Alpha-1 Antagonists in PTSD or Cocaine Dependence?

[firedoor]

Terazosin, doxazosin, prazosin...has anyone used these?

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[Scorcher31]

I've used prazosin QHS in combination with an ssri on most ptsd patients on our inpatient unit with some success. Probably used it all of 10 times so my sample is very small and the results are questionable at best. Three patients felt like it stopped their nightmares completly, three felt the intensity of their nightmares and resultant anxiety/sympathetic sx had decreased around half, and four noticed no difference at all.

 

[billypilgrim37]

Terazosin, doxazosin, prazosin...has anyone used these?

Prazosin is the only one that crosses the blood brain barrier. I've heard of docs using the others as well, but theoretically they should be useless, and this is a major pet peeve of our pharmacists.

 

[masterofmonkeys]

I use prazosin a TON in my PTSD patients (spent a fair amount of time at the VA spa), and for anyone who could tolerate it without orthostatic hypotension got good results.

I also started using it BID for the hyperarousal->irritability->outburst crowd with good results as well, although not as good as the nightmare results.

 

[billypilgrim37]

What's been your dose range and titration schedule?

 

[whopper]

There is empirical data showing Prazosin does help with PTSD, but it never got an FDA approval. It should definitely be considered a treatment option. My suspicion is its a generic, so the money is not to be had with an added FDA approval, hence no one will pay for $$ needed to get it done.

As for cocaine, I've never seen any data that any medication helps. A few times a study comes out showing some potential for benefit, but then later studies show the original study was off. The last time I've seen a comprehensive article on all the advancements in this area was about 2 years ago, so there might have been something I missed.

There was some hubbub about 4 years ago that Tegretol could yield some benefit, but when a follow-up study was done, Tegretol showed no benefit.

 

[doctor4ever]

I also use a lot of Prazosin. It has worked for almost all of my PTSD (combat or sexual trauma) patients with nightmares. Not really that great for flashbacks. Most patients will first report having a decrease in frequency and intensity of nightmares and once the dose is higher they will report "I can't remember the last time I had a nightmare." Spouses will report that the patient thrashes around less at night.

I titrate pretty quickly, because patients may stop taking it if they don't see results. The average effective dose I've seen is 8-15mg PO qHS. I can only think of a few patients that didn't respond with high dosages. Hypotension hasn't been a huge problem either (may need to lower other BP meds). When I start Prazosin I tell patients to not stand up too quickly in the morning and to sit on the edge of the bed for 5 min and then stand up.

The way I titrate depends on the age and frailty of the patient.

Young patients with no major medical conditions: 5mg PO qHS x 1 week, then 10mg PO qHS x 1 week, then 15mg PO qHS

Middle-aged patient with no major medical conditions: 2mg PO qHS x 1 week, then 4mg PO qHS x 1 week, then 6mg PO qHS x 1 week, then 8mg PO qHS. If they have a partial response with 8mg PO qHS, I increase to 10mg PO qHS (easier to take too because they make 5mg Caps)

Older patient with multiple medical conditions: 1mg PO qHS x 1 week, then 2mg PO qHS x 1 week, then 3mg PO qHS x 1 week, then 4mg PO qHS. If they have a partial response with 4mg PO qHS, I increase to 6mg PO qHS x 1 week, then 8mg PO qHS

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2919672/

 

[billypilgrim37]

great link, thanks d4e.

 

[Chrismander]

The way I titrate depends on the age and frailty of the patient.

Young patients with no major medical conditions: 5mg PO qHS x 1 week, then 10mg PO qHS x 1 week, then 15mg PO qHS

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2919672/

You can go this fast without troubles? In my PTSD clinic last year none of the attendings had heard of prazosin and could not give me any guidelines, so I would start with 1 mg qhs for fear of hypotension and gradually work up from there. You've had no troubles just starting 5 mg straight away on a young combat vet with no medical problems? If that's the case, it probably explains why my results with it were crap...

 

[Scorcher31]

I'm not to familiar with the literature with regards to dosing. I was having success with just 2mgs. I was under the impression you diddnt have to go into the higher doses used for hypertension. If anyone has an article that talks about doses let me know.

 

[firedoor]

As for cocaine, I've never seen any data that any medication helps. A few times a study comes out showing some potential for benefit, but then later studies show the original study was off. The last time I've seen a comprehensive article on all the advancements in this area was about 2 years ago, so there might have been something I missed.

Yeah, there's some current research about alpha-1 antagonists in cocaine dependence in terms of reducting intoxication and cravings (I heard an addictionologist recently verbalize some guarded hope about this):

http://www.trialscentral.org/theefficacyofpraz-intrtrid-147264.htm

http://clinicaltrials.gov/ct2/show/NCT00880997

However, disulfuram seems to be the baddest boy on the psychopharm street regarding cocaine dependence (the caveat is that it may significantly increase cocaine levels if co-ingested):

http://archpsyc.ama-assn.org/cgi/reprint/61/3/264.pdf

I recently saw a show on the Discovery Channel where L-DOPA was used for cocaine dependence...has anyone had experience with this?

 

[Scorcher31]

I'm pretty sure prazosin has been tried in the past for cocaine withdrawal along with clonidine, phenobarb and a bunch of other meds. From what I have heard, nothing works well for cocaine withdrawal.

We see a lot more alcohol, opiate and benzo withdrawal though and those are really the only ones I would treat. I never really see barb or GHB withdrawal which should obviously also be treated. I know plenty of docs who wont even treat opiate withdrawal with anything other than clonidine.

 

[Scorcher31]

Whoops I thought you were talking about withdrawal. Sorry about that. I haven't heard anything yet about these trials but hey you never know.

 

[whopper]

Thanks for the info. Only research I've seen showing some promise after the Tegretol hubbub (until you mentioned the above links) is the cocaine vaccine research, but the data you mentioned is perhaps something that could be of interest with more research.

There is street-talk that Seroquel can help calm cocaine withdrawal. Since it also works on alpha receptors, this does make the above research sound like it maybe onto something. Does Seroquel really help? I don't know but cocaine dependent people are willing to shelve out big bucks for it.

In my PTSD clinic last year none of the attendings had heard of prazosin and could not give me any guidelines,

There's actually some good data about this, and it's been published in credible journals. Some of the links have been written above, but some of the data has made it to APA publications.

This is definitely a teaching/learning opportunity for you to present this to the attendings at the clinic. A good attending is someone that is still a good student. Medicine is a life-long learning profession. No one can ever know everything in the field, and a good attending will flat out admit they don't know something and use the lack of knowledge to be that little bump for both him/her and the student to turn it into a learning opportunity.

A bad attending will get red-faced and then try to mentally bully a resident by demanding they answer questions that hardly anyone would know when a resident brings up an issue where the attending doesn't know WTF is going on. I've seen that happen too many times.

 

[jpmorrissette]

Is there a way to remove antagonists and agonist to lower tolerance levels?

 

[hamstergang]

I also use a lot of Prazosin. It has worked for almost all of my PTSD (combat or sexual trauma) patients with nightmares. Not really that great for flashbacks. Most patients will first report having a decrease in frequency and intensity of nightmares and once the dose is higher they will report "I can't remember the last time I had a nightmare." Spouses will report that the patient thrashes around less at night.

I titrate pretty quickly, because patients may stop taking it if they don't see results. The average effective dose I've seen is 8-15mg PO qHS. I can only think of a few patients that didn't respond with high dosages. Hypotension hasn't been a huge problem either (may need to lower other BP meds). When I start Prazosin I tell patients to not stand up too quickly in the morning and to sit on the edge of the bed for 5 min and then stand up.

The way I titrate depends on the age and frailty of the patient.

Young patients with no major medical conditions: 5mg PO qHS x 1 week, then 10mg PO qHS x 1 week, then 15mg PO qHS

Middle-aged patient with no major medical conditions: 2mg PO qHS x 1 week, then 4mg PO qHS x 1 week, then 6mg PO qHS x 1 week, then 8mg PO qHS. If they have a partial response with 8mg PO qHS, I increase to 10mg PO qHS (easier to take too because they make 5mg Caps)

Older patient with multiple medical conditions: 1mg PO qHS x 1 week, then 2mg PO qHS x 1 week, then 3mg PO qHS x 1 week, then 4mg PO qHS. If they have a partial response with 4mg PO qHS, I increase to 6mg PO qHS x 1 week, then 8mg PO qHS

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2919672/

I know this post is old, but for anyone reading it now I want to point out that the titration schedule given by the poster is not supported by the article he linked to. The article summarizes studies that started at 1mg and went up to an average of only 3mg. Sure, some patients needed the higher doses, but starting above 1mg and aiming, from the start, for 15mg is over-medicating.

 

[xlithiumx]

I know this post is old, but for anyone reading it now I want to point out that the titration schedule given by the poster is not supported by the article he linked to. The article summarizes studies that started at 1mg and went up to an average of only 3mg. Sure, some patients needed the higher doses, but starting above 1mg and aiming, from the start, for 15mg is over-medicating.

Agreed. Most young healthy women can't tolerate more than 1-2 mg without significant orthostasis, and I've never seen a pt require more than 5mg in any given dose. This is in approaching 100 pts treated with prazosin for nightmares.

 

[vistaril]

Terazosin, doxazosin, prazosin...has anyone used these?

Practically everyone I've ever run into uses prazosin in PTSD.

 

[Jester25]

Yup. Use it for PTSD. Start at 1. The highest i ever went was 6mg with 1 patient, although he didn't get any more benefit than when he was on 5 so we decreased it back down. Generally got good results in the 2-4mg range.

 

[goldennugget]

Terazosin, doxazosin, prazosin...has anyone used these?

I've started using quite a bit of doxazosin for cocaine dependence in my addictions clinic. Personally, I have not felt that topamax, disulfiram (or really any other medication for that matter) has really helped until I started using doxazosin. I've been using about 4mg daily for starters, sometime titrating up to 8mg dose (per a pilot study that was released sometime earlier last year). Granted my N is pretty small...probably about 9 to 10 people, but I honestly can't think of any of those patients who said it did NOT help. I've had a few even say, "that stuff really works!" I'm not touting it to be a miracle med by any means, by from my experience it with it so far, it has been promising.


As for doxazosin, I am a big fan of using it in those with chronic nightmares. Ballpark estimate- I would say about 20% have said it completely stopped the nightmares (and the nightmares would reappear if they missed doses), about 30% report some benefit in frequency and/or intensity, and the other 50% have no benefit or were lost to follow up. Keeping in mind though that for some in the 50% group, they may not have been able to tolerate it , or had side effects, so we possibly didn't get to a therapeutic dose.

Has anyone ever tried other agents for nightmares such as clonidine or cyproheptadine? I've only tried each one of those once, but would be interested in hearing what others' experiences are.

 

[whopper]

It's been a few years since I've last posted on this thread but the data on Prazosin at this point is solid for nightmares. Clinically I've given it to many more patients over the last few years with large success.

The mechanism as to why it reduces nightmares raises a lot of questions. I've heard from some that it lowers time in REM sleep. If that is the case, yeah, ok, maybe that's it, but data with sleep shows that REM is required and to deprive someone of REM causes problems that are not seen in the patients with Prazosin, and they say they feel quite rested while on it.

Another issue is despite what some have said, the data suggests it can actually increase time in REM:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2350188/