Tizanadine vs. Clonidine, Guanfacine

[aim-agm]

I'm a psychiatry resident with many patients who have many psychiatric and non-psychiatric symptoms which would benefit from treatment with an alpha-2 agonist. For example, TBI from MVA, so has issues with impulsivity, anger/aggression, anxiety, and PTSD but also chronic pain, especially back pain. In an effort to reduce polypharmacy and increase efficacy I am considering starting/changing-to alpha-2 agonists
I am discussing with my psychiatry supervisors, but I hoped for some insight/wisdom from a pain management perspective. Thank you in advance.

1. Is there a reason tizanidine is used over clonidine as a muscle relaxant? The short half-life of the former has been problematic in my very limited experience (e.g. doesn't last through the night, leading to early awakening).

2. How effective is this drug class from your standpoint as a muscle relaxant, analgesic?

3. Comparatively, how effective is guanfacine from a pain management standpoint in practice? My readings indicate it's better tolerated than imidazolines (less hypotension) but also less effective, but they don't qualify how much less (25%? 50%?)

4. Any recommended readings on the intersections of our specialties?

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[Orin]

Tizanidine seems to have less vasoactive effects and is a more effective skeletal muscle relaxer as compared to clonidine. The differences here are likely caused by the alpha receptor subtype selectivity for the various agents, but I would have to dive into the literature more to give you a better answer.

Clonidine definitely appears to work with epidurals/spinals, and I do find efficacy with oral/transdermal formulations for neuropathic pain states and also comorbid anxiety/ADHD/PTSD. I have not used guanfacine. I will have to look more into it for my hypotensive patients that might benefit.

In addition to the vasoactive issues, there are some urinary issues in older males for this pathway, and some odd interactions with SSRIs/SNRIs.

 

[lobelsteve]

 

[aim-agm]

Tizanidine seems to have less vasoactive effects and is a more effective skeletal muscle relaxer as compared to clonidine. The differences here are likely caused by the alpha receptor subtype selectivity for the various agents, but I would have to dive into the literature more to give you a better answer.

Diving into the literature has left me more confused, either because the pharmacology is too advanced, I'm missing something, and/or conflicts in the literature (esp regarding pharmicodynamics). I'm sure I'm very wrong somewhere, but below is a quick summary of my lit review:

The main receptors involved are alpha1, alpha2 (and it's subtypes), and imidazoline.

What stands out about tizanidine is that it has much greater affinity for imidazoline receptor than for alpha receptors, which should make it more hypotensive and less analgesic than clonidine/guanfacine, but it appears there is some argument that imidazoline agonism is actually the MOA for pain in this class.

Tizanadine may also have much greater affinity for alpha2a than 2b and 2c, as opposed to clonidine and guanfacine which appear to have relatively equal affinities across subtypes; unclear if this is important and there would be some argument it would make tizanidine less effective.

Alpha1 agonism is argued to counteract analgesic effects in this class and clonidine is noteable for this agonism, but it's quite difficult to find quantitative information regarding the alpha1 actions of tizanadine and guanfacine, and at least the former is noted to also be an alpha1 agonist.

 

[Ducttape]

from my clinical experience -

tizanidine does not do that much from a pain standpoint. the main mechanism of action that I see is anxiolysis.

clonidine seems to have some slight benefit with pain modulation, particularly intrathecal. have tried it topically with rare success.


neither are my first or second or third line of medications for pain, but tizanidine is first line for "muscle relaxant" and anxiety associated with pain. and opioid withdrawal.