S7 E13: Antihistamines & Eczema; Long Term Opioids or Self-Directed CBT for Pain

Welcome to the Hot Topics podcast from NB Medical with Dr Neal Tucker. In this summer sizzler, we have three new pieces of research for clinicians in general practice. 

First, do antihistamines help with managing atopic eczema, or do they do more harm than good? Does which one we use matter? 

Second, exploring the pain relief achieved by opioids in the short and long term. Are there new lessons to be learned? 

Third, for an alternative way of managing chronic MSK pain, could self-directed CBT be the solution?

References

BMJ Antihistamines and eczema

UK data on use of antihistamines for eczema

Eczema Care Online

BJGP Opioid effects on pain over time

JAMA Self-directed CBT for chronic MSK pain

Podcast on chronic pain with Rangan Chatterjee and Howard Schubiner

www.nbmedical.com/podcast

Transcript

Introduction

Neal Tucker 0:00

It's Friday, the 7th of August, and this is the Hot Topics Podcast. Welcome to the Hot Topics Podcast from NB Medical with me, Neal Tucker, as usual. This is the summer edition. Not because I have any specific research that's summer based, but simply because I'm sweating profusely whilst recording this. To get that image out of your mind, here's the plan for today. Three pieces of new research, as usual, relevant for us in general practice. First, in the BMJ this week, antihistamines. Do they have a role in the management of eczema? And if so, which ones? Second, in the BJGP, how does duration of treatment of opioids affect their effectiveness? I thought we knew the answer to this, but do we? And finally, in JAMA, the Journal of the American Medicine Association, can CBT help with chronic pain? And if so, can self-directed treatment work as well or perhaps even better than clinician-based

What's in the news?

Neal Tucker 1:08

treatment? What's in the news? Oh, it's all going on in the government since we last talked. We've got a new health secretary now, of course. That's not happened for at least a month. Um, can Yvette Cooper save UK healthcare? Probably not. Perhaps the new Prime Minister will with the National Care Service? Probably not. Will AI save us all? Not if a new study looking at the success of the AI multinational palantiers attempts to streamline hospital discharge is correct. It found no noticeable improvement in cutting delays, according to the BMJ reporting on this queue. Much arguing, at least it isn't being forced onto general practice without a clue about how or why we would be using it. Oh wait, no, that's happening in plenty of places. Maybe not with Palantir, but with a whole bunch of AI other stuff, which brings us on to a plug for NB Medical's upcoming Tuesday evening clinic in September on AI in general practice. If you want to know the what, the how, the why, the why nots, then come along and join us at 7:30, 15th of September. It'll be a longer clinic than usual, 90 minutes to allow us a bit more time for discussion. This is a very big topic for us to cover. I'm running the clinic. I've got that pleasure. I'll be joined by my colleague Will Duffin from NB and by our partners, Geeky Medics. So they were set up by a GP, uh, they specialise in medical student training, they've got extensive experience in using AI tools in healthcare. So they're good people to talk to as well. As usual, quiet on live courses over August on nbmedical.com, but it all kicks off again in September. I've just finished helping write the updated Hot Topics book and we'll be putting the presentations together for the updated course soon. Lots more coming, so check out the website and remember if you sign up to NB Plus for just over £300 a year, you can come on or catch up with as many different courses as you like.

Do antihistamines help with managing atopic eczema?

Neal Tucker 3:18

Okay, time to start the research. First off, antihistamines for atopic dermatitis, a systematic review and network meta-analysis of randomised trials. That's the title from the BMJ's paper last week. The question here is whether antihistamines benefit or harm as add-on therapy for atopic eczema. Hands up, I was under the impression that they probably don't help much, so I've never really prescribed them. But according to the authors, 20% of patients in the UK with atopic eczema are prescribed antihistamines. At least that was between 2009 and 2018. I'll put that data, that's from a separate paper, in the references as well.

Neal Tucker 4:04

I was pretty surprised by that figure. But perhaps I shouldn't be. Eczema can be really itchy and annoying, particularly for kids or perhaps parents watching their kids scratching the bejeebus out of themselves, and antihistamines are good for itchy things. They inhibit histamine activity when its released by mast cells and basophils and in the words of the BMJ therefore inhibit local neuronal, vascular, and inflammatory cell activation that manifests as itch and skin inflammation. Sounds good. What's the problem? Itch due to eczema is not histamine mediated. So antihistamines shouldn't really work at all. But the thing with medicine and the human body is that you can go back to first principles. You can predict outcomes based on our understanding of physiology, and still weird stuff happens. Sometimes good, sometimes bad.

Neal Tucker 4:59

Turns out the research has not been as negative as I thought regarding antihistamines in this area, merely inconclusive. So what about this new research? This then was a systematic review, a network meta-analysis. Who does just a normal meta-analysis these days? They laugh you out of the laugh you out of the research building. It was of randomised controlled trials as add-on therapy to oral antihistamines. Also, they looked at H2 blockers and mast cell stabilizers that you and I would never really use in this context. The authors were examining for changes to dermatitis severity using the oSCORAD scale. No, I've never heard of it before either, and we're not going to go to detail about it now. There are some things that we just don't need to know. They also looked at itch severity, rated from 1 to 10, sleep disturbance, quality of life, and also any harms that might come from the antihistamines. I'm pretty sensitive to them. So even the non-drowsy ones knock me off a little, and I've been harmed by falling asleep multiple times during social occasions at friends' houses who have cats, to which I am allergic, and then being taken the piss out of. You wouldn't want the same fate to fall upon your patients.

Neal Tucker 6:15

Forty-seven trials were included, which amounted to just over 6,000 children and adults with mostly moderate to severe atopic dermatitis. What did they find? Well, antihistamines, both newer and older generations, don't do much for eczema. They don't help the rash. There was a statistically significant reduction in dermatitis severity, but it was way below the minimal clinically important difference threshold. They didn't help for itch, same pattern again. The authors could detect a difference, but it was too small to mean anything in the real world. They didn't improve sleep disturbance, to which I'm slightly surprised about. Then again, I wasn't in any of these trials, nor did they reduce the rate of exacerbations of eczema. They did probably affect cognition, at least the older generation antihistamines like chlorphenamine. Whilst for newer generation one, newer generation ones, it was a bit of a mixed bag. Loratadine didn't appear to, but citirazine did, although the numbers were pretty small. We're talking something like 17 in a thousand users, and that rate is a quarter of the number of people they found having some kind of cognitive issues compared with older style antihistamines, chlorphenamine much, much worse.

Neal Tucker 7:37

So in conclusion, antihistamines don't really help eczema. They don't help eczema-related itch, eczema-related sleep disturbance, or exacerbations, while first generation antihistamines in particular can have detrimental effects such as increased cognitive impairments and discontinuation due to side effects. As the authors put it, these findings provide evidence against routine antihistamine use in a topic dermatitis management and will inform updated clinical guidelines. Well, if not antihistamines, what does work? Well, of course, going back to basics, lots of emollients and appropriately potent topical steroids for an appropriate period of time. The latter has been in the news recently, of course, for concerns about topical corticosteroid withdrawal syndrome. Have you come across this, which is more of an unknown quantity than perhaps the BBC report I read last week might have suggested? There's a really interesting editorial on it in this month's BJGP, which is worth a read. I'll try and remember to put a link to that in the podcast description as well. In the meantime, there is a fantastic website that we can post, signpost patients and parents to called eczema care online. So you might have not come across this before. It was born out of UK primary health care research teams doing research on managing eczema, and it's a brilliant resource, giving loads of information about the treatment options, evidence-based ways to use them optimally, discussions about exacerbators, lifestyle measures, and much, much more. It's clear, it's instructive. I learned a lot from it. I think it's really worth getting patients to use it, and I'll put a link to that in the podcast description as well.

Pain relief achieved by opioids in the short and long term

Neal Tucker 9:30

Right, next, another paper I thought we knew the answer to. What does treatment duration do to the effects of opioids? Surely they don't work in the long term. That's why we avoid them. Oh, and of course, addiction, abuse, diversion, constipation, cognitive impairment, and the rest. Now, one of the things I've never really understood is when we have patients, particularly those with chronic pain, and we've tried all the medical options that you can think of, and having run out of options, you refer your patient to the pain clinic hoping for some magic alternative. Maybe there's a special injection, perhaps there's some implantable nerve suppression device that could be helpful here. And then you get the clinic letter back and they say, please prescribe MST to this, let's say, young person with depression and functional pain. Or even better, could you prescribe a fentanyl patch for this multi-morbid elderly lady riddled with arthritis on a zimmer frame with a rectal prolapse? I think I'll pass on that advice, thanks. I've watched the Netflix show on OxyContin and the Sacklers and I know where this all ends.

Neal Tucker 10:41

But is I've always wondered, am I missing something? Do the pain clinics, the pain experts, know something that you and I do not? Are long-term opiates better than we think? This new paper in this month's BJGP is titled Impact of Treatment Duration on the Effectiveness of Opioid Analgesia, a systematic review and meta-analysis. Yes, uh, another review and meta-analysis. Sometimes it feels like there's no truly original research other than for weight loss drugs anymore. But this paper fills an important gap because the authors suggest that it's the first of its type to address whether effectiveness of opioid analgesia changes over time, specifically for people with chronic low back pain or osteoarthritis. Two conditions I typically never think about prescribing opiates for.

Neal Tucker 11:36

The primary outcome the authors were looking for was attainment of clinically important pain relief, which is defined as moderate or at least a 30% improvement in pain through use of opioids compared to either placebo or a pain management program as a control group, with a secondary outcome of on-treatment pain scores. They then compared this between short-term use, which is up to four weeks, intermediate-term use, which is four to twelve weeks, or long-term use, which is over 12 weeks. 27 trials were included, 19 of which looked at OA, 7 for back pain, and one looking at both. 58% of the group were female, and the average age of the participants was 57 years old. They found with moderate certainty that opioid recipients were more likely to be responders with short-term treatment compared to control groups, about 40% more likely to have improvement in their pain with treatment with opioids compared to placebo or a pain management course. That's over four weeks. After four weeks, the benefit was lost. Opioids were no more effective than the control groups. And although, from the data, it you can't say this for sure because it wasn't a statistically significant reduction by 12 weeks. There was a trend that opioids were actually making people's pain worse. Things had flipped from the first four weeks of use. What's going on there? The authors discuss that opioids with longer-term use may actually increase pain sensitivity through an effect called opioid-induced hyperalgesia.

Neal Tucker 13:29

The dark twist here, of course, is that as the treatment makes the pain increase, the logical thing to do is increase the dose of the treatment more, driving a miserable opiate-driven feedback loop. Where does that leave us when we've exhausted all the options? Clearly, as most of us have already chosen to believe, long-term opiates are pretty bad news for most people most of the time.

Managing chronic MSK pain - could self-directed CBT be the solution?

Neal Tucker 13:57

So perhaps the answer is in our third paper published in JAMA this week. It looks at whether self-directed CBT for chronic pain with asynchronous personalised feedback could be better than clinician-delivered CBT. We like to use medicines for chronic pain. It feels like we're doing something. Patients often like being prescribed a medication for chronic pain because it feels like they're doing something. You and I, and most of our patients, once they've gone through this kind of cycle, now know that most of the time the medication doesn't make any difference. But pain is also hugely influenced by the mind, even if it is physical in origin. I've watched that film where that US hiker gets stuck in the middle of nowhere with no help on the way and has to chop their arm off to get out. Given my reaction to a paper cut, it would seem impossible that you could cut your own arm off. And yet, with the right mindset and a fear of death, anything is possible.

Neal Tucker 15:00

And yet, psychological therapies for chronic pain are underused. Perhaps we don't believe will this paper change our minds? One of the limitations of talking therapies is the need to talk to someone, and there aren't that many someones out there, particularly in a cash-strapped NHS, so self-directed CBT would be great if it worked. Now, I'll be honest, I haven't completely got my head around that active intervention in this study. So self-directed CBT for chronic pain included 10 weekly modules with pain management skills, training and education, daily goals for skill practice, and a goal-based walking program. Participants had 11 weeks of a daily interactive voice response assessment during which you answered various questions over the phone. It's all automated, I think. And then they collected data on pain, sleep, step count, engagement with skills practice, and much more. And then each week the participant would receive a personalised voice message based on their responses from a health coach who apparently took just 20 minutes per week per participant. Although I could also see that this could be performed entirely by AI, probably in a slightly dystopia near future.

Neal Tucker 16:22

So that was the active treatment. The control group received clinician-delivered CBT. It could be face-to-face, by phone, video, whatever worked and was normally used locally. The number of sessions varied for that, depending on the patient's needs, somewhere between 4 and 11. They recruited 764 veterans with chronic musculoskeletal pain in the US. The mean age was 53, 40% were female, they were an ethnically diverse population. The primary outcome was patient-reported pain, measured by the seven-item brief pain inventory interference subscale. We won't go into more detail about that one. After a four-month period, it scored from one to ten. A change in one is the minimum clinically important difference. They also followed up at six months and 12 months to see if the effect was durable, and they had a range of other markers such as pain intensity, sleep, depressive symptoms, and so forth that they collected as other secondary outcomes.

Neal Tucker 17:35

The results then, at four months, the self-directed CBT was better than clinician-delivered CBT for reduction in pain. The baseline scores on that seven-item scale came out as 6.7 and 6.8 for the active and control group. At four months, this reduced down to 5.3 in the self-directed group. So that's a drop of what 1.4 almost like 25% drop, but only 6.2 in the clinician group, which doesn't meet that minimum clinically important difference. The benefit was durable, so it was maintained at 6 and 12 months follow-up. And that self-directed group also did better on all the other secondary markers that they looked at. The scores reported in this way are difficult for you and I, I think, to interpret what it's actually likely to mean for our patients. But they qualify this in a more user-friendly way by telling us that what percentage of participants were responders. So 23% had improvement of at least a minimal level, 21% a moderate improvement, and 12% a substantial improvement.

Neal Tucker 18:50

No one was ever expecting miracles here, so those results actually sound quite reasonable to me. And patients who are otherwise being resistant or their symptoms have been resistant to medical therapy, that seems like quite a good result. Of course, back in the UK, in general practice, you and I don't have access to whatever online tool and health coaches they use for this study. But I guess the lesson from this paper is it does inform us that we can be positive about another option for our patients beyond just medication. This patient actually reminds me of a book that my wife told me about a few weeks ago, which has changed the way she's approached many of her patients with chronic pain. It's called Unlearn Your Pain by an American guy called Howard Schubiner. I haven't read the whole book yet, but it's quite a compelling proposition. He talks about how, particularly, chronic pain often doesn't have a physical basis, or if it did initially, over time it's likely that that has resolved, but the brain learns how to feel this pain and perpetuates it. And this is called neuroplastic pain. To improve this type of pain, physical treatments won't work. You and I, of course, see that all the time. A different approach is required, focusing on the mind. Often people might have had past trauma and that needs to be addressed, or there may be other issues in life. And he terms this process brain reprocessing therapy. Probably people can achieve this by themselves reading the book a lot of the time. There's also a really good podcast on this that he did with Rangan Chatterjee. I'll put the link to the podcast description to that too. It's really, really worth a listen. I think maybe we need to start trying to change the way we think about managing chronic pain because a lot of the time what we're doing, especially drug-led, just isn't being very successful.

Neal Tucker 20:53

Okay, that wraps up the research and the podcast for today. I'll be back on the 11th of September with more news and research relevant to us in general practice. In the meantime, enjoy the rest of your summer. I'll see you on the other side. Take care. Bye bye.