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Moderately-Dosed Mirtazapine w/ Low- to Moderately-Dosed SNRI (California Rocket Fuel et. al)

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Looking to hear different experiences combining mirtazapine with any of the following: venlafaxine, desvenlafaxine, duloxetine, bupropion, or any other similar norepinephrine-heavy antidepressant.

I was taking a combination of Depakote/Trintellix/Rexulti/Vyvanse. Have been experiencing some serious mania and heavy drinking and recently discontinued the Trintellix+Rexulti until my pdoc appt this coming Wednesday when we can talk about it in greater depth. We may decide to continue Trintellix, Rexulti, or both. However, I am also seriously considering other options if my pdoc will consider them, this being one of them.

Currently, to bring the mania in check I've been taking Depakote ER 1500mg at bedtime and Klonopin up to 1mg/day divided tid. I've also been continuing my Vyvanse so that I can continue working. My desire for alcohol has pretty much disappeared over the past three days as these changes have set in. I feel kinda slow and my husband thinks I'm mopey, but I'm not irritable or snappy, and I'm still getting things done around the house and being productive. I'm signed into work and (sort of) getting things done. So in that regard, I'm being a better human being than I was before I suppose. But I know this is unsustainable. My last doses of Trintellix+Rexulti were Thursday evening, and I know that they have long half-lives. It'll take some time before real depression rears its ugly head again, but it will happen. It always does, and I kinda want to get in front of it.

The reason why I ask about mirtazapine, especially in the context of norepinephrine reuptake inhibitors is because in the past, my depression has responded well to olanzapine, which has some strong 5HT2 and alpha-2 antagonism like mirtazapine. They also share potent antihistamine effects, but mirtazapine isn't a considerable anticholinergic so even though there's weight gain, there shouldn't be considerable effect on "metabolics". Pair that with the fact that my favorite antidepressants were always the SNRIs. They were far more motivating than any other antidepressant I took, Trintellix being the exception.

Mirtazapine also has a lot of data for depression and comorbid alcoholism, and if I get up to 30mg or so and it isn't enough, I can always add duloxetine in 20mg increments if my pdoc is open to it.

Thoughts

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10 hours ago, browri said:

Looking to hear different experiences combining mirtazapine with any of the following: venlafaxine, desvenlafaxine, duloxetine, bupropion, or any other similar norepinephrine-heavy antidepressant.

I was taking a combination of Depakote/Trintellix/Rexulti/Vyvanse. Have been experiencing some serious mania and heavy drinking and recently discontinued the Trintellix+Rexulti until my pdoc appt this coming Wednesday when we can talk about it in greater depth. We may decide to continue Trintellix, Rexulti, or both. However, I am also seriously considering other options if my pdoc will consider them, this being one of them.

Currently, to bring the mania in check I've been taking Depakote ER 1500mg at bedtime and Klonopin up to 1mg/day divided tid. I've also been continuing my Vyvanse so that I can continue working. My desire for alcohol has pretty much disappeared over the past three days as these changes have set in. I feel kinda slow and my husband thinks I'm mopey, but I'm not irritable or snappy, and I'm still getting things done around the house and being productive. I'm signed into work and (sort of) getting things done. So in that regard, I'm being a better human being than I was before I suppose. But I know this is unsustainable. My last doses of Trintellix+Rexulti were Thursday evening, and I know that they have long half-lives. It'll take some time before real depression rears its ugly head again, but it will happen. It always does, and I kinda want to get in front of it.

The reason why I ask about mirtazapine, especially in the context of norepinephrine reuptake inhibitors is because in the past, my depression has responded well to olanzapine, which has some strong 5HT2 and alpha-2 antagonism like mirtazapine. They also share potent antihistamine effects, but mirtazapine isn't a considerable anticholinergic so even though there's weight gain, there shouldn't be considerable effect on "metabolics". Pair that with the fact that my favorite antidepressants were always the SNRIs. They were far more motivating than any other antidepressant I took, Trintellix being the exception.

Mirtazapine also has a lot of data for depression and comorbid alcoholism, and if I get up to 30mg or so and it isn't enough, I can always add duloxetine in 20mg increments if my pdoc is open to it.

Thoughts

Will your pdoc be ok initiating a combo of ADs this close to a breakthrough of manic symptoms? 

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11 hours ago, Iceberg said:

Will your pdoc be ok initiating a combo of ADs this close to a breakthrough of manic symptoms? 

Oh no definitely not a combo. To be clear, the manic episode and its corresponding symptoms have largely resolved with a few days of just Depakote and Klonopin. So I do think he will re-introduce an antidepressant today (appt moved up to 11:15AM Eastern), but I'm hoping for a different one.

Early on in my treatment, we realized that the doses of atypical antipsychotics I needed to control my mood symptoms were doses I couldn't tolerate due to side effects. However, I can tolerate fairly high doses of anti-convulsants which do a fairly good job at controlling my mania. Right now without an antidepressant on-board and just doing Depakote/Klonopin/Vyvanse, I'm cool as a cucumber. But invariably as the half-lives of Trintellix and Rexulti wear off (2-3 weeks for total wash-out) I will likely start to feel depression again. It is the middle of Winter and I just always generally learn towards the depressive side of things.

I'm wondering if I'm finding something similar with my antidepressant. Historically, my depression responded really well to olanzapine, which is another 5HT2A/2C antagonist and alpha-2 antagonist. I'm wondering if it will respond well to mirtazapine due to the similar pharmacological qualities, not to mention mirtazapine is also a 5HT3 antagonist like Trintellix, which should help with depression as well. Antidepressant effect through antagonism overall.

THEN, if I get to 30mg on mirtazapine and go for several weeks and find it's just not enough, we add back in an SNRI in small increments. My preference would be to just drop in at 50mg of desvenlafaxine OR start at 20mg of duloxetine and increase every few weeks to a max of 60mg.

Also, I would maintain the current increased Depakote dose as well as the Klonopin to ensure mood stability while we test this theory. Admittedly, I also want to find a combination that doesn't make use of an antipsychotic at all because I don't like dopamine antagonism and my stimulant constantly fighting back and forth to keep me focused.

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16 minutes ago, browri said:

Oh no definitely not a combo. To be clear, the manic episode and its corresponding symptoms have largely resolved with a few days of just Depakote and Klonopin. So I do think he will re-introduce an antidepressant today (appt moved up to 11:15AM Eastern), but I'm hoping for a different one.

Early on in my treatment, we realized that the doses of atypical antipsychotics I needed to control my mood symptoms were doses I couldn't tolerate due to side effects. However, I can tolerate fairly high doses of anti-convulsants which do a fairly good job at controlling my mania. Right now without an antidepressant on-board and just doing Depakote/Klonopin/Vyvanse, I'm cool as a cucumber. But invariably as the half-lives of Trintellix and Rexulti wear off (2-3 weeks for total wash-out) I will likely start to feel depression again. It is the middle of Winter and I just always generally learn towards the depressive side of things.

I'm wondering if I'm finding something similar with my antidepressant. Historically, my depression responded really well to olanzapine, which is another 5HT2A/2C antagonist and alpha-2 antagonist. I'm wondering if it will respond well to mirtazapine due to the similar pharmacological qualities, not to mention mirtazapine is also a 5HT3 antagonist like Trintellix, which should help with depression as well. Antidepressant effect through antagonism overall.

THEN, if I get to 30mg on mirtazapine and go for several weeks and find it's just not enough, we add back in an SNRI in small increments. My preference would be to just drop in at 50mg of desvenlafaxine OR start at 20mg of duloxetine and increase every few weeks to a max of 60mg.

Also, I would maintain the current increased Depakote dose as well as the Klonopin to ensure mood stability while we test this theory. Admittedly, I also want to find a combination that doesn't make use of an antipsychotic at all because I don't like dopamine antagonism and my stimulant constantly fighting back and forth to keep me focused.

You don’t feel that Remeron + SNRI carries the risk of increased cycling? ... that’s an actual question I’m not trying to tell you it’s a bad idea

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6 minutes ago, Iceberg said:

You don’t feel that Remeron + SNRI carries the risk of increased cycling? ... that’s an actual question I’m not trying to tell you it’s a bad idea

No I certainly do think that combining two antidepressants in bipolar disorder carries an even higher risk of cycling than one does alone. My hope is that mirtazapine as a baseline antidepressant will carry a lower risk than an SSRI or an SNRI, but the beauty of mirtazapine is that if it is dosed appropriately, you should theoretically be able to add 20mg or 40mg of duloxetine to it in times like seasonal depression when the mirtazapine alone isn't enough

I also keep in mind that I've technically been taking two antidepressants for years now. I think anyone who has taken Rexulti can vouch that it certainly has antidepressant effects but it isn't a very good mood stabilizer. So with Trintellix+Rexulti together, I never stopped to consider that I might be a little out of control. Now I'm curious to explore the other end of the spectrum, which is mirtazapine, as a potent antihistamine and blocker of 5HT2 and alpha-2 receptors should provide that calming antidepressant effect I felt that I got from olanzapine but become more stimulating as you increase, which is not something olanzapine could really do unless you had fluoxetine on-board.

I think as people with bipolar disorder, we constantly live in risk, and our treatment is about managing that risk. For me, I think I haven't been appropriately managing the risk that is Trintellix+Rexulti, and it has culminated in a manic episode with lots of drinking, extreme irritability, etc. Drinking in particular, mirtazapine appears to be very good for depression with comorbid alcohol abuse issues due to its sedative effect.

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Well @Iceberg we're doing it. The mirtazapine part at least. Started 7.5mg this past Tuesday evening. Increase to 15mg this coming Wednesday the 20th. Then appt with pdoc on the 26th to likely increase further to 30mg. Fingers crossed.

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5 hours ago, browri said:

Well @Iceberg we're doing it. The mirtazapine part at least. Started 7.5mg this past Tuesday evening. Increase to 15mg this coming Wednesday the 20th. Then appt with pdoc on the 26th to likely increase further to 30mg. Fingers crossed.

Good luck!!!

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On 1/15/2021 at 7:34 PM, Iceberg said:

Good luck!!!

So far so good. Did 7.5mg Remeron last Tuesday evening through Saturday evening. Then last night was my first dose of 15mg. My appointment with my pdoc isn't until next Tuesday, but I'm going to call in over my lunch break to see if they have any appointments at the end of this week instead. Not sure I feel like waiting until next Tuesday.

My impressions so far: I like this med. Definitely helps my sleep. I normally have no interest in eating during the day. Now I do. I actually will eat just about anything that isn't nailed down. That's gotten a tad better as days have gone on but DAMN. I also feel the exact opposite of agitated and irritable. In fact I feel like I am in an agitation/irritability vacuum right now which is positively delightful coming from Trintellix 20mg and Rexulti 2mg which had me REALLY keyed up.

Current downside, I'm pretty sedated. I can't tell I'm taking a stimulant anymore. My behaviors are even consistent with untreated ADHD. Like distractibility. I go to sleep earlier than usual and if I didn't have to force myself to get up for work, on the weekends I'm sleeping in sometimes until 9 or so, which is unlike me. However today is the first day I haven't felt as sedated as I have been which might be consistent with the dose increase. 7.5mg Remeron can apparently be very sedating. Come to learn it doesn't necessarily get more stimulating as you increase, it just becomes less and less sedating.

Had the electric shock sensations all last week. They were the worst on like Thursday through Saturday but I don't feel them much anymore. By half-life, Trintellix should be washed out by the 22nd, Rexulti by the 28th.

Grandfather passed away last night after a long run of medical issues, randomly getting COVID-19 which was the banana peel that he slipped on to fall in his grave (my grandmother's expression). Much like how I've been feeling about everything over the past few weeks my mood oscillated between numbness and wanting to break down and cry. But I think I'm handling it fairly well.

Haven't had any cravings for alcohol either, which proved my theory kinda. But the increased Depakote and addition of Klonopin certainly hasn't hurt. That being said, I think that starting tomorrow I'm going to try simply going without daytime PRN Klonopin where possible and try to keep it to just the evening 0.5mg. I personally don't do well with chronic benzo use (>2-4 weeks).

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4 hours ago, browri said:

So far so good. Did 7.5mg Remeron last Tuesday evening through Saturday evening. Then last night was my first dose of 15mg. My appointment with my pdoc isn't until next Tuesday, but I'm going to call in over my lunch break to see if they have any appointments at the end of this week instead. Not sure I feel like waiting until next Tuesday.

My impressions so far: I like this med. Definitely helps my sleep. I normally have no interest in eating during the day. Now I do. I actually will eat just about anything that isn't nailed down. That's gotten a tad better as days have gone on but DAMN. I also feel the exact opposite of agitated and irritable. In fact I feel like I am in an agitation/irritability vacuum right now which is positively delightful coming from Trintellix 20mg and Rexulti 2mg which had me REALLY keyed up.

Current downside, I'm pretty sedated. I can't tell I'm taking a stimulant anymore. My behaviors are even consistent with untreated ADHD. Like distractibility. I go to sleep earlier than usual and if I didn't have to force myself to get up for work, on the weekends I'm sleeping in sometimes until 9 or so, which is unlike me. However today is the first day I haven't felt as sedated as I have been which might be consistent with the dose increase. 7.5mg Remeron can apparently be very sedating. Come to learn it doesn't necessarily get more stimulating as you increase, it just becomes less and less sedating.

Had the electric shock sensations all last week. They were the worst on like Thursday through Saturday but I don't feel them much anymore. By half-life, Trintellix should be washed out by the 22nd, Rexulti by the 28th.

Grandfather passed away last night after a long run of medical issues, randomly getting COVID-19 which was the banana peel that he slipped on to fall in his grave (my grandmother's expression). Much like how I've been feeling about everything over the past few weeks my mood oscillated between numbness and wanting to break down and cry. But I think I'm handling it fairly well.

Haven't had any cravings for alcohol either, which proved my theory kinda. But the increased Depakote and addition of Klonopin certainly hasn't hurt. That being said, I think that starting tomorrow I'm going to try simply going without daytime PRN Klonopin where possible and try to keep it to just the evening 0.5mg. I personally don't do well with chronic benzo use (>2-4 weeks).

I’m glad it’s so far so good! May it continue to help!

Sorry for your loss too. 

Edited by Wonderful.Cheese

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