Welcome to the Oxford University Psychology Podcast series. My name is Daniel Maun and I've got Professor Phil Cohen here with me today.
Thank you for coming, Phil. Thanks for the invitation. It's really good to have you because you've done some really interesting work over the past,
well, several years, really, and very engaged in psychopharmacology.
And your particular area of interest is an antidepressant medication is basically the treatment of mood disorders,
particularly depression doesn't respond well to other treatments.
OK, and well, could you just begin by telling us what your main areas of interest are in that field,
as is trying to understand how the medicines might work, try to understand what the underlying pathophysiology is of the condition,
why some depressed people don't seem to recover as well as one would like, and then trying to come up with new treatments,
maybe pharmacological in my particular case, that might be helpful in patients with that kind of problem.
When you talk about depression.
Do you see it as a unified entity or do you see depression as an umbrella diagnosis of which there are sort of many conditions within that?
I think it must be like that, that it's a common condition.
The features are fairly variable. And I suppose when when you're a psychiatrist, you tend to work in one particular area.
So people who have quite severe depression, quite disabled by it, are not doing well with first line treatment.
So you have that particular group in mind when you work as a psychiatrist.
So you're working at the more severe end of the spectrum compared to perhaps what most people
might have encountered in their daily life with people they know who might have been depressed.
You you're thinking that the people you see are perhaps more functionally impaired or does it look different?
Is the character or nature of the condition particularly different? Is there something you look at or.
I think that that's that's right, because depression is very common and often treated very successfully in primary care.
And so people would respond to psychological treatments, maybe FirstLine antidepressant medication, if that was necessary.
So I'd say that the people that I would see in most psychiatrists, the depression would be unremitting.
And that's a feature which causes a lot of distress for the patients, because if you're depressed,
you often feel things aren't going to improve and this is confirmation of it.
So it's severe, it's long standing and it seems very hard to shift.
Certainly true. As you said, in those circumstances, it can be functionally disabling.
So people who are often very capable, very accomplished, find that they can't work properly and their personal lives are extremely disrupted.
We've had antidepressants for over 50 years now as a psychiatrist who been using them effectively in many cases,
whereas the sort of the the front line not advancing area in antidepressants research at the moment,
I think the main advances in my professional career have been the fact that more antidepressants are available and they're safe and better tolerated,
but by themselves, they're not necessarily more effective than the older ones.
So the failure to make more effective treatments has been a disappointment.
On the other hand, because more drugs are available, you could usually find something that suits an individual.
Moreover, it gives a chance for treatment combinations, and some patients with resistant depression seem to respond to that approach.
So I think practically we're doing better, but individually we haven't really got a drug that's made a huge difference in terms of effectiveness.
You've done some work into the effects of ketamine on people with with depression.
I was wondering whether you could tell us a bit about that. Yes, that's an interesting development.
And we started from observations made in the United States that intravenous ketamine,
which is a widely used anaesthetic and has been used as a model for various psychiatric disorders when given to patients with acute depression,
made them feel much better, essentially back to normal about an hour or two after the infusion of a sub anaesthetic dose,
particularly intriguingly, in about half the patients, that effect persisted for a few days.
So it was a striking effect because normally anti-depressants take a long time to work.
Several weeks. They don't work that fast, therefore, and no one can imagine treatments that work quickly.
For example, sleep deprivation sometimes use in that way. It's unusual for a quick acting effect to be sustained.
Further, ketamine pharmacologically works in a very different way from our standard antidepressant treatment.
It blocks a kind of glutamate receptor.
So it's another neurotransmitter from the ones we normally think about in terms of antidepressant action.
And therefore it may provide clues to a whole new class of anxiety depressants,
which, as I was saying, we badly need to improve on what we're doing at the moment.
That's really interesting. And have you seen any? Well,
has there been any evidence suggesting that ketamine is potentially an effective
antidepressant that has an effect that lasts longer than a few days before,
tried various ways to extend the effects? They've tried giving courses of treatment and they've tried using orally
administered glutamate like drugs in the hope of extending the effects of ketamine.
My own experiences thus far, that's not been as successful as one would like.
And so I was left with a tantalising position that you can get people out of severe depression for a for a few days or a week,
but you're not confident you'll be able to sustain it. And that's a major problem.
Thank you. And you've touched on on an issue in in in depression as a psychiatrist,
which is that we have lots of drugs at our disposal now that we can use to help patients with that depression.
But often there's there's not much difference in the in the efficacy or the effectiveness of that medication.
There's often quite different side effect profiles. Yes.
Is there is there anything you could advise people who are beginning to psychiatrists who are beginning treatment of somebody with depression?
Were there any particular class of drugs you suggest to begin with? And what's your standard sort of approach?
Well, I think for most of us now, the early stages of treatment are set by guidelines.
So if you read something like the nice guidelines, it'll tell you what circumstances to think about medication and then what you might use first line.
And so that's tackled very competently by GPS, usually for psychiatrists.
As I said, you're a bit further down the line.
People often tried a psychological treatment, perhaps a couple of the standard first line antidepressants,
such as the SSRI locksmithing, drugs like that.
And so we're then left in that position wondering what to do next.
And I think you'd have to say that the treatment guidelines tend to be based on trials,
evidence, and there's not a lot of evidence about next step treatments.
So this is where your clinical experience and your knowledge of the patient becomes absolutely paramount.
And what is it about the patient that helps you? What kind of things do you look for in a patient that helps you make those clinical decisions?
I think there are a number of aspects, obviously, in any psychiatric consultation.
One of the fascinating things is that you have to live in a sort of first person world trying to access the experience of the individual and also
somehow synthesise that or fuse that with a third person scientific notion of what's going on perhaps at a neurochemical neuropsychological level.
And that's one of the challenges, one of the excitements of doing psychiatry.
So the first thing is to make a good emotional connexion with the patient, to really understand what their experiences are,
to put this depression in the context of their life, and actually particularly helpful to get an idea of what's not right now.
What would they be like if they were, well, how are things gone when they were?
Well, that way you can't get a notion of how much it looks like an illness that somebody should be able to make a good recovery from.
Often seeing a partner or friend is very helpful in that sort of situation.
So that's the first thing, a really thorough assessment at a psychological level.
Have you done any research on on this sort of level of clinical decision making on particular drugs that happen in particular circumstances?
You've done some work with a.
Medicine and and things like that with that lead you into making a decision in a particular circumstance with the patient.
Well, that's been that's. Been a goal of many researchers and many research authorities to try and
stratify patients to try and work out what treatments should you give someone,
because there are many different drugs with slightly different pharmacological mechanisms.
And often you just have to go through things in a careful empirical way.
And that can take several weeks or months,
which obviously is very disheartening to someone who's depressed anyway and is rather despairing about the future.
If there was a way we could identify what to use, that will be fantastic.
But at the moment, the current treatments we've got, the current investigations, brain imaging, Gene's clinical characteristics,
not terribly helpful in trying to predict what someone's actually going to be helped by,
but that's an area where there needs to be substantial progress. So in a sense,
we are in a position where the crucial part of of of clinical decision making and a
lot of the research that you've done over the years has really pointed to the fact
that we need a an accurate and sort of personal engagement with the patient to
really understand their situation and then to make decisions based based on that.
Yeah, there are the old fashioned medications tricyclic antidepressants and the modern modern medications, serotonin based medications.
Do you feel, looking back, that we've I know you said there's no there's no benefit in effectiveness,
but do you think we've we've come a long way since then? I think the point of view of treating a broader range of people with depression,
we probably have my own feeling is actually probably because I'm fairly elderly now that the tricyclics are still a little bit more effective,
but they're hard to take and they're dangerous in overdose. So they're not easy to use over.
The SSRI are effective for many patients in primary care.
They're much easier to take. They're safer.
And so that is a kind of useful, practical advance in treatment, even though they may not be any better than the older ones in terms of effectiveness.
So we've talked a lot about the clinical aspects of how clinical decision making has changed.
And in a sense, we have a lot more options for treating a lot a lot of different types of people.
In what ways is the knowledge developed? We've we've we've grown rapidly in our ability to image the brain,
our ability to understand all the different neurochemicals and the synaptic processes that are going on.
What do you think are the really real advanced advances in not in knowledge about about your your work?
I think we're much more sophisticated in our understanding of what the problem represents,
even though sometimes that just makes you realise how little you actually do know.
But it's certainly changed from when I was training in the sense people thought in terms of a single neurotransmitter
causing depression to little serotonin to the adrenaline or a particular brain region causing depression.
I think what we have now is a much more sophisticated understanding of the neural circuitry that underpins depression,
the distributed circuitry that seems to somehow express emotional distress,
and the way that the neurochemistry maps onto neuropsychology, what serotonin actually doing in terms of people's experience,
how does boosting serotonin change neuropsychological processes that can lead people to feel better?
So I think we've got a fuller understanding is easier to talk to people about what you think is going wrong.
Unfortunately, it hasn't led to new pharmacological treatments yet because this is a distributed circuitry
and more integrated understanding doesn't necessarily finger a particular molecule.
I think in a way might be more helpful for improving psychological treatments because they probably do work more at a systems level.
And perhaps understanding what's going wrong with the neuropsychological system might
eventually lead to more targeted psychological treatments involving brain training.
I could see that actually as being an outcome while we still struggle on to try and improve pharmacological treatment.
Okay. There was a recent editorial by John Kerry's, amongst others in the BJP site,
looking at how perhaps we need to change the way we think about classifying bipolar disorder based on their response to lithium therapy.
Yes. And I wonder whether you. Do you think that the there is a case for that in depression,
because some people that they they might they might argue whether they are depressed or not or they might
there might be some discussion about whether that they they have a particular type of depression or not.
And I wonder whether there would be a case for perhaps phenomenologically or or or
diagnostically of the condition better because of their response to a particular antidepressant.
Yes, I think that's a very interesting idea. We keep trying to stratify, to classify, to understand people,
because if we can distinguish very different kinds of disorder under this umbrella depression, we probably will be able to improve treatment.
And it's interesting that the conventional ways of doing it by various clinical presentations, by genes, family history hasn't been very successful.
So doing it in terms of treatment response is very intriguing idea and seems to
me at a practical level to fit in with what people might do clinically anyway.
So I'm in favour of it. And just just before we go, Phil, could you tell us a bit about what your thoughts are about being an academic psychiatrist?
And have you enjoyed your of you enjoyed your career?
Oh, I think I've been enormously lucky because you're dealing with the most important and interesting problems.
As I said, it's this combination of being able to engage in people's experience,
to have the privilege of understanding someone's life history with them and at the same time fusing that with a third person scientific objective,
trying to help them both at a personal level and through scientific approaches.
I can't think of anything which would be more rewarding. Well, thank you very much.
Thank you for coming. And thank you for tuning in to the Oxford University Psychiatry Focus series.
We hope you listen to some more. Thank you.