There's so much anecdotal evidence out there that Mirtazapine at 30mg and above can be extremely stimulating and even cause insomnia, that I don't think we can honestly say "it's not less sedating at higher doses". Being on 30mg, for me, was a completely different experience to being on 15mg - the polar opposite in fact. And this seems to be incredibly common. Why there's no imperical evidence to support something that's such a common experience seems very strange. A similar issue is the common claim that Mirtazapine doesn't blunt emotions for many people like SSRIs and SNRIs are known to do. Again, the imperical evidence isn't there, but when you start talking to people about their experiences you'll find dulling of emotions is extremely prevailant with this drug. There are even videos on TH-cam of doctors claiming, that unlike SSRIs, the mechanism of Mirtazapine doesn't cause a loss of emotions and/or sex-drive. I personally think this is just theoretical and the research simply hasn't been done.
I was prescribed mirtazapine on Monday. I have chronic anxiety, insomnia, pain & RLS. The next day, after a reasonable night’s sleep, I actually felt different. The day after, I was feeling almost a bit more relaxed & today, I feel more improvement. I am 72 & existing, not living, for the past 2 - 3 years. I have little faith in doctors & do not like taking meds. The doctor I saw was a general family consultant here in Spain. He is the 1st doctor who has actually listened to me & not sat in front of a screen, typing away. I now feel that there is a possibility to recover from the awful place I am in. I have hope.
And if somebody is moving from 15mg to 30mg their H1 receptors have probably already greatly desensitized. So it appears the higher doses are less sedating
As a patient with bipolar disorder who has taken Quetiapine (for a year+), would you say that Mirtazapine has quite a similar profile when it comes to the experienced effect? (due to high H1 affinity (sedation & weight gain / metabolic effects, insomnia treatment starting from lower doses), anti-depressant / serotonergic effects at higher doses, anxiolytic effects, possible cardiac/QT side effects, increases liver enzymes, etc. For someone who had little luck with Quetiapine (due to insufficient anti-depressant efficacy, and dropout due to weight gain and sedation side effets (esp daytime & difficulty waking up) + building tolerance to the sleep-promoting effect over time, + concerns over liver issues (having developed steatosis from the weight gain)), Mirtazapine doesn't look like it would be a much different experience no? Thank you for these videos, always educational for me as a patient.
Not medical advice.. no, surprisingly they’re much different. Mirtaz offers no protection in mania, and is actually problematic at non low doses. My intuition would’ve guessed mirtaz would be good in bipolar, but it’s not. If you’re looking for a helpful read on bipolar meds check out the CANMAT guidelines for bipolar. Has great tables.
@@PsychoFarm A subset of patients with non-clinically relevant hypomania could see high doses of Mirtazapine less sedating due to genetic sensitivity to alpha 2? High clinical doses could potentially have altered pharmacodynamics, we do not know what these are outside of the studied ranges. While using the lens of sequential binding it checks out that moving from the normal dosage ranges to the high dose ranges might erroneously lead people to the assumption Mirtazapine is less sedating at these high dosage ranges. We actually just don't know because we haven't tested it nor would we due to the increased dropout rate of the normal clinical population. Yet it is possible there is a small subset of the clinical population that tolerates higher doses both in the side effects whilst receiving more activation via alpha 2 and increased efficacy of antidepressants reducing psychomotor slowing. Clinical wisdom does show that some people simply need higher doses for some medications again here altered pharmacodynamics could lead to differed outcomes.
I take Guanfacine and Bupropion.my nurse suggested Mitrazapine for my insomnia at 7.5mg, now seeing that it is an a2 antagonist could it make Guanfacine less effective? I hope thats not the case because Guanfacine has been a life changer
Not trying to troll, but have you reflected on the truth and value of receptor theory? This channel seems to go quite hard, in the spirit of Stahl. As a purely clinical psychiatrist I have started to view pharmacodynamics as mainly a way to "professionalize" our niche of the medical field, without actually being that usefull in daily practice. I care about outcomes, not receptors. My knowledge of the differences in receptor profiles has probably never benefited my patients apart from avoiding side effects (anticholinergics etc). The only thing it really has done is give me a way to sound smart. Regarding actual psychiatric treatment effect nothing is gained from knowing what 5-HT receptor subtype or even which monoamine a particular drug targets. I would love to be proven wrong.
Regarding your last line, as a pharmacist, I care a lot about such things because that's where my drug interactions come in. Mirtazepine in particular may find a niche in older patients more likely to suffer from insomnia and weight loss, and this patient population also tends to have complex medication lists that have to be sorted through. I think there's value in being able to give some weight to certain side effects that may appear on the surface to add up or to cancel each other out, when in reality, we end up seeing one drug's effect predominate. I take your overall point that you could just shortcut the thinking and look at the patient's individual outcomes, but in terms of coming up with that initial plan or when trying to optimize therapy, some knowledge here is beneficial, even if ultimately, you're simply going to listen to your patient and adjust accordingly.
Yes, I have thought a lot about it. It's suprising to hear I go hard into the neurobiology, when I think I'm pretty strongly less in the biological camp compared to colleagues. I also have videos based more on cognitive psych and psychoanalytic thought. Like every lens to view a patient, I think it's important to learn it well, learn the limitations, and then move on. I think with every one of my videos, any sort of education on receptors is directly linked to a clinical aspect of the medication. I like to imagine that if my videos have done anything, I hope that they have led to people using more appropriate dosing (lower doses), and also to dose appropriately to different indications. The receptor model provides a useful framework for why that would be. I also think I instill in these videos a pretty heavy dose of skepticism about our models. Maybe not on this one in particular, but in others, I do. I'd argue my knowledge of receptors has benefited patients. I dose SSRIs lower than colleagues. I dose anti-psychotics more appropriately relative to colleagues. I avoid under-dosing medications for certain indications (like thinking trazodone 50 mg or mirtazapine 3.75 will help their depression). I avoid putting patients on medications that aren't appropriate. I get less excited about newer medications with good marketing. I don't naively think simplified things like 5-HT7 will make my patient a cognitive wizard. I never try to sound smart with my patients. Any sort of thoughts of receptors or dosing is done in the background, and only the clinical expectations is communicated. I get incredibly annoyed when I see a psych trying to sound smart to a patietn with receptor hand-waving. I think me and Stahl are quite different. He acts as if what he's presenting is factual, and markets new brand name drugs. Meanwhile, I'm pushing for under-utilized medications, or teaching about commonly used medications used inappropriately. Also he took 7 million in industry funding last year, whereas I'm behind on rent.
@PsychoFarm Thank you for this thoughtful answer. I believe that the question about correct dosing is distinct from receptor pharmacology. One can know that most common antidepressants usually have their best effects at lower dose intervals, considering all factors. I think we fully agree here. However, this belief is based on actual data about outcomes rather than theoretical or hypothetical understandings of receptor affinities. Also, I want to make it clear that I never try to sound smart in front of patients in this regard. But, I admit I have used pharmacology to appear knowledgeable when addressing younger colleagues. I'm working on avoiding this behavior. Regarding patients, I often find a need to downplay ideas about 'low serotonin' and similar concepts, since at least where I work, it's quite common for patients to have these elaborate conceptions. I think they express a genuine desire to make sense of something that is very hard to understand, so I would of course never hold it against them. Yes, I'm aware that you have a different focus in other videos. Thanks again for your thoughts. Much appreciated.
@kma3647 I do agree that some knowledge is important, particularly when considering side effects. However, for interactions, I don’t think I could ever reason my way to an understanding based solely on receptor affinity or chemical structure. For instance, why does escitalopram create somewhat dangerous interactions with some PPI drugs, while sertraline or fluoxetine apparently does not? I get a bit disillusioned by the fact that I can’t really predict treatment effects, only side effects. Whether the drug works as intended (and this is most apparent in treating depression) seems like a roll of the dice.
@@broken-dimension-remind "For instance, why does escitalopram create somewhat dangerous interactions with some PPI drugs, while sertraline or fluoxetine apparently does not?" I guess what's confusing here is that you're asking why you can't deduce a PK interaction from a pharmacodynamic standpoint. Sertraline, Fluoxetine, and Escitalopram all have their minimum effective on depression dose when they block 80% of SERT, irrespective of the milligram amounts. This isn't a coincidence, it's entirely to due with their interaction with the receptor in question, SERT. There's a reason you're not using 5 mg of zoloft or 50 mg of lexapro. You probably don't even think about the fact that you're restricted to using very small ranges of medications. "Whether the drug works as intended (and this is most apparent in treating depression) seems like a roll of the dice." Can't predict treatment effects? Huh? You can't predict exactly how someone will respond, or which they'll respond most to. But you can make major predictions depending on the medication. You seem to be taking "we don't know excatly what will happen" and turning it into: "Let's throw the whole paradigm out".
This is from Google; Can mirtazapine cause chronic fatigue? It's interesting to note that mirtazapine may cause 'sleep disorders', with fatigue also being a common side effect. While mirtazapine may help you to sleep better while you're taking it, it's well recognised that insomnia can develop after stopping taking the drug. My Question; Hey, sry to ask This here but i need help, i took mirtazapine for 2 months 30mg Then did the stupidity to stop abruptly, which medication can i take to reverse that fatigue effect? Plz anything would help, please answer freely, i promise to ask My doctor first
The idea that Mirtazapine has value for treating meth addiction is just mind-boggling to me. That such a strong sedative could help cravings for one of the strongest stimulants known just feels completely counterintuitive to me. At least based on the substitution model of opioid addiction treatment with mu agonists, I would have expected only something like modafinil or pitolisant to have any value. Almost reminds me of how thiazide diuretics are used to treat nephrogenic diabetes insipidus or how ativan works for catatonia.
H1 blockade is going to attenuate dopamine release and reduce drug-seeking behaviour? Modafinil also is proposed to work via H1agonist, DAT and orexin agent. Here is it working as a weak substitute as opposed to a dopamine blocker
Been on it 25 years. 15 mg . But… I want off. Heard it’s going to be hard very hard as TH-camrs have mentioned. I bought a scale that will weigh out in 10 % A month increments for reducing. I originally went on it for. Depression. Absolutely no weight gain
There's so much anecdotal evidence out there that Mirtazapine at 30mg and above can be extremely stimulating and even cause insomnia, that I don't think we can honestly say "it's not less sedating at higher doses". Being on 30mg, for me, was a completely different experience to being on 15mg - the polar opposite in fact. And this seems to be incredibly common. Why there's no imperical evidence to support something that's such a common experience seems very strange. A similar issue is the common claim that Mirtazapine doesn't blunt emotions for many people like SSRIs and SNRIs are known to do. Again, the imperical evidence isn't there, but when you start talking to people about their experiences you'll find dulling of emotions is extremely prevailant with this drug. There are even videos on TH-cam of doctors claiming, that unlike SSRIs, the mechanism of Mirtazapine doesn't cause a loss of emotions and/or sex-drive. I personally think this is just theoretical and the research simply hasn't been done.
I was prescribed mirtazapine on Monday. I have chronic anxiety, insomnia, pain & RLS. The next day, after a reasonable night’s sleep, I actually felt different. The day after, I was feeling almost a bit more relaxed & today, I feel more improvement. I am 72 & existing, not living, for the past 2 - 3 years. I have little faith in doctors & do not like taking meds.
The doctor I saw was a general family consultant here in Spain. He is the 1st doctor who has actually listened to me & not sat in front of a screen, typing away. I now feel that there is a possibility to recover from the awful place I am in.
I have hope.
Keep us posted. I think you'll find it a big help
And if somebody is moving from 15mg to 30mg their H1 receptors have probably already greatly desensitized. So it appears the higher doses are less sedating
Congratulations on your work! Keep it up!
If possible, post more videos on cognitive/ psychoanalytical models.
As a patient with bipolar disorder who has taken Quetiapine (for a year+), would you say that Mirtazapine has quite a similar profile when it comes to the experienced effect? (due to high H1 affinity (sedation & weight gain / metabolic effects, insomnia treatment starting from lower doses), anti-depressant / serotonergic effects at higher doses, anxiolytic effects, possible cardiac/QT side effects, increases liver enzymes, etc.
For someone who had little luck with Quetiapine (due to insufficient anti-depressant efficacy, and dropout due to weight gain and sedation side effets (esp daytime & difficulty waking up) + building tolerance to the sleep-promoting effect over time, + concerns over liver issues (having developed steatosis from the weight gain)), Mirtazapine doesn't look like it would be a much different experience no?
Thank you for these videos, always educational for me as a patient.
Not medical advice.. no, surprisingly they’re much different. Mirtaz offers no protection in mania, and is actually problematic at non low doses. My intuition would’ve guessed mirtaz would be good in bipolar, but it’s not. If you’re looking for a helpful read on bipolar meds check out the CANMAT guidelines for bipolar. Has great tables.
@@PsychoFarm A subset of patients with non-clinically relevant hypomania could see high doses of Mirtazapine less sedating due to genetic sensitivity to alpha 2?
High clinical doses could potentially have altered pharmacodynamics, we do not know what these are outside of the studied ranges. While using the lens of sequential binding it checks out that moving from the normal dosage ranges to the high dose ranges might erroneously lead people to the assumption Mirtazapine is less sedating at these high dosage ranges. We actually just don't know because we haven't tested it nor would we due to the increased dropout rate of the normal clinical population. Yet it is possible there is a small subset of the clinical population that tolerates higher doses both in the side effects whilst receiving more activation via alpha 2 and increased efficacy of antidepressants reducing psychomotor slowing. Clinical wisdom does show that some people simply need higher doses for some medications again here altered pharmacodynamics could lead to differed outcomes.
I take Guanfacine and Bupropion.my nurse suggested Mitrazapine for my insomnia at 7.5mg, now seeing that it is an a2 antagonist could it make Guanfacine less effective? I hope thats not the case because Guanfacine has been a life changer
How does more noradrenaline help with anxiety?
loved the pearls section
Great stuff!
Will 15 mg help with depression.
Would you have to taper 3.75 mg..take for horrible insomnia with pain and also underweight.
i have the same question
amazing job!
Not trying to troll, but have you reflected on the truth and value of receptor theory? This channel seems to go quite hard, in the spirit of Stahl. As a purely clinical psychiatrist I have started to view pharmacodynamics as mainly a way to "professionalize" our niche of the medical field, without actually being that usefull in daily practice. I care about outcomes, not receptors. My knowledge of the differences in receptor profiles has probably never benefited my patients apart from avoiding side effects (anticholinergics etc). The only thing it really has done is give me a way to sound smart. Regarding actual psychiatric treatment effect nothing is gained from knowing what 5-HT receptor subtype or even which monoamine a particular drug targets. I would love to be proven wrong.
Regarding your last line, as a pharmacist, I care a lot about such things because that's where my drug interactions come in. Mirtazepine in particular may find a niche in older patients more likely to suffer from insomnia and weight loss, and this patient population also tends to have complex medication lists that have to be sorted through. I think there's value in being able to give some weight to certain side effects that may appear on the surface to add up or to cancel each other out, when in reality, we end up seeing one drug's effect predominate. I take your overall point that you could just shortcut the thinking and look at the patient's individual outcomes, but in terms of coming up with that initial plan or when trying to optimize therapy, some knowledge here is beneficial, even if ultimately, you're simply going to listen to your patient and adjust accordingly.
Yes, I have thought a lot about it. It's suprising to hear I go hard into the neurobiology, when I think I'm pretty strongly less in the biological camp compared to colleagues. I also have videos based more on cognitive psych and psychoanalytic thought.
Like every lens to view a patient, I think it's important to learn it well, learn the limitations, and then move on. I think with every one of my videos, any sort of education on receptors is directly linked to a clinical aspect of the medication. I like to imagine that if my videos have done anything, I hope that they have led to people using more appropriate dosing (lower doses), and also to dose appropriately to different indications. The receptor model provides a useful framework for why that would be. I also think I instill in these videos a pretty heavy dose of skepticism about our models. Maybe not on this one in particular, but in others, I do.
I'd argue my knowledge of receptors has benefited patients. I dose SSRIs lower than colleagues. I dose anti-psychotics more appropriately relative to colleagues. I avoid under-dosing medications for certain indications (like thinking trazodone 50 mg or mirtazapine 3.75 will help their depression). I avoid putting patients on medications that aren't appropriate. I get less excited about newer medications with good marketing. I don't naively think simplified things like 5-HT7 will make my patient a cognitive wizard.
I never try to sound smart with my patients. Any sort of thoughts of receptors or dosing is done in the background, and only the clinical expectations is communicated. I get incredibly annoyed when I see a psych trying to sound smart to a patietn with receptor hand-waving.
I think me and Stahl are quite different. He acts as if what he's presenting is factual, and markets new brand name drugs. Meanwhile, I'm pushing for under-utilized medications, or teaching about commonly used medications used inappropriately. Also he took 7 million in industry funding last year, whereas I'm behind on rent.
@PsychoFarm Thank you for this thoughtful answer.
I believe that the question about correct dosing is distinct from receptor pharmacology. One can know that most common antidepressants usually have their best effects at lower dose intervals, considering all factors. I think we fully agree here. However, this belief is based on actual data about outcomes rather than theoretical or hypothetical understandings of receptor affinities.
Also, I want to make it clear that I never try to sound smart in front of patients in this regard. But, I admit I have used pharmacology to appear knowledgeable when addressing younger colleagues. I'm working on avoiding this behavior. Regarding patients, I often find a need to downplay ideas about 'low serotonin' and similar concepts, since at least where I work, it's quite common for patients to have these elaborate conceptions. I think they express a genuine desire to make sense of something that is very hard to understand, so I would of course never hold it against them.
Yes, I'm aware that you have a different focus in other videos. Thanks again for your thoughts. Much appreciated.
@kma3647 I do agree that some knowledge is important, particularly when considering side effects. However, for interactions, I don’t think I could ever reason my way to an understanding based solely on receptor affinity or chemical structure. For instance, why does escitalopram create somewhat dangerous interactions with some PPI drugs, while sertraline or fluoxetine apparently does not? I get a bit disillusioned by the fact that I can’t really predict treatment effects, only side effects. Whether the drug works as intended (and this is most apparent in treating depression) seems like a roll of the dice.
@@broken-dimension-remind "For instance, why does escitalopram create somewhat dangerous interactions with some PPI drugs, while sertraline or fluoxetine apparently does not?"
I guess what's confusing here is that you're asking why you can't deduce a PK interaction from a pharmacodynamic standpoint. Sertraline, Fluoxetine, and Escitalopram all have their minimum effective on depression dose when they block 80% of SERT, irrespective of the milligram amounts. This isn't a coincidence, it's entirely to due with their interaction with the receptor in question, SERT. There's a reason you're not using 5 mg of zoloft or 50 mg of lexapro. You probably don't even think about the fact that you're restricted to using very small ranges of medications.
"Whether the drug works as intended (and this is most apparent in treating depression) seems like a roll of the dice."
Can't predict treatment effects? Huh? You can't predict exactly how someone will respond, or which they'll respond most to. But you can make major predictions depending on the medication. You seem to be taking "we don't know excatly what will happen" and turning it into: "Let's throw the whole paradigm out".
This is from Google; Can mirtazapine cause chronic fatigue?
It's interesting to note that mirtazapine may cause 'sleep disorders', with fatigue also being a common side effect. While mirtazapine may help you to sleep better while you're taking it, it's well recognised that insomnia can develop after stopping taking the drug. My Question; Hey, sry to ask This here but i need help, i took mirtazapine for 2 months 30mg Then did the stupidity to stop abruptly, which medication can i take to reverse that fatigue effect? Plz anything would help, please answer freely, i promise to ask My doctor first
I have a fat Belly from mirtazapine 7.5mg
So true!! I can’t get it to move!!
@@leannebc8536 me too very fat belly I can't loose weight
Ugh me too. The one thing I hate about this drug
I’m getting one too!
I’m starting to take this and this is something I’m really worried about
The idea that Mirtazapine has value for treating meth addiction is just mind-boggling to me. That such a strong sedative could help cravings for one of the strongest stimulants known just feels completely counterintuitive to me. At least based on the substitution model of opioid addiction treatment with mu agonists, I would have expected only something like modafinil or pitolisant to have any value. Almost reminds me of how thiazide diuretics are used to treat nephrogenic diabetes insipidus or how ativan works for catatonia.
H1 blockade is going to attenuate dopamine release and reduce drug-seeking behaviour? Modafinil also is proposed to work via H1agonist, DAT and orexin agent. Here is it working as a weak substitute as opposed to a dopamine blocker
Love that meta-analysis. Vortioxetine ranked more effective than clomipramine. What a joke
Been on it 25 years. 15 mg . But… I want off. Heard it’s going to be hard very hard as TH-camrs have mentioned. I bought a scale that will weigh out in 10 % A month increments for reducing. I originally went on it for. Depression. Absolutely no weight gain
How is it going
Definitely do it over a long period I’d say two years
gotta comment to never get this as mono
Huh??