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Fallout2019

Cymbalta and Serequel XR combo for MDD

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Hi all,

9 weeks ago I began Cymbalta and Serequel XR for depression and I have felt little improvement in my mood. 1 week ago I went from 60mg to 80mg duloxetine daily, but I have consistently been taking the serequel XR at a 50mg dose for the duration of my treatment. My GP seems reluctant to up the dosage of the serequel at this point and I am confused as to why, as from what I have read online serequel XR begins to be effective as an adjunct to antidepressants at a 150mg dose, at which point it begins to inhibit the reuptake of norepinephrine. However, from my understanding Cymbalta is already a potent inhibitor of norepinephrine, so what possible antidepressant benefit am I getting from this combo? Is there some antidepressant synergy with my current two medications or not? My doctor seems to know about as little as me about these things, which is why I've come online to ask you guys instead! Has anyone had success with a similar combo of meds as mine? And can anyone here possibly attempt to explain the antidepressant efficacy of this combination of meds? I'm contemplating coming off the serequel entirely as I worry that it is possibly negating the effect of my Cymbalta by blocking serotonin and dopamine (I assume that at a 50mg dose it is highly unlikely that the serequel is blocking much serotonin or dopamine, if any at all, but I still worry). 

The pharmacology of medications is so confusing! Would you guys suggest that I try coming off the serequel or possibly increasing it to 150 mg? (the alleged antidepressant dose). I'm also confused as to why my GP started me on BOTH medications at the same time, as it surely could have been possible that the Cymbalta might have worked on its own. Ugh. It's all so very confusing, If anyone can be of any help here at all then I'd appreciate any information and advice. 

By the way, my GP currently refuses to refer me to a psychiatrist at this point as he says that my depression is not severe enough. 

Thank you. Sending lots of love and hugs to you all.

Ryan.

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It is so hard to know how to answer questions about the right combination of meds.  I think you are asking all the right questions.  

I took cymbalta by itself for several years with good results.  

I encourage you to ask your doctor your questions and if the answers don’t make sense to you find a psychiatrist or other doctor that has more experience with mental health meds 

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That's BS that your pdoc won't refer you to a pdoc. If he isn't treating you properly with medications, you have every right to have a recommendation to a pdoc.

You're right in that Seroquel doesn't become an antidepressant until 150-300 mg, where it begins to robustly inhibit reuptake of norepinephrine.

There's no real worry about it canceling out the effects of serotonin and dopamine. Its dopamine antagonism is very weak compared to other antipsychotics (800 mg is where it really blocks dopamine). The serotonin antagonism is actually a good thing. Blocking the 5-HT2A and 5-HT2C receptors causes increased dopamine and norepinephrine release--it "cuts the brake line" so to speak for the release of those neurotransmitters. Also, it has 5-HT1A partial agonism which helps with anxiety and depression, as well as helps negate EPS.

The only things about Seroquel and its active metabolite are that they are a potent antihistamine and anticholinergic, the former of which can cause weight gain, the latter of which can increase chances of dementia (supposedly) as well as diabetes.

Do you have a lot of anxiety? That may be why your doc put you on such a low dose and won't raise it, because he's probably trying to use it as a substitute for a benzo, which is ridiculous in my opinion.

If you don't have a lot of baseline anxiety, I would recommend giving Abilify or even Vraylar a trial (if your insurance covers it) instead of Seroquel XR. Vraylar has a copay coupon that gives you the first fill for free and the rest for as little as $15 depending on how much your insurance wants to charge for it.

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On ‎7‎/‎5‎/‎2019 at 8:40 PM, Tim 52 said:

It is so hard to know how to answer questions about the right combination of meds.  I think you are asking all the right questions.  

I took cymbalta by itself for several years with good results.  

I encourage you to ask your doctor your questions and if the answers don’t make sense to you find a psychiatrist or other doctor that has more experience with mental health meds 

Thank you Tim! It's good to hear that you had decent results with Cymbalta for a number of years. 

I will be asking my questions to my GP tomorrow and if he says that he is unsure of any of the answers then I am going to ask if I can be treated with someone with more knowledge on the subject. 

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17 hours ago, mikl_pls said:

That's BS that your pdoc won't refer you to a pdoc. If he isn't treating you properly with medications, you have every right to have a recommendation to a pdoc.

You're right in that Seroquel doesn't become an antidepressant until 150-300 mg, where it begins to robustly inhibit reuptake of norepinephrine.

There's no real worry about it canceling out the effects of serotonin and dopamine. Its dopamine antagonism is very weak compared to other antipsychotics (800 mg is where it really blocks dopamine). The serotonin antagonism is actually a good thing. Blocking the 5-HT2A and 5-HT2C receptors causes increased dopamine and norepinephrine release--it "cuts the brake line" so to speak for the release of those neurotransmitters. Also, it has 5-HT1A partial agonism which helps with anxiety and depression, as well as helps negate EPS.

The only things about Seroquel and its active metabolite are that they are a potent antihistamine and anticholinergic, the former of which can cause weight gain, the latter of which can increase chances of dementia (supposedly) as well as diabetes.

Do you have a lot of anxiety? That may be why your doc put you on such a low dose and won't raise it, because he's probably trying to use it as a substitute for a benzo, which is ridiculous in my opinion.

If you don't have a lot of baseline anxiety, I would recommend giving Abilify or even Vraylar a trial (if your insurance covers it) instead of Seroquel XR. Vraylar has a copay coupon that gives you the first fill for free and the rest for as little as $15 depending on how much your insurance wants to charge for it.

I'm from the UK and over here it is seemingly very difficult to get a referral to a psychiatrist unless you are a danger to yourself or others. Very frustrating. I am going to ask again tomorrow when I see my GP if he is willing to refer me a psychiatrist but I am almost certain he is going to say no. 

Thank you so much for all of the very useful information about serequel's antidepressant mechanism of action. You explained it very well.

I did have a high amount of anxiety when I was prescribed the serequel, yeah. I was also experiencing feelings of derealization but I personally believe that was due to withdrawing from mirtazapine at the time. I felt like I was in a dream world when I was on mirtazapine and then I crashed back to reality when I withdrew from it and I think it just confused the hell out of my brain and caused oodles of anxiety and panic.

Can I just ask why you feel that Abilify or Vraylar may be better choices? Do you think they might work slightly better in terms of treating the depression?

 

 

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Hi guys,

I have seen a doctor (he was a trainee GP) and he reluctantly upped my dosage of serequel XR to 150mg. The increased dose made me feel weird when I took it last night and I started to become a little panicky, felt drunk when I woke up in the morning too but thankfully the dizziness has subsided a bit throughout today. I'm really hoping that this combo does the trick, if not then I might try Effexor in combination with the serequel instead. I'm just so sick of feeling rubbish, getting desperate now. 

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On 7/8/2019 at 7:26 AM, Fallout2019 said:

I'm from the UK and over here it is seemingly very difficult to get a referral to a psychiatrist unless you are a danger to yourself or others. Very frustrating. I am going to ask again tomorrow when I see my GP if he is willing to refer me a psychiatrist but I am almost certain he is going to say no. 

Thank you so much for all of the very useful information about serequel's antidepressant mechanism of action. You explained it very well.

I did have a high amount of anxiety when I was prescribed the serequel, yeah. I was also experiencing feelings of derealization but I personally believe that was due to withdrawing from mirtazapine at the time. I felt like I was in a dream world when I was on mirtazapine and then I crashed back to reality when I withdrew from it and I think it just confused the hell out of my brain and caused oodles of anxiety and panic.

Can I just ask why you feel that Abilify or Vraylar may be better choices? Do you think they might work slightly better in terms of treating the depression?

 

 

Oh, I see. Very sorry to here that. I didn't realize that's how things were in the UK regarding psychiatrists. That's definitely something to note if I chose to move to another country... lol.

You're welcome, and thank you!

Oh no, I'm sorry to hear that. 😞 Hopefully the seroquel is working in your favor.

I just suggested those because they're more "metabolically friendly" medicines: less weight gain, less chance of diabetes, less increases in cholesterol, etc. In my personal experience, Abilify was my brain glue, but it unfortunately came with a nasty side effect of compulsive buying due to being a dopamine partial agonist. I'm currently in the process of switching to Vraylar, and I feel brighter, lighter, livelier, and feel like actually interacting with people. But I have to go down on the Abilify slowly because otherwise I'll lose my mind! lol

They probably won't do too much for anxiety, but then again, everyone is different. Personally, Abilify in low doses was so stimulating it made me hypomanic, and high doses were physically stimulating, almost like taking a stimulant (which I do take, but it felt like it augmented the effects of them). No anxiety resulted from Abilify. Vraylar is kind of the same was as Abilify, but different in some ways. It's really hard to put my finger on it, but it's nice too.

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On ‎7‎/‎10‎/‎2019 at 9:32 PM, mikl_pls said:

Oh, I see. Very sorry to here that. I didn't realize that's how things were in the UK regarding psychiatrists. That's definitely something to note if I chose to move to another country... lol.

You're welcome, and thank you!

Oh no, I'm sorry to hear that. 😞 Hopefully the seroquel is working in your favor.

I just suggested those because they're more "metabolically friendly" medicines: less weight gain, less chance of diabetes, less increases in cholesterol, etc. In my personal experience, Abilify was my brain glue, but it unfortunately came with a nasty side effect of compulsive buying due to being a dopamine partial agonist. I'm currently in the process of switching to Vraylar, and I feel brighter, lighter, livelier, and feel like actually interacting with people. But I have to go down on the Abilify slowly because otherwise I'll lose my mind! lol

They probably won't do too much for anxiety, but then again, everyone is different. Personally, Abilify in low doses was so stimulating it made me hypomanic, and high doses were physically stimulating, almost like taking a stimulant (which I do take, but it felt like it augmented the effects of them). No anxiety resulted from Abilify. Vraylar is kind of the same was as Abilify, but different in some ways. It's really hard to put my finger on it, but it's nice too.

Hiya! 

I'm really glad to hear that the Vraylar is having such a positive effect on you so far! Wishing you the very best with your treatment.

Sadly I've felt no improvement in mood with the 150mg serequel XR so far (I realise it's still early days though!). You said that the serequel starts to inhibit the reuptake of norepinephrine at 150mg - is that the same for the other antidepressant mechanisms of action that you listed? Are the other mechanisms dose dependant too, and thus only begin working at 150mg? I'm just wondering because obviously my Cymbalta already inhibits norepinephrine too, so surely my only one of my two medications can inhibit the reuptake of norepinephrine? I hope I'm making sense. I'm just hoping that going up to the 150mg serequel will be a worthwhile move on my part and that there will be some antidepressant efficacy beginning soon. Thanks again for all of your help. 

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