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Dr. Bob is Robert Hsiung, MD,
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Posted by Mtom on August 14, 2020, at 10:21:24
Long and complicated (as my posts tend to be). When my depression started a good number of years ago, I started finding myself unable to contain my temper. Have always been a bit temperamental, but became frequent and intense.
As depression worsened, so did my temper (as well as anxiety). Quick to anger, frequently flying off the handle (generally just with spouse, a few times with other close family, can still control with others).
About 2 ½ years ago started on SSRIs. Long ago tried Zoloft and couldnt tolerate it so stayed away from ADs until things worsened in early 2018. Dr suggested Citalopram or Escitalopram which are generally thought to be best tolerated SSRIs. Tried Cit first it skyrocketed my anxiety, agitation, ton of other intense side effects. Three months later switched to Esc, still intensified my anxiety (although less so) and many other side-effects, even starting very low dose and increasing gradually.
It helped a small bit with temper but wasnt helping with depression and increased anxiety etc., so a year ago added very low dose Mirtazapine with intention to cross titrate slowly, increasing Mirtazapine, decreasing escitalopram. Anxiety improved a bit, and started having intermittent periods of improved depression plus greatly reduced ruminating and anger outbursts.
Last winter was temporarily as high as 12.5 mg Mirt but at that dose anxiety started increasing again (I was also still taking low dose Escitalopram). Dr and I thought maybe the Norepinephrine (Noradrenaline) effect of Mirtazapine had kicked in and was adding to the anxiety effect of the Escitalopram, so backed down to about 8 mg Mirt which helped.
Had a few relatively good months. But I could still feel the Escitalopram side effects, wanted rid of them so weaned off it over the last couple of months.
As I weaned down to tiny doses of Esc, I started to fly off the handle with anger again. Was then still taking only 8 mg Mirt. Then I stopped Esc completely about 3 ½ weeks ago.
Since reducing and stopping Esc, some of its side effects have improved. But anger has increased and I stopped getting much depression relief from the Mirt anymore at this dose. Plus Im ruminating more again although taking Esc on its own hadnt stopped that, only adding Mirt did.
My doctor thinks now that Im off Escitalopram I need to start titrating Mirtazapine higher to make up for this. Does this seem to make sense? I started titrating it up 2 weeks ago and now am at 10 mg, will keep increasing slowly. I know 15 mg is usual starting dose, but Im ultra sensitive.
Im concerned about this anger (and more depression and ruminating) returning. Hoping as I increase Mirt it will improve and as Im no longer taking Esc hoping the anxiety wont kick in with higher Mirt doses as it did last winter.
OR. Is it possible Im still feeling residual withdrawal effects from stopping the Escitalopram? Anxiety and brain fog etc. did increase as I stopped Esc and I had a particularly rough period my last 2 weeks of taking tiny Esc doses then a couple weeks after stopping completely (things have recently improved a bit).
FYI, I am not bipolar. Ive been evaluated for this a few times and have no other symptoms for manic episodes.
Thoughts?
Posted by Mtom on August 14, 2020, at 10:23:53
In reply to Depression anger and ADs (Mirt and Esc), posted by Mtom on August 14, 2020, at 10:21:24
Just adding to the subject line of my previous post as limited space to enter long subjects. Scroll down my previous post (also below) to see question about Escitalopram withdrawal.
> Long and complicated (as my posts tend to be). When my depression started a good number of years ago, I started finding myself unable to contain my temper. Have always been a bit temperamental, but became frequent and intense.
>
> As depression worsened, so did my temper (as well as anxiety). Quick to anger, frequently flying off the handle (generally just with spouse, a few times with other close family, can still control with others).
>
> About 2 ½ years ago started on SSRIs. Long ago tried Zoloft and couldnt tolerate it so stayed away from ADs until things worsened in early 2018. Dr suggested Citalopram or Escitalopram which are generally thought to be best tolerated SSRIs. Tried Cit first it skyrocketed my anxiety, agitation, ton of other intense side effects. Three months later switched to Esc, still intensified my anxiety (although less so) and many other side-effects, even starting very low dose and increasing gradually.
>
> It helped a small bit with temper but wasnt helping with depression and increased anxiety etc., so a year ago added very low dose Mirtazapine with intention to cross titrate slowly, increasing Mirtazapine, decreasing escitalopram. Anxiety improved a bit, and started having intermittent periods of improved depression plus greatly reduced ruminating and anger outbursts.
>
> Last winter was temporarily as high as 12.5 mg Mirt but at that dose anxiety started increasing again (I was also still taking low dose Escitalopram). Dr and I thought maybe the Norepinephrine (Noradrenaline) effect of Mirtazapine had kicked in and was adding to the anxiety effect of the Escitalopram, so backed down to about 8 mg Mirt which helped.
>
> Had a few relatively good months. But I could still feel the Escitalopram side effects, wanted rid of them so weaned off it over the last couple of months.
>
> As I weaned down to tiny doses of Esc, I started to fly off the handle with anger again. Was then still taking only 8 mg Mirt. Then I stopped Esc completely about 3 ½ weeks ago.
>
> Since reducing and stopping Esc, some of its side effects have improved. But anger has increased and I stopped getting much depression relief from the Mirt anymore at this dose. Plus Im ruminating more again although taking Esc on its own hadnt stopped that, only adding Mirt did.
>
> My doctor thinks now that Im off Escitalopram I need to start titrating Mirtazapine higher to make up for this. Does this seem to make sense? I started titrating it up 2 weeks ago and now am at 10 mg, will keep increasing slowly. I know 15 mg is usual starting dose, but Im ultra sensitive.
>
> Im concerned about this anger (and more depression and ruminating) returning. Hoping as I increase Mirt it will improve and as Im no longer taking Esc hoping the anxiety wont kick in with higher Mirt doses as it did last winter.
>
> OR. Is it possible Im still feeling residual withdrawal effects from stopping the Escitalopram? Anxiety and brain fog etc. did increase as I stopped Esc and I had a particularly rough period my last 2 weeks of taking tiny Esc doses then a couple weeks after stopping completely (things have recently improved a bit).
>
> FYI, I am not bipolar. Ive been evaluated for this a few times and have no other symptoms for manic episodes.
>
> Thoughts?
Posted by linkadge on August 14, 2020, at 14:32:59
In reply to Depression anger and ADs (Mirt and Esc), posted by Mtom on August 14, 2020, at 10:21:24
My first antidepressant was citalopram and it was soon after augmented with mirtazapine. So, I know this combination well. I've had some issues with anger myself, but I can attest to two things:
1) SSRI withdrawal can definitely increase anger
2) Mirtazapine can also cause angerMirtazapine has a few effects which can increase anger. The first is the 5-ht2c antagonism. Activating this receptor tends to inhibit aggression and mirtazapine blocks the receptor (which can increase anger). The 2nd effect is the alpha-2 antagonism (which as you mentioned will increase norepinephrine output). Some other drugs which block this receptor can also cause this effect. The third property is the antihistamine effect. This can make you tired and less able to process feelings of anger. It can also increase appetite which can lead to being 'hangry' (hungry + angry).
I tried going off citalopram and onto mirtazapine only, but it wasn't quite effective enough (had feelings of sadness that wouldn't go away). Also, the irritability got worse during this transition. Theoretically it is possible you **may** notice an improvement in anger with a higher dose. Depression itself can cause anger and so if you get a resolution in your depression this may resolve. However, don't beat yourself up if you don't.
You have a few options which I would recommend:
1) take a very low dose of escitalopram (I'm not sure if you can get it in liquid form). Even 2.5mg of escitalopram can help offset some of the mirtazapine effect.
2) try a small dose of a mood stabilizer like tegregol. Even though you aren't bipolar, small doses of mood stabilizers can really take the edge off. I have a *possible* diagnosis of bipolar (like you I have found antidepressants very hard to tolerate anxiety wise). However, I have found that small doses of meds like tegretol, lamictal, or lithium to really help and are remarkably easy to tolerate (actually easier than antidepressants). Tegretol totally chilled me out. Anticonvulsants can calm the temporal lobes which tend to fire erratically when people get pissy. Gabapentin / pregabalin may also be worth asking about.
3) supplements like omega-3, magnesium, niacin or vitamin C can help buffer excess adrenaline release.
4) a bit of 5-htp may help both anger and SSRI withdrawal. I have taken 5-htp together with mirtazapine without any problems.
Linkadge
Posted by Mtom on August 14, 2020, at 15:24:52
In reply to Re: Depression anger and ADs (Mirt and Esc), posted by linkadge on August 14, 2020, at 14:32:59
Thanks Linkadge, you have lots of experience, it's good to bounce thoughts off you.
However, my anger got significantly better "after" I added on Mirtazapine a year ago, so that doesn't seem to be the cause of this sudden relapse. I had been on Escitalopram about 8 months before adding Mirt and still had anger issues through that time, although maybe slightly less than when taking nothing. And I did take just 2.5 mg of Escitalopram with the Mirt for some time (I had reduced Esc to this dose some time after starting Mirt and I did feel somewhat better after reducing Esc which, as noted, always gave me a ton of side-effects, not that Mirt is without them, just different). The anger started coming back only when I lowered my Esc dose more (using a razor knife) and then stopped it entirely. The reason I've been thinking maybe I've been having a withdrawal effect is because Escitalopram on it's own did not help much with anger, whereas adding Mirtazapine did quite signficantly.
I felt groggy/drowsy in the morning when first starting Mirt, but that mostly went away over time (although I still linger a bit in bed in the morning).
I have put on some weight (OK as I was underweight), but strangely, my appetite is if anything decreased (to the point where I've sometimes been a bit concerned, but I'm quite nutrition conscious and eat a wide variety of all food groups - excluding high glycemic carbs).
I think anticonvulsants might have been discussed some time back with my Dr., she must have been reluctant but will have to ask.
I've been taking high EPA Fish Oil for several years, Magnesium Glycinate daily, upped my Vitamin C when Covid broke out.
I once took 5HTP on it's own (no AD) and became increasingly anxious on it. I seem to be very sensitive to things that increase serotonin activity.
As the last few days have been slightly but noticeably better, I'm thinking it might have been the remnants of SSRI withdrawal making me feel worse and increasing hostility (and I had other symptoms that are noted as discontinuation symptoms). I think I'll stick to 10 mg Mirt another week, then increase again slightly.
> My first antidepressant was citalopram and it was soon after augmented with mirtazapine. So, I know this combination well. I've had some issues with anger myself, but I can attest to two things:
>
> 1) SSRI withdrawal can definitely increase anger
> 2) Mirtazapine can also cause anger
>
> Mirtazapine has a few effects which can increase anger. The first is the 5-ht2c antagonism. Activating this receptor tends to inhibit aggression and mirtazapine blocks the receptor (which can increase anger). The 2nd effect is the alpha-2 antagonism (which as you mentioned will increase norepinephrine output). Some other drugs which block this receptor can also cause this effect. The third property is the antihistamine effect. This can make you tired and less able to process feelings of anger. It can also increase appetite which can lead to being 'hangry' (hungry + angry).
>
> I tried going off citalopram and onto mirtazapine only, but it wasn't quite effective enough (had feelings of sadness that wouldn't go away). Also, the irritability got worse during this transition. Theoretically it is possible you **may** notice an improvement in anger with a higher dose. Depression itself can cause anger and so if you get a resolution in your depression this may resolve. However, don't beat yourself up if you don't.
>
> You have a few options which I would recommend:
>
> 1) take a very low dose of escitalopram (I'm not sure if you can get it in liquid form). Even 2.5mg of escitalopram can help offset some of the mirtazapine effect.
>
> 2) try a small dose of a mood stabilizer like tegregol. Even though you aren't bipolar, small SAMe has been studied as an adjunctive therapy to antidepressant drugsof mood stabilizers can really take the edge off. I have a *possible* diagnosis of bipolar (like you I have found antidepressants very hard to tolerate anxiety wise). However, I have found that small doses of meds like tegretol, lamictal, or lithium to really help and are remarkably easy to tolerate (actually easier than antidepressants). Tegretol totally chilled me out. Anticonvulsants can calm the temporal lobes which tend to fire erratically when people get pissy. Gabapentin / pregabalin may also be worth asking about.
>
> 3) supplements like omega-3, magnesium, niacin or vitamin C can help buffer excess adrenaline release.
>
> 4) a bit of 5-htp may help both anger and SSRI withdrawal. I have taken 5-htp together with mirtazapine without any problems.
>
> Linkadge
>
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Posted by Lamdage22 on August 14, 2020, at 21:29:42
In reply to Re: Depression anger and ADs (Mirt and Esc), posted by linkadge on August 14, 2020, at 14:32:59
+1. Luckily I stopped before I had any outbursts. What you angry about? Do you have reason to be or are you just a "hothead"?
> 2) Mirtazapine can also cause anger
Posted by Lamdage22 on August 14, 2020, at 21:55:26
In reply to Re: Depression anger and ADs (Mirt and Esc), posted by linkadge on August 14, 2020, at 14:32:59
Could Tegretol be taken as needed and produce this calming effect?> 2) try a small dose of a mood stabilizer like tegregol. Even though you aren't bipolar, small doses of mood stabilizers can really take the edge off. I have a *possible* diagnosis of bipolar (like you I have found antidepressants very hard to tolerate anxiety wise). However, I have found that small doses of meds like tegretol, lamictal, or lithium to really help and are remarkably easy to tolerate (actually easier than antidepressants). Tegretol totally chilled me out. Anticonvulsants can calm the temporal lobes which tend to fire erratically when people get pissy. Gabapentin / pregabalin may also be worth asking about.
Posted by linkadge on August 16, 2020, at 8:21:01
In reply to Re: Depression anger and ADs (Mirt and Esc) » linkadge, posted by Mtom on August 14, 2020, at 15:24:52
When you say you feel angry, is it something that comes in bursts? (i.e. you feel fine and then just flip out), or is it kind of a lingering feeling of just being irritable for longer periods if time?
The former scenario may be indicative of more of an 'explosive' type of anger (i.e. intermittent explosive disorder) which may better respond to something like an anticonvulsant.
I personally take medical marijuanna (more CBD than THC) and it helps with anxiety and irritability. The CBD has some anticonvulsant properties.
What were your main side effects from escitalopram?
Linakdge
Posted by linkadge on August 16, 2020, at 8:22:37
In reply to Re: Depression anger and ADs (Mirt and Esc), posted by Lamdage22 on August 14, 2020, at 21:55:26
>Could Tegretol be taken as needed and produce this >calming effect?
I would say it could. Although stopping and starting it could be a bit hard on the system (depending on the dose). I remember taking 50mg of it with citalopram and it REALLY augmented the anti-anxiety effect.
Linkadge
Posted by creepy on August 18, 2020, at 3:01:14
In reply to Depression anger and ADs (Mirt and Esc), posted by Mtom on August 14, 2020, at 10:21:24
sounds a lot like me except that max dose of escitalopram actually killed the usual SSRI anger 100% it was great, except for the apathy.
citalopram made me very very irritable. fluoxetine as well.
sertraline was pretty good. vortioxetine causes irritability and apathy its very strong in that regard Im taking the smallest amount possible to stave off depression and keep the apathy from getting too bad.
Ive never found a fix for the irritability but I bet it has something to do with getting away from SSRIs which I am trying to do.
Posted by Mtom on August 18, 2020, at 10:10:09
In reply to Re: Depression anger and ADs (Mirt and Esc), posted by creepy on August 18, 2020, at 3:01:14
> sounds a lot like me except that max dose of escitalopram actually killed the usual SSRI anger 100% it was great, except for the apathy.
> citalopram made me very very irritable. fluoxetine as well.
> sertraline was pretty good. vortioxetine causes irritability and apathy its very strong in that regard Im taking the smallest amount possible to stave off depression and keep the apathy from getting too bad.
> Ive never found a fix for the irritability but I bet it has something to do with getting away from SSRIs which I am trying to do.I was already getting increasingly irritable as my depression worsened, before starting ADs. At some point on ADs the temper flares stopped and much less easily irritated. Im sure this was after I added Mirtazapine and at the same time lowered my Escitalopram dose. Escitalopram on its own made my anxiety bad and other side effects, adding Mirt helped anxiety and also helped depression and motivation, something Esc never really did much. But the improvement was inconsistent, still ups and downs and could still feel Esc side effects, even on low dose. I felt the Escitalopram could be intefering with the positive effects of the Mirtazapine.
I was still taking fairly low doses of Mirt when I tapered and stopped Esc and irritation with temper flares returned. Depression worsened, so did ruminating which had stopped when I added Mirt (Esc on its own had not helped with ruminating or much with depression adding Mirt helped both to a noticeable although inconsistent degree).
BUT, I had also reduced my Mirt dose while tapering Esc (reasons too long and complicated to explain).
I think I maybe went too low on Mirt, especially as I was also stopping Esc. Dont want to go back on Esc because I felt out of it a lot when on it, anxious, demotivated, brain fog and other things.
Talked with my Doc and am now increasing Mirt dose. I actually never quite got up to the usual starting dose really sensitive to all ADs so always start low and go slow. But think I need to get Mirt dose up to therapeutic level now that Ive stopped Esc. And it's still possible my recent issues have been withdrawal effects as I tapered then stopped Esc and decreased Mirt around same time.
You liked sertraline but I tried long ago, was awful, over the top anxiety and agitation. Were all so different. Tried Citalopram before Escitalopram, also intense agitation, anxiety, jitteryiness. Esc had slightly less intense adverse effects but still not good, just cant seem to tolerate SSRIs. Adding Mirt had improved things and Ill see how it goes with higher Mirt doses.
Posted by creepy on September 3, 2020, at 18:57:17
In reply to Re: Depression anger and ADs (Mirt and Esc), posted by Mtom on August 18, 2020, at 10:10:09
Im convinced the SSRIs are the cause of the excessive irritability. I can deal with what the depression itself brings but when I take these drugs it makes things worse.
Not sure what the mechanism is for mirtazapine. Its sedating effect? Usually for me if I take an antihistamine with SSRI Im still angry I just have no energy to direct it and it is internalized.
Posted by jay2112 on November 4, 2020, at 17:27:55
In reply to Re: Depression anger and ADs (Mirt and Esc), posted by creepy on September 3, 2020, at 18:57:17
Mirtazapine has some good serotonin antagonistic qualities. But, I found the norepinephrine effects, way too intense. I believe Escitalopram is the strongest binding to serotonin available. Risperdal can slice away at the irritability of Escitalipram. But, Risperdal has it's own risks.
Jay
Posted by undopaminergic on November 5, 2020, at 2:55:53
In reply to Re: Depression anger and ADs (Mirt and Esc) » creepy, posted by jay2112 on November 4, 2020, at 17:27:55
> Mirtazapine has some good serotonin antagonistic qualities. But, I found the norepinephrine effects, way too intense.
>It is also a very strong anti-histamine, so it typically induces some degree of sedation.
> I believe Escitalopram is the strongest binding to serotonin available.
>As far as I know, escitalopram is the most serotonin-selective, but paroxetine is the strongest.
-undopaminergic
Posted by Mtom on November 5, 2020, at 8:13:09
In reply to Re: Depression anger and ADs (Mirt and Esc) » jay2112, posted by undopaminergic on November 5, 2020, at 2:55:53
undopaminergic - re: the sedation - I found when I first started Mirtazapine, even very low doses, it would put me to sleep quickly and initially a bit groggy in the morning. But this largely wore off, especially the morning grogginess - even when I increased the dose (but still taking a low dose)
Jay2112 - In what way did you find the norepinephrine effect too intense, what were your symptoms? I seem to hit a wall of increased side-effects plus reduced efficacy when I increase my Mirtazapine over a certain, still relatively low dose. I've wondered about the norepinephrine effect becoming more predominant at increased doses and causing problems. My Doctor has been encouraging these increases because I've had only partial response to Mirtazapine at the lower doses, intermittent but inconsistent periods of feeling better, more motivated, more energetic, etc. But the trend has been that this response seems to reverse after I go beyond a certain dose.
This seems to be supported by this paper showing a u-shaped dose/response curve for most antidepressants, including Mirtazapine - where response decreases after a certain dose. Maybe my "peak" is just lower than average....
https://www.thelancet.com/action/showPdf?pii=S2215-0366%2819%2930217-2Escitalopram produced an intense anxiety-agitation-jitteryness syndrome which lessened over time but never completely went away (same thing has happened, only worse, with other SSRIs I've tried). It improved further when I reduced to a small dose of escitalopram and added Mirtazapine. One might suspect it was the antihistamine effect of Mirtazapine that was offsetting anxiety, however I seem to have built up tolerance to this effect, which I read is common with antihistamines. So I suspect it is something else in the way Mirtazapine is impacting neurotransmitters.
> > Mirtazapine has some good serotonin antagonistic qualities. But, I found the norepinephrine effects, way too intense.
> >
>
> It is also a very strong anti-histamine, so it typically induces some degree of sedation.
>
> > I believe Escitalopram is the strongest binding to serotonin available.
> >
>
> As far as I know, escitalopram is the most serotonin-selective, but paroxetine is the strongest.
>
> -undopaminergic
>
Posted by Lamdage22 on December 6, 2020, at 5:32:27
In reply to Re: Depression anger and ADs (Mirt and Esc), posted by creepy on September 3, 2020, at 18:57:17
Mirtazapine makes me angry, too.
Posted by Lamdage22 on December 6, 2020, at 5:32:51
In reply to Re: Depression anger and ADs (Mirt and Esc), posted by Lamdage22 on December 6, 2020, at 5:32:27
Its why i stopped.
This is the end of the thread.
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