Switching to a TCA fear of tachycardia

[SideFX]

I am due to meet with my psychiatrist and we have discussed switching to a TCA, as I am suffering from depression and panic…I am currently poly drugged and it has never truly worked. I’m 6 years on and tried to reduce pregabalin, until I hit withdrawal and have been struggling this past 2 and a half months - Any input or chance to discuss my fears and concerns would be most welcomed

[panic_down_under]

I am due to meet with my psychiatrist and we have discussed switching to a TCA, as I am suffering from depression and panic. I am currently poly drugged and it has never truly worked. I'm 6 years on and tried to reduce pregabalin, until I hit withdrawal and have been struggling this past 2 and a half months - Any input or chance to discuss my fears and concerns would be most welcomed

Assuming you're in reasonable health with no significant cardiovascular disease you're unlikely to experience significant cardio side-effects even at the maximum recommended TCA dose. For your peace of mind ask your GP to do an ECG/EKG before starting the TCA and then a few weeks after you're stabilised on an effective dose.

[SideFX]

Assuming you're in reasonable health with no significant cardiovascular disease you're unlikely to experience significant cardio side-effects even at the maximum recommended TCA dose. For your peace of mind ask your GP to do an ECG/EKG before starting the TCA and then a few weeks after you're stabilised on an effective dose.

I don’t have any heart problems that I’m aware of but tachycardia scares me so so so much and it’s a huge gamble with my life. Albeit I’m going through severe mornings of depression and anxiety most of the day !!!!! I did once try amitriptyline, whilst on 30mg mirtazapine and 30mg Duluxotine and the first time just felt very very sedated. But when I tried it again still on the above and only a few days later I just wanted it to knock me out, however I experienced extremely high heart rate and was in extreme distress. I have spoken with you before PDU it was years ago and have been through many breakdowns and lots of meds. But never a TCA except for the above experience with amitriptyline and that has made me very fearful of TCA’s - Your thoughts would be welcomed and some guidance on TCA’s too please. Feel free to ask any questions and thank you PDU

[panic_down_under]

I don't have any heart problems that I'm aware of but tachycardia scares me so so so much and it's a huge gamble with my life. Albeit I'm going through severe mornings of depression and anxiety most of the day !!!!!

Tachycardia is not necessarily life threatening in the short term for a reasonably health person and can be controlled, plus anxiety is itself a risk factor.

I did once try amitriptyline, whilst on 30mg mirtazapine and 30mg Duluxotine and the first time just felt very very sedated. But when I tried it again still on the above and only a few days later I just wanted it to knock me out, however I experienced extremely high heart rate and was in extreme distress.

...But never a TCA except for the above experience with amitriptyline and that has made me very fearful of TCA's

What happened while taking the other meds doesn't mean the same will happen with a TCA alone. Anxiety may also have been a factor. I'm not surprised that the cocktail was very sedating for mirtazapine is a very sedating antihistamine and so is amitriptyline.

Given you have panic disorder imipramine (Tofranil) may be the better TCA. It was the 'gold standard' TCA for panic disorder before SSRIs became available and the first AD I was on for PD. The recommended maximum daily dose is 200mg, or up to 300mg for hospital inpatients, however, I seem to require a strong dose to get a good result from ADs and was on 300-350mg for about 5 years. There were no cardiovascular side-effects noted in my annual ECGs.

Fwiw, in one of his books David Healy recounts how imipramine was developed and mentions that its inventor took up to 1,000mg/day while testing it for safety. Back in the 1950s drug trials were an unknown concept, the developers were also the guinea pigs.

Are you still on pregabalin and if so what is the dose? What other medications are you taking?

[SideFX]

Tachycardia is not necessarily life threatening in the short term for a reasonably health person and can be controlled, plus anxiety is itself a risk factor.



What happened while taking the other meds doesn't mean the same will happen with a TCA alone. Anxiety may also have been a factor. I'm not surprised that the cocktail was very sedating for mirtazapine is a very sedating antihistamine and so is amitriptyline.

IÂ’ve been on Mirt for over a decade and it has little sedative effect on me know. However only 10mg of Amatrip was like taking Mirt for the first time and I was glad of it to be honest and taken by surprise by the huge panic attack on the second time, with the same cocktail I think. I want something that agrees with me and wonÂ’t be hell to live with.

IÂ’m currently on the following:
30mg Mirtazipine
20mg Brintellix
10mg Diazepam
400mg Pregabalin

And took me 6 long years to be 70% ish better, but I never felt right, I was coping though with many side affects!!!!!

Given you have panic disorder imipramine (Tofranil) may be the better TCA. It was the 'gold standard' TCA for panic disorder before SSRIs became available and the first AD I was on for PD. The recommended maximum daily dose is 200mg, or up to 300mg for hospital inpatients, however, I seem to require a strong dose to get a good result from ADs and was on 300-350mg for about 5 years. There were no cardiovascular side-effects noted in my annual ECGs.

Fwiw, in one of his books David Healy recounts how imipramine was developed and mentions that its inventor took up to 1,000mg/day while testing it for safety. Back in the 1950s drug trials were an unknown concept, the developers were also the guinea pigs.

With regard to imipramine IÂ’m not sure how easy it is to get from UK pharmacies ???? I know Amatrip and Clompit are easy to getÂ…My mum was on imipramine and lorazepam for nearly 3 decades and she was fine with them.

I will be shortly meeting with a Pdoc and TCAÂ’s will be the option discussed. As I have tried reducing pregabalin and went into huge withdrawal and been up dosing with minimal success. So IÂ’m now on a roller coaster of depression anxiety and times when I feel okayish !!!! I am thinking do I need to come off Mirt and Brint to try a TCA ??? Or can I stay on low dose Mirt, as that would be less of a shock to my already sensitised CNS ??? Your thoughts PDU. I want to go into the discussion fully armed and fully informed about TCAÂ’s

BTW The meds I have previously had susses with are:

20mg Peroxatine from 2002 to 2010 (I stopped and started 3 times and the third time, it almost killed me. Having seizures and all sorts.

375mg Venlafaxine, with 30mg Mirtazipine, 25mg Diazepam from 2011 to 2017 (During this time I came off the benzo and reduced the Ven to 150mg) this reduction was a walk in the park, I was so stable.

Reason for stopping the above, always sexual dysfunction!!!

Then I went on the pill merry go round and can no longer tolerate any SRI meds, the only way I have tolerated Brint is due to Pregabalin, which has helped to mitigate some of its horrific side effects and now that is bitting me on the arse !!!!

Are you still on pregabalin and if so what is the dose? What other medications are you taking?

See above current list of 4 meds PDU any thoughts pal ???

[panic_down_under]

I'm currently on the following:
30mg Mirtazipine
20mg Brintellix
10mg Diazepam
400mg Pregabalin

And took me 6 long years to be 70% ish better, but I never felt right, I was coping though with many side affects!!!!!

Sigh Your doctor/s seem to be from the 'kitchen sink' school of prescribing. Just keep on throwing meds at the problem until hopefully they strike the 'magic' combination that cures all the patient's problems. It never works. In large part because there usually isn't any rhyme or reason behind the meds and doses selected. For example, what is the point in prescribing both diazepam and pregabalin which do essentially the same thing. Why not just increase the dose of one of them until or works and if it doesn't within its dose range discontinue it (and yes, I understand pregabalin was apparently prescribed to enable you to tolerate vortioxetine which is another crazy idea, imunho!).

With regard to imipramine I'm not sure how easy it is to get from UK pharmacies I know Amatrip and Clompit are easy to get

I have no idea whether imipramine is readily available in the UK. I'd be surprised if it isn't, but clomipramine (Anafranil) would be my second choice. Like imipramine is is only a weak antihistamine.

My mum was on imipramine and lorazepam for nearly 3 decades and she was fine with them

Having a close relative who did well on a med does improve the odds of it working for you though it isn't a guarantee. She might have done even better without the lorazepam.

As I have tried reducing pregabalin and went into huge withdrawal and been up dosing with minimal success

I suspect the only med in your cocktail that is actually doing much is the pregabalin which has me wondering how much of the withdrawal symptoms were actually just the dose dropping below its therapeutic window.

I am thinking do I need to come off Mirt and Brint to try a TCA

You won't need to come of mirtazapine, but I doubt it is actually doing much so I don't see the point of being on it. But that's an issue for another day. Yes, you will need to come off vortioxetine (Trintellix aka Brintellix). According to the NHS guideline, switching to imipramine can be done either by a cross-taper over 2-4 weeks, or by stopping vortioxetine and then starting imipramine after some days. Given the choice I'd do the cross-taper, but I suspect the Pdoc will be more comfortable with the second option [Edit: on reflection given your previous experience with amitriptyline tapering off vortioxetine before starting imipramine is probably the wiser choice]. For clomipramine you will need to taper off vortioxetine and then start on the TCA.

Imo, there also needs to be consideration given to discontinuing the diazepam as it is almost certainly inhibiting the effectiveness of vortioxetine to some degree and will have the same effect on the TCA too [1]. How much I can't say as while diazepam and the other benzodiazepines do block neurogenesis, the mechanism by which ADs (also therapy) work, pregabalin may have some protective effect on this by speeding up the maturation of the new brain cells the ADs stimulate into growth. Just how much pregabalin might be countering the effects of diazepam I can't say, but the sooner you come off it the better, although I'd wait until you're stabilised on the TCA as changing two meds at the same time is a bad idea as you can't be sure which might be causing any problems that arise.

Reason for stopping the above, always sexual dysfunction!!!

Unfortunately, there are only two ADs which do not usually cause sexual dysfunction, bupropion (Wellbutrin) and trazodone. Bupropion is by far the most stimulating AD, far too stimulating for most with anxiety disorders, though some do well on it. Trazodone might be worth considering at some later date.

There are ways of reducing the impact of sexual dysfunction.


References:

[1]
Boldrini M, Butt TH, Santiago AN, et al. (2014)
Benzodiazepines and the potential trophic effect of antidepressants on dentate gyrus cells in mood disorders.
Int J Neuropsychopharmacol. Dec;17(12):1923-33 (Abstract | Full text)

Sun Y, Evans J, Russell B, et al (2013)
A benzodiazepine impairs the neurogenic and behavioural effects of fluoxetine in a rodent model of chronic stress.
Neuropharmacology. Sep;72:20-8 (Abstract)

Song J, Zhong C, Bonaguidi MA, et al (2012)
Neuronal circuitry mechanism regulating adult quiescent neural stem-cell fate decision.
Nature. Sep 6;489(7414):150-4 (Article | Study full text)

Wu X, Castren E. (2009)
Co-treatment with diazepam prevents the effects of fluoxetine on the proliferation and survival of hippocampal dentate granule cells.
Biol Psychiatry. Jul 1;66(1):5-8 (Abstract)

See also: the 'Ugly' part of Benzodiazepines: The Good, The Bad, and the Ugly.

[SideFX]

Sigh Your doctor/s seem to be from the 'kitchen sink' school of prescribing. Just keep on throwing meds at the problem until hopefully they strike the 'magic' combination that cures all the patient's problems. It never works. In large part because there usually isn't any rhyme or reason behind the meds and doses selected. For example, what is the point in prescribing both diazepam and pregabalin which do essentially the same thing. Why not just increase the dose of one of them until or works and if it doesn't within its dose range discontinue it (and yes, I understand pregabalin was apparently prescribed to enable you to tolerate vortioxetine which is another crazy idea, imunho!).

I have to agree PDU they had lost ideas and kept throwing things at me and none, except pregabalin helped and then for short spurts


I have no idea whether imipramine is readily available in the UK. I'd be surprised if it isn't, but clomipramine (Anafranil) would be my second choice. Like imipramine is is only a weak antihistamine.

Again totally agree I think imipramine is available, but am so so scared of the consequences of change. It really really scares me that I will now lose my life to this terror !!!!


Having a close relative who did well on a med does improve the odds of it working for you though it isn't a guarantee. She might have done even better without the lorazepam.

Again totally and I told them that in hospital 6 years ago and they came back with Trazadone which did nothing, absolutely nothing

Then second hospitalisation and they came back with Brintillex and pregabalin, on top of Mirtazipine and diazepam

I suspect the only med in your cocktail that is actually doing much is the pregabalin which has me wondering how much of the withdrawal symptoms were actually just the dose dropping below its therapeutic window.

I didn’t realise how much pregabalin was doing until I went into withdrawal and now it is no longer having the same effect. It’s lost it’s helping hand now and I’m feeling really a hopeless case once more !!!! Sorry I’ve had enough of this illness and it’s taken soo much from me !!!!

You won't need to come of mirtazapine, but I doubt it is actually doing much so I don't see the point of being on it. But that's an issue for another day. Yes, you will need to come off vortioxetine (Trintellix aka Brintellix). According to the NHS guideline, switching to imipramine can be done either by a cross-taper over 2-4 weeks, or by stopping vortioxetine and then starting imipramine after some days. Given the choice I'd do the cross-taper, but I suspect the Pdoc will be more comfortable with the second option [Edit: on reflection given your previous experience with amitriptyline tapering off vortioxetine before starting imipramine is probably the wiser choice]. For clomipramine you will need to taper off vortioxetine and then start on the TCA.

I have read the NICE guidance on switching and imipramine can be cross tapered, with low dose of the TCA. But won’t I get even worse with the withdrawal from brintillex ???? And I can’t handle that !!!!

Imo, there also needs to be consideration given to discontinuing the diazepam as it is almost certainly inhibiting the effectiveness of vortioxetine to some degree and will have the same effect on the TCA too [1]. How much I can't say as while diazepam and the other benzodiazepines do block neurogenesis, the mechanism by which ADs (also therapy) work, pregabalin may have some protective effect on this by speeding up the maturation of the new brain cells the ADs stimulate into growth. Just how much pregabalin might be countering the effects of diazepam I can't say, but the sooner you come off it the better, although I'd wait until you're stabilised on the TCA as changing two meds at the same time is a bad idea as you can't be sure which might be causing any problems that arise.

Again totally agree would have to stop brintillex before starting Clomiprimine and again I’m so so scared of where that will take me and the cost of change, which could be the end of me PDU !!!
Can I ask should I still expect a response within 6–12 weeks at a therapeutic dose ????

I don’t know how I will react to a TCA and my only barometer is that time I mixed Amatriptyline with other AD’s and tachycardia scares me. I’m not bothered about sedation that’s fine as I would take before bed - Your thoughts please on my experience with amatriptyline please ????

Unfortunately, there are only two ADs which do not usually cause sexual dysfunction, bupropion (Wellbutrin) and trazodone. Bupropion is by far the most stimulating AD, far too stimulating for most with anxiety disorders, though some do well on it. Trazodone might be worth considering at some later date.


Tried both and not touching either one ever again bupropion made me angry back in 2011 and Trazadone did absolutely nothing, not a thing and caused me to fall asleep easy, but wake up every hour. So woke up 7/8 times a night, it was a terrible meditation for me !!

Im so unsure, but know I can’t continue much longer until something happens and I feel hopeless and helpless. It’s a horrible position

In the past 6 years I just battled my way through things and got to about 65/70% recovery. But never full remission as I have always had in the past. I don’t know what to do and feel wrecked by all mental health, I’ve no time for it anymore I’ve lost all hope PDU !!! Sorry !!!

There are ways of reducing the impact of sexual dysfunction.


References:

[1]
Boldrini M, Butt TH, Santiago AN, et al. (2014)
Benzodiazepines and the potential trophic effect of antidepressants on dentate gyrus cells in mood disorders.
Int J Neuropsychopharmacol. Dec;17(12):1923-33 (Abstract | Full text)

Sun Y, Evans J, Russell B, et al (2013)
A benzodiazepine impairs the neurogenic and behavioural effects of fluoxetine in a rodent model of chronic stress.
Neuropharmacology. Sep;72:20-8 (Abstract)

Song J, Zhong C, Bonaguidi MA, et al (2012)
Neuronal circuitry mechanism regulating adult quiescent neural stem-cell fate decision.
Nature. Sep 6;489(7414):150-4 (Article | Study full text)

Wu X, Castren E. (2009)
Co-treatment with diazepam prevents the effects of fluoxetine on the proliferation and survival of hippocampal dentate granule cells.
Biol Psychiatry. Jul 1;66(1):5-8 (Abstract)

See also: the 'Ugly' part of Benzodiazepines: The Good, The Bad, and the Ugly.

!!!

[panic_down_under]

am so so scared of the consequences of change.

There are only two potential consequences, the TCA doesn't work, in which case you're no worse off than you are now, or it does and in 6 months you'll be wondering what all the fuss was about.

It really really scares me that I will now lose my life to this terror !!!!

"Lose your life" because of tachycardia? Even if the TCA should trigger it tachycardia is not often fatal in the otherwise reasonably healthy and can be controlled fairly easily. Anxiety itself is a risk factor not only for heart disease, but all causes of premature death, some directly, but mostly by encouraging unhealthy behaviors such as sedentary lifestyles, poor diets, drug use, both legal and illegal, etc.

Fwiw, I've been on a very high dose of the TCA dosulepin which is the most cardio toxic AD produced for nearly 30 years. At one time it had about 70% of the UK market, but has since been removed from the British National Formulary and the UK drug regulator has recommended only psychiatrists and other special-care doctors be allowed to prescribe it to new patients. Yet, my nearly 80 yo ticker is unfazed, although I began taking a blood pressure med following a partial lung removal 18 years ago because this places extra pressure on the heart.

they came back with Trazadone which did nothing, absolutely nothing

...Trazadone did absolutely nothing, not a thing and caused me to fall asleep easy, but wake up every hour. So woke up 7/8 times a night, it was a terrible meditation for me !!

At what dose? That it sedated you suggests it was at the sub therapeutic range. Because of the way it works trazodone becomes less sedating as the dose increases and sedation is usually only minor once in the therapeutic range, especially with the slow-release formulation which is better at keeping plasma levels above the sedation threshold. It is usually not effective at doses below 225mg and most need to take at least 300mg to get a response.

But won't I get even worse with the withdrawal from brintillex ????

Possibly. If not for your experience with amitriptyline I'd be suggesting doing a cross taper to reduce the risk. Not so much because I think switching to the TCA will cause a repeat physically, but because you're possibly psychologically primed to experience it. An anxious mind can produce our worst nightmares if given half a chance. But the Pdoc will be in a better position to make that call.

Can I ask should I still expect a response within 6-12 weeks at a therapeutic dose ????

That's the usual time frame.

I've no time for it anymore I've lost all hope PDU !!!

Your situation is far from hopeless. The main problem seems to have been the medical advice you've been given. Hopefully, this is about to change. Also, have you tried therapy? The cognitive/behavioural (CBT, REBT, etc) and mindfulness therapies can be at least as effective as ADs.

[SideFX]

There are only two potential consequences, the TCA doesn't work, in which case you're no worse off than you are now, or it does and in 6 months you'll be wondering what all the fuss was about.

It’s the unknown PDU there’s a potential that in 6 months I could be in an even worse position. As Brintellix will be raising Sert for sure and that will be playing some part in me not being in the very very dark place and due to family history, I don’t want to loose my life to MH too !!!! That’s the fear not tachycardia as a side effect. So it would be a huge leap of faith to make that change and I ain’t got it in me to go on that pill merry go round again pal !!! It’s a nightmare to be in that position, when all you can think about is ending your life !!!!

"Lose your life" because of tachycardia? Even if the TCA should trigger it tachycardia is not often fatal in the otherwise reasonably healthy and can be controlled fairly easily. Anxiety itself is a risk factor not only for heart disease, but all causes of premature death, some directly, but mostly by encouraging unhealthy behaviors such as sedentary lifestyles, poor diets, drug use, both legal and illegal, etc.

I live a verity clean life excellent diet, don’t drink don’t smoke don’t do dugs. Please see response above re the tachycardia possibility. It doesn’t scare me it’s falling back into that hole…Im too old pal to fight that and hold down a job to pay the mortgage, as I live alone pal !!!

Fwiw, I've been on a very high dose of the TCA dosulepin which is the most cardio toxic AD produced for nearly 30 years. At one time it had about 70% of the UK market, but has since been removed from the British National Formulary and the UK drug regulator has recommended only psychiatrists and other special-care doctors be allowed to prescribe it to new patients. Yet, my nearly 80 yo ticker is unfazed, although I began taking a blood pressure med following a partial lung removal 18 years ago because this places extra pressure on the heart.

That’s very reassuring PDU and I don’t get on with SRI’s anymore, don’t know why, seems my body and brain have said no. So that’s why im thinking TCA and my experience with Amatrip doesn’t concern me, as it had no other side effect, it did not make anxiety fly through the roof. In fact quiet the opposite with sedation and again that doesn’t bother me…I have read that imipramine is less cardio toxic than Amatrip?????

At what dose? That it sedated you suggests it was at the sub therapeutic range. Because of the way it works trazodone becomes less sedating as the dose increases and sedation is usually only minor once in the therapeutic range, especially with the slow-release formulation which is better at keeping plasma levels above the sedation threshold. It is usually not effective at doses below 225mg and most need to take at least 300mg to get a response.

Trazadone instantly brought back my labido and we went well into the 200’s with it. It was useless and I just couldn’t stop thinking of ending my life. So then a second hospitalisation, where I was introduced to vortioxatine and pregabalin. Which didn’t give me relief. But i battled 6 years and ain’t got that left in me!!!! My Pdoc mention hospitalisation if switching to a TCA, she did seem open to the idea, which did surprise me !!!!


Possibly. If not for your experience with amitriptyline I'd be suggesting doing a cross taper to reduce the risk. Not so much because I think switching to the TCA will cause a repeat physically, but because you're possibly psychologically primed to experience it. An anxious mind can produce our worst nightmares if given half a chance. But the Pdoc will be in a better position to make that call.


I am thinking bump pregabalin back to max of 600mg and see if that offers relief enough to continue working. However I feel it may not now have the same effect and that I will further down the depression tunnel!!!! I ain’t got the strength to battle through again pal and that’s the dilemma???

That's the usual time frame.

Well non of these meds have offered relief in anywhere near a 12 week max timeline. It’s taken me 4/5 years to get to about 60/70% so my question is what role each med had played and if vortioxatine started working, I would be in full remission and be able to drop pregabalin and the benzo. But the truth is I think my body and brain naturally regenerated to some extent, purely by pushing through the pain and it was pain day after day, month after month and year after year !!! And now I have landed on a snake, in my game of snakes and ladders and not sure if I’ve stopped skidding down, or is there more to come, I don’t honestly know the answer to that one.

But what I do know is full remission has never happened and I’m 6 years on and getting older pal !!!!

Your situation is far from hopeless. The main problem seems to have been the medical advice you've been given. Hopefully, this is about to change. Also, have you tried therapy? The cognitive/behavioural (CBT, REBT, etc) and mindfulness therapies can be at least as effective as ADs.

I’ve been through so much CBT I’m sick of it and it had zero effect on my MH it’s what the NHS throw at everyone and for me it’s s definite nope useless. I’m very self aware and well read on meds and their mechanism of action and I’ve heard many a story of people who can’t tolerate SSR’s Yet get on great with TCA’s and I don’t know why. Is this something you could shed light on PDU ???

[panic_down_under]

Well non of these meds have offered relief in anywhere near a 12 week max timeline. It's taken me 4/5 years to get to about 60/70%

Which indicates the improvement was more likely from just the normal ebb and flow of these disorders than the meds.

I have read that imipramine is less cardio toxic than Amatrip?????

Apparently so: Brown TC, 1979.

and I've heard many a story of people who can't tolerate SSRs Yet get on great with TCAs and I don't know why.

I'm one of them. SSRIs make me manic. The TCAs and MAOIs don't. It comes down to how individual biology meshes with the med.

My Pdoc mention hospitalisation if switching to a TCA, she did seem open to the idea, which did surprise me !!!!

Then grab the opportunity with both hands. At my worst I needed to be hospitalised to switch meds. It beats facing the side-effects and increased anxiety and depression on your own at home where the mind has a lot of time to ruminate!