Are sleeping tablets outperforming performing placebo?
Following on from their discussion in Part 1 of Sleep and Sleep Disorders, today Andrew and Mark dive deeper to help unravel the complexities underlying treatment success and failures. They explore the primary pharmaceutical interventions and where complementary medicine may be an adjunct or alternative to help achieve better, more restorative sleep.
Covered in this episode
[00:47] Welcoming back Dr Mark Donohoe
[01:51] The downsides of benzodiazepines
[06:20] Differentiating between acute and chronic insomnia
[09:05] Case taking to determine sleep quality and quantity
[13:27] Choosing the right magnesium
[16:50] Does GABA work for sleep?
[18:25] SSRIs versus 5-HTP
[21:54] How the environment impacts sleep
[25:39] Can you rejuvenate receptors after benzodiazepine use?
[29:50] Cognitive-behavioural therapies for insomnia
[32:38] Sleep drugs are no more effective than placebos
[36:06] Melatonin use
[41:35] Phosphatidylserine and decreasing cortisol
[44:04] Recap: What actually works for sleep?
[47:35] Closing remarks
Andrew: This is FX Medicine. I'm Andrew Whitfield-Cook. Joining us in the studio again today is Dr Mark Donohoe, who earned his medical degree from Sydney Uni in 1980, worked in the hospital system for three years before opening his own general practice on the New South Wales Central Coast. And this is where patient groups such as farmers, who could not afford to be sick, presented with complex illnesses which had just been left undiagnosed and untreated by his peers. Mark attests that this is where his real medical education began.
So he then delved into environmental medicine, nutritional medicine, and now, lifestyle medicine with fellowships in each modality. Dr Donohoe is renowned for unravelling complex illness caused by toxic exposures, creating the first low-exposure integrative hospital in Australia, and remains a staunch vanguard for patient advocacy and health. Welcome back to FX Medicine, Mark. How are you doing?
Mark: I'm not a grandfather of anything this time.
Andrew: Well, sage.
Mark: It's good to be back, Andrew.
Andrew: Now today is part two where we'll be discussing some treatment choices. Part one of our sleep series is where we discussed the dysfunction, what goes wrong.
Andrew: So, I guess, let's start off with some of the more medical treatment choices, and what went wrong. I remember Ruth Cracknell, an ad on TV.
Andrew: This was when I was learning nursing. And this was a plea from even the medical community to stop using benzos, benzodiazepines. Indeed, back in those days, it was called the benzodiazepine receptor.
Andrew: The GABAA receptor. So, tell us where we've come from, and what went wrong. What lessons, hard lessons did we learn?
Mark: In the 1970s, when I was a tiny, tiny child — very, very, very young at those times — we had a group of chemicals called barbiturates. And they had become very, very famous for deaths of people like Marilyn Monroe. The world at that time in the 1960s and '70s largely ran on amphetamines to get you up in the morning and barbiturates to put you off at night. Lots and lots of deaths were occurring.
And in my first years of medicine, the brave new world — thank God, those have gone — now, we have a new group of drugs called benzodiazepines, non-addictive, non-habit-forming, can be used if and when we want them with no adverse effects whatsoever. The late 1970s brought us, as a group of doctors to feel that there was now a magic pill that anytime people were stressed, needed sleep, that we had now a pill to do that. And in my first years as an intern and a resident, a registrar, a famous drug which was known as Mogadon.
Andrew: The moggies.
Mark: Yeah. The Mogadon was used to keep hospitals quiet, especially where old people were in a hospital. It made everyone's life a lot easier. And it took a long while to recognise that what we were doing was chemical straightjacketing of a lot of people. We could make them sleep. We couldn't easily get them up in the morning to do anything, but well, you know, that made for an easier time in the hospitals and nursing homes anyway.
Andrew: But even then, you'd get patients who were getting dependent, showing dependency on moggies. And you would use higher and higher doses to get the same effect.
Mark: Yes. So, there was an issue of, “Is this addiction with escalating dose, withdrawal responses with those kind of things?" Or was this just habituation, that people started to depend on this?
And I think that the lesson learned is, when you chuck chemicals at the brains and the minds of people, there's no such thing as “non-habit-forming.” The new normal for that person is the drug dependent person. And that becomes what you now say...well, is the baseline for them. Are they the same person that they were before? No, not at all.
But that learning process of hearing, we had bad old days in medicine, we've got brand new drugs that fix all our problems, that's now happened 20 times in my career in different areas of pharmacology.
The rule of thumb is, every drug has downsides. There are no perfect drugs. There are no perfect ways of treating anything, and especially when you get into chemicals that manipulate the mind, the GABA receptors. This concept of “All they're doing is keeping the GABA channel open,” how benign does that sound? It sounds so much like “It's just like you don't have enough serotonin.” It's “You just don't have enough of an adrenaline receptor effect.”
Every time we make a drug, there's a story that goes with it. And we doctors are probably the most gullible group. Over a career, you think, "Ah, how could I think that that was right again?"
Andrew: The limitations is that a drug does one thing really well, normally.
Mark: And it normally does it for the short-term.
Mark: So, what we gain in the short-term, we pay for in the long-term. So, the design of a drug... You're exactly right. The design of a drug is to do a particular thing. If you ignore everything else that it does or does not do, everything else that it does or does not change, the ability of drugs to do a particular job is unsurpassed. That's the science of medicine. What we're not so hot at is, what happens 1 month, 12 months, 5 years, 25 years down the line?
Andrew: And what about the elegance of the human body? Controlling mechanisms.
Andrew: Anyway, we're getting onto a pathology sort of thing.
Mark: I know. We cannot get too philosophical, because last time we became a little bit philosophical. And we ended up not dealing with the treatments. So, today, we need to deal with the treatment.
Mark: The movement in the college of GPs is to do anything to have non-drug therapies. However, there is still a division that we've got to make for all practitioners. There is a thing which is acute insomnia, which is often revolving around a particular issue, a particular stressor for a person, an identifiable stress. Insomnia can happen as a grieving process. It can happen when work stresses are extremely high. It can happen for short periods of time. And there is no real problem with the use of symptomatic treatment, just as you would use paracetamol for headaches in a person with headaches that's only short-term.
You can still use benzodiazepines. The classic ones are no longer the long-acting ones like nitrazepam and flunitrazepam. They tend to be temazepam. People will know it because that's what people take when they're going on flights overseas to try and get their sleep on a flight.
And for short-term use… and by acute insomnia we're meaning where the person is feeling that they're getting less than 50% of the sleep they need over a four-week period or less. In those circumstances, even the RACGP guidelines are quite cool about using short-term benzodiazepines. And that typically is a temazepam 10 or 20 mg. It's not the kind of thing every naturopath can prescribe, and it's probably not the kind of thing that every doctor is now comfortable with prescribing. We sent it out like sweets and lollies in years past.
Andrew: Mother's little helper.
Mark: Yeah. Well, mother's little helper was, you know, the...it's had various incarnations over time. Bex was mother's little helper, as you remember.
Andrew: Oh, was it?
Mark: Yeah. And it was a cup of tea, a Bex, and a good lie down was the Mogadon of the 1970s and '80s. We ruined a lot of kidneys on that occasion. We've done a lot of deaths from respiratory suppression earlier than that. And then we've now got an attitude towards the benzodiazepines, which is, they are evil, pure evil. And I think that that's the right attitude to have, because for short-term symptomatic treatment, it's still a very effective way. And for people who are going through something where there's a known short-term reason why they cannot sleep, it's a thing that can establish...
Andrew: An added stressor in their life, for instance.
Mark: That's right. Something that's clearly identifiable and is not going to go on for a long period. Now, that's not always the case. People think work stresses are short-term, and then they become long-term, and then they become, you know, retrenchment. So, you've got to be a little bit careful about saying it's only short-term.
Andrew: Yeah. This is where we had the issues previously with, you know, "I only use it short-term." Of course, that became chronic use.
Mark: I know. I know. And that takes time in a consultation. Look, for many, many people, the best sleep inducer is a glass of wine or a drink of alcohol before bed. I'm not promoting the use of alcohol for sleep, but I'm saying that has tended to be how people got past their anxieties, put themselves off to sleep.
Andrew: But that's the good side of alcohol. It wasn't Winston Churchill, it was somebody else that said...who was asked once, "Is alcohol bad? You know, surely, it's bad." And he was saying, "Well, if you mean the alcohol that robs the household of the weekly rent and causes violence and things, well, obviously, that's the bad alcohol. But if you're talking about the social engagement and the salubriants and things like that, well, obviously, that's the good alcohol."
Mark: The snifter brandy or a good cognac.
Andrew: Yes. So, which one are you talking about?
Mark: Yes, which alcohol. But alcohol cannot easily be recommended by doctors. If you go and say, "Go and have a couple of drinks before bed," we all tend to turn our nose up at that. We're after something a little more sophisticated. But alcohol has been the traditional way in which people get over the anxieties that can sometimes lead to sleep changes.
Now, the second thing to say about sleep is, people who suffer insomnia, it's like, are you suffering pain? There's no really good objective measure of insomnia except that the person feels that they're not getting the sleep that they need. The reason I say that is, when people suffer insomnia, they underestimate the amount of sleep that actually happens during the night.
And so, the anxiety and insomnia kind of rolling snowball gathers size and importance in the person's life. And very often, in the early stages, it is possible for some people to simply say, "You are estimating sleep inappropriately," that you are getting more sleep than you think. Because every study done has people estimate their sleep of when they believe they have insomnia around about 60% is what they estimated of the actual sleep they have, when you put the electrodes on and see whether they're asleep.
Andrew: But is this just because people confuse sleep with rest?
Mark: Whatever it is, they're underestimating their sleep.
Mark: Yeah. And so, it is difficult to say to people, if you go and meditate, if you go and put...if you go and do breathing, that is the equivalent of sleep. It's not exactly the equivalent of sleep, but it does the rest, and it does allow people to function for longer periods of time. We'll come onto that with the non-drug approaches to insomnia in just a minute.
But the first thing to say is, often just talking to a person and saying, "You may believe you are getting very little sleep. You're getting more than you think." And the body, unless there is pathology going on… you do have certain types of diseases that do predispose to very, very abbreviated and awful sleep. Even obstructive sleep apnea is one of those, where you can change the sleep pattern and it has nothing to do with anxiety or anything. It has to do with the physics of breathing.
So you do need, as a doctor, to cover those things. Do you have obstructive sleep apnea? I'd think that the OSA testing now is probably… we're leaving that in the past because what we do know about doing the sleep studies is when you take a person and put them in an institution or you put electrodes all over them...
Andrew: It's a special.
Mark: ...whatever you say, that sleep is not the same as the other nights of sleep.
Andrew: No. No.
Mark: Some people in the hospital get their best night, they come back and they say, "That's the first night I've had a decent sleep in years." And other people, it's just distressing. And the interpretation of it is less and less capable of helping us out. So, unless you've got a big guy who's drinking lots of alcohol and you think that they're just not breathing most of the night, severe obstructive sleep apnea still needs to be diagnosed because daytime sleepiness and other consequences arise.
But beyond that, the interpretation of sleep is poorly done by the person who's lacking the sleep. Once you think you're lacking sleep, anxiety builds. As anxiety builds, sleep gets further and further away.
And so, it is one of those automatic functions that when you lose control, there's a total loss of control. And the anxiety that's provoked itself has to be dealt with. And I think that's where you've got a very good early intervention with herbs that can settle anxiety.
Mark: Yes. A herb. You can tell how close I am to herbalism.
But in terms of non-drug approaches that are still pharmacological, magnesium is really, really important. And I think that there's evidence that the magnesium and the threonine, the magnesium threonate as a combination, does a better job of settling that hyper-responsiveness, that heightened super-responsiveness, that alertness of the nervous system, and brings it down. And it settles the muscles, and it does allow for a certain calmness. Epsom salt baths are another very, very popular thing.
Andrew: Yeah. Now, this is something where we get into not just the mineral, the supposed active we talk about, but where the ligand that it's joined to is an important factor in which agent you would choose.
Andrew: You know, if you wanted to choose magnesium oxide, you get to a point where there's a bowel tolerance.
Andrew: You're not going to get much sleep that night.
Mark: Oh, that's cruel.
Andrew: No, that's right. But, you know, then there's the magnesium citrate, the magnesium bisglycinate or diglycinate it's called. But then, obviously, the magnesium threonate.
Andrew: They've each got different sort of niceties to them. And I guess one of my things is, as long as you're not going to have an upset tummy, and my thing that I've learned over years is, smaller doses throughout the day.
Andrew: Not one big dose at night. Don't ask for a heavy hitter. It won't work for you. In smaller doses, it's better.
Mark: People still tend to take their magnesium at night. And so, there is... The psychological side of sleep management is still important. What you do in the evening tends to predispose to better or worse sleep.
So, people who feel that they're in good control of their sleep, it tends to be the nighttime pattern, the nighttime ritual that gets things into a pattern of function. And so, magnesium is typically most of it is taken at night. But I do agree with you. If you're giving magnesium and you want the tissue levels to remain high right through the day, then doing small amounts… people load their magnesium into a bottle of water, carry it with them through the day. Sip that bottle of water all the way through the day.
Andrew: Far better results.
Mark: Yeah. You get far better results, and you get no bowel tolerance issues. However, people still take their dose at night, and it becomes, when do you take you temazepam? You would take it at night. When do you take your magnesium? You take it at night. When do you do your warm shower, your bath, you know... Well, exercise is in fact at the other end of the day. So, the evidence is stronger for it being daytime exercise to exhaust yourself to be ready for the nighttime.
But I think the magnesium... I was impressed by this last year's BioCeuticals conference. All the speakers were honing in on magnesium threonate. And so, I started trying that. I was not a big fan of it because it was expensive, difficult to do, compounded. And things that cost a fortune have a negative impact on people's health and life as well.
But as magnesium threonate becomes more available, I think the opportunity will be there. Because in the past, we prescribed threonine to help do the settling for... So, threonine has the amino acid, and now, the magnesium threonate can combine two good nutrients and give it in a way that may allow for absorption and tissue levels that have a dual action.
Mark: Well, I want to deal with one first, and that is GABA.
Andrew: Right. Okay.
Mark: There is an interesting issue just to be dealt with there, because GABA does not cross the blood-brain barrier.
Mark: However, a lot of people that we see in our practices with illnesses like chronic fatigue syndrome, gastrointestinal disorders, loss of the barrier system around the place, have disrupted blood-brain barriers. And GABA can work very, very well. But it does not work on a... you know, today, you take your dose...
Andrew: But there is also the gut-brain interface.
Mark: Yes. Yeah. And so, the working... Which way are we actually working there? But there is a strange thing about GABA. GABA use, maybe even like a gram or two a day, you can over a period of just a week or so find very significant differences in sleep tendencies.
Now, I am not able to even understand why that happens. But over and over, people and patients say the same thing, "I take the GABA, I take the GABA. Nothing happens for a week or two." And then sleep patterns start to fall back into their normal shape and pattern.
I'm not sure that I understand that. But I'm not against people trying something like that where at least, or in that kind of GABA/glutamate, that kind of...as Henry Oscieki used to say, “the war between the two neurotransmitters.” If it really is that and you can up the GABA availability, the body seems to do something to cut some of that internally, or maybe use this in the external part in the gut or elsewhere managed.
I’m not a big fan of serotonin reuptake inhibitors, but again, we do have things where drugs that bind onto the 5-hydroxytryptamine receptors around the place do have effects on sleep. But they're all very indirect. So, what's the favourite thing of doctors? We'll give a low-dose antidepressant to someone and say, "This might help sleep." We give low-dose antipsychotics. This might help sleep. It does remind me of the days where we had televisions that were made of cathode ray tubes, and they would go on the blink and you would hit them on the left and nothing would happen. Then you'd kick them and nothing would happen. And then you built the antenna area, and it came back to life. It was old. See, there is the method of treatment.
Andrew: But that method of treatment only works if there is enough serotonin in that synapse to be prevented for reuptake, i.e. you've got enough there.
Mark: Right. So, you've got to have...
Andrew: You've got to make enough.
Mark: You've got to have your 5-HTP.
Andrew: So, there comes your 5-HTP, which is your immediate precursor, your 5-hydroxytryptophan rather than 5-hydroxytryptamine which is 5-HT.
Andrew: So, how cautious do we have to be using a substrate like 5-HTP?
Mark: I don't know that we need to be cautious because the alternative is if the person is not sleeping and not functioning. This is, as I said, the whacking the TV on the right-hand side and seeing what happens. So, I'll be truthful. With a lot of sleep treatment, even... I mean, I have a bit of experience in this recently.
Even the best experts in the areas, the psychiatrists will disagree one with another. No two of them agree on exactly which to do. The psychiatrists tend to move more towards the antipsychotics at very low doses. The general practitioners tend to move towards the antidepressants typically, the serotonin reuptake inhibitors at pretty low doses. Everybody's fiddling around on the edges there.
The medical management of it, once you make the benzodiazepines evil, doctors are struggling to find out, "Well, what else do I do?" It's easy for a specialist to say, "You shall not use these things that give symptomatic treatment." But the doctor GP is left with the question, "Well, what do I do to help this person?" And over the last six months, I've been finding out that that is a common problem that people present with, and we really struggle to have a good evidence-based approach to it.
Now, the thing that I think that we could say with the amino acids is, there are people who respond to 5-HTP. There are people who respond to serotonin reuptake inhibitors, but there is no predictability. You cannot talk to the person and ask them questions before that guide you into a better mode of treatment.
And so, we're left still at the moment with a vague thing of, “You suffer from insomnia.” Anxiety is involved. Techniques of going to bed are involved. There's a whole lot of players in that field that separate one person from another. And if we call it, “We're treating insomnia,” then we're not doing what really happens in integrative and in alternative types of medicine.
We're not paying attention to the person and their circumstances. We're saying, "The thing that's wrong is insomnia,” where for some people, it's anxiety. For some people, it is stresses that are in their workplace and should really obviously be dealt with. For some people, it is having a child who's a two-year-old, and then having another one and not getting sleep for very, very obvious reasons.
Mark: And so, separating those into different categories, I think, is the number one thing we do as practitioners. We say, "Can we look for causes? Can we go deeper?" I think that there is a huge proportion of people who are super, super sensitive to environmental effects around them. Put them in the city. And the ambulances and the fire engines that are in the background of their life forever, are always there.
Some of those people respond really well to these new sleep buds. They put things in their ear, and the world disappears a little bit around them, and they've got quiet. In evolutionary terms, we never had cities. We might have had lions and tigers, I mean, all those kind of terrible things. But we didn't have that constant buzz in the background of the world.
And the second thing is...
Andrew: Which is really funny for city dwellers because that constant buzz can sometimes be almost like a security blanket.
Mark: It can be.
Andrew: It’s really interesting.
Mark: It can be that kind of white noise, but there are still... And I hear this all the time. See, "I'm a deep sleeper. I've never heard a siren in my life." But my partner...
Andrew: Shall we make the sound?
Mark: Yeah. My partner does actually hear all of those, and it brings a wakefulness. That's what sirens are for. They're to get you, you know, to pay attention. And so, that heightened sensitivity, what we call central sensory sensitivity...
Andrew: Oh, we could so go off on a tangent here, Mark.
Mark: We could. But that super sensitivity comes up for people who live in particular areas. Interestingly, for many people who live in the city, me included, the country when it goes quiet is horrible.
Andrew: Yeah, yeah.
Mark: There's something missing from my life, and I can't sleep without that white noise.
Andrew: And there's this period of transience where you need to get used to the new environment. People from the country slowly get used to the city noises.
Mark: There are two senses that are really...well, three senses, I'll say. One of them is auditory. So, the city or the country, or whatever the outside environment is, impinges on the hearing of a person and keeps them at that level of wakefulness, which sees them awake multiple times through the night.
The other one is a little bit self-imposed, but in the city, there's always light. And we do ourselves no service by taking screens into our rooms, having television in a bedroom, taking screens into rooms, and having lots of street lights outside that just infiltrates. It's never fully dark in a city. It's really, really hard to do that.
So, some people are very light-sensitive, and some people voluntarily take their screens into their room and spend their nights just before they go to bed, looking at a screen with lots of blue light, and wonder why they're not heading off to sleep straight afterwards.
Some get up in the night and check the stock exchange or check the international trading things, and wonder why they're not sleeping well. And that's because the anxiety of that associated with the light in their room just never lets you get to sleep.
Andrew: So, it's really interesting now that even these blue light devices have got a night shift.
Mark: They've got a night shift. And the question is, is that effective?
Andrew: Well, it's still light.
Mark: It is. And there's still some blue in it. Removing all the blue creates a very poor experience. And as you know from Apple, Google, we all like people to have the good experience of the nice screen that looks just beautiful.
Andrew: I'm laughing here because I am one of these culprits. And I find that one of my rituals to get off to sleep is to watch a few YouTube videos of British comedy or funny dogs jumping into lakes.
Andrew: Bedtime. But my wife hates it. And, you know, even...I think it was two nights ago. She woke me up because she was like, "Oh, can you turn your mobile over?" that sort of thing. I was already asleep.
Mark: Right. So you couldn't turn it over.
Andrew: Yeah, I woke her up by doing... But I just wanted to circle back for a tick. Forgive me for sort of getting off-track a bit, but I think we need to cover it. And that is the old issue with the benzos.
Andrew: Once you've damaged those receptors, can you rejuvenate normal functioning of those receptors, or are you forevermore dysfunctional?
Mark: No, you're not forevermore dysfunctional, but it is a long journey. So, people who are coming off benzodiazepines, it looks like, "Oh, what's the half-life of them?" Six hours, four hours. It should be very easy, shouldn’t it? Because by the time you come to the next night, you've eliminated 80% to 90% of it.
Andrew: That depends if your receptors are there.
Mark: Yeah, but the same goes with alcohol. We clear out alcohol pretty quickly as well. But the impact that it leaves on the brain, on the nervous system afterwards is quite profound, and can eventually lead to... it could cause Wernicke-Korsakoff type syndromes even though the alcohol level at that time is zero.
So, we do have the problem. And I think, now, benzodiazepine withdrawal is seen more as a process of, you stick with the benzodiazepines and you introduce something else. The popular one is CBTI at the moment, but you do something that changes the need for it. And you come down very, very slowly.
So, a typical dosage would be a reduction over, say, three to four months rather than the week or two that you would expect just from the half-life of them. So, that time period often goes to two years for some people as well.
Andrew: Yeah. I'm gonna give a shout-out here to an old podcast I did with a dear pharmacist friend of mine, Greg Mapp, who created a whole clinic indeed. He started a clinic called Mirikai at Burleigh Heads around drug dependency. And this was both prescription and illicit. So, there's two podcasts that I did with Greg Mapp.
Mark: And when you teach a group of doctors, there are no dependencies, these are the new type of drugs, they don't create addiction, you have to be careful how you define addiction. The old ones tended to be very literally addictive, induce enzymes, and you had horrible effects both of taking the drug and of coming off the drug.
Andrew: And then you get a new safe one called zolpidem.
Mark: Yeah. That's right. Every time, the Z drugs.
Andrew: Which, oh… hang on…
Mark: Yeah. So, you're right. Every time we believe the fairy tale, and every time you put a chemical in to change brain function, there are consequences that are unexpected. And there are variations person to person for whom these drugs are just terrible news and it's a bad idea to introduce them. And you can pick that often people who've had a family history of alcoholism, drug dependency, brothers or sisters have drug dependencies, there is something about this dopaminergic effect that you have an effect, then you have indirect effects on dopamine, things are unintended consequences. And it can be as simple as "I really like sleep." That's how the person expresses it. "Therefore, I take this drug."
And when you try and withdraw too quickly, you don't get classic withdrawal effects. You don't get the nausea, vomiting, diarrhoea. You don't get some of the things that you would otherwise get. But what you get is no return to the normal that was the normal before the drug came in. And so, you're asking...
Andrew: Perfect drug.
Mark: Yeah, to put up with the... That's right. The very thing. And I think that I'm cynical. The way that we're moving from the benzodiazepines is they were the old drugs. They're all off patent. There's new ones that are now preserve the sleep cycle, preserve the structure of sleep. We're all very big about, "Oh, we… They were the bad old days.”
Andrew: I love the term "But we now know."
Andrew: Dot, dot, dot.
Mark: We now understand that you need to preserve the sleep structure. And so, the new drugs, the Z drugs come along and we think, "Oh, these will be different." And deep down, they're not. They're just another way of not doing the hard work of non-drug approaches to sleep.
And one part that we're good at in integrative medicine, naturopaths are very good at, is spending the time to find out why. And most doctors don't do that. You know, in 5 or 10 minutes, you can say, "Is work stressful?" "Work is stressful." That is what goes on the notes: work, stress, benzodiazepine, three weeks.
Mark: And then you say, "That thing is handled. If they come back, we'll go deeper."
I think it is useful that we have this thing called CBTI, cognitive-behavioural therapies for insomnia. But when you go back on the history of CBTI, it's a committee that's made the decision of, "Here's the little bits of evidence that we have that sleep deprivation may work, that going back, having a habit forming that the bedroom is only used for sleep." There are a bunch of components to CBTI which every little bit has got its own little bit of evidence, and then you whack it together in a committee and say, "Why don't we do all of this?"
And I have not yet found one patient in my practice who has responded well to CBTI, which is delivered in the way that it... the so-called protocol for it is done. Everyone has to vary it. Some people become very anxious about the deprivation that's required. You actually reduce your sleep hours intentionally. And for people who get anxiety about those effects, it just worsens sleep. It doesn't improve it.
So, what I've found is, CBTI's usefulness is, here's half a dozen things called CBTI and a practitioner who understands sleep. And if you choose carefully from the little half dozen things that are meant to be done there, then you can find a way back to sleep with the help of that practitioner.
Now, as you and I both know, there is thing called a placebo effect. And the placebo effect depends not on what the patient believes, but what the practitioner believes and how much the patient trusts the practitioner. And so, the concept of a placebo effect is, Western medicine is the greatest placebo of all time. Doctors passionately believe that we are the only scientifically-based group of people who know what we're really doing. We believe passionately.
A friend of mine said many years ago, "Bugger evidence-based medicine. Penicillin used to work for viral sore throats brilliantly." And once you know it doesn't work, you can't do that. And he published a paper in the MJA that penicillin should be considered a placebo that works for all kinds of sore throats as long as the doctor believes in it. The same thing goes for sleep therapies. If the doctor is not confident, if the practitioner is not confident about what they're doing, that lack of confidence is conveyed to the patient...the patient, the client or the non-sleeper.
So, one thing to be clear about is, confidence of the practitioner that they've got tools that can help and that they will put them together in an individual way is the number one most important thing for the non-sleeping person. If they know that person will work through stuff with them rather than, "Here's the next pill. Here's the next pill. Here's the next pill." I know it's possible and very simple for you to end up with four different doctors, four different treatments, three incompatible drugs, and then be expected to sleep. And some people still do.
Andrew: You do raise a very interesting question there, though, with regards to that placebo effect. And that is, should the practitioner be allowed to prescribe a placebo? In the olden, olden, olden days of pharmacy, you would see a script coming across saying, "Tinct aqua."
Mark: Did you?
Andrew: Which is water.
Andrew: You would see a patient come in, saying, "The doctor has given me a script for a draught." What was this draught? And those days are gone because we're now clouded by litigious...
Mark: I don't know that they're gone. When the doctor gives a script for a serotonin reuptake inhibitor for reactive depression, that is a placebo. It doesn't work. It's not anything better than placebo. What we've now found is temazepam for sleep, even in acute stages, doesn't work better than placebo. We think we're prescribing actives, but what's actually happening is, the majority of the benefit is coming from...
Andrew: Can you just say that again? Temazepam when prescribed for?
Mark: For acute and chronic sleep disorders works no better than placebo. So, we know that it induces sleep, but we as doctors should be not surprised by the fact that we believe things to be true. We've been through it a hundred times with penicillin for sore throats, that when we believe something, we convey confidence to a person.
The person has the confidence that they say, "My practitioner is looking after me." And when you take that out of the equation, then two things are clear. For reactive depression, the common types of depression which is anxious depression, there is no antidepressant effect of antidepressants. It works in severe depression, endogenous depression that we used to call it. Definitely works in those cases, which is where the trials are done.
But when you come down to reactive depression, grieving, all the common reasons that people are stressed, antidepressants, the whole story of “you don't have enough serotonin,” is absolute BS.
Andrew: That raises massive questions on drug research.
Mark: It does. It does, but it's happened all the way since drugs were first produced. And so, what drug companies will do is they'll find a disease, and they aim a treatment for that disease. They look for something that will change a receptor. And then when it comes down to it, they choose the worst possible case of heart disease with cholesterol inhibitors. They choose people who've had a heart attack highly likely to have the next one. And then apply it to everybody who's got a raised cholesterol.
So, the problem that we have in medicine is, we want drug trials to be cost-effective. So, we choose worst-case scenarios, see that something works in those occasions. Severe insomnia that people are going crazy over, you can put a person to sleep with a sufficient dose of temazepam. That's true. But when it comes to day-to-day use of temazepam, it doesn't prove better than placebo.
And so, that's part of the reason why there's a move away from the benzodiazepines that they do a job, the long-term consequences of which you pay for, all the benzodiazepines over many years for millions of people.
And when it comes time to stop it, you cannot stop that from going on. So, create a problem by the use of the benzodiazepines, but you don't solve that problem because now you've got to have something else to get you out of the insomnia that's going to happen when you withdraw from that.
Andrew: But it's now used for insomnia. And I wonder about the formulation that's approved on the Australian PBS, Pharmaceutical Benefits Scheme. I question it.
Mark: You mean the melatonin that's available on prescription in pharmacies?
Andrew: Yeah. So, in Australia, it's called Circadin. And it's a controlled release formula. Right?
Andrew: How does that mimic natural melatonin release?
Mark: It doesn't. We have a cycle, and every practitioner knows this. There is a dance between melatonin and cortisol, alright? That dance between melatonin and cortisol is an intimate two-way feedback response. The melatonin rises and then falls in the early hours of the morning, and supposedly, the light is the discriminating agent there. And as a result, cortisol rises. And the dance between the two is: as one rises, the other one falls.
We have this concept of stress as disturbing the circadian rhythm of the adrenal glands, but you can disturb that circadian rhythm by disturbing melatonin. I'm not sure that measuring melatonin is all that useful, but a loss of diurnal cycle sees one very clear thing, and that is, you lose the diurnal cortisol. You don't have the peak in the morning and the trough in the afternoon. You can have inversions of that, in fact, where normal levels for morning are about 350 to 400, and normal levels for the afternoon about a half to a third of that. You can have it go the other way, and there is no way that person has a normal sleep cycle. So, if you're being very literal, you'd say, "I'll just give you cortisol in the morning."
It doesn't work out all that well to give prednisone to people for the next 25 years of their life because we do damage their bones and we do damage just about everything else. So, melatonin has become the control, the kind of...the neurobiological controller. And we dump melatonin in there.
Now, for some people, they take melatonin drops, and it gets them off to sleep. But the thing about melatonin is, it doesn't have an effect on the sleep of the night that you're about to take it. It can reset the cycle, help you reset for London or New York time or something else if you're taking it the future time zone. But after a short period of time of people improving their sleep on melatonin, they think of it like they think of temazepam, and it works.
And that's the real pain that if they get a Circadin script or if they get a melatonin script, once the body has got a bit of a hint that the diurnal circadian rhythm of melatonin and cortisol works, it's the placebo effect. On the end, they just take their melatonin on the nights that they feel, "Oh, I'm going to have a tough night." And it relaxes them, and it allows them to feel that they're under some control.
And this is a real problem for me. When people say, "I don't take melatonin all that much, but on nights where I know I’m going to have a bad sleep, I just dump a lot of it in one night." And I'm caught saying...
Mark: Yeah. And I'm at the point where I'm about to say, "Well, that's not how it works." And then I think, "Well, hang on. It is working." If melatonin has harm to do by doing it in that way, then I'm unaware of it at the moment. People do end up taking melatonin as if it were a benzodiazepine, and they get an outcome. They take temazepam and get an outcome. It doesn't mean that what we're doing is the right thing. It means that we're tricking the body into, "Hey. Guess what? It's sleep time and you can relax because you've got something now to support you in your sleep."
And I think that comes back to the next thing that we have to deal with is, a kind of regimen at night without it being too tightly controlled, without it being fearfully controlled. "Oh, if I miss my tablet by a minute, I'm in trouble." An evening regimen of...I've exercised through the day, I've expended energy, I have a pattern which is, when do you have your meal, when do you start to wind down for bed, where do you put your devices around the place? Even if you're on medications, taking them at a similar time each night, that pattern convinces the body that sleep is back under control.
And so, reestablishing a sleep cycle is often nothing more than establishing a pattern in the evening of a warm shower, of meditation, of doing breathing, of the four in hold, four out hold. There's something about patterns that remind you of the time to sleep, that induce the body to fall asleep. And there's something about anxiety of missing some part of that protocol that often keeps people awake. They remember, as they're about to fall asleep, "Oh, I didn't take my melatonin." And they probably become super anxious about it and can't fall asleep without going down and getting their melatonin.
Andrew: So, I wanted to give another shout-out. I mean, you admit freely that herbs are not your forte. So, Norelle Hentschel and I did a couple of podcasts on sleep hygiene. So, again, listeners, if you want to look her up, you can learn more about sleep hygiene there.
Mark, I did want to just ask about things like... You know, we've spoken about the long game. Nutrients, particularly, magnesium does not necessarily work for that night. Melatonin does not necessarily work for that night. Same with HTP. So, we need to be really reinforcing that this is a longer-term strategy.
Mark: That's exactly right.
Mark: I don't know. I think... Well, the reason I don't use it is, I haven't thought of it until you just told me. Let's be honest.
Andrew: So, 400 to 600 milligrams per day...
Mark: Of phosphatidylserine.
Andrew: Divided doses, with meals always, and never at night.
Andrew: Because you'll get wired. But yeah. I mean, it's mainly used with athletes to decrease cortisol.
Andrew: But if cortisol is the issue...
Mark: Well, cortisol is the issue, but cortisol is usually… it's the loss of diurnal variation. So, the ones where you can predict that melatonin will work very well… when morning cortisol is, say, 180 to 200, way below where you would think of a normal one, and the afternoon is 220 or 30, then you know that reestablishing a cycle and trying to bring the cortisol up [is the focus].
And I will tell you, melatonin of any type, the Circadin or the sustained release or the rapid release, you can within a four-week period have cortisol levels that have got that 2:1 ratio morning to afternoon by tricking the body with the melatonin.
You can also do it with bright light therapy. Right? So, getting people so that they wake up at a particular time each day. They set the alarm and they get the right light…
Andrew: With bright light. The RAS.
Andrew: Reticular activating system. Yeah?
Mark: That's right. And so, there is that rapid melatonin decline, which is just a signal going on inside the body. "Wake up time. There's the sunlight. Time to get moving again."
There are also some people for whom the normal sleep pattern is you go to bed at 1 a.m. and you wake up at 10 or 11 a.m. And we call those people, children. And teenagers specifically, we have a whole problem with sleep disorders that we are putting teenagers through high stresses of, say, high school certificate and other exams where their future life is dependent on it. And then wanting them to be there at 7 in the morning and going to bed at the wrong time.
The natural circadian rhythm for a teenager is very different to a 60-year-old teacher who really needs to get their early night's sleep. The natural rhythm is that they will be awake at around about 10, 11 in the morning. And there's lots of people in education now talking about schools where you match it, not to when mum and dad have to go to work in the morning and then come home at night...
Andrew: Which is going to cause all sorts of problems.
Mark: It's going to cause problems, but it is true that their cycle is different. Matching it to the person's cycle is what we're really needing.
Andrew: Take us through the hallmarks of this, why it's so good.
Mark: CBTI works when people do not become too obsessed about every last detail and when they work with a practitioner who is well-trained in CBTI. I am not the world's number one fan of cognitive-behavioural therapies, but putting a pattern and a structure to what you do to allow yourself to get to sleep, turning the bedroom into a place where you only sleep: you don't go there for other things. You don't read books and things. You stay out of the bedroom until it's sleep time. You distress the body a little way shortening sleep hours so that the person is wanting to get to sleep. A really important part is expending energy in the early part of the day.
Mark: Getting to do your exercise, moving the muscles, convincing the body that the daytime is the daytime. People go into their shell when they have insomnia and think, "Oh, I better rest all the time." That's the worst thing for the mind when it's looking for, "When do I actually sleep?"
So, CBTI provides structure and framework. It provides a protocol that people can trust. The magnesium threonates and providing adequate nutrient availability, getting the gut functioning well, also settles sleep. And I should mention, this thing that you probably haven't heard of called stewed apple, probiotics and Saccharomyces. I don't think I've ever mentioned that before.
Andrew: We’ll put that recipe up on the website again.
Mark: But you would be surprised how many people... I did not even pay attention to sleep. They come back and say, "My gut is better, and weirdly, I'm sleeping better." Whether or not they've solved their other problems, often pain and the like, if you work via the gut and get a really good functional gut, it's surprising how capable that is of organising a sleep-wake cycle.
Beyond that, what do we do? It tends to be, well, yoga, meditation, breath. Getting cycles back in the body where the body gets confident about holding its own cycles together so that there is tiredness at the end of the day. Food that is nutritious but not excessive.
And then a pattern of maybe breath work, yoga, mindfulness, depends on what the person needs. Or even a hobby, something that they just love to do. And then taking out all of the lights...
Andrew: So, reward.
Mark: Yeah, a reward.
Andrew: Reward system.
Mark: And at the end of the day, at the end of another fulfilling day, sleep is returning not because we have brutally beaten the person into a sleepful mode, but because there's a tiredness and exhaustion which is useful at the end of that day. And that's how we can guide them as practitioners.
Our confidence makes a big difference to the person in front of us. And when we just go back for, "Here's a pill, here's a pill, here's a pill. Oh, I don't know why it's not working," that loses the confidence of the person. So, I think people have their insomnia managed best by a practitioner who's confident that their techniques can add something to their quality of sleep.
Andrew: I think the days of the "magic pill" might work in a short-term treatment plan, if you like, but only when...
Mark: Do work in a short term.
Andrew: ...used with a long-term framework, which includes lifestyle issues. And I think that's where we're going.
Mark: Yes. And time with the person is important. Their ability to tell you why they're not sleeping and for you to listen as a practitioner, half the time, gives you the very answer that you need. What needs to be fixed for that person is bloody obvious if you have the time to listen.
Mark: It's been a pleasure again. It always is, Andrew.
Andrew: This is FX Medicine. I'm Andrew Whitfield-Cook.