Hello and welcome to BJGP Interviews.

My name is Nada Khan and I'm one of the associate editors of the bjgp.

Thanks for listening to this podcast today.

In today's episode, we're speaking to Dr.

Sini Banu, who is a GP in an academic clinical lecturer based in the Department of Primary Care and Population Health at University College London.

We're here to talk about her recent paper in the BJGP titled Antidepressants and Risk of Postural Hypertension, A Self Controlled Case Series Study in UK Primary Care.

So, hi Cinny, it's really nice to meet you today.

I guess this is an interesting area to cover, especially as the prescribing rates for some antidepressant medications are increasing.

But I don't know what your feeling is, but I'm not sure if many GPs would actually know that antidepressants are associated with poison postural hypertension.

So, yeah, talk us through that.

Yeah, so I think that's one of the reasons this study is so important.

So definitely from conversations that I've had with gps that I work with and it's not commonly recognized that postural hypotension is associated with antidepressants, though it is by geriatricians, for example, where it's very.

Well recognized and in this study used a big database to look at the risk of new postural hypertension associated with the use of antidepressants in people aged over 60.

I guess there's quite a lot of in depth stuff in the methods, but I guess just for a summary for people who are interested in what you did, do you mind just sort of going over it at sort of like a high level?

Yeah, yeah.

So we looked at a big database, what we call a routine primary care database called imrd.

And essentially this captures data from software that gps use like EMIS and Vision System and captures a whole load of information like problems, symptoms and prescriptions.

So we went into this database and identified everyone over the age of 60 that might be eligible during our study period.

And for this we looked at people that were contributing at least one full year of data between 2010 and 2018.

And then within that we identified people with a first diagnosis of postural hypotension.

And then again we made subgroups according to people who had this diagnosis but also had a first prescription of a new antidepressant during that time.

And what we were interested in, and the methodology is called a self controlled case series, we weren't interested in who got postural Hypotension, because everyone was a case, but rather when that diagnosis happened in relation to antidepressant exposure.

And we'll talk about those different time points in a bit, but I wonder if you could just talk us through why that focus on people aged over 60 and why this is so important, especially in that age group.

Yes, so two big reasons.

So, postural hypotension is very, very common in people aged over 60 and we know that it affects around a third of people living out in the community.

It's largely under recognized and under detected by gps and in prim care.

And postural hypotension in older adults has significant risk of adverse complications and long term effects, including risk of being admitted to hospital, falls, fractures, but also later down the line it increases your risk of stroke and cognitive decline.

So it's a really important common diagnosis.

We're probably not managing as well as we can in primary care.

Second is that antidepressants are actually used quite commonly in this group of patients.

So we know that for people with late life depression, they're more likely to be given an antidepressant treatment for their depression rather than another therapy.

So over 80% of people with depression in this age group are given an anti, are prescribed an antidepressant.

So there's very high risk with both the exposure and the outcome.

And I guess this comes back to the fact that, yes, a lot of GPs might not know about this as a risk.

So it's really important that you've done this research.

And so you looked at these different time points of people after starting their antidepressants and risk of postural hypertension.

But talk us through what you found here.

So in people who were taking one of the most commonly prescribed antidepressant classes, SSRIs, what did you find here about the risks?

Yeah, so we actually found some really interesting time variable trends with the risk of postural hypotension associated with ssri.

So we looked at two specific time periods.

And that was initiating the drug, which was between a short period, days 1 to 28, and then days 29 to 56, which we treated as initiation, and then a continuation period, day 57 onwards.

And what we've seen in SSRIs, but also all of the antidepressant drugs, is this peak in your risk of developing a new diagnosis of postural hypotension within that acute day 1 to 28 period.

And so that was mimicked across SSRIs, tricyclic antidepressants and the other antidepressant group for SSRIs in particular, we noticed a fourfold increase in that day 1 to 28 peak that gradually declined as time went on.

And tricyclic antidepressants and other antidepressants had a similarly increased peak, not to the same extent, but about twofold that declined with time.

And we know that tricyclic drugs are often prescribed for other things as well, like pain.

So do we need to be careful when prescribing it at lower doses for things like neuropathic pain?

We didn't look into dosing, but it's certainly likely that the majority of these prescriptions were prescribed in low doses for other indications, like neuropathic pain, as you.

You've said, and insomnia.

And we've already seen a twofold increased risk in that acute initiation period, likely for low doses.

So there is certainly a risk to be aware of in older patients that we're prescribing tricyclic antidepressants to.

And it's likely that as the dose increases, that this risk increases.

And I think one thing that's really important here is that the effect sizes are actually pretty significant.

So this could represent a fairly significant risk for patients, especially in that initial peak time that you mentioned.

Absolutely, yes.

And I think there's certainly a striking risk associated with SSRIs in this group, and a lot of it depends on the context of the person you're prescribing this medication to.

So whilst we know there's a fourfold increased risk in this study, you may be more cautious with someone who is at greater risk of postural hypotension at their baseline anyway, either related to advancing age or other chronic conditions like diabetes or Parkinson's, for example.

And I think what's really interesting is you point out in the paper that actually postural hypertension isn't highlighted as a common side effect in the BNF for these drugs.

So it seems with such a significant effect that probably that's something that should be highlighted.

Yes, that's something I think is really, really important.

So you'll often see hypotension cited as a side, but they are quite different and the assessment is different and how you might manage it would be different too.

So I think it's definitely really important that that increased risk of postural changes in blood pressure is documented for these medications.

I think it's interesting because often when people start these medications, they might have an early review with a GP about how they're getting on with it.

And often that that initial review really focuses on mood and how they're coping and may touch on side effects.

But I'm not sure that at the moment that sort of initial review would include a check for postural hypertension, for instance.

I think it's unlikely.

And whilst many of us may be very good at asking about side effects more broadly, I think one of the barriers here is that a lot of patients may not recognize the symptoms of postural hypotension, or if they experience dizziness on standing and it's transient, they may not think it's important to report to their gp.

And that's something that we've gauged from our PPI group that are involved in this study.

So really, it does need for a clinician to ask directly about postural symptoms and maybe even check their lying and standing blood pressure.

I guess that overlaps with what I was going to ask next, really, which was really, what should we be telling people starting these medications?

And is there anything that GP should be doing differently in practice as a result?

Yeah.

So I think some really simple things about just warning patients that they might experience these side effects and symptoms to report, like dizziness on standing or other symptoms like blurred vision or feeling light headed on standing upright, are important to make note of and to report to report back in itself will make a huge difference.

But just also some general advice around reducing falls risk during this period.

Once you've initiated an antidepressant, which will look different from person to person, things like keeping well hydrated and reducing alcohol intake are all conservative measures that can reduce your risk of postural hypotension and its adverse outcomes.

And we know that for some medications, side effect profiles might only last in that first initial period.

So often for SSRIs, for instance, I might mention to a patient, you may experience some gastrointestinal type symptoms for the first couple of weeks, but they may ease.

So do you think your findings would support that of maybe being a bit more cautious in that first month?

But then how would you recommend we monitor that?

Or do you think it's really that initial peak that people need to be looking out for?

Yeah, it's an interesting question.

And certainly the results in this study where we looked at the three antidepressants, that's what the consistent trends seem to show, that it's the early acute period that's of greatest risk and your risk subsides over time.

And it probably does align in the way that different adverse effects like you've mentioned GI adverse effects and the pharmacodynamics and pharmacokinetics of a drug lead to this initial period being the highest risk.

So what I would say is I think that period is definitely a key time where it seems that giving this type of preventative advice and potentially even monitoring people who are at high risk is of greatest importance.

But whether or not they're completely risk free later down the line, I think that's a difficult question to answer.

And again, it will be different based on who you have in front of you and what their underlying risk of developing postural hypotension is at baseline.

Yeah.

And I think this study is really important in highlighting that risk because I think there are some drug classes where you may be, as you say, quite cautious about prescribing because of a risk of postural hypertension.

So you may be very cautious with the beta blocker in an elderly patient.

But it's important, I think, to highlight these other drug classes as potential culprits because we.

You don't want people falling over and.

Absolutely, absolutely.

Yeah.

And I think traditionally we associate these antihypertensive and cardiovascular drugs as the ones to have the greatest effects.

But a lot of studies show that this group of drugs, but also antidepressants and alpha blockers used for urinary symptoms all have very, very high risk of drug induced postural hypotension.

So yeah, hopefully it highlights that range of risk.

Yeah.

And as you've mentioned, with some of these other drugs, for instance alpha blockers or antihypertensives, often they will be co prescribed, especially in a more elderly population.

So it's really great to highlight the risk of additional drug classes as well.

But yeah, I think that's been a really interesting discussion with a lot of really key take home messages for practitioners to take back to their work and to their patients.

So yeah, I just wanted to say thanks very much for joining me to talk about this.

Great.

Thank you so much.

Thanks for having me and thank you.

All very much for your time and for listening to this BJGP podcast.

Cindy's original research article can be found on bjgp.org and the show notes and podcast audio can be found@bjgplife.com and Cindy has told me that she will be presenting this work at the Society for Academic Primary Care Conference which is happening in Cardiff this year.

Thanks again for listening and bye.