Web site.

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Frantic World Dot.com. If you'd like to support further research in this area, you could visit Oxford mindfulness dot org.

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That's all one word. And follow the links to the development campaign.