SMRs in problematic polypharmacy: case based discussions

Emma Bryant
Hi, everyone and welcome to the podcast about insomnia from the NHS Specialist Pharmacy Service [SPS]. This podcast is a follow up on a webinar that we ran on the 14th of April, and if you’ve not managed to catch up on that, I’d recommend watching that first before listening to this podcast. We had some really interesting questions during the webinar that unfortunately, we just didn’t have time to cover. So, we thought it would be helpful to invite back our expert, Dr. Rania Ward, Principal Pharmacist for Sleep Medicine, to answer some of the questions and share more of her knowledge to support primary care colleagues in this area.

Rania, welcome and thank you for coming back to share some more about insomnia.

Rania Ward
Thank you, Emma, thanks for inviting me back.

Emma Bryant
I’ll jump straight in with the questions. So, we had some questions around the sleep cycle and shift patterns for people who are working nights, for example, and those who only get, say, four to 5 hours sleep per night. Any hints or tips on what that would look like?

Rania Ward
I’m really glad that this question actually came up because it is important. As we all know, you know, we as humans have a very regular sleep-wake cycle, it is called our circadian rhythm, and it roughly runs around 24 hours. It’s 24 hours and 18 minutes but we say it’s roughly 24 hours. And it’s really governed by exposure of light versus darkness; that’s the most strongest cues for us in maintaining this rhythm is our light and dark phases of the day. And so when people undertake shift work, it really throws off that. People who have regular shift work, so they work predominantly in the night and then sleep during the day, the circadian rhythm can adjust to that, although it’s not always perfect, it can adjust to it. But when, you know, you’re working some days 12 hours, other days you’re doing, you know, 12 hours overnight or 12 hours during the day, then it can be very difficult to, for the circadian rhythm to adjust to the working pattern, and, you know, rotating workers never really get that chance. The result is kind of a chronic circadian misalignment, which is a problem. But it is where melatonin actually has the most evidence to correct. It is about timing, it is about making sure that your, you fall asleep, or you can sleep at the time where you have the opportunity to sleep, but it can also be very, very difficult. So, it requires much more of an individualised approach; someone to sit down with you, go through your shift patterns, see where you are, where you have rest periods and then undertake sleep during specific times according to that schedule and to know when you can’t and you have to manage with other means and use melatonin to help as well. So actually, melatonin is licensed for shift work, but it really needs a conversation. It needs someone to sit down with you and go through your own pattern and then advise accordingly.

Emma Bryant
Lovely, thanks Rania. And can the sleep be cumulative during the day? So, if someone gets say, 4 hours overnight but then catches up at different times and there’s no daytime dysfunction, is that anything to be concerned about?

Rania Ward
You know what? I wish I could say yes, we can acquire sleep throughout the whole day, but actually, as I said sleep is a very timed process. It thrives on regularity. So, trying to sleep whenever you can during the day actually undermines the ability to sleep properly at night which is, which obtains the most restorative aspects for you. And I wouldn’t encourage it. That’s not to say that, you know, if you know that you’re going to have a really late night, and have a quick nap during the lunchtime, or if you know that you’re going to have a very stressful time that’s going to leave you to stay out late or be late or something, then a quick 10, 20, 30 minute nap can help with that. But to have it as a regular catch up and then deprive yourself, that’s not going to be, that’s going to make things a lot worse and actually predispose you to having chronic sleep difficulties.

Emma Bryant
Lovely, thank you, Rania. So, are there any particular cautions or red flags that we need to be aware of in relation to insomnia and treatment?

Rania Ward
Certainly, before you can think of treatment, really it is the red flags that you need to understand. In order to know what the red flags are, I guess you need to understand what could mimic insomnia or make it appear that it’s insomnia when actually there’s another driver. And in order to know that, you kind of need to understand what differential diagnosis could there be in insomnia. And typically, the most coexisting, or most frequently coexisting condition with insomnia is actually obstructive sleep apnoea. About 50% of patients actually have sleep apnoea. And this is a sleep disordered breathing condition that leads to pauses in breathing during the night or shallow breathing during the night. It does have cardiovascular outcomes, so impacts, so it’s very important to assess for this. This can be asking certain questions like, are you snoring heavily? Has your partner noticed that you pause in breathing? Have you put on weight recently? Do you have high blood pressure? Those are kind of risk factors to ask around sleep disordered breathing. If there is any worry that that is the concern, then it would be a referral to, for a further assessment of that.

The other red flag in coexisting with, very typically coexisting with insomnia is, and there’s a confusion around it as well, is circadian rhythm disorders. So, typically a lot of young patients might present with this problem where they find it very difficult to fall asleep at the right times, or socially accepted times. This is also tied in with often neurodevelopmental conditions, so autism, ADHD [attention deficit hyperactivity disorder], the backgrounds of these patients are predisposed to circadian problems. So, where we find that we start falling, feeling sleepy around 10/11[pm] typically, these types of patients don’t actually feel sleepy until maybe 1/2 o’clock in the morning. This could be confused with a sleep onset insomnia problem, but actually it’s more of a circadian delayed phase disorder. So, they feel sleepy later than what we would, but once they are asleep, they actually sleep through, you know, 8/9 hours, 7/8, 7 to 9 hours as usual. So that’s around questioning, you know, once you get to sleep, are you, do you sleep continuously? Often with a lot of insomnia patients, they won’t sleep continuously, they will wake up, interrupted during the night and then they might not wake up, you know, they might wake up earlier than 7 to 9 hours as well. So, one of the questions around, with particularly if you, if there is a history of ADHD or autism or other neurodevelopmental conditions like dyspraxia and dyslexia, all that, these kind of questions around do you feel sleepy at bedtime? When it’s bedtime, what is your bedtime? Is it 10/11? Okay, but are you sleepy at that time? That’s a very, very key question to ask, and if they’re not, they’re feeling wide awake, and then you ask them well when is it that you feel sleepy? Then they tell you it’s, you know, 1/2 o’clock in the morning, sometimes even 3/4, and then you know that actually this is a much more circadian rhythm element.

The other main differential diagnosis with insomnia disorder is restless leg syndrome, so movement disorders. And these are questions around movements at bedtime or in the early evening. So often patients will say, I do get uncomfortable sensations in my legs, it causes, it has a very strong urge for me to walk around and often it is relieved by movement. It is actually, that is the diagnosis for it. It’s uncomfortable sensations, strong urges to move, and it’s relieved by movement. If questions around that, then it kind of tells you that there is a movement disorder here, limb movement disorder going on, and that needs to be treated because often it happens in the first part of the night, but it can happen throughout the night. There is also another condition called periodic limb movement disorder within the night, and whilst patients are aware of restless leg syndrome, they’re not aware of periodic limb movement disorder. And this is the movement of the legs in a periodic time, in bursts of periods throughout the night. And they’re not aware of that, but often the symptoms that they will say is that yes, it interrupts, I’m waking up several times I’m not sure why, and then during the day they’re actually feeling quite sleepy.

And that brings me onto the next question to ask patients is that some people will say, I can’t sleep at night, but then they’re very sleepy during the day. If that is the case, that’s certainly a red flag for a sleep disorder that’s happening at night. It’s probably not, less likely, I would say, less likely to be insomnia, more likely to be something wrong that’s going on in their sleep. And so asking about daytime, excessive daytime sleepiness is an important red flag.

Emma Bryant
Leading on from that, I guess one of the questions was around, is it better to treat the underlying cause and get some natural sleep or to add in hypnotics fairly quickly so that people start to get some sleep even though it’s kind of that unnatural sort of forced sleep?

Rania Ward
That’s a very good question. I would say it really depends on how distressed that individual is, how open they are to want to deal with it in a, in the most primary intervention of insomnia, as in the most evidence based, or whether they need, they just are so distressed, they need something urgently right now to make them fall asleep because they’re at the end of their capacity. It really depends on the desperation of the patient in front of you. If they have had this for a long time and a few more weeks is not gonna make much of a difference, then this is the time to actually intervene with non-pharmacological approaches. If they’re super desperate, you have to treat that distress. That is very important to treat that distress. So, it is about using, as NICE guidance indicates, z-drugs for a specific short time, and this is three to seven days. The maximum I would say for z-drugs or a short course of benzodiazepines is up to four weeks. If you are prescribing benzodiazepines for more than seven days, it becomes extremely difficult to get patients off at that point, and I would really encourage not to do that. But you can prescribe it up to seven days, up to four weeks rather, if needs be. But again, it is about whether the patient is fully engaged in actually wanting to overcome their insomnia through non-pharmacological approaches, but even if they aren’t, really, we should be encouraging that because that is the first line and which we’ll talk about in the next few questions as well.

Emma Bryant
Lovely, thanks, Rania. Looking at the pharmacological options, we have some patients around, asking around low dose mirtazapine, low dose trazadone, and promethazine, and I just wondered if you could expand a little bit about your thoughts on those other options.

Rania Ward
Yeah, I mean a lot of GPs as we know, they do prescribe mirtazapine. They’re not too familiar with trazodone. Mirtazapine always thought of as, oh, especially if there’s anxiety/depression, we can deal with two aspects of the problem in one go. Typically, that’s not the case with mirtazapine. It’s actually low dose, very low dose, 7.5mg, 15, up, some people in 15 mg more effective. I’ve found, I’ve noticed that 7.5 is really effective of the older person and 15 is probably more effective than 7.5 for middle aged, you know, 40’s/50’s, so that’s something to think about. But I don’t, I wouldn’t say that it is a medication that you should go to. These medicines, trazodone as well, low dose, more effective, particularly in the elderly, but again, these medicines are options, but they’re not the go to places. It’s only when you, again the patient is very distressed, needs something now. The impact on mood is likely very low. It’s, you know, GPs think that it’s acting on the mood plus the sleep, but actually the effect on the mood is very low. It’s more likely that the patient is now sleeping longer than, these medications have an impact on deep sleep, on sleep latency so people can sleep, they don’t take too long to fall asleep, they have achieved deep sleep and more hours of sleep. And the resultant effect of sleeping better then helps the mood rather than the actual pharmacological action of the drugs on, you know, serotonin/noradrenaline reuptake. So, it’s much more on the sleep elements. They, as I said I think that they are they are options. But if, I would reserve them if the first line treatment is not available, or cannot be given. And there are lots of contraindications, not contraindications but barriers to obtaining the first-line treatment, which we will go on to soon.

Emma Bryant
Thank you. Could you elaborate a little bit more on the role of melatonin and its sort of safety and prescribing issues of long-term use of melatonin.

Rania Ward
Yeah, absolutely. Melatonin, you know, is, it’s one of these medications that while it’s quite easily available on the internet, and luckily now we have medical grade melatonin where we didn’t several years ago, it was all unlicensed, but now we have it available to us. And it is considered in the sleep world, it is considered quite a benign medication. There is no potential for addiction, there is no tolerance. Well, I say there’s no tolerance, people can get used to its effects so that it becomes ineffective, but they’re not dependent on its use. There’s a huge psychological element to taking it, so often they, people do think that, oh, I’ve taken my melatonin and therefore that’s the reason why I’m sleeping. In actual fact melatonin is very ineffective for insomnia. It has a license for use in insomnia in the over 55’s because we have genuine evidence that the pineal gland, which secretes melatonin, calcifies over time and so it’s not producing the levels that are required or the mechanisms around melatonin secretion and use is not as effective as we get older and therefore that’s why it could be more effective in this group. But overall, melatonin is actually not very effective for insomnia, and if it is effective then probably is likely a circadian element to their problem. But long-term we have people on melatonin for many, many years, and we don’t have the kind of long-term data on the effect and people are worried about that, but we haven’t really found that it is something to worry about and you can, it is one of the medications you can take long-term, you can stop immediately without having any problems. You know, there are some side-effects with melatonin. The most common ones is morning sedation. Headaches can be a problem and quite vivid dreaming. Some people also, a small proportion of people do experience hot flushes, and this is quite underreported actually, but when you’re considering it in the menopausal or perimenopausal stages, then that’s something to actually talk about with the patient that could arise, might not, could, it is, to see if that happens or not is to try it. But it is, that can result with the use of melatonin, and obviously the hot flushes can wake a person up, changes in temperature and the vasodilation aspects of it is, can wake people up whilst on melatonin, so that counter, is counterproductive to what you’re trying to treat. So, these are just things or factors you need to explore with the patient and speak to them about.

Emma Bryant
The NICE [guidance] doesn’t recommend melatonin for dementia…

Rania Ward
That’s right.

Emma Bryant
…and I just wondered what your thoughts are around that.

Rania Ward
Yes, melatonin isn’t recommended for dementia, only because the evidence is just so poor, particularly with severe dementia. It is a very difficult situation when you have dementia and the person’s wandering in the night. The most important thing to do in this is actually the regularity of the day for the dementia patients. So, ensuring that they have light, bright light in the morning, they do have a light exposure during the day, there’s regularity in their mealtimes, there’s regularity in activities during the day. It is a whole 24-hour care that is required and routine that needs to be in place. And you, although it’s not recommended in dementia, we do know that depending on the background of what, of where the dementias come from, whether it’s Parkinson’s or Alzheimer’s, there is evidence of use of melatonin in those backgrounds and therefore dementia is a by-product of those other neurodegenerative conditions where we know the circadian rhythm is disrupted. So rather than saying a blanket no in dementia, it does depend on what that dementia has been based on, you know, which degenerative condition is behind it as well, whether you should try it and see if that works, and if it works then that’s great, then if it doesn’t work then you know that, you know, it’s much more about the behaviours of the routine and the regularity of the routine that’s important.

Emma Bryant
Great, thank you, Rania. Leading on from that, are there any different approaches for patients with serious mental health illness [SMI] conditions? And those without, is there any particular approaches that are more or less beneficial that you’ve come across in those with SMI?

Rania Ward
Yeah, I think, you know, the approach is always going to be the same actually, whether it is serious mental illness or there is no mental illness in terms of insomnia. They need, you need to treat insomnia on its own right. Insomnia has actually been shown to be a prodromal sign, or an accelerant to serious mental illness, illnesses. And therefore, if you notice insomnia happening in people with schizophrenia or bipolar, it can indicate whether there’s going to be a manic episode or there’s going to be a psychotic episode; it can be a sign to say there’s going to be a dysregulation. We know that depression, ok, is predicted by insomnia. So, if you, if insomnia happens, you are twice as likely to become depressed than it, to those who are predisposed to getting depression than if you didn’t have insomnia. So, we know that it’s actually this sleep that’s, that is offset that then leads to a mental change. And therefore, if you see insomnia occurring, it really needs to be addressed, it needs to be addressed in line with that serious mental illness as well. And if you catch it enough before the serious mental illness occurs, then that could help reduce the episode or even not, or if not even manifesting. So, the actual treatment is to treat the insomnia alongside, if it’s too late and you, you know, it’s there, the SMI is there, then it needs to treat both at the same time.

Emma Bryant
Great, thank you for that. Could you please share your thoughts on the new medicines that have coming out for insomnia and how they compare to some of the old, and other sleep medicines available.

Rania Ward
Yeah, I have to say to you that, you know, daridorexant is a kind of scientific breakthrough, not in the sense that we, you know, that it’s ground-breaking, it’s in the sense that we’ve not had any sleep medications since the sixties. And these benzodiazepines and z-drugs, they are blunt tools, they’re blunt instruments that work across the brain, there’s no specificity to them and they work by just damping down the brain causing sedation. We want to move away from those, that type of medication. We want targeted treatments based on scientific evidence that, what is happening in our wake-sleep cycle, why is it being disrupted? And so daridorexant is actually the first in the UK to address the science behind insomnia. It is trying to address the hyperarousal theory that we think is going on in insomnia. So, we believe that there is a disruption in sleep by causing arousals, spontaneous arousals, and daridorexant works by targeting the arousals and stamping them down. And the pathways involved in our arousal process called orexin, it’s specific neurons in our brain that are responsible for keeping us awake, we feel that, we think that they are being triggered during the night and therefore antagonising them and switching them off will help restore sleep again. I mean, I welcome that. So, in comparison to what we have already, I welcome the fact that we’ve got a targeted medication that’s specific for chronic insomnia where we didn’t have before. So that’s a plus.

The second is that it really does not act in the same way in terms of, even the side-effect profile of daridorexant doesn’t, is not the same as the others. There is, in my experience, and I’ve prescribed this medication hundreds of times, I have not seen any dependency, any addiction potential. You can stop the medication, they might feel bad. I usually say drop down to 25mg before stopping completely, but otherwise people just come off very easily. The only thing that I’ve noticed, my experience with this medication, is that it takes a very long time to have an effect. It’s very long. It’s very important to tell patients that this is not like if you’ve had zopiclone in the past and you take one tablet tonight, you’re not going to fall asleep the next night. This medication takes weeks to have a build-up effect, and I don’t personally assess patients until they’ve been on the medication for three months. That’s the peak effect that you get, this is according to the trials that has been undertaken for the drug that it’s, it plateaus in effectiveness at three weeks, three months. And what you get at three months is what you’re going to get. And if you don’t get much, that’s it, you won’t get much. But if you get amazing results, and this is the other aspect of daridorexant, it’s very polarizing: so some people have called it absolutely lifesaving, transformative. Other people have said, I have, do not have any effect at all on this medication, and that’s a shame, but that’s what we have. So, the issues with this medication, although the side-effect profile is much more favourable, it’s slower acting, it takes a long time to peak in activity, and the activity may or may not be there. So that’s the, that is the package with daridorexant. So, I would say also, you know, with any of the medications, the first line intervention, which we will hopefully talk about is the basis to it, it actually makes the drugs work better and helps patients come off drugs if they’re addicted.

Emma Bryant
So, touching on that: non-pharmacological treatments, Rania. There’s apps out there, there’s, you know, other sort of skills that patients can learn around, sort of, sleep hygiene. Where does that all fit when a patient walks in to your, you know, medication review, to your pharmacy? Kind of, where would you start with, you know, the process? What, where do apps and non-pharmacological therapy fit into this?

Rania Ward
Yeah, so obviously, you know, by this point you’ve asked them about their day-to-day habits and their routines and their bedtimes. You’ve gone through the red flags. We’ve talked about certain treatment options. But put the treatment options to one side unless they’re absolutely distressed and therefore you can give them the first line medications which is z-drugs and benzos. But if you don’t need to go there, then I would strongly, really encourage patients to undertake cognitive behavioural therapy for insomnia [CBTi]. And this might be slightly out of our comfort zone as, as pharmacists thinking, oh, this is talking therapies, but actually CBTi, it is such a shame that it’s called that because it really isn’t that. It is a five-component program. It is a structured program, only focuses on sleep. The CBT, the cognitive behavioural aspect is just one of the five components, it’s not the leading one. And it’s really there because after many, many years of insomnia, patients have very held beliefs about their sleep, about themselves, about the insomnia, and so it is about unlocking that cognitive fix, that bind by using certain techniques like acceptance therapy and paradoxical intention therapy, these things are that we don’t know but therapists know. But you don’t have to do that if you focus on the other components. The other components are sleep education, they’re relaxation therapy, sorry, relaxation techniques that you can tell patients, they’re, a part of the program is called sleep restriction therapy, and this is kind of restructuring sleep, consolidating the amount of sleep hours the person sleeps and then elongating it over time. You can get trained to do how to do that. And stimulus controls, making the bed environment a stimulus to sleep. These are all certain techniques that we, if we learn them, we can impart them quite easily, and this is what I do in my clinic, very easily onto patients and it makes a huge difference without going into the psycho-dynamic areas or therapy trained aspects of it. There are specific aspects of the CBTi program we can tell patients in order to help them. And it is definitely a sell to patients though, because as soon as they say, they hear CBTi, they think it’s talking therapies, they think it’s CBT for anxiety and depression. It is not that way at all. It is a very structured sleep focused, techniques and activities we want them to do in order to restore their sleep. And if the person is open to non-pharmacological approaches, because they really must know that the drugs they wear off with time, there is no medication that can be used long term. The brain adapts to its use and even if people say I swear that if I had my temazepam, and if I don’t have it, I will never sleep, I think though that’s dependence rather than actual pharmacological action at this point, after 20/30 use, 30 years of use, it’s likely that it’s not the case that they’re, they need that medication for their sleep. So the long-term intervention for chronic insomnia is cognitive behavioural therapy. It is 70 to 80% effective, 50% of patients come off medications, 30 to 40% become good sleepers, and for a complex chronic condition like chronic insomnia, these are good statistics for non-pharmacological approaches that actually cannot be met long-term by drugs.

Emma Bryant
I guess where will people learn a bit more about the sleep medicines and insomnia? Where can colleagues get some more information about that? ‘Cause I think these sort of tip, hints and tips, you know, they might want some further information around those.

Rania Ward
Yeah, absolutely. Actually we’ve just launched a network called the National Sleep Pharmacy Network. I would encourage listeners to go onto our website and make contact with us. We are a small group of, expanding group of sleep pharmacists in the UK and we want to be the face and voice of sleep pharmacy because we deal with sleep complaints day in, day out within our day job. And we tackle some of the grey areas around medications and the sleep disorders and the types of patients we see and the overlaps with mental health and other neurological conditions. So it is a, it’s a fascinating field. So I would encourage those who are interested to look at our website. We want to also be aiming to be the site where we have all the resources all in one page. It takes a lot of effort and time obviously, so we are still trying to manage with all that.

There are other educational places that you can go and go to. One of them is the Royal College of GPs. You have to create an account on their website first, and there is a module on insomnia that’s free of charge. Other modules are not free of charge, but the insomnia, they’ve made it free. It is under the mental health section, which is another problem we have because insomnia has been tucked under mental health all the time and whilst mental health problems do coexist with insomnia, it is a standalone sleep disorder, not really specifically apt for mental health. And so that’s one area.

The royal phar-, the Royal College of Pharmacy, they also have a program on insomnia. So they have webinars, they have e-modules, everything that I’ve talked about in this, not really actually, I’ve talked a lot more than I would have done in the modules, but in terms of the background, the science, the approach, the step-by-step way of assessing a patient, what you need to look out for, and the medication elements, the kind of guidelines there are available to look at and the resources that are out there, those are in those modules. So you can have a look at them too.

There are also, if you’re wanting some education where it’s much more, you know, getting a certificate or a degree or a diploma, there are sleep medicine courses run by Oxford, Strathclyde, and I think we are hopefully going to be working with Surrey, University of Surrey. They have a very big sleep research centre there. They’re looking to open a course as well. There’s one in Bristol. I don’t think there is one in London, but there might be. So yes, so there are proper education diplomas and master’s certificates that you can undertake if you’re so interested.

Emma Bryant
That’s great. Thank you so much, Rania, for coming back and giving us this, kind of, follow up to the webinar that we ran and answering some of the questions that we couldn’t get round to in the actual webinar. I really hope everyone who’s listening to this has found it useful.

We’re always really keen to hear from you as listeners about suggestions on topics you want us to cover. Our contact details are available on the website. Please remember to register on the website and opt in to receive our weekly SPS bulletin and this will make sure you’re always informed of our most up to date content and you’ll receive information about our upcoming events. We also have a WhatsApp channel that you can register for and you can follow us on LinkedIn under NHS Specialist Pharmacy Service. Thank you all very much for listening.