Depression in Neurological Disease by Prof Alan Carson, 28 January 2021
The full podcast can be watched here. It is open to the public.
[Please note: this transcription may have errors. It starts approximately 40 minutes in to the podcast]
We’ve got a fantastic lecture coming up at the end of the spring term from Carmine Pariante. He’s one of the world’s authorities on this. So, this is just a sort of flyer, really, for what he’s going to be telling us about. But there’s a lot of evidence to suggest that inflammatory factors are involved in depressive illness.
And the kind of idea goes that in early stages of evolution, having an effective inflammatory response was highly valued genetically. But as the threats to our life have started to change over time, the same things that would have saved me as a hunter-gatherer are not so good for me as a fat shrink sitting at his desk relatively safe from many threats except eating too much cream cakes. And it is less adaptive. And this overactivity of the immune system is associated with depressive illness. And what we’re seeing is this kind of idea that during acute stress, enhanced glucocorticoid receptor, rather, sensitivity leads to control of inflammation.
But in chronic stress, steroid resistance starts to occur, and we get increased inflammatory response and all its neurotoxic effects. And people are starting to look at these types of models whereby we’re seeing stress at a neural level acting and creating these entities known as damage -associated molecular patterns, but also this sort of intriguing notion of the microbiome in our gut and how that’s impacting and getting and associated molecular patterns, triggering off these inflammatory cascades that do seem to be very pro-depressive.
And there is reasonably strong evidence now, particularly for things like Interleukin -6, goes up in big cohort studies a year or so before people develop depressive illness. I think the hope is that this may lead to new drug therapies in the long run. But I will leave Carmine Pariante to tell us more about that. And I’m going to return to things I actually understand, because I’m now starting to bluff wildly at this level. And that is sticking people on pills. Huge amount of evidence about antidepressants. If you want to read in detail, I think this is the best of the currently available systematic reviews from John Geddes’ group. One of the things, though, you have to be aware of and just showing this thing is that the majority of the comparisons are with newer drugs and people bring new drugs to market. No one really wants to do a trial to see if amitriptyline works and similarly for acceptability.
So, what’s the bottom line? The bottom line is antidepressants work. They are modestly effective. I think If you look at this and you look at other evidence that’s available, you would say that tricyclic or dual-acting drugs are slightly more effective than SSRIs. But there is not huge difference between agents.
And similarly, in terms of tolerability, it’s not a huge difference between drugs. People want to spend ages talking about what’s the easiest to take drug. Actually, it’s not that different. And you do get significant nocebo effect, which we have to be aware of.
[Please watch original podcast for Prof Alan Carson talking through slides]
Now, it’s always difficult, I find, to translate these forest plots into what is that that’s clinically meaningful. This is quite a helpful summary they’ve prepared, which is that about 20 to 40 people out of 100 took a placebo get improvement and about 40 to 60 out of 100 on an antidepressant get an improvement. So, we are enhancing outcome. I do always worry though about placebo because we tend to look down on it and kind of the take -home message seems to be that about 20 out of 100 will get better. But it is worth remembering that if you want to activate placebo response if you actually build it up, the better it is. And in a sense, you might argue that psychotherapies, in essence, are really about promoting the placebo response to the optimal level. I say that as somebody who thinks himself as a psychotherapist, but you’re trying to get these natural healing things optimized. So, you know, don’t just remember that when you look at that difference. And this is one thing I really want to emphasize: antidepressants prevent relapse.
You will have the relative risk of relapse and the longest studies in the literature are 10 years. So, if you’re giving somebody an antidepressant, you really need them to be on it for about six months for a first episode. And if people have had two or more episodes over three years, I think you should be talking to them about potential long-term treatment for relapse prevention.
And in neurology, I’ll just rush through these in the interest of time, far fewer trials, as you would expect. I should just have highlighted that referred to depression in general, but pretty much the same findings. And again, I don’t think you’d want to make too much of it, but the evidence again favours that tricyclics might be more efficacious.
[Please watch original podcast for Prof Alan Carson talking through slides]
A lot of these studies come in stroke populations. You’ve got elderly people that just had strokes, and they’re just not feeling well enough to really participate. So, I think clinical experience would suggest that psychotherapies have more to offer, but you do need to think who you’re offering the treatment to. And suicide, if somebody’s talking about depression, do ask. It’s almost common sense. You know, you get worried when they have a plan and they have a lack of protection and they have social isolation and, in such circumstances, refer for help immediately. Vague suicidal ideation, but telling you protective, I don’t necessarily think you need to do much. And I sort of in between, do ask your local friendly shrinks for help if you want to.
And just the word that, of course, it’s all very well having details on efficacy, but actually getting people to take tablets out of the bathroom locker and swallow them when they’re miserable and feeling life’s not worthwhile problematic. I think we spend too much time worrying about the type of drug and not enough time worrying about will people take whatever that drug is that we’ve prescribed and putting systems in place like nursing support, pharmacy support to assist is probably actually of far more value than worrying about the individual agent we’re prescribing.
So, what should you do if you’re not a psychiatrist? You should ask about symptoms. You should initiate treatment yourself. Remind the patient and drugs take a few weeks to work, ask very briefly about self-harm. You don’t need to labour it. I think it’s best just to get used to one SSRI, one tricyclic, one modern antidepressant, get familiar with them. If patients respond to medication, continue for six months. Refer treatment failures, take it from there.
And just one final cautionary note: lots of people think antidepressants are addictive and can cause physical harm. You do get a withdrawal syndrome, and that sometimes needs to be helped, although I think a large part of its nocebo. But they’re not addictive in the sense of craving after discontinuation. So just a little bit of education around these things can be of use
So, I’ll stop there. I just want to say that being upset and depressed, not the same thing. I think the concept of mental depression may be helpful. I think these are common complications of neurological disease. I think antidepressants are beneficial. Explain why you’re prescribing carefully. Start low and go slow. I’ve not mentioned ECT or TMS, but both work in neurological populations. And I think psychotherapy has a role, but it may be a bit more about case selection. And I shall stop at that, and I’ll be happy to answer questions or debate any aspect.