Alpha blockade

[Celexa]

I'm curious people's thoughts and experiences with alpha blockade in PTSD.

Obviously prazosin is used fairly frequently for nightmares. The research evidence is not exactly the strongest. My personal experience has been of two types: either the med doensnt do jack, or it is ****ing magical.

Not just prazosin, either--I had a patient recently who reacted poorly to prazosin so I tried guanfacine. It's been life-changing for them to not wake up every night reliving their trauma in their dreams. The patients this has worked for often have suffered for years being cycled through antidepressants. They're incredibly grateful, and often shocked, that a medication could make such a clear change.

We do a lot of things in psychiatry that aren't well defined or supported in the literature, but this sticks out to me as being a little atypical in that I experience dramatic success fairly commonly, yet the data is meh. And nightmares seem an odd thing to respond to placebo effects.

Just some Sunday morning musing. What has your experience been?

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[Bartelby]

I have prescribed prazosin often. I agree, sometimes it does nothing but in some cases the change seems clear and unambiguous for nightmares. If nightmares persist after trauma-focused therapy (or if they are hugely distressing for the patient) I think it is very much worth a try. The side effect burden also seems minimal in my experience, just occasional orthostasis when used carefully.

 

[wolfvgang22]

I prescribe prazosin often for relief of PTSD nightmares as well. It is well tolerated. Usually for my patients it isn't completely effective in stopping nightmares but reduces them 50 to 80 percent, so it's worth prescribing. I start with 2mg QHS and avoid more than 10mg. I have to watch out for primary care placing older male patients with BPH on tamsulosin, because that's their go to for BPH.

Sometimes I have been prescribing clonidine 0.1mg daily to BID PRN for PTSD patients who tend to have anxiety and severe anger outbursts when other medications arent effective. It works well but has a higher propensity to cause sedation and hypotension and falls. It has reduced domestic violence incidents, fights, and road rage for some of the patients. For those patients with serious anger problems I sometimes also use PRN low dose Haldol. Obviously only after SSRIs and therapy have been tried or offered and failed or not tolerated.

I haven't prescribed guanfacine since I was doing child psychiatry but I'm considering it as an addition to the arsenal now that you bring it up.

 

[Celexa]

I haven't prescribed guanfacine since I was doing child psychiatry but I'm considering it as an addition to the arsenal now that you bring it up.

Yeah the guanfacine was def an off beat choice for an adult. Pt hadnt had a true trial of prazosin but retrying not an option. Nightmares far and away the symptom they most wanted help with but they also had a pretty convincing hx for ADHD which had never been treated. So I decided why the heck not, let's try guanfacine. Sometimes you hit a home run on the first pitch....

I use clonidine too but my sense is guanfacine is often better tolerated/less overtly sedating (which can be either a plus or a minus depending on the pt).

 

[Penguin10]

I'm curious people's thoughts and experiences with alpha blockade in PTSD.

Obviously prazosin is used fairly frequently for nightmares. The research evidence is not exactly the strongest. My personal experience has been of two types: either the med doensnt do jack, or it is ****ing magical.

Not just prazosin, either--I had a patient recently who reacted poorly to prazosin so I tried guanfacine. It's been life-changing for them to not wake up every night reliving their trauma in their dreams. The patients this has worked for often have suffered for years being cycled through antidepressants. They're incredibly grateful, and often shocked, that a medication could make such a clear change.

We do a lot of things in psychiatry that aren't well defined or supported in the literature, but this sticks out to me as being a little atypical in that I experience dramatic success fairly commonly, yet the data is meh. And nightmares seem an odd thing to respond to placebo effects.

Just some Sunday morning musing. What has your experience been?

I have had similar experiences with enough positive ones to be enthusiastic about offering prazosin when it seems relevant.

I found this article by David Osser helpful in thinking about the evidence base and clinical use:

Comorbid PTSD: Update on the Role of Prazosin

Prazosin appears to be effective and perhaps the best medication for selected patients, including those with bipolar disorder.

www.psychiatrictimes.com

He discusses the large negative VA trial and unpacks why that may have happened. I haven't read the results manuscript for that trial recently, but I recall being struck by the authors extended discussion of factors contributing to the negative trial, much more depth than is typical.

Osser also points out some evidence for elevated/hypertensive blood pressure as a response predictor and active AUD as associated with non-response.

 

[esob]

Is anyone familiar with Bessel van der Kolk's ideas regarding this blockade? I recently read "The Body Keeps the Score"; he advocates that this would worsen things. The gist that I got was that reintegrating the traumatic experience was necessary to establish the trauma as a past experience rather than continually re-experiencing it as a current event. It seems some FMRI studies back this up.

 

[clausewitz2]

Is anyone familiar with Bessel van der Kolk's ideas regarding this blockade? I recently read "The Body Keeps the Score"; he advocates that this would worsen things. The gist that I got was that reintegrating the traumatic experience was necessary to establish the trauma as a past experience rather than continually re-experiencing it as a current event. It seems some FMRI studies back this up.

Van der Kolk's ideas, although having many vociferous adherents, are not...hmm...necessarily representative of the totality of scientific evidence, shall we say.

 

[nexus73]

prazosin, clonidine, propranolol...have had similar benefit from each anecdotally

 

[annoyedpsychiatrist]

ive actually had a lot of benefit in my patients with PTSD nightmares. Though just my experience. Most of mine tend to respond in some way, although others not at all. Overall people seem to tolerate it well either way, i just watch for the above mentioned things.

 

[Merovinge]

Absolutely love Prazosin for nightmares, effect size in practice over the past 7-8 years is several times that which I see in the research. Given the safety profile I feel like I prescribe more Prazosin then 95% of child/adolescent psychiatrists. I cannot tell you how many kids have had nearly lifechanging experiences on this medication over the years.

Clonidine, guanfacine are great for many reasons, definitely will try at night if prazosin does not work for nightmares. Still underused in the ADHD population and if some value in for some kids with sensory issues/overstimulation.

I use a fair amount of propranolol in adolescents with hypertension or tachycardia (which is somehow fairly common in the population I treat) for anxiety or trauma and see good results in that population.

 

[smalltownpsych]

Is anyone familiar with Bessel van der Kolk's ideas regarding this blockade? I recently read "The Body Keeps the Score"; he advocates that this would worsen things. The gist that I got was that reintegrating the traumatic experience was necessary to establish the trauma as a past experience rather than continually re-experiencing it as a current event. It seems some FMRI studies back this up.

If patient has constant or frequent nightmares then it doesn’t seem to help them to reintegrate in my experience. My patients who get some relief from prazosin are better able to do the work of CPT during sessions and CPT has been demonstrated to reduce symptoms. Not to say that I don’t talk to patients about content of their nightmare as that can often help with the reprocessing or at least give us some ideas as to how to structure the therapy.

 

[mistafab]

There were several huge studies looking at VA data on prazosin vs clonidine. It appeared both had been "tolerated" for purpose of improving sleep. Neither seemed to alter PTSD symptoms outside of sleep. Effect size wasn't great. Both seemed to have issues with durability of the treatment (unclear why).

I think the data on either is actually not that great. And the data that does exist is not great quality. I'd say it's in the bucket of give it a shot, but don't be afraid to drop it if it isn't useful. Prazosin data specifically also had wide range of doses in the literature. Clonidine dosing was more uniform, with minimal data for effectiveness in sleep prior to reaching 0.1 mg.

From personal experience, I hada handful of folks find prazosin helpful for reducing nightmares. I found cessation of treatment due to AE's much higher than the rate reported in the literature (predominantly orthostatic symptoms). My success rates on the med are quite low compared to # of trials.

 

[Stagg737]

Agree with the above that they're all valid options that are worth a shot. My general algorithm for trauma-related nightmares is:

Prazosin -> topiramate -> mirtazapine -> cyproheptadine -> clonidine/guanfacine/Ambien

I think a solid 75% of my patients do well with either prazosin or topiramate and end up on one or the other.

Mirtazapine has some decent a2 blockade but is also hit or miss for nightmares, but even if nightmares don't get better some people just get better sleep anyway and are generally less reactive (has some off-label indications for anxiety/panic attacks). I've also found that some vets just do incredibly well with mirtazapine or wellbutrin monotherapy for PTSD. No idea why, but if it works...

For me, cypro is a much more hit or miss med. I've had some patients where nothing else worked but cried tears of joy because they could actually sleep with it and others say it didn't do anything or just made them feel hungover. Not something I regularly suggest, but good to keep in the back pocket and actually has the best data (which isn't really good) after prazosin and topiramate.

Clonidine and guanfacine are worth trying if others fail and nightmares are frequent/distressing.

I'll also occasionally break out Ambien if there isn't an underlying personality issue. It's far from optimal, but I had a few vets who said it was the only thing that actually worked because they just didn't dream/didn't remember on it and spouses could confirm. I don't like Ambien or benzos, but one of my attendings who specialized in our VA's PTSD clinic said his first priority was always to get his vets sleeping by any means necessary, as nothing really improved until they could consistently get decent sleep.

 

[Stagg737]

Yeah the guanfacine was def an off beat choice for an adult. Pt hadnt had a true trial of prazosin but retrying not an option. Nightmares far and away the symptom they most wanted help with but they also had a pretty convincing hx for ADHD which had never been treated. So I decided why the heck not, let's try guanfacine. Sometimes you hit a home run on the first pitch....

I use clonidine too but my sense is guanfacine is often better tolerated/less overtly sedating (which can be either a plus or a minus depending on the pt).

Guanfacine also tends to have a much lower risk of rebound symptoms like rebound HTN unless you're using clonidine ER.

prazosin, clonidine, propranolol...have had similar benefit from each anecdotally

I haven't had much success with propranolol** for nightmares and have actually had patients report the opposite of vivid dreams or nightmares. Pretty sure we also had a thread on here about that somewhat recently.

From personal experience, I hada handful of folks find prazosin helpful for reducing nightmares. I found cessation of treatment due to AE's much higher than the rate reported in the literature (predominantly orthostatic symptoms). My success rates on the med are quite low compared to # of trials.

This is basically the opposite of my experience. I'd say 50% of my patients notice benefit significantly from prazosin with doses <5mg and almost never complain of AE's. When they do, they're either elderly with reactive BPs in general or have a lot of medical co-morbidities. I also counsel pretty extensively regarding orthostasis and always ask about it on f/up.

 

[mistafab]

Guanfacine also tends to have a much lower risk of rebound symptoms like rebound HTN unless you're using clonidine ER.


I haven't had much success with prazosin for nightmares and have actually had patients report the opposite of vivid dreams or nightmares. Pretty sure we also had a thread on here about that somewhat recently.


This is basically the opposite of my experience. I'd say 50% of my patients notice benefit significantly from prazosin with doses <5mg and almost never complain of AE's. When they do, they're either elderly with reactive BPs in general or have a lot of medical co-morbidities. I also counsel pretty extensively regarding orthostasis and always ask about it on f/up.

Are you working at a VA? I ask because the literature/ AES were low in VA data… but those were mostly ex-military, predominantly middle aged men. I expect that pop is far less likely to have orthostatic sx than civilian ptsd folks trialed on these meds.

 

[Stagg737]

Are you working at a VA? I ask because the literature/ AES were low in VA data… but those were mostly ex-military, predominantly middle aged men. I expect that pop is far less likely to have orthostatic sx than civilian ptsd folks trialed on these meds.

Not currently, I've found civilians to tolerate it just as well until they get into the geri range. Even my cluster B patients have done alright with it outside of those with significant medical co-morbidities (which I have several of) or EDs.

ETA: I actually saw more orthostatic issues in my VA outpt population, however I ended up inheriting what was previously the geriatric panel, so to be expected to a certain extent.

 

[clozareal]

Prazosin seems like the magic bullet for some of my patients. I will often try it before an SSRI, despite it not being FDA approved for PTSD whereas SSRIs are (although has poor evidence or efficacy).

Some people like doxazosin as an alpha-1 blocker for PTSD because you don't have to dose it multiple times a day if you are using it for daytime hypervigilence symptoms. I haven't tried this in my practice myself yet.

I do like David Osser's comments about the negative PTSD trial. His psychopharm algorithm uses much higher doses than I've needed to use in my practice. Here is what he says:

Suggested dosing protocol for males (11): begin with 1 mg at bedtime for 2 nights. If tolerated, 2 mg is given on days three through seven. If nightmares remain problematic and no adverse effects have been noted, 4 mg is given for days 8-14. Additional increases may be made as necessary to 6 mg at bedtime on day 15, 10 mg on day 22, and 15 mg on day 29, and 20 mg on day 36. The median effective dose was 16 mg daily.(12) It was also given in mid-morning for daytime symptoms starting with 1 mg after two weeks of night dosing. Mean mid-morning dose was 4 mg.

Suggested dosing for females: start with 1 mg hs and increase by 1 mg weekly as tolerated. 10 mg was the highest dose used and the mean effective dose was 7 mg at bedtime. The mid-morning dose reached an average of 2 mg. The reason for this gender difference in dosage is unclear.(13)

P.S. Just to be clear so that no one is confused especially those not in medicine, guanfacine and clonidine are alpha-2 agonists whereas prazosin is an alpha-1 antagonist (blocker).

 

[Stagg737]

Prazosin seems like the magic bullet for some of my patients. I will often try it before an SSRI, despite it not being FDA approved for PTSD whereas SSRIs are (although has poor evidence or efficacy).

If you look at the HSS algorithm (which Osser is highly involved with), they actually recommend Prazosin as first line therapy over SSRIs or trazodone if there is sleep disturbance with nightmares or nighttime hyperarousal.

 

[mistafab]

My question for you all. The literature seems to show that these alpha 1 agents improve sleep and reduce nightmares, though have no effect on PTSD symptom burden otherwise.

Is that your experience? Have you all seen improvements outside of sleep? Personally, I have not, though I would have expected better sleep to lead to better symptoms overall.

 

[Celexa]

My question for you all. The literature seems to show that these alpha 1 agents improve sleep and reduce nightmares, though have no effect on PTSD symptom burden otherwise.

Is that your experience? Have you all seen improvements outside of sleep? Personally, I have not, though I would have expected better sleep to lead to better symptoms overall.

My experience is that when the nightmares go away and the pt is actually getting sleep, there are MANY secondary effects on mood and anxiety, which has implications for both avoidance and hypervigilance. Is it bc of the med itself working on those symptoms? A secondary effect mediated through the sleep and absence adrenergic activation all night? Does it matter? I don't think it does, ultimately.

Like I mentioned at the top, the patients who get benefit get such clear and obvious benefit on so many levels I end up not knowing how to feel about the fairly unimpressive studies in terms of clinical practice. With the relative low risk and the possibility for dramatic benefit it's moving higher and higher in my personal algorithm.

 

[whopper]

IMHO Guanfacine should be considered as an off-label sleep aid as I too have had good experience with it helping people sleep. Of course the patient should be screened for hypotension and warned of it. I'd rather a patient be on Guanfacine vs several of the sleep meds out there such as Zolpidem, or any of the Z-meds or benzos.

 

[clozareal]

IMHO Guanfacine should be considered as an off-label sleep aid as I too have had good experience with it helping people sleep. Of course the patient should be screened for hypotension and warned of it. I'd rather a patient be on Guanfacine vs several of the sleep meds out there such as Zolpidem, or any of the Z-meds or benzos.

I hope it gets studied for this indication, but since it's generic it most likely won't. I would rather a patient be on guanfacine than many other sleep meds such as mirtazapine (weight gain), trazodone (priapism. after seeing 2 cases on the inpt psych unit requiring intracavernosal phenylephrine injection, I'm much more wary. One had tolerated trazodone before but hadn't taken it for years) and of course the controlled ones.

 

[clausewitz2]

My experience is that when the nightmares go away and the pt is actually getting sleep, there are MANY secondary effects on mood and anxiety, which has implications for both avoidance and hypervigilance. Is it bc of the med itself working on those symptoms? A secondary effect mediated through the sleep and absence adrenergic activation all night? Does it matter? I don't think it does, ultimately.

Like I mentioned at the top, the patients who get benefit get such clear and obvious benefit on so many levels I end up not knowing how to feel about the fairly unimpressive studies in terms of clinical practice. With the relative low risk and the possibility for dramatic benefit it's moving higher and higher in my personal algorithm.

The answer about the mismatch between your experience and research may lie in the structural issues that make a lot of PTSD research at the VA suspect. The Psychology Forum can tell you aaaaaaall about this.

 

[whopper]

I've also noticed Guanfacine, and it's not surprising cause it's FDA indicated for ADHD, treats anxiety but way mostly ADHD anxiety from kids who feel anxious unless they move around a lot. I theorize that Akathisia really is medication-induced Hyperactive ADHD.

 

[whopper]

Adding, I've never seen Guanfacine help nightmares, but I hardly give it for nightmares. I give it first or second-line for ADHD people with insomnia. Only meds with decent evidenced-based data for nightmares are Prazosin, Clonidine, and Trazodone.

 

[Stagg737]

Adding, I've never seen Guanfacine help nightmares, but I hardly give it for nightmares. I give it first or second-line for ADHD people with insomnia. Only meds with decent evidenced-based data for nightmares are Prazosin, Clonidine, and Trazodone.

Except trazodone also commonly causes vivid dreams and worsens nightmares in individuals with PTSD. It's not something I'd never use, but it's further down my algorithm because I've had more than a couple patients scream at me that trazodone made their nightmares far worse...

 

[aim-agm]

Adding, I've never seen Guanfacine help nightmares, but I hardly give it for nightmares. I give it first or second-line for ADHD people with insomnia. Only meds with decent evidenced-based data for nightmares are Prazosin, Clonidine, and Trazodone.

I've used it for nightmares with success.

 

[esob]

prazosin, clonidine, propranolol...have had similar benefit from each anecdotally

Propranolol is interesting because I recently noted that beta blockers in general and propranolol specifically had nightmares listed as a SE.

 

[forchinet121]

Someone mentioned topamax for nightmares? I’ve never heard of that is that common? These are the best threads where we can actually learn something instead of talking about money for the millionth time

 

[clozareal]

Topiramate has been pretty good for anger, anxiety, irritability, and overall mood lability in my practice. I use it for those who have antipsychotic induced weight gain or just want to lose weight in general since it can decrease carb cravings, especially because metformin seems to be better at preventing weight gain than helping with weight loss. I haven't tried using it for nightmares but that's interesting. I find that if I don't go over 150mg, people don't have the cognitive blunting that gives the stigma of Dopamax.

 

[Stagg737]

Someone mentioned topamax for nightmares? I’ve never heard of that is that common? These are the best threads where we can actually learn something instead of talking about money for the millionth time

Topiramate has been pretty good for anger, anxiety, irritability, and overall mood lability in my practice. I use it for those who have antipsychotic induced weight gain or just want to lose weight in general since it can decrease carb cravings, especially because metformin seems to be better at preventing weight gain than helping with weight loss. I haven't tried using it for nightmares but that's interesting. I find that if I don't go over 150mg, people don't have the cognitive blunting that gives the stigma of Dopamax.

As I said above, I use it as a second line for trauma-related nightmares with a fair bit of success. I start at 25mg QHS and tell patients they can double that dose in 3-4 days if the feel like they need to. The (limited) data for it suggests increasing by 25mg weekly up to 200mg QHS, but I don't usually go above 100mg. At lower doses I've found it to be pretty effective with minimal to no side effects other than occasionally patients feeling a bit groggy in the morning. Even if they experience mild cognitive blunting, for those patients it's not necessarily a bad thing since that tends to counteract the lability/autonomic activation that they are almost certainly complaining about.

 

[forchinet121]

As I said above, I use it as a second line for trauma-related nightmares with a fair bit of success. I start at 25mg QHS and tell patients they can double that dose in 3-4 days if the feel like they need to. The (limited) data for it suggests increasing by 25mg weekly up to 200mg QHS, but I don't usually go above 100mg. At lower doses I've found it to be pretty effective with minimal to no side effects other than occasionally patients feeling a bit groggy in the morning. Even if they experience mild cognitive blunting, for those patients it's not necessarily a bad thing since that tends to counteract the lability/autonomic activation that they are almost certainly complaining about.

Very good I will try this never heard of it before

 

[esob]

Topiramate has been pretty good for anger, anxiety, irritability, and overall mood lability in my practice. I use it for those who have antipsychotic induced weight gain or just want to lose weight in general since it can decrease carb cravings, especially because metformin seems to be better at preventing weight gain than helping with weight loss. I haven't tried using it for nightmares but that's interesting. I find that if I don't go over 150mg, people don't have the cognitive blunting that gives the stigma of Dopamax.

I had a neuro attending that mentioned the reason people lose or maintain weight on Topamax was b/c it altered the taste of sodas and hence people subsequently cut soda from their diet.

 

[clausewitz2]

I had a neuro attending that mentioned the reason people lose or maintain weight on Topamax was b/c it altered the taste of sodas and hence people subsequently cut soda from their diet.

Eh, I've had several patients tell me it just makes all food seem kind of aversive, not just sodas. One of them was a crunchy vegan type to begin with so not someone who was swilling Pepsi.

 

[Merovinge]

I had a neuro attending that mentioned the reason people lose or maintain weight on Topamax was b/c it altered the taste of sodas and hence people subsequently cut soda from their diet.

All carbonic anhydrase inhibitors mildly push downward on appetite, this is not related to specifically the taste of soda 🤣