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I’ve moved up to 50mg of imipramine. I’m having some issues, I’m very overstimulated. My hands a shaking it’s making me clumsy it even going to my voice. I’ve had the same issues with SSRI/SNRIs this isn’t as bad as that. I’m also very twitchy.
 

The drug is helping me with some things but I can’t work like this. 1.5mg of Ativan has hardy touched it. I don’t know if I should push through and hope it goes away or just give up. It’s really hard to concentrate. I’m not sure if I’m just very sensitive to any med that blocks reuptake. 
 

Last resort I’ve take 25mg of Seroquel.

Edited by crazyguy82
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3 hours ago, crazyguy82 said:

I’ve moved up to 50mg of imipramine. I’m having some issues, I’m very overstimulated. My hands a shaking it’s making me clumsy it even going to my voice. I’ve had the same issues with SSRI/SNRIs this isn’t as bad as that. I’m also very twitchy.

Do you think you can tolerate the effects in the short term? Highly likely that some of those side effects will go away or become less intense as you adjust to the increase in dosage. 

3 hours ago, crazyguy82 said:

The drug is helping me with some things but I can’t work like this. 1.5mg of Ativan has hardy touched it. I don’t know if I should push through and hope it goes away or just give up. It’s really hard to concentrate. I’m not sure if I’m just very sensitive to any med that blocks reuptake. 

Have you ever had gene testing done? Like GeneSight or any of those other psych genetic panels that one can do? It may provide guidance as to whether or not reuptake inhibition is something you definitely want to stay away from.

3 hours ago, crazyguy82 said:

Last resort I’ve take 25mg of Seroquel.

Does 25mg of Seroquel help when 1.5mg of Ativan doesn't?

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Yes I can tolerate this in the short term no problem. It worries me it won’t go away like the other meds.

It is very odd that the Ativan didn’t control it 1mg normally plenty. I ended up taking 50mg of Seroquel. It took a little while but it stopped. I fell asleep for an hour or so and woke up feeling calm but tired.

Im wondering if it is interacting with the lamotragine as that is quite stimulating. I used to have a tremor with Moclobermide but  much less. On a bad day I used the Ativan to control it.

Any way I can always stop taking it 50mg isn’t a huge dose to come off.

I don’t think we have that gene sight in the uk but I will check.

Update. I have found something similar I have emailed them for information.

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15 hours ago, crazyguy82 said:

Yes I can tolerate this in the short term no problem. It worries me it won’t go away like the other meds.

Not likely. You'll most likely adjust if you were able to with your previous medications. If you weren't able to tolerate SSRIs or SNRIs though, the prognosis with tricyclic antidepressants isn't great. Although the improved efficacy may override that. Only time will tell.

15 hours ago, crazyguy82 said:

It is very odd that the Ativan didn’t control it 1mg normally plenty. I ended up taking 50mg of Seroquel. It took a little while but it stopped. I fell asleep for an hour or so and woke up feeling calm but tired.

So this tells me that maybe the agitation is serotonergic in nature. I imagine you felt this way starting up on SSRIs and SNRIs as well? Initially, serotonergic activation from serotonin reuptake inhibition can cause some pretty serious agitation, and it's fairly normal to control SRI startup effects with benzodiazepines like Ativan (lorazepam). However, the fact that quetiapine is what did it for you tells me that blunting the effects at serotonin receptors helps to calm things for you. So my next question would be whether or not you could get in the habit of taking quetiapine at bedtime every night instead of taking it as a PRN ("as needed").

15 hours ago, crazyguy82 said:

Im wondering if it is interacting with the lamotragine as that is quite stimulating. I used to have a tremor with Moclobermide but  much less. On a bad day I used the Ativan to control it.

Not likely. Lamotrigine is a glutamate reducing agent, but in some ways it can increase glutamate output in some areas. And this is why lamotrigine can be activating in the beginning. Imipramine may have a similar effect but it's downstream of its effects on serotonin. Inhibit the serotonin transporter, serotonin builds up in the synapse, 5HT1A receptors became hyper-activated, leading to increases in downstream release of dopamine, further downstream release of glutamate, which then REDUCES dopamine release. Checks and balances in the brain are weird. So now that I think about it, because lamotrigine can in some ways potentiate glutamate signaling, it's possible I suppose that the initial imipramine period may in some ways feel similar to starting up on lamotrigine, or lamotrigine may be making you more sensitive to the startup effects of SRIs. Either way, a benzodiazepine should be able to control it, but more may be required, and round the clock coverage may be required as well.

So for me, my pdoc would prescribe clonazepam 0.5mg tablets. Then he would have me take half a tablet in the morning, half a tablet around noon, and a whole tablet around 6PM. That would give me 1mg in a day, and clonazepam has such a long half-life that if you take it continuously, after a few days, the sedation goes away and you just generally feel quite calm. Then you slowly reduce your dose. Perhaps first by eliminating the noon dose, then reducing the evening dose to half a tablet, then eliminating the morning dose, then after several days eliminate the evening dose altogether.

Still, the fact that quetiapine was more effective makes me wonder if you should just continue with daily lamotrigine/imipramine/quetiapine, then you probably wouldn't need the lorazepam during the day or the zopiclone at night because quetiapine can handle that. Better not to use benzo's or Z-drugs long term if you can help it.

15 hours ago, crazyguy82 said:

Any way I can always stop taking it 50mg isn’t a huge dose to come off.

I don’t think we have that gene sight in the uk but I will check.

Update. I have found something similar I have emailed them for information.

Oh good! I always forget that those tests aren't as readily available overseas. Glad you found one though! What's it called?

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Thanks for the post it must have take you ages to type.

I already take 300mg of Seroquel at bedtime. Its not very often I take it in the day. It worked well. It has been better today. Bit grim this morning and much better this afternoon. 

I had a tremor on Moclobermide especially in the morning. I don’t mind that as long as it doesn’t effect my voice.

I take 3.75mg of Zopiclone each night I sometimes take 7.5 mg. I really hope it getter better, I think this medication could be helpful. Something happened today that would normal upset me and it didn’t. That’s a big deal for me.

i will stay with the 50mg for 3 weeks and review it from there. My consultant was looking for a dose of at least 100mg. I am really jumping the gun I have only been taking it for 2 weeks. My experience with other meds is perhaps causing anxiety as I’m expecting the same.

That testing is super expensive if imipramine fails I will give it ago. It’s called myogenes.The only option left is MAOI as I did well on Moclobermide it does sound like a good last resort option. 
 

I forgot to say I could tolerate citalopram it did help my mood but not anxiety. Mirtazapine was great but it stoped working after about 8 months. 75mg of Effexor was fine anymore cased agitation. I took Cymbalta for about a year but it felt too strong. I had start up effects effects but it did get better after 4 weeks. Prozac wasn’t good I lasted 2 weeks it made me suicidal. I don’t generally have suicidal thoughts. I think my brain is very complicated when it come to ADs.

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12 hours ago, Iceberg said:

out of curiosity, was there ever any mention of combining the Effexor and mirtazapine? that is somewhat of a go to for difficult cases, but not sure if they really do that where you are 

I have tried that I put on a load of weight very quickly. I found it was far to powerful, I’ve found stronger isn’t always better.

12 hours ago, Iceberg said:

do you have vortioxetine as an option? 

I haven’t heard of this before could be a option.

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22 hours ago, crazyguy82 said:

I already take 300mg of Seroquel at bedtime. Its not very often I take it in the day. It worked well. It has been better today. Bit grim this morning and much better this afternoon. 

Ah okay. I didn't realize that Seroquel was a daily medication for you. So what are your total daily doses of everything?

22 hours ago, crazyguy82 said:

i will stay with the 50mg for 3 weeks and review it from there. My consultant was looking for a dose of at least 100mg. I am really jumping the gun I have only been taking it for 2 weeks. My experience with other meds is perhaps causing anxiety as I’m expecting the same.

Yeah try not to expect side effects, because then they will definitely happen. You know that.

22 hours ago, crazyguy82 said:

That testing is super expensive if imipramine fails I will give it ago. It’s called myogenes.The only option left is MAOI as I did well on Moclobermide it does sound like a good last resort option. 
 

Yes it looks like they use the same Genecept assay that's used by one of the major companies over here in the States. Most importantly regarding the test is that it probably won't reliably tell you what WILL work for you but rather what WON'T so that the merry go round of medications is less of a process of elimination.

22 hours ago, crazyguy82 said:

I forgot to say I could tolerate citalopram it did help my mood but not anxiety. Mirtazapine was great but it stoped working after about 8 months. 75mg of Effexor was fine anymore cased agitation. I took Cymbalta for about a year but it felt too strong. I had start up effects effects but it did get better after 4 weeks. Prozac wasn’t good I lasted 2 weeks it made me suicidal. I don’t generally have suicidal thoughts. I think my brain is very complicated when it come to ADs.

I'd be curious then if escitalopram may work for you. It's arguably more potent than citalopram and better for anxiety too in my experience. The fact that you tolerated mirtazapine for so long but can't get higher than 75mg on Effexor and think Cymbalta is too strong tells me that energizing antidepressants aren't what you're looking for. That rules out a good amount of them but leaves you with citalopram, escitalopram, and paroxetine. The remaining ones: sertraline, fluoxetine, duloxetine, venlafaxine, et. al. would just be stimulating for you.

4 hours ago, crazyguy82 said:

I have tried that I put on a load of weight very quickly. I found it was far to powerful, I’ve found stronger isn’t always better.

I haven’t heard of this before could be a option.

In the U.K. vortioxetine is called Brintellix. It should be available to you now that you've tried several different antidepressant options.

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So currently I’m taking 300mg IR Seroquel at bed time. 100mg IR in the day I don’t take it, but I can I don’t like the tired feeling. 
 

300mg lamictal I spread this out 100mg x3. Imipramine currently 50mg. Zopiclone at night mostly 3.75mg sometimes 7.5mg. I get 28mg of Ativan per month I use this as little I can, I have been on it all the time it was a bitch to get it down to PRN.

I would give mirtazapine another go but I’m worried about the weight gain with Seroquel. I am lucky that Seroquel doesn’t cause me any issues with weight. Long term lorazepam did cause weight gain.

My consultant is quite good they give me control over my meds. If I asked for more Seroquel or Lamictal they say yes. I don’t ever ask for any more Ativan or Zopiclone they just let that ride. It’s never spoken about.I have quite a good stock of meds.

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Brintellix might be worth trying before an MAOI, as some find it to work better than SSRIs and it would probably be less of a pain in the ass... although maybe expensive. While its efficacy may not be as proven as some MAOI options, it may also be able to work without causing the "too strong" effect you described in previous combo 

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1 hour ago, Iceberg said:

Brintellix might be worth trying before an MAOI, as some find it to work better than SSRIs and it would probably be less of a pain in the ass... although maybe expensive. While its efficacy may not be as proven as some MAOI options, it may also be able to work without causing the "too strong" effect you described in previous combo 

It’s more modern and doesn’t have all the interactions. As I’m in the UK I don’t pay anything for my medications. The NHS gets them far cheaper than you pay in the US. If the imipramine is a flop I was ask for it.

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i had increased anhedonia when i started on clomipramine, and not too long after a dose increase i found it eased up quite a lot. clomipramine is a TCA, not an SSRI, but i figured i'd drop my two cents in.

if you're experiencing anhedonia as a side effect of a med, it would follow that raising/lowering the dose could have an effect. some ADs can be more stimulating at higher doses, which sometimes helps. i also know low-dose abilify is sometimes used as an adjunct to an AD due to it's energizing effects. what i've gathered from hanging around here is that anhedonia seems to be harder to treat/cure than other depression symptoms, and doesn't tend to resolve itself without psychotropic intervention.

what's your daily zoloft dose?

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On 5/29/2020 at 10:07 AM, crazyguy82 said:

So currently I’m taking 300mg IR Seroquel at bed time. 100mg IR in the day I don’t take it, but I can I don’t like the tired feeling. 
 

300mg lamictal I spread this out 100mg x3. Imipramine currently 50mg. Zopiclone at night mostly 3.75mg sometimes 7.5mg. I get 28mg of Ativan per month I use this as little I can, I have been on it all the time it was a bitch to get it down to PRN.

I would give mirtazapine another go but I’m worried about the weight gain with Seroquel. I am lucky that Seroquel doesn’t cause me any issues with weight. Long term lorazepam did cause weight gain.

My consultant is quite good they give me control over my meds. If I asked for more Seroquel or Lamictal they say yes. I don’t ever ask for any more Ativan or Zopiclone they just let that ride. It’s never spoken about.I have quite a good stock of meds.

This is really hard to put a finger on. I didn't realize you were on doses of quetiapine and lamotrigine that high. That speaks more to a treatment for bipolar depression than anything, and the fact that any sort of serotonin reuptake inhibitor makes you anxious (including the imipramine that you're currently trying) also makes me think serotonin antagonists are actually going to be your drug of choice. However, what's notable with quetiapine at that dose is the prominent norepinephrine reuptake inhibition (NRI). It's possible that this may make you feel nervous during the day. With the NRI effect combined with antagonism of pre-synaptic alpha-2 adrenergic receptors, there would be even further adrenergic output. This can make you feel a persistent fight-or-flight response, or in constant state of stress in a manner of speaking.

Believe it or not, my recommendation would be to talk to your pdoc about reducing your quetiapine and lamotrigine. Going down on quetiapine may make you feel less "revved up", thus less need for lorazepam during the day. The lower dose may also make it easier to sleep without zopiclone or lower zopiclone dose / less frequency. Also, most of the data shows that lamotrigine doesn't usually provide additional benefit above 200mg. It may be worth talking to your pdoc about 100mg twice a day, or 50mg in the AM and 150mg in the PM.

From there, if your anxiety has improved but you're still depressed, it may be worth talking to your pdoc about adding a little bupropion. I see from your signature that one isn't listed as a previous trial. Although you're in the U.K. and I believe that the Royal College of Psychiatrists in London has yet to accept/appreciate bupropion's antidepressant effects, preferring instead to use it only for smoking cessation. However, in the U.S. bupropion/quetiapine is a popular combo due to bupropion's low propensity for causing manic switch. Its norepinephrine-dopamine preferring profile also complements quetiapine's pharmacodynamics. This combination may be dicey because there's a 50/50 chance it can bring your anxiety back or make it worse, but there's also a chance it could reduce your anxiety further. Would just be curious what it would do for your sleep.

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On 4/3/2020 at 6:04 AM, Blahblah said:

This makes sense. I initially was given Bupropion to counter the indifference, but that did nothing, seems a weak DRI (or maybe if you lack Dopamine in general, there's too little there for re-uptake?) This is the reason why pdoc added ritalin (a miracle at first, and now, not so much)...

What was your dose of Bupropion ? Bupropion is a relatively weak DNRI but works fine at 300 mg, prefabilly 450 mg. Look at the receptor affinities and you will see. So you counter with a high dose. 

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3 hours ago, browri said:

This is really hard to put a finger on. I didn't realize you were on doses of quetiapine and lamotrigine that high. That speaks more to a treatment for bipolar depression than anything, and the fact that any sort of serotonin reuptake inhibitor makes you anxious (including the imipramine that you're currently trying) also makes me think serotonin antagonists are actually going to be your drug of choice. However, what's notable with quetiapine at that dose is the prominent norepinephrine reuptake inhibition (NRI). It's possible that this may make you feel nervous during the day. With the NRI effect combined with antagonism of pre-synaptic alpha-2 adrenergic receptors, there would be even further adrenergic output. This can make you feel a persistent fight-or-flight response, or in constant state of stress in a manner of speaking.

Believe it or not, my recommendation would be to talk to your pdoc about reducing your quetiapine and lamotrigine. Going down on quetiapine may make you feel less "revved up", thus less need for lorazepam during the day. The lower dose may also make it easier to sleep without zopiclone or lower zopiclone dose / less frequency. Also, most of the data shows that lamotrigine doesn't usually provide additional benefit above 200mg. It may be worth talking to your pdoc about 100mg twice a day, or 50mg in the AM and 150mg in the PM.

From there, if your anxiety has improved but you're still depressed, it may be worth talking to your pdoc about adding a little bupropion. I see from your signature that one isn't listed as a previous trial. Although you're in the U.K. and I believe that the Royal College of Psychiatrists in London has yet to accept/appreciate bupropion's antidepressant effects, preferring instead to use it only for smoking cessation. However, in the U.S. bupropion/quetiapine is a popular combo due to bupropion's low propensity for causing manic switch. Its norepinephrine-dopamine preferring profile also complements quetiapine's pharmacodynamics. This combination may be dicey because there's a 50/50 chance it can bring your anxiety back or make it worse, but there's also a chance it could reduce your anxiety further. Would just be curious what it would do for your sleep.

Much of that makes sense!

I thought the lamotragine dose was to high myself. I decreased to 275mg last week and to 250mg this week, and work down to 200mg. I am having memory issues and mind blanks.

The results with imipramine have so far been good. I am anxious that will never change and I have been in a better mood. The agitation and restless is acceptable, significantly lower than SSRI and SNRIs apart from citalopram, up to 30mg dose.

Ive taken 300mg or quetiapine for 10 years. It’s never occurred to me that it could cause stimulation. Around what dose were you thinking? 200mg?  I have an appointment in 3 weeks time with my Pdoc, I will bring it up. I can’t split the 300mg tablets they a like bullets. I think she will say no at them moment. My failed attempt with Prozac a few weeks back screwed me right up.

Ditching the Zopiclone sounds like a great idea, that imipramine dose knock me out it my not be needed. I hadn’t thought of that. I am taking another 4 weeks off work so plenty of time of time for trial and error.

Are you a doctor or same kind you seem to know your stuff. My new psychiatrist is really good. I had a rubbish one for years, he was very heavy handed with medication. I didn’t trust him very much, he tried to put me on mirtazapine with Moclobermide that wasn’t a good idea. I declined because of the weight issues in the past.

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3 hours ago, crazyguy82 said:

Much of that makes sense!

I thought the lamotragine dose was to high myself. I decreased to 275mg last week and to 250mg this week, and work down to 200mg. I am having memory issues and mind blanks.

The results with imipramine have so far been good. I am anxious that will never change and I have been in a better mood. The agitation and restless is acceptable, significantly lower than SSRI and SNRIs apart from citalopram, up to 30mg dose.

Ive taken 300mg or quetiapine for 10 years. It’s never occurred to me that it could cause stimulation. Around what dose were you thinking? 200mg?  I have an appointment in 3 weeks time with my Pdoc, I will bring it up. I can’t split the 300mg tablets they a like bullets. I think she will say no at them moment. My failed attempt with Prozac a few weeks back screwed me right up.

Make sure anything you do is done with your doctor's approval. The concern with lamotrigine is decreasing too fast and precipitating seizures, although it looks like you did take it slowly which is good at least. The likelihood any mind blanks were coming from lamotrigine is pretty high. On 200mg myself, I had plenty of issues with word recall specifically.

It's possible that SSRIs and SNRIs can cause true restlessness for some people. I mentioned in a previous post that imipramine has anticholinergic effects and this may be helping you to tolerate the SRI and NRI effects.

And yes, with quetiapine, starting around 150mg to 200mg, there is a norepinephrine stimulating effect that picks up and becomes stronger as you get to 300mg. From there, it generally doesn't increase considerably and is drowned out by blockade of adrenergic receptors.As I said previously, between that and the alpha-2 antagonism, it's liable to possibly make you feel "nervous" even though your general anxiety level may be lower. Said another way, perhaps you have less anxiety "spiking" during the day and a more steady low level nervousness that never goes away. Nervousness is a known side effect of quetiapine, albeit less common unless your sensitive to those kinds of things.

3 hours ago, crazyguy82 said:

Ditching the Zopiclone sounds like a great idea, that imipramine dose knock me out it my not be needed. I hadn’t thought of that. I am taking another 4 weeks off work so plenty of time of time for trial and error.

Hey if you're taking time off work, even better. Now is definitely the time to figure this stuff out before you have to get back to it. I hate doing med changes and having to work at the same time. Sometimes it's fine, but sometimes it's just miserable.

3 hours ago, crazyguy82 said:

Are you a doctor or same kind you seem to know your stuff. My new psychiatrist is really good. I had a rubbish one for years, he was very heavy handed with medication. I didn’t trust him very much, he tried to put me on mirtazapine with Moclobermide that wasn’t a good idea. I declined because of the weight issues in the past.

Nope :) I just read more than I probably should. But my pdoc has told me before that he thinks I may have missed my calling soooooooo....... ;) 

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