QT intervals and baclofen

[Spellers]

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[kronkcarr]

I'm interested to hear what happens at 25 mg. did you talk with your dr about baclofen? Prior to my taking baclofen I had atrial fib and after a month I had another EKG and there was no fib. Very interesting.

[Spellers]

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[summerglow]

I'm a 47 year old female in good health other than problem drinking. I started baclofen before the summer and hit my switch on the 24th May. I drink about once a month but feel no urge in between. I go to the gym regularly and there is no history of heart disease in my family. I recently had an ECg for a procedure and it identified that I have a prolonged QT interval. They compared it to an ECG that was done 2 years ago when it was fine. The only medication I take is baclofen so I googled. Turns out that there are studies indicating that baclofen can cause drug-induced prolonged QT intervals, which can be fatal. I'm on 50mg currently and going to reduce it to 25 mg and have another ECG done. Scary stuff.

Slightly off the subject, but I suffered blurred vision, had my eyes tested and they had deteriorated by a great deal in the month I took BAC. I cut the dose down to 20, had eyes retested, and they were the same as before BAC I can only assume that Baclofen was the cause "for me"...I am now on 10mg's and going to stop and try Naltrexone (again).

Apologies for barging in on this conversation, but I do think it's important for us to share our concerns.

Summerglow

[Spellers]

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[Spellers]

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[terryk]

I did find a reference that it can be induced by baclofen.

Hi Spellers, could you post the article you are referring to?

-tk

[terryk]

Baclofen is not on the list of drugs to avoid at the SADS - sudden arrhythmic death syndrome website: http://www.sads.org.uk/drugs_to_avoid.htm

nor is it on the comprehensive list at https://www.crediblemeds.org/new-drug-list/ under QTDrugs Lists > Drugs to Avoid in Congenital Long QT

This is the only reference I could find mentioning Baclofen and QT intervals searching the MEDLINES database at http://www.ncbi.nlm.nih.gov/

http://www.ncbi.nlm.nih.gov/pubmed/?term=baclofen+prolongs+qt

J Cardiovasc Pharmacol Ther. 2012 Mar;17(1):102-9. doi: 10.1177/1074248410395020. Epub 2011 Feb 11.
Tizanidine (Zanaflex): a muscle relaxant that may prolong the QT interval by blocking IKr.
Kaddar N1, Vigneault P, Pilote S, Patoine D, Simard C, Drolet B.
Author information
Abstract
BACKGROUND:

Tizanidine (Zanaflex) is a centrally acting imidazoline muscle relaxant that is structurally similar to clonidine (α(2)-adrenergic agonist) but not to other myorelaxants such as baclofen or benzodiazepines. Interestingly, cardiac arrhythmias and QT interval prolongation have been reported with tizanidine.
OBJECTIVE:

To evaluate the effects of tizanidine on cardiac ventricular repolarization.
METHODS:

(1) Whole-cell patch-clamp experiments: HERG- or KCNQ1+KCNE1-transfected cells were exposed to tizanidine 0.1-100 ??mol/L (n = 29 cells, total) to assess drug effect on the rapid (I(Kr)) and slow (I(Ks)) components of the delayed rectifier potassium current. (2) Langendorff retroperfusion experiments: isolated hearts from male Hartley guinea pigs (n = 6) were exposed to tizanidine 1 ??mol/L to assess drug-induced prolongation of monophasic action potential duration measured at 90% repolarization (MAPD(90)). (3) In vivo wireless cardiac telemetry experiments: guinea pigs (n = 6) implanted with radio transmitters were injected a single intraperitoneal (ip) dose of tizanidine 0.25 mg/kg and 24 hours electrocardiography (ECG) recordings were made.
RESULTS:

(1) Patch-clamp experiments revealed an estimated IC(50) for tizanidine on I(Kr) above 100 ??mol/L. Moreover, tizanidine 1 ??mol/L had hardly any effect on I(Ks) (5.23% ?? 4.54% inhibition, n = 5 cells). (2) While pacing the hearts at stimulation cycle lengths of 200 or 250 ms, tizanidine 1 ??mol/L prolonged MAPD(90) by 8.22 ?? 2.03 (6.7%) and 11.70 ?? 3.08 ms (8.5%), respectively (both P < .05 vs baseline). (3) Tizanidine 0.25 mg/kg ip caused a maximal 11.93 ?? 1.49 ms prolongation of corrected QT interval (QTc), 90 minutes after injection.
CONCLUSION:

Tizanidine prolongs the QT interval by blocking I(Kr). Patients could be at risk of cardiac proarrhythmia during impaired drug elimination, such as in case of CYP1A2 inhibition during drug interactions.

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Tizanidine (Zanaflex) is not Baclofen.

I cannot find any evidence that suggests that Baclofen prolongs QT Interval.
-tk

[terryk]

Hi Spellers, I replied to this post (top quote) on 11-08-2015 10:18 AM, here (in the thread where it was originally posted). You said that you have been away this past week, maybe you missed it?

I posted on here re the QT intervals and Terry K responded that he could find zero evidence of this in his medical info gathering. Search my posting history and you will see this. Yet my cardiologist ( a top Prof in the UK) did see it as a factor. And keep in mind that Ameisan passed away of a heart attack tho no history and he regularly went to the gym (could be due to periods of high blood pressure while drinking, like with me). Of course this could all be entirely unrelated but is it responsible for some dude on here gathering medical cases to say unrelated to baclofen?



This is my issue with this site and the baclofen 'koolaid'. It's been my view since I was first came upon this forum. The minimisation of other peoples' experience and SE with 'oh no, Baclofen is the miracle'.

Hi Spellers, I'm sorry if my input on the forum has rubbed you the wrong way - I've never intended to minimize anyone's experience or downplay their reporting of baclofen side-effects. On the contrary, as someone who had a long, and very difficult titration fraught with side-effects, I feel that I've droned on and on about the subject to a fault:

Hey John, I'm with you there. The side effects are very real and they can be an enormous impediment to reaching one's switch. I've been meaning to chime in here after calling lo0p out and having a conversation with him about the "manufacturing side-effects" comment (I still owe you a response Lo0p). I had intense side-effects during my titration, many of which I've reported in my posts here. When I was experiencing them, they really hadn't been reported by others, so it's not like I imagined them in myself after reading about them on this forum. It was actually a revelation, when I read that others *also* had shocks to the hands and auditory/visual hallucinations as well (and a whole bunch other stuff).

[...]



Even going up 10mg every seven days I could guarantee myself a flush of familar side-effects on the 2nd day after the increase: Increased somnolence, dialed up intensity of shocks to hands, and the fleeting static/guy-in-my-face-trying-to-kill-me hallucination when I opened my eyes after dozing off for a second.

I had a bad experience with rapid titration (I posted a bit of it here before). It involved complete detachment with reality, constant visual/auditory hallucinations, rapid pulse/high bp, and severe electric shocks to my hands that caused me to drop anything I was holding for more than 15-20 seconds (many broken dishes and glasses). This was a jump from 150 to 235+ in a day or two and the SE were still increasing after 5 days when I eventually wound up in the ER, wrestled down and strapped to a gurney by 5 security guards (head/each arm/each leg). Admitted to the hospital for 5 days, my baclofen dose was restricted to 80mg/day and dosed sporadically. Then the real fun began and I had my partner smuggle in more baclofen to counteract my withdrawal unbeknown to my doctors . I was ready to give up and titrate down at that point, but realized I had to stabilize at 150 before I could do anything else. After 10 days, things calmed down a bit and I switched from a loaded dosing scheme of 8/12/6 40/40/80 to an even 8/4/12 60/60/60. Things improved and the side effects lessened, so I decided to start back titrating up. Upon each increase, I would notice my side effects would peak on the 2nd or 3rd day after the increase. So if I increased one day and didn't feel anything the 2nd day, I came to learn that *another* increase would bite me in the ass with even more hallucinations, shocks to the fingers and somnolence. Even at an increase of 10mg/5-7 days I would get more shocks for 2 days, the typical "slide show/color" hallucinations, a really terrible feeling sleepiness, and the most disturbing part: upon waking up from micro-naps, 25% of the time I would be greeted by the image of someone standing right over my face about to *kill?* me. Every single time I would scream and lunge across the bed or couch at this apparition and try to tear it apart with my fists. Very disturbing for me and more so for my girlfriend who learned very quickly to stay far away from me if she had to wake me up.



Maybe 3-4 months later I reached my switch (9/26/10 - after 7 months total) at 280mg/day and have floated around there: 240mg/day 8/2/7/12 60/60/60/60 today. My side effects peaked around 2 weeks *after* my switch, but are 99% completely gone now. PRN doses *really* screw me up entirely (I can't take them), missing a dose and waiting until the next is FAR better for me than trying to double and catch up (LeVin agrees here).

And not just *my* side-effects: https://www.mywayout.org/community/me...ml#post1641949



As far as prolonged QT interval goes, I am sorry that you are experiencing this. I remember the thread you started about this very clearly, and I'm sorry that my response to it pushed you away from posting here:

I'm a 47 year old female in good health other than problem drinking. I started baclofen before the summer and hit my switch on the 24th May. I drink about once a month but feel no urge in between. I go to the gym regularly and there is no history of heart disease in my family. I recently had an ECg for a procedure and it identified that I have a prolonged QT interval. They compared it to an ECG that was done 2 years ago when it was fine. The only medication I take is baclofen so I googled. Turns out that there are studies indicating that baclofen can cause drug-induced prolonged QT intervals, which can be fatal. I'm on 50mg currently and going to reduce it to 25 mg and have another ECG done. Scary stuff.

I did find a reference that it can be induced by baclofen.

Hi Spellers, could you post the article you are referring to?



-tk

Baclofen is not on the list of drugs to avoid at the SADS - sudden arrhythmic death syndrome website: Drugs to avoid



nor is it on the comprehensive list at https://www.crediblemeds.org/new-drug-list/ under QTDrugs Lists > Drugs to Avoid in Congenital Long QT



This is the only reference I could find mentioning Baclofen and QT intervals searching the MEDLINES database at National Center for Biotechnology Information

http://www.ncbi.nlm.nih.gov/pubmed/?term=baclofen+prolongs+qt

J Cardiovasc Pharmacol Ther. 2012 Mar;17(1):102-9. doi: 10.1177/1074248410395020. Epub 2011 Feb 11.

Tizanidine (Zanaflex): a muscle relaxant that may prolong the QT interval by blocking IKr.

Kaddar N1, Vigneault P, Pilote S, Patoine D, Simard C, Drolet B.

Author information

Abstract

BACKGROUND:



Tizanidine (Zanaflex) is a centrally acting imidazoline muscle relaxant that is structurally similar to clonidine (α(2)-adrenergic agonist) but not to other myorelaxants such as baclofen or benzodiazepines. Interestingly, cardiac arrhythmias and QT interval prolongation have been reported with tizanidine.

[...]

CONCLUSION:



Tizanidine prolongs the QT interval by blocking I(Kr). Patients could be at risk of cardiac proarrhythmia during impaired drug elimination, such as in case of CYP1A2 inhibition during drug interactions.



-------------------------

Tizanidine (Zanaflex) is not Baclofen.



I cannot find any evidence that suggests that Baclofen prolongs QT Interval.

-tk

Drug acquired prolonged QT interval is a serious, potentially life-threatening condition and the motivation for my response to your assertion was borne entirely out of concern for anyone who could be effected by it, not least of all myself. I did not intend to stifle the dialog, nor did I think that the conversation was over. I would still like to read the article(s) that you are referring to.



For my own peace of mind, I've continued to research the subject. Except for 2 patients who reportedly experienced prolonged QT intervals after suicide attempts of massive overdoses of many pharmaceuticals where baclofen was a coingestant (+ Alcohol and 10,000 to 20,000 mg of Lamotrigine in one case, + Alcohol, Diazepam, Nebivolol, Benzodiazepine Related Drugs, Cocaine in the other case), I still cannot find a single connection to baclofen and QT intervals mentioned in the literature or anywhere, and I feel confident that it is not a risk for most people. But off course I am not a Cardiologist, or any kind of medical professional - I do not know you, or the first thing about diagnosing your health - and I am absolutely not discounting the possibility that baclofen is causing your arrhythmia. If I was in your position, and I could determine that baclofen was indeed responsiible, I would discontinue it and make a full report here. Good luck, I wish you the best in your recovery.

-tk



EDIT: Some good info - Mechanisms, Risk Factors, and Management of Acquired Long QT Syndrome: A Comprehensive Review

[Spellers]

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[Spellers]

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[terryk]

I did read all of your replies on the other threads. And no, I am not implying that your prolonged QT intervals are not caused by HDB - I'm not a doctor, I don't know what's causing them. I said, and maintain, that I cannot find a connection in the literature or anywhere. You said that you had indeed found studies indicating that baclofen can cause drug-induced prolonged QT intervals, and I found that alarming - much more so than your personal story.

I have a history (and a family history) of heart problems, and I know how frightening they can be. I do wish you the best, and hope you do report back here if you find some definitive answers.

-tk

[terryk]

I did mention both of those cases in my original reply. They are reports of suicide attempts with multiple drug intoxications. The Lamotrigine mentioned is 50-100x the daily dose.....


hey, are you using bold type in your posts now?

Cardiovasc Toxicol. 2015 Oct;15(4):394-8. doi: 10.1007/s12012-014-9300-0.
Evolving Electrocardiographic Changes in Lamotrigine Overdose: A Case Report and Literature Review.
Chavez P1, Casso Dominguez A2, Herzog E1.
Author information
Abstract

Lamotrigine overdose usually follows a benign pattern, and the majority of cases reported involve a co-ingestant. Prior reports have suggested the possible use of intravenous lipid emulsion in cases of severe sodium channel blockade. We describe the electrocardiographic changes in a massive lamotrigine overdose treated with intravenous lipid emulsion. A 36-year-old male with bipolar disorder ingested 13.5 g of lamotrigine in a suicidal attempt. The lamotrigine level was 78.0 μg/mL. Comprehensive drug screen was negative for all screened compounds. The electrocardiogram demonstrated a prolonged QRS complex and signs suggestive of sodium channel blockade. Refractory to treatment with sodium bicarbonate was treated with intravenous lipid emulsion, with immediate resolution of the electrocardiographic changes. Lamotrigine inhibits the voltage-gated sodium channel opening, attenuating the release of excitatory neurotransmitters. Cardiac intraventricular conduction could be delayed in cases of lamotrigine overdose resulting in QRS and QTc prolongation and R waves >3 mm in leads I and aVR. A potential role for intravenous lipid emulsion therapy has been described in patients with toxic levels of lamotrigine and electrocardiographic changes refractory to the treatment with sodium bicarbonate. Intravenous lipid emulsion has been successfully used in the treatment of lamotrigine cardiac toxicity.
KEYWORDS:

Electrocardiogram; Intravenous lipid emulsion; Intraventricular conduction delay; Lamotrigine

[terryk]

Hey Spellers, I'm going to bed. I really didn't mean to argue here with you. I hope you figure out and resolve both your heart and alcohol issues - and report back about them here.

If you're not already using the NIH MEDLINE database at Home - PubMed - NCBI you should, it's much better than google.
-tk

[Spellers]

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