Non controlled sleep options?
Started by lockian
There’s not that many you have: trazodone, doxepin, seroquel, TCA, remeron, clonidine, vistaril, maybe I’m missing some?
Sleep hygiene is all well and good, but have you done a sleep diary or tried sleep restriction? The cruel irony is that many people with primary insomnia appear to genuinely need less than 8 hours of sleep per night but are very anxious about the fact that they are not able to achieve this.
Am certainly trying this too.
Probably olanzapine short term if you really need a big gun.
So I am curious - if it is to the point that you are seriously considering Zyprexa and diabetes as preferable to the sleep problem, why the reluctance re: controlled substances?
Also, what's the ESS?
The "exant" meds are schedule IV but there have been no recorded cases of dependence/addiction.
Also Ramelteon is a great med when it works.
Also Ramelteon is a great med when it works.
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Can you expound on what this means a bit? Specifically what you mean about aligning with sleep in depression?
Yes, there is a great deal of evidence that a misalignment between the circadian drive and sleep drive correlates with depression. This is one reason sleep restriction works. Not just increasing the sleep pressure of the homeostatic drive, but pushing back the circadian phase a notch such that both drives peak at close to the same time. We know that increasing sleep drive also can impact the circadian system as well.
This misalignment may be why those with depression have REM onset abnormalities. Lithium has circadian effects as well and this is hypothesized to be one of the mechanisms by which it treats depression. Recall sleep restriction is in itself helpful for depression.
Ultradian refers to manipulation of the NREM and REM sleep cycles. It is probably the next target of treatment in insomnia. Buy the stock early if you can.
Seriously, read Lewy's work on phase angle delay. Good stuff.
This misalignment may be why those with depression have REM onset abnormalities. Lithium has circadian effects as well and this is hypothesized to be one of the mechanisms by which it treats depression. Recall sleep restriction is in itself helpful for depression.
Ultradian refers to manipulation of the NREM and REM sleep cycles. It is probably the next target of treatment in insomnia. Buy the stock early if you can.
Seriously, read Lewy's work on phase angle delay. Good stuff.
Documented history of substance use disorder and controlled medication misuse.
I've always been curious - I know carbamazepine interacts with adenosine receptors and it's been speculated that this is why it can be sedating. Has anyone in the sleep literature ever looked at this agent in particular and its circadian consequences (as has been done for lithium etc)?
I would imagine it’s like the inverse of caffeine and adenosine. But there’s an interesting line of research with the interaction of ictal events and sleep wake cycles; and anticonvulsants as a moderator.
But carbamazepine interacts with everything, so…
Its action seems to be selective to different receptor subtypes and more complicated than just an agonist (i.e. inverse of caffeine) so I am not sure we can reason well a priori about this. Also will need to look into whether Trileptal has the same interactions; if it doesn't it might be a reason why it seems to have much less efficacy for bipolar d/o than Tegretol. But yes, carbamazepine manages to interact meaningfully with itself, among other things ...
The american academy of sleep guidelines on treating insomnia basically is summarized as "we dont really know what to tell you but its possible belsomra, ambien, etc works". Referring to someone to sleep medicine, my experience has been they really tend to just focus on cpap, ive yet to see one offer any advice on sleep medications.
What i use the most of would be trazodone, ramelteon, doxepin depending on the patient. On occasion gabapentin or vistaril. If depression/anxiety is a factor and i dont have to worry about weight gain then im not opposed to remeron. I generally try to avoid seroquel for sleep. Maybe ill start considering belsomra for some people.
What i use the most of would be trazodone, ramelteon, doxepin depending on the patient. On occasion gabapentin or vistaril. If depression/anxiety is a factor and i dont have to worry about weight gain then im not opposed to remeron. I generally try to avoid seroquel for sleep. Maybe ill start considering belsomra for some people.
My thoughts exactly.. AASM guidelines are basically crap. Also at least around me insurance doesn't tend to pay for ramelteon unless patient has tried ambien, sometimes also lunesta. I advise patients to try OTC stuff first. Also if they just sit around the house and do nothing all day - forget it, no medication is gonna fix their sleep-wake cycle
There is also some evidence that a weekend camping has a strong effect on disturbances in circadian rhythm. You can offer that evidence to people. Some really like it. Most won't do it.
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Underrated. Do something meaningful and effortful with your life.
I want to make sure I understand things properly- I am a first year psych resident. All the meds you listed, with the exception of clonidine, block CNS histamine receptors, correct?
So nearly all of our non-controlled sleep meds are antihistaminergic and variation in pt response probably has to do with variations in absorption/metabolism?
Additional non-controlled insomnia options that I am aware of that I haven't seen listed yet include the orexin antagonists and CBT-I, though neither seem to be accessible for most people.
Naw. There are melatonin receptor agonists, such as melatonin and ramelton. There are BZ like agents, which are all controlled. There are histamine agents like doxepin, mirtazapine, Benadryl, valerian tea, and some of the antipsychotics. There are orexin receptor antagonists like suvorexant, lemborexant, and most recently dardorexant. Then there are behavioral interventions like CBT-I, sleep hygiene training, and less common ones (e.g., camping, pulling a Forest Gump and running until you drop).
Yes you are correct that these are histaminergic antagonists but that doesn’t mean much because even though they share that one receptor in common they have several receptors that are different that may be contributing to efficacy, this is why you can see someone respond well to Benadryl then not to vistaril or seroquel but not Zyprexa, etc
To quote myself from a similar thread:
Melatonin: First line with great risk:reward ratio, often at least partially effective, and incredibly safe and virtually impossible to overdose on (therapuetic index >>10,000). Slightly finicky to use because of chronotropic effects, so I typically use scheduled rather than PRN. Sometimes use ramelteon but usually due to insurance/cost issues
Sympatholytics: Very effective, especially when etiology of insomnia is hyperarousal (e.g. anxiety, PTSD), usually well tolerated but effects on BP can be limiting in elderly. Alpha-1 antagonism (i.e. prazosin) is most within the beaten path, alpha-2 agonism (e.g. clonidine, guanfacine) seems to be more powerful and treats some non-psychiatric contributors to insomnia (e.g. pain). Use beta-blockers (e.g. propranolol) less frequently, but they are also option.
Antihistamines: Other mainstay, usually effective and well tolerated, have added benefit of being easy to also use as PRNs for anxiety. Need to be wary of anticholinergic effects. My other concern with them is that most have very long half-lives, which means that daytime side effects are more likely as is development of tolerance, e.g. one dose of mirtazapine 15 mg will have enough H1 occupancy for continuous soporific effect for days and days.
Anticholinergics: Sometimes in select patients (i.e. young), in large part because diphenhydramine has one of the shorter half lives among antihistamines.
5-HT2 Antagonists: There aren't any "pure" 5HT2 antagonists as far as I'm aware. For example, trazodone also is avid for alpha-1, and to a lesser degree H1. Cyproheptadine is a much, much more potent 5-HT2 antagonist but is also a very, very avid H1 antagonist, and has the same order of magnitude Ki for muscarininc receptors as 5HT2. Notably, they both have ~8 hour half life which is a point in their favor. I use trazodone quit a bit with good efficacy and tolerability (usually start at 25-50 mg and titrate to effect). Cyproheptadine should be great for sleep but I haven't really used it much at all.
Orexin antagonists: Have considered multiple times but ultimately cost is prohibitive.
Misc: Gabapentin and D2 antagonists can be useful for sedating effects, although risk:reward is usually less favorable
Melatonin: First line with great risk:reward ratio, often at least partially effective, and incredibly safe and virtually impossible to overdose on (therapuetic index >>10,000). Slightly finicky to use because of chronotropic effects, so I typically use scheduled rather than PRN. Sometimes use ramelteon but usually due to insurance/cost issues
Sympatholytics: Very effective, especially when etiology of insomnia is hyperarousal (e.g. anxiety, PTSD), usually well tolerated but effects on BP can be limiting in elderly. Alpha-1 antagonism (i.e. prazosin) is most within the beaten path, alpha-2 agonism (e.g. clonidine, guanfacine) seems to be more powerful and treats some non-psychiatric contributors to insomnia (e.g. pain). Use beta-blockers (e.g. propranolol) less frequently, but they are also option.
Antihistamines: Other mainstay, usually effective and well tolerated, have added benefit of being easy to also use as PRNs for anxiety. Need to be wary of anticholinergic effects. My other concern with them is that most have very long half-lives, which means that daytime side effects are more likely as is development of tolerance, e.g. one dose of mirtazapine 15 mg will have enough H1 occupancy for continuous soporific effect for days and days.
Anticholinergics: Sometimes in select patients (i.e. young), in large part because diphenhydramine has one of the shorter half lives among antihistamines.
5-HT2 Antagonists: There aren't any "pure" 5HT2 antagonists as far as I'm aware. For example, trazodone also is avid for alpha-1, and to a lesser degree H1. Cyproheptadine is a much, much more potent 5-HT2 antagonist but is also a very, very avid H1 antagonist, and has the same order of magnitude Ki for muscarininc receptors as 5HT2. Notably, they both have ~8 hour half life which is a point in their favor. I use trazodone quit a bit with good efficacy and tolerability (usually start at 25-50 mg and titrate to effect). Cyproheptadine should be great for sleep but I haven't really used it much at all.
Orexin antagonists: Have considered multiple times but ultimately cost is prohibitive.
Misc: Gabapentin and D2 antagonists can be useful for sedating effects, although risk:reward is usually less favorable
Cyproheptadine is a fine medication for sleep in children, however it needs to be used for patients that want to gain weight (e.g. psychostimulant induced anorexia, ARFID or ARFID ish kids, chronically ill children - has research in CF for this). Appetite stimulation is not otherworldly like Zyprexa/Clozapine but is noticeable.
Orexin antagonists are definitely worth knowing about for patients with good insurance and of course for when they eventually become generic, risk/benefit profile seems favorable compared to many options used presently.
I have a handful of adult patients on cyproheptadine for this very reason. Histories of restricting EDs, terrified of falling back into bad habits, but chronically struggling to eat under anything less than optimal conditions. Mostly effective so far in maintaining healthy weight ranges when it doesn't just put them to sleep.
Isn't cyproheptadine also useful in SSRI induced anorgasmia?
yes
I honestly so far have gotten the best results with sildenafil/tadalafil, men and women both.
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Do they help with anorgasmia in addition to ED?
Yes, hence why I have prescribed them to biologically female people.
EDIT: I should say that the speculation is that this still largely works via increased genital congestion.
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Yeah best evidence in men and women too, recent Carlat podcast about this.
Is that on App Store?
They work with all phases of the sexual response cycle in all genders, except for the subset of people they don't work for.
