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Dr. M,
Just wanted to say how happy I am and most likely the whole forum community is that you returned to posting. Even if its only for a little bit your answers are always so crucial. Hasnt been the same without you.
Having said that in the last few months I have finally optimized all my hormonal dysfunctions and my thyriod, sex hormones, insulin sensitivty, and cortisol are all where they sould be.
However despite these positive developments I still suffered from depresion . Anehodia, brain fog, reduced pleasure, addictive tendencies etc etc.
Anytime I got a neurotransmitter metabolites such as 5hiaa or vanilmandelate etc etc tested they always came back chronically low. This further makes sense as I have tested positive for the MTHFR mutation which predisposes one to lower neurotransmitter production.
This has lead me to finally turn to psychiatrct meds to remedy my final remaining symptoms.
Out of all the research I did on the topic I found the MAIO class of drugs to be particularly promsing with EMSAM being on the top of my list.
I found a Pdoc in NYC who used it often and he started me on the 6mg/24 hour patch. Withing a few days you can feel a difference in how you feel . Definetly a profound pro-dpamine effect where I am markedly more social, more motivated, resist cravings well, and get more done.
However I definetly still want to try the 9mg and 12 mg doses to see if I can get further improvement.
Dr. M in your clinical experience do people eventually build tolerance to the dopamine stimulating properies of emsam through receptor downregulation?
Do you find differences in how people feel when you raise their doses to 9mg and 12 mg doses? If so do you think this is because more MAO A is being inhibited in the brain and serotonin and norepinephrine are able to mediate their anti depresant affects?
And finally what lifestyle changes in your opinion can one make that would encourage a high dopamine receptor sensitivty?
I have read studies where caloric restriction and avoiding addictive activites can help but wanted to see what you thought.
Once aggain thanks if you ever get around to this. Your the man
Monamine Oxidase Inhibitors (MAOI) – like Selegiline in the EMSAM transdermal patch – block the destruction of serotonin, dopamine, and norepinephrine produced in the body. MAOIs generally increase Serotonin primarily, dopamine secondarily, unless the dose is low enough (e.g. 5-10 mg a day of Selegiline orally, when dopamine can be increased more prominently).
Whenever dopamine signaling is increased – no matter what the form – one will always lose a certain number of dopamine receptors, leading to a reduction in the effectiveness of treatment. The dose at which this occurs varies from person to person. With EMSAM, many people improve significantly with the 6 mg/24H patch. Does this warrant a trial at the higher dose to see if they work better? Depends on the person. One can always return to the previous dose if higher ones cause more adverse effects or have no improvement.
Note that when one finds an antidepressant that works, great. If the antidepressant seems to stop working, then generally, it is not the antidepressant that stopped working. Rather, some other problem was not addressed in the body that caused further changes that caused depression to return.
Depression – at its core – is the sum of numerous factors in the body that lead to an overall pro-inflammatory signaling state. Antidepressants only address a few – particularly those in the nervous system. It is important to look for and address problems in the endocrine system, immune system, gastrointestinal system, etc. These systems along with cellular metabolism and nutrition are components of the mind, determining thought and mental function.
Dopamine is one of the anti-stress signals. When one experiences higher levels of stress, dopamine signaling is reduced.
Lifestyle interventions which aim to help a person maintain a relaxed state despite stress help change nervous system structure and processing to maintain dopamine signaling. These include participating in practices such as yoga and therapeutic interventions involving mindfulness and other forms of therapy. Many times, people have not developed adequate skills to manage their stress and problems because of earlier experiences in life. Psychotherapy with a therapist one feels comfortable with would be very helpful to help restructure nervous system connections to a healthier state. Regular exercise (but not in excess since exercise itself is a stress) helps maintain a sense of wellbeing and help externalize stress.
Addictive substance use are attempts by a person to improve their sense of well-being. Unfortunately, these also have adverse effects that cause the opposite – an impaired ability to function. This a person may not realize until he or she hits bottom given a human’s ability to rationalize away the truth. Humans have an amazing ability to rationalize – its built right into the nervous system – a function of the left cerebral cortex called the interpreter. It can blind you from many things in an attempt to find some semblance of the truth.
Low nutrient density food is so common these days, it is difficult to avoid eating excess calories. Unfortunately, fat cells when excessively large, send leptin and pro-inflammatory signals to get the nervous system to stop a person from eating. When done chronically, the pro-inflammatory signals predispose a person to depression when other problems in the body occur. Caloric restriction helps maintain one’s weight and thus controls adipose cell signals to more positive signals.
Intermittent fasting also helps reduce pro-inflammatory signaling by avoiding overly activating the immune system – which goes into action every time we ingesting a food to help protect us from pathogens in the food. When the immune system is already over-activated from other causes (e.g. infection, autoimmune illness, allergies, etc.), excessive eating adds fuel to the fire of ongoing pro-inflammatory signaling that contributes to depression.
It is a push and pull balance, however. When foods do not have enough nutrition, people have to eat more in order to feel better. When the body is starved of nutrients, the brain will trigger appetite to help find the nutrients it needs. Thus, it would be difficult to do caloric restriction or intermittent fasting in a person who has ongoing nutritional and other problems which would outweigh the attempt to reduce calories.
@DrMariano 4672 wrote:
Monamine Oxidase Inhibitors (MAOI) – like Selegiline in the EMSAM transdermal patch – block the destruction of serotonin, dopamine, and norepinephrine produced in the body. MAOIs generally increase Serotonin primarily, dopamine secondarily, unless the dose is low enough (e.g. 5-10 mg a day of Selegiline orally, when dopamine can be increased more prominently).
Whenever dopamine signaling is increased – no matter what the form – one will always lose a certain number of dopamine receptors, leading to a reduction in the effectiveness of treatment. The dose at which this occurs varies from person to person. With EMSAM, many people improve significantly with the 6 mg/24H patch. Does this warrant a trial at the higher dose to see if they work better? Depends on the person. One can always return to the previous dose if higher ones cause more adverse effects or have no improvement.
Note that when one finds an antidepressant that works, great. If the antidepressant seems to stop working, then generally, it is not the antidepressant that stopped working. Rather, some other problem was not addressed in the body that caused further changes that caused depression to return.
Depression – at its core – is the sum of numerous factors in the body that lead to an overall pro-inflammatory signaling state. Antidepressants only address a few – particularly those in the nervous system. It is important to look for and address problems in the endocrine system, immune system, gastrointestinal system, etc. These systems along with cellular metabolism and nutrition are components of the mind, determining thought and mental function.
Dopamine is one of the anti-stress signals. When one experiences higher levels of stress, dopamine signaling is reduced.
Lifestyle interventions which aim to help a person maintain a relaxed state despite stress help change nervous system structure and processing to maintain dopamine signaling. These include participating in practices such as yoga and therapeutic interventions involving mindfulness and other forms of therapy. Many times, people have not developed adequate skills to manage their stress and problems because of earlier experiences in life. Psychotherapy with a therapist one feels comfortable with would be very helpful to help restructure nervous system connections to a healthier state. Regular exercise (but not in excess since exercise itself is a stress) helps maintain a sense of wellbeing and help externalize stress.
Addictive substance use are attempts by a person to improve their sense of well-being. Unfortunately, these also have adverse effects that cause the opposite – an impaired ability to function. This a person may not realize until he or she hits bottom given a human’s ability to rationalize away the truth. Humans have an amazing ability to rationalize – its built right into the nervous system – a function of the left cerebral cortex called the interpreter. It can blind you from many things in an attempt to find some semblance of the truth.
Low nutrient density food is so common these days, it is difficult to avoid eating excess calories. Unfortunately, fat cells when excessively large, send leptin and pro-inflammatory signals to get the nervous system to stop a person from eating. When done chronically, the pro-inflammatory signals predispose a person to depression when other problems in the body occur. Caloric restriction helps maintain one’s weight and thus controls adipose cell signals to more positive signals.
Intermittent fasting also helps reduce pro-inflammatory signaling by avoiding overly activating the immune system – which goes into action every time we ingesting a food to help protect us from pathogens in the food. When the immune system is already over-activated from other causes (e.g. infection, autoimmune illness, allergies, etc.), excessive eating adds fuel to the fire of ongoing pro-inflammatory signaling that contributes to depression.
It is a push and pull balance, however. When foods do not have enough nutrition, people have to eat more in order to feel better. When the body is starved of nutrients, the brain will trigger appetite to help find the nutrients it needs. Thus, it would be difficult to do caloric restriction or intermittent fasting in a person who has ongoing nutritional and other problems which would outweigh the attempt to reduce calories.
thank you for your thoughtful answer.
I actually follow a Paleo style diet with protein and fat content making up some 85-90% of my daily calories and the 10-15% of my calories coming from carbs, and this is mostly in the form of vegetables before workouts to fuel my weight lifting.
I have found this dietary approach to be crucial to recovery from many of the problems that plagued my body. It completly reversed my insulin resistance and helped to get my cortisol to good levels.
I even believe it helped lower my norepinephrine output on my fractured catecholamines test and played a part in curing my premature ejaculation and anxiety which were a result of that.
So I am definetly on the same page as you that nutritional is crucial in a well functioning body.
I actually see my psychiatrist this upcoming wendsday and Im sure one of the things we will discuss is upping the dose of emsam from 6mg to 9mg (possibly 12 mg) . And ofcourse as you said if the higher doses are not what I hope then I can always return to the 6mg dose and go with that as it does have positve benefits.
I also absolutly agree with you that depresion is a result of multiple system wide dysfunctions.
In my case fixing my hypothyroid, low T , and insulin resistance already made me markedly less depressed. But something was still missing for lack of a better phrase.
It obviously makes sense that any dopamine promoting drug such as emsam will cause some degree of dopamine receptor down regulation. But I suppose people still experience positive effects because the overall dopamine “signal” is higher . I believe this is the case with me.
So essentially to sum I found that fixing hypogonadism, fixing hypothyroid, fixing partial insulin resistance, and raising cortisol (natually ) improved my functionality and well being some 70% which is ofcourse signficant.
Im hoping directly augmenting neurotransmitters with emsam is the final step and will fix the remaining symptoms.
Thanks again Dr. M for your time.
A “Paleo” diet is still incomplete. Just remember that primitive people wasted nothing and traditional diets waste fewer nutrients than the Paleo diets.
@js367124 4648 wrote:
Dr. M,
Just wanted to say how happy I am and most likely the whole forum community is that you returned to posting. Even if its only for a little bit your answers are always so crucial. Hasnt been the same without you.
Having said that in the last few months I have finally optimized all my hormonal dysfunctions and my thyriod, sex hormones, insulin sensitivty, and cortisol are all where they sould be.
However despite these positive developments I still suffered from depresion . Anehodia, brain fog, reduced pleasure, addictive tendencies etc etc.
Anytime I got a neurotransmitter metabolites such as 5hiaa or vanilmandelate etc etc tested they always came back chronically low. This further makes sense as I have tested positive for the MTHFR mutation which predisposes one to lower neurotransmitter production.
This has lead me to finally turn to psychiatrct meds to remedy my final remaining symptoms.
Out of all the research I did on the topic I found the MAIO class of drugs to be particularly promsing with EMSAM being on the top of my list.
I found a Pdoc in NYC who used it often and he started me on the 6mg/24 hour patch. Withing a few days you can feel a difference in how you feel . Definetly a profound pro-dpamine effect where I am markedly more social, more motivated, resist cravings well, and get more done.
However I definetly still want to try the 9mg and 12 mg doses to see if I can get further improvement.
Dr. M in your clinical experience do people eventually build tolerance to the dopamine stimulating properies of emsam through receptor downregulation?
Do you find differences in how people feel when you raise their doses to 9mg and 12 mg doses? If so do you think this is because more MAO A is being inhibited in the brain and serotonin and norepinephrine are able to mediate their anti depresant affects?
And finally what lifestyle changes in your opinion can one make that would encourage a high dopamine receptor sensitivty?
I have read studies where caloric restriction and avoiding addictive activites can help but wanted to see what you thought.
Once aggain thanks if you ever get around to this. Your the man
Depends on which MTHFR mutation you have as well as other down stream mutations will dictate what recommendations would be needed. I am one of the clinical nutritionist dealing with this gene in the United States. It has been a huge game changer in Dr’s I have worked with in relationship to these cases. Where there is one mutation there are bound to be more.
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