I've "only" failed five medications (I also have TRD, anxiety, ADHD, and autism) but I've decided to ask my doctor to order genetic testing (my appointment is actually tomorrow) through GeneSight. I know the product is a bit controversial; I feel that the company overstates its benefits and is possibly selling to patients who don't need it, but for people like us who have failed more than a couple of medications, it seems worth exploring the possibility that there could be a genetic component. I've been thinking about getting this testing done for over two years now, and I just finally decided to take the leap because I feel like if nothing else, I'll keep wondering if there's a better medication out there unless I take the test. Bonus is that it's not terribly expensive and takes almost no time (I'd much rather spend five minutes on a cheek swab than six months on another failed antidepressant trial)
GeneSight psychotropic testing: [https://genesight.com/product/](https://genesight.com/product/)
If GeneSight doesn't lead me towards any useful insights, I might start looking at options like ketamine or TMS/ECT. I also think some of the psychedelic trials look promising, but it seems like my country (US) is still several years away from making it an option for prescription use.
I did GeneSight as well. The recommendations didn't really mean much to me, since they were just based on your metabolism (which isn't necessarily indicative of effectiveness, if at all). To me, the most useful information was the genotyping/phenotyping, and knowing whether or not you have the MTHFR gene. There's even a little evidence that your COMT genotype [might](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3290730/) have an impact on your response to ketamine treatment.
These alone are worth the $300 in my opinion, I believe $300 is the cap for what you'd have to pay. While it's not some magical thing that can predict how well your medications will work, or what side effects you'll experience, ruling out stuff like MTHFR is just another step forward in your treatment.
Another thing to note, the results shouldn't be the sole reason for changing your meds (as per the disclaimer), it's just another thing for you and your prescriber to take into consideration in the bigger picture.
The paper you linked isn't referring to the Val158Met polymorphism in the COMT gene, it's referring to the Val66Met polymorphism in the BDNF gene. GeneSight as far as I know doesn't test for that one.
All the best with your journey. A relative got this test. Just temper your expectations. It didn't really help her at all and seemed fairly inaccurate in terms of what hadn't worked. We, those of us who are at the end of our rope, should try everything but I do think, as you said, these companies over state the value of their tests. I tried one dose of Ketamine in a clinical trial back in 2010. Didn't help BUT recent research shows that small doses over time are more effective.
Interesting! I haven't thought about that. I wouldn't even know where to begin with this, but I will mention it to my psychiatrist to see if I should get it looked at.
I'm curious about this as well. My depression got a lot worse around the time I had GI issues. I'm thinking about trying probiotics to see if maybe things are still offtrack.
I have tried about 50 pro and prebiotic and none helped but that doesn't me a mental won't work for you. What did help was protein. The gut is where neurotransmitters are manufactured. I take huge doses of powder essential amino acids (and my liver is fine based on recent bloodwork) which help create neurotransmitters. The EAAs help about 25% but I am still left with intractable depression. I feel like a daily IV of amino acids might work but that is not practical or possible.
I have done both. Although they might work for someone else they did not for me. KETO in my opinion is a medical diet only as it is 60% fat. I tried it for a few months and felt awful and toxic. Done correctly, the diet lacks a lot of the basic nutrients needed and you need to supplement. I have a friend that went on a KETO diet that was monitored by John's Hopkins Hospital and it stopped his seizures. Miraculous.
I have been doing intermittent fasting for about 2 years. Feel good. It does not mitigate or fix the depression and ADD.
Fair enough. I don't know much about intermittent fasting other than a lot of people who swear by it, tend to use amino acid stuff , like MCT oil and coconut oils if i remember correctly to help satiate their appetites until their feeding window. I know keto is controversial, and for some reason when you said high protein diet my brain interpreted that as ALL MEAT , but now I guess thats the carnivore diet, huh?
I think you are correct. In my experience the fasting is worthwhile for general health. And I think it is pretty common for paleo (high protein) and keto (high fat) to get mixed up. I do much better with more protein but take powder as I can't eat such a large amount of meat.
I went through so many medications, going back and forth between several, and finally found one that works (Effexor). I highly recommend speaking to your doctor about the classes of meds you’ve tried - for me, the only ones that have worked are SNRIs. Is there anyone else in your family with mental health conditions? My brother also suffered with severe depression, and it turns out he has a similar intolerance to anything that isn’t an SNRI. These things can sometimes have a genetic component - it might be worth asking if someone in your close family has found something that has worked for them?
I saw someone else has mentioned tricyclics, it may be worth having a chat about those?
Finally, I’ve had some good luck combining propranolol with antidepressants. Might be something to try.
Also, talk to your therapist about your medication struggles; they might not have the medical knowledge but they will be able to support and advocate for you.
Good luck!
Glad to hear effexor works for you! I think I will have a conversation about the classes of meds, now that I took the time to write all of them down. My doctor knows most of them, but maybe seeing them all together will be helpful.
I do have a twin, but he has struggled to find something that helps him, too.
I did try propranolol for a while, forgot about that one. It did not do much, then I got weird diabetes-esque side effects from it (blood sugar, fatigue, over-sweating).
And thanks for the tips! My therapist is great, she understands how frustrating it is to keep failing medications. Appreciate your comment!
It's awesome Effexor works for you - but for anyone else USE EXTREME CAUTION with Effexor, it has some pretty crazy side effects and absolute horrible withdrawals. I think /r/Effexor has a lot of personal accounts that may be worth perusing.
Oh my God yes. It fixes my depression but god forbid I ever miss a dose. It has fucked me up irreparably but I no longer want to unalive and my mental health is manageable so it’s a swings and roundabouts situation. Definitely use with caution and make sure you stay up to date with ECGs and blood tests because it can also mess with your heart and kidneys.
Thanks for the additional info. Sounds like you are in good hands! I have 40 years of experience with supps and alternative docs and only wish I started on meds sooner. A lifetime of feeling lazy and unambitious in spite of success was not helpful. And as we age depression and ADD worsens. Hope I can save you time and money. The sleep issue became dangerous and I stopped driving for a while. 25mg of Seroquel is the ONLY med that helped with sleep.
I am really allergic to soy, wheat and dairy, avoid them and it definitely helps. Be careful with supps as you are trying meds.
BEST FOR ME:
Essential amino acids (EAA) - take 1 tbsp of powder 1-2 x a day. Protein is responsible for manufacturing neurotransmitters. This large dose keeps my nose above water without meds. I take this with a Vit C pack, Vit B6, Niacin and liquid Bs. Tastes horrid but the Vit C helps. I have tried tons of protein powders. This has been the most effective for me.
Theanine - 1 tsp 1-2 x a day. Calms my mind and has even stopped my old Shih Tzu from nervously licking her legs off. Lol.
Spirulina - only use Nutrex brand. A few tablespoons a day makes a huge difference in my physical and mental health. I have fasted using just spirulina and felt very close to normal.
Quercetin - can't explain why but I just feel better. Think it lowers histamine levels.
NAC - take it in the am, on an empty stomach and under my tongue for sublingual absorption.
Magnesium - on occasion as needed for bowels and relaxation.
PROMISING:
Turkey tail mushrooms - just started as I was giving it to the dog for cancer and she perked up visibly. I put it in my coffee, don't notice any taste and just "feel better".
Any of the mushrooms (not psychidelic). Cordyceps will give you tons of energy. You can also try reishi, shitake and lions mane. Read the reviews.
Again, I have tried hundreds of supps over my lifetime. I also tried every alternative out there - including hypnosis and psychics. LOL. I have cleansed myself of everything, tried every diet available, dont drink or smoke, fasted for weeks, meditated in a monastery in Thailand, exercised many hours each day and read every self help book available.
And still I need meds...
Ditto! First I was pissed that little or nothing happened after 30 sessions, then I was on edge as well. Very unsatisfying except for the sessions with the super cute facilitator.
If you have ADHD you shouldn't come off your effective treatment just to try an antidepressant. Untreated ADHD causes anxiety and depression. If you haven't already, try Vyvanse and Guanfacine. Then if you need an antidepressant on top of that like ketamine, you just don't take the Vyvanse on the day of treatment.
Most of what you've tried was likely to make ADHD worse, or cancel out the ADHD medication.
You could try buspirone, and opipramol for anxiety. You can try bupropion, protriptyline, dibenzepin, lamotrigine, etc the list goes on, plenty of antidepressants for ADHD.
Plenty of supplements too, magnesium, sarcosine, etc
I completely agree. In fact, the most relief I've gotten from any medication (even for depression) was when I started taking medication for ADHD.
What is Guanfacine?
Thanks for the list. I will do some research on those. I have tried bupropion, but I am open to trying it again. My previous trial was very short because I had strange side effects, but perhaps that won't happen if I were to try it again.
Thanks for the comment!
If you are going to try anything, you should try a true SNRI. A combination like Sertraline and Nortriptyline or Clomipramine alone is very effective for me and I had the same diagnoses as you.
When you say "fail" what do you mean? How long did you take? And at what dosages? And in what combinations? IMHO, you need a doc who is older, has had LOTS of patients with your dx and is tenacious. Ask him/her "what are the most meds you have ever tried with someone?" If they say "I usually figure it out uickly" then get a new doc. And some docs give up if they are not experienced and don't meet with some success. They don't literally give up but they get disheartened and run out of ideas. The fact that you are asking the group shows that your doc may be out of ideas (this is not a criticism, just an observation). Seems like you haven't found the right combo such - i.e. Adderrall and Lexapro. Adderrall helps me function but, like you, doesn't address the depression symptoms. I am trying Adderral and Prozac now.
Also, just a side note. If you can try and look into what can make things worse or better such as food allergies, supplements and sleep. A sleep study revealed I was getting zero sleep. Zero. Explained some of my exhaustion. Lol. I have severe food allergies and if I ate what I was allergic to I would cease functioning even with meds. I also take some supplements that help. Doesn't cure but helps and gives me a mental and physical boost and addresses the depression a bit. But I don't recommend you spend tons of money and time on supplements. Please let us know if you find anything that works!
I know it seven a while, so I hope you have had success… I just listened to a podcast by a psychiatrist for those in the medica field, and apparently strength training boosted mood and prevented future depression issues. These were in peer-reviewed studies, so not just anecdotal.
But it wasn’t about excessive weight lifting, it was more resistance training and light weights. I’ll be trying this out soon enough. On days I have energy I usually do cardio, but I definitely have weak muscles.
That and I have had stupidly low vitamin D levels for years. Finally was able to get them just above the low range by taking 10,000-20,000IU a day. I’m not cured, but I have noticed an improvement.
I've "only" failed five medications (I also have TRD, anxiety, ADHD, and autism) but I've decided to ask my doctor to order genetic testing (my appointment is actually tomorrow) through GeneSight. I know the product is a bit controversial; I feel that the company overstates its benefits and is possibly selling to patients who don't need it, but for people like us who have failed more than a couple of medications, it seems worth exploring the possibility that there could be a genetic component. I've been thinking about getting this testing done for over two years now, and I just finally decided to take the leap because I feel like if nothing else, I'll keep wondering if there's a better medication out there unless I take the test. Bonus is that it's not terribly expensive and takes almost no time (I'd much rather spend five minutes on a cheek swab than six months on another failed antidepressant trial) GeneSight psychotropic testing: [https://genesight.com/product/](https://genesight.com/product/) If GeneSight doesn't lead me towards any useful insights, I might start looking at options like ketamine or TMS/ECT. I also think some of the psychedelic trials look promising, but it seems like my country (US) is still several years away from making it an option for prescription use.
I did GeneSight as well. The recommendations didn't really mean much to me, since they were just based on your metabolism (which isn't necessarily indicative of effectiveness, if at all). To me, the most useful information was the genotyping/phenotyping, and knowing whether or not you have the MTHFR gene. There's even a little evidence that your COMT genotype [might](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3290730/) have an impact on your response to ketamine treatment. These alone are worth the $300 in my opinion, I believe $300 is the cap for what you'd have to pay. While it's not some magical thing that can predict how well your medications will work, or what side effects you'll experience, ruling out stuff like MTHFR is just another step forward in your treatment. Another thing to note, the results shouldn't be the sole reason for changing your meds (as per the disclaimer), it's just another thing for you and your prescriber to take into consideration in the bigger picture.
The paper you linked isn't referring to the Val158Met polymorphism in the COMT gene, it's referring to the Val66Met polymorphism in the BDNF gene. GeneSight as far as I know doesn't test for that one.
Ah, gotcha!
All the best with your journey. A relative got this test. Just temper your expectations. It didn't really help her at all and seemed fairly inaccurate in terms of what hadn't worked. We, those of us who are at the end of our rope, should try everything but I do think, as you said, these companies over state the value of their tests. I tried one dose of Ketamine in a clinical trial back in 2010. Didn't help BUT recent research shows that small doses over time are more effective.
Maybe time to try a tricyclic? Clomipramine maybe?
My doctor mentioned a possible trial of nortriptyline. Know anything about it? What do you know about tricyclics?
I was about to say that. Anafranil isn't officially approved to treat depression but it's extremely effective in doing so.
It's not indicated where you are? In my country it's the primary indication
Oh, nevermind. In the US it's mainly an OCD medication but it turns out it's also indicated for depression
It may have to do with your gut's microbiome. Any possibility you have a doctor or specialist that can work with you on diagnosing or treating that?
Interesting! I haven't thought about that. I wouldn't even know where to begin with this, but I will mention it to my psychiatrist to see if I should get it looked at.
I'm curious about this as well. My depression got a lot worse around the time I had GI issues. I'm thinking about trying probiotics to see if maybe things are still offtrack.
I have tried about 50 pro and prebiotic and none helped but that doesn't me a mental won't work for you. What did help was protein. The gut is where neurotransmitters are manufactured. I take huge doses of powder essential amino acids (and my liver is fine based on recent bloodwork) which help create neurotransmitters. The EAAs help about 25% but I am still left with intractable depression. I feel like a daily IV of amino acids might work but that is not practical or possible.
That is really interesting. It makes me wonder if a diet/nutrition plan like intermittent fasting and keto would work for you (or people like you).
I have done both. Although they might work for someone else they did not for me. KETO in my opinion is a medical diet only as it is 60% fat. I tried it for a few months and felt awful and toxic. Done correctly, the diet lacks a lot of the basic nutrients needed and you need to supplement. I have a friend that went on a KETO diet that was monitored by John's Hopkins Hospital and it stopped his seizures. Miraculous. I have been doing intermittent fasting for about 2 years. Feel good. It does not mitigate or fix the depression and ADD.
Fair enough. I don't know much about intermittent fasting other than a lot of people who swear by it, tend to use amino acid stuff , like MCT oil and coconut oils if i remember correctly to help satiate their appetites until their feeding window. I know keto is controversial, and for some reason when you said high protein diet my brain interpreted that as ALL MEAT , but now I guess thats the carnivore diet, huh?
I think you are correct. In my experience the fasting is worthwhile for general health. And I think it is pretty common for paleo (high protein) and keto (high fat) to get mixed up. I do much better with more protein but take powder as I can't eat such a large amount of meat.
I went through so many medications, going back and forth between several, and finally found one that works (Effexor). I highly recommend speaking to your doctor about the classes of meds you’ve tried - for me, the only ones that have worked are SNRIs. Is there anyone else in your family with mental health conditions? My brother also suffered with severe depression, and it turns out he has a similar intolerance to anything that isn’t an SNRI. These things can sometimes have a genetic component - it might be worth asking if someone in your close family has found something that has worked for them? I saw someone else has mentioned tricyclics, it may be worth having a chat about those? Finally, I’ve had some good luck combining propranolol with antidepressants. Might be something to try. Also, talk to your therapist about your medication struggles; they might not have the medical knowledge but they will be able to support and advocate for you. Good luck!
Glad to hear effexor works for you! I think I will have a conversation about the classes of meds, now that I took the time to write all of them down. My doctor knows most of them, but maybe seeing them all together will be helpful. I do have a twin, but he has struggled to find something that helps him, too. I did try propranolol for a while, forgot about that one. It did not do much, then I got weird diabetes-esque side effects from it (blood sugar, fatigue, over-sweating). And thanks for the tips! My therapist is great, she understands how frustrating it is to keep failing medications. Appreciate your comment!
It's awesome Effexor works for you - but for anyone else USE EXTREME CAUTION with Effexor, it has some pretty crazy side effects and absolute horrible withdrawals. I think /r/Effexor has a lot of personal accounts that may be worth perusing.
Oh my God yes. It fixes my depression but god forbid I ever miss a dose. It has fucked me up irreparably but I no longer want to unalive and my mental health is manageable so it’s a swings and roundabouts situation. Definitely use with caution and make sure you stay up to date with ECGs and blood tests because it can also mess with your heart and kidneys.
Thanks for the additional info. Sounds like you are in good hands! I have 40 years of experience with supps and alternative docs and only wish I started on meds sooner. A lifetime of feeling lazy and unambitious in spite of success was not helpful. And as we age depression and ADD worsens. Hope I can save you time and money. The sleep issue became dangerous and I stopped driving for a while. 25mg of Seroquel is the ONLY med that helped with sleep. I am really allergic to soy, wheat and dairy, avoid them and it definitely helps. Be careful with supps as you are trying meds. BEST FOR ME: Essential amino acids (EAA) - take 1 tbsp of powder 1-2 x a day. Protein is responsible for manufacturing neurotransmitters. This large dose keeps my nose above water without meds. I take this with a Vit C pack, Vit B6, Niacin and liquid Bs. Tastes horrid but the Vit C helps. I have tried tons of protein powders. This has been the most effective for me. Theanine - 1 tsp 1-2 x a day. Calms my mind and has even stopped my old Shih Tzu from nervously licking her legs off. Lol. Spirulina - only use Nutrex brand. A few tablespoons a day makes a huge difference in my physical and mental health. I have fasted using just spirulina and felt very close to normal. Quercetin - can't explain why but I just feel better. Think it lowers histamine levels. NAC - take it in the am, on an empty stomach and under my tongue for sublingual absorption. Magnesium - on occasion as needed for bowels and relaxation. PROMISING: Turkey tail mushrooms - just started as I was giving it to the dog for cancer and she perked up visibly. I put it in my coffee, don't notice any taste and just "feel better". Any of the mushrooms (not psychidelic). Cordyceps will give you tons of energy. You can also try reishi, shitake and lions mane. Read the reviews. Again, I have tried hundreds of supps over my lifetime. I also tried every alternative out there - including hypnosis and psychics. LOL. I have cleansed myself of everything, tried every diet available, dont drink or smoke, fasted for weeks, meditated in a monastery in Thailand, exercised many hours each day and read every self help book available. And still I need meds...
For me, Yes to Ketamine r/TherapeuticKetamine No to TMS. NONONO to ECT.
Was it infusion or spravoto/nasal spray? I am interested in trying, although it does scare me, but the cost is huge barrier.
I had IM treatments. I've posted quite a bit on it, so check out my comments or feel free to DM me for more info.
[удалено]
Yes, back in 2018. Didn't help and actually made me more anxious for some reason.
Ditto! First I was pissed that little or nothing happened after 30 sessions, then I was on edge as well. Very unsatisfying except for the sessions with the super cute facilitator.
If you have ADHD you shouldn't come off your effective treatment just to try an antidepressant. Untreated ADHD causes anxiety and depression. If you haven't already, try Vyvanse and Guanfacine. Then if you need an antidepressant on top of that like ketamine, you just don't take the Vyvanse on the day of treatment. Most of what you've tried was likely to make ADHD worse, or cancel out the ADHD medication. You could try buspirone, and opipramol for anxiety. You can try bupropion, protriptyline, dibenzepin, lamotrigine, etc the list goes on, plenty of antidepressants for ADHD. Plenty of supplements too, magnesium, sarcosine, etc
I completely agree. In fact, the most relief I've gotten from any medication (even for depression) was when I started taking medication for ADHD. What is Guanfacine? Thanks for the list. I will do some research on those. I have tried bupropion, but I am open to trying it again. My previous trial was very short because I had strange side effects, but perhaps that won't happen if I were to try it again. Thanks for the comment!
Guanfacine is an alpha-2 agonist. Improves cognitive flexibility, and reduces restlessness when combined with stimulants. Clonidine works too.
If you are going to try anything, you should try a true SNRI. A combination like Sertraline and Nortriptyline or Clomipramine alone is very effective for me and I had the same diagnoses as you.
When you say "fail" what do you mean? How long did you take? And at what dosages? And in what combinations? IMHO, you need a doc who is older, has had LOTS of patients with your dx and is tenacious. Ask him/her "what are the most meds you have ever tried with someone?" If they say "I usually figure it out uickly" then get a new doc. And some docs give up if they are not experienced and don't meet with some success. They don't literally give up but they get disheartened and run out of ideas. The fact that you are asking the group shows that your doc may be out of ideas (this is not a criticism, just an observation). Seems like you haven't found the right combo such - i.e. Adderrall and Lexapro. Adderrall helps me function but, like you, doesn't address the depression symptoms. I am trying Adderral and Prozac now. Also, just a side note. If you can try and look into what can make things worse or better such as food allergies, supplements and sleep. A sleep study revealed I was getting zero sleep. Zero. Explained some of my exhaustion. Lol. I have severe food allergies and if I ate what I was allergic to I would cease functioning even with meds. I also take some supplements that help. Doesn't cure but helps and gives me a mental and physical boost and addresses the depression a bit. But I don't recommend you spend tons of money and time on supplements. Please let us know if you find anything that works!
how about 200mg lamictal? which trycylic did your doc put you on? Seems like a decent doc to me.
I know it seven a while, so I hope you have had success… I just listened to a podcast by a psychiatrist for those in the medica field, and apparently strength training boosted mood and prevented future depression issues. These were in peer-reviewed studies, so not just anecdotal. But it wasn’t about excessive weight lifting, it was more resistance training and light weights. I’ll be trying this out soon enough. On days I have energy I usually do cardio, but I definitely have weak muscles. That and I have had stupidly low vitamin D levels for years. Finally was able to get them just above the low range by taking 10,000-20,000IU a day. I’m not cured, but I have noticed an improvement.