Post-Traumatic Stress Disorder (PTSD) symptoms in your ... · Prevalence rates for PTSD in the general population have been estimated at 6.1-12.3% A 2008 study of 11,441 veterans

Post-Traumatic Stress Disorder (PTSD)

management: What you can do to manage

symptoms in your patients (or at least to not

make them worse)Michael Shuman, PharmD, BCPP

Assistant Professor, Pharmacy Practice

Rosalind Franklin University of Medicine and Science College of Pharmacy

Clinical Pharmacy Specialist, Mental Health

Captain James A. Lovell Federal Health Care Center

Dr. Shuman declares no conflicts of interest, real or apparent, and no financial

interests in any company, product, or service mentioned in this program, including

grants, employment, gifts, stock holdings and honoraria.

Disclosures and Conflict of Interest

At the conclusion of the program, the pharmacists will be able to:

1. Discuss the general role of pharmacotherapy in treatment of core PTSD

symptoms, based upon the 2017 VA/DoD treatment guidelines

2. Identify common symptoms/comorbidities associated with PTSD and their

management

3. Describe how individual clinicians can evaluate his or her practice site in

order to minimize triggers and ensure comfortable treatment environment

Pharmacist Objectives

All of the following are considered core symptoms of PTSD, except _________.

A. Exaggerated startle response

B. Vivid nightmares

C. Fear of losing control

D. Altered patterns of thinking

Pre-Test Questions

According to the 2017 VA/DoD treatment guidelines, which of the following is

classified as having a significant level of benefit in management of PTSD

symptoms?

A. Venlafaxine

B. Amitriptyline

C. Mirtazapine

D. Prazosin

Pre-Test Questions

Which medication results in negative therapeutic outcomes when used in

management of PTSD symptoms?

A. Lorazepam

B. Propranolol

C. Paroxetine

D. Nefazodone

Pre-Test Questions

Patient Case

68 yo Caucasian male veteran of the Vietnam War with past history of PTSD,

hypertension, and pulmonary embolism

Vividly describes multiple traumatic events which occurred during the course

of his military service

Attempts to isolate himself from group settings

Avoids certain actions or scenery which remind him of past traumatic events

RC

Gray EN, Shuman MD, McGrane IR. Ment Health Clin. 2013; 2 :18

RC’s medication list

Lisinopril 10mg by mouth every morning

Sertraline 200mg by mouth every morning

Warfarin 5mg by mouth Mo-We-Fr and 7.5mg Su-Tu-Th-Sa

Prazosin 1 mg by mouth every night

Trazodone 150mg by mouth every night

Chief complaint is nightmares which occur 2-3 times per week

Wakes up trembling and sweating, unable to go back to sleep

Blood pressure stable at 124/68; not interested in prazosin dose increase

Incident of orthostasis in October 2017

RC

Overview of PTSD

Prevalence rates for PTSD in the general population have been estimated at

6.1-12.3%

A 2008 study of 11,441 veterans listed the prevalence of PTSD as 12.1%

PTSD is the most common psychiatric diagnosis in veterans of OEF/OIF

Rates are generally stable

In 1987, an estimated 15% of Vietnam-era veterans had PTSD

4.5% (male) and 6.1-15.9% (female) still met criteria in 2015

Epidemiology of PTSD

Rothbaum BO, Killeen TK, Davidson JRT, et al. J Clin Psychiatry. 2008;69:520-525.

VA/DoD clinical practice guideline for the management of posttraumatic stress disorder and acute stress disorder. 2017.

Marmar CR, et al. JAMA Psychiatry. 2015; 72(9): 875-81.

Diagnostic Criteria for PTSD

Exposure to actual or threatened death, serious illness, or sexual violence

Recurrent, involuntary, and intrusive distressing memories of or related to the

traumatic event(s)

Psychological distress, physiologic reactivity, or dissociation in response to

cues that remind the individual of the traumatic event(s)

Efforts to avoid distressing reminders of the traumatic event(s)

Incomplete recall of details related to the traumatic event(s)

Distorted views of self or the surrounding environment

Anhedonia

Hyperarousal

Diagnostic Criteria for PTSD (paraphrased)

Diagnostic and Statistical Manual of Mental Disorders, 5th edition. American Psychiatric Association: Washington, DC; 2013.

The Nutshell

PTSD

Flashbacks

Cognitive Changes

Hyper-arousal

Avoidance

One

Month

Duration

SSRIs

Two agents (sertraline, paroxetine) carry FDA approval for use

Strong evidence for use of fluoxetine (off label)

Lack of clear evidence for citalopram, escitalopram, fluvoxamine, though SSRIs as a class recommended for use

SNRIs

Venlafaxine

Strong evidence for use; lack of data for duloxetine, desvenlafaxinethough SNRIs as a class are recommended for use

Treatment Recommendations:

Significant evidence of benefit

(highest level)

VA/DoD clinical practice guideline for management of post-traumatic stress. 2010.

Kalhh. https://pixnio.com/computer-

arts/3d-computer-

graphics/spirituality-tombstone-

marble-stone-cemetery-funeral-

gravestone. Public domain.

Mirtazapine

Nefazodone

Phenelzine (MAOI)

Amitriptyline, imipramine (TCAs)

Prazosin

For nightmares


Some benefit


Benzodiazepines (harm)

Tiagabine

Guanfacine

Valproate (monotherapy)

Topiramate

Risperidone (adjunct)


No benefit



Unknown benefit

Prazosin (for global

symptoms)

Atypical antipsychotics

Conventional

antipsychotics

Buspirone

Non-benzodiazepine

hypnotics

Bupropion

Lamotrigine

Gabapentin

Trazodone (adjunct)

Propranolol

Clonidine


VA/DoD Clinical Practice Guideline

for the Management of

Posttraumatic Stress Disorder and

Acute Stress Disorder. Version 3.0

The Game Changer

Creative Commons License. 2005.

Individualized trauma-focused psychotherapy now

recommended over pharmacotherapy

Focus on specific agents

Prazosin gets downgraded

In with the new


b. 2017Zivya. https://commons.wikimedia.org/wiki/File:NewBaby.jpg. 2012.

Pros

Better evidence in treating core PTSD symptoms

Longer duration of response

Fewer side effects

Cons

Not always available or may not be preferred by the patient

In these situations, pharmacotherapy or non-trauma-focused

psychotherapy may be utilized

Can also consider pharmacotherapy for specific breakthrough

symptoms (though not specifically mentioned in the guidelines)

Individualized trauma-focused

psychotherapy now recommended

over pharmacotherapy


b. 2017

Focus on specific agents

Strong evidence FOR use as

monotherapy

Sertraline (FDA approved)

Paroxetine (FDA approved)

Fluoxetine

Venlafaxine

Weak evidence FOR use as

monotherapy: only if other

treatments fail

Imipramine (TCA)

Phenelzine (MAOI)

Weak evidence AGAINST

use as monotherapy

Citalopram

Amitriptyline (TCA)

Insufficient evidence for OR

against

Escitalopram

Desipramine (TCA)

Desvenlafaxine

…Pretty much every other TCA,

SSRI, SNRI, and MAOI

VA/DoD Clinical Practice Guideline for the Management of Posttraumatic Stress Disorder and Acute Stress Disorder. 2017.

b. 2017

Weak evidence AGAINST use as monotherapy or

augmenting agent for global PTSD symptoms

Insufficient evidence for or against use in treatment of

nightmares

Prazosin gets

downgraded

VA/DoD Clinical Practice Guideline for the Management of Posttraumatic Stress Disorder and Acute Stress Disorder. 2017.

b. 2017

Centrally acting alpha1 blocker

Utilized specifically in the treatment of nightmares

Doses of up to 50mg have been reported, though

clinically a maximum of 10-15mg is the norm

Risk of orthostasis minimized by initiating at 1mg at

bedtime, titrating upward by 1-2 mg every 3-7 days

Efficacy previously established through smaller trials

Veterans and civilians alike

Why does this matter?

Koola MM, Varghese SP, Fawcett JA. Ther Adv Psychopharmacol. 2014; 4(1): 43-7.

Raskind MA, et al. J Clin Psychiatry. 2000; 61:129–33.

Raskind MA, et al. Am J Psychiatry. 2003; 160:371–3.


Taylor FB, et al. Biol Psychiatry. 2008; 63(6): 629–32.

Kung S, Espinel Z, Lapid MI. Mayo Clin Proc. 2012; 87(9): 890–900.

A Strong Start

Raskind (2000)

4 Veterans trialed on prazosin (open label)

2 with complete remission of traumatic nightmares at dose of >5mg

2 with 50% reduction at dose of 2mg

Raskind (2003)

10 veterans (avg. dose = 9.5mg)

Crossover trial

Significant improvement across multiple symptom domains, particularly distressing dreams

Raskind (2013)

67 active duty service members randomized to prazosin (avg daily dose 19.6mg men, 8.7mg women) or placebo

Significant improvement in combat-related trauma nightmares, sleep quality, and global impression of change

Raskind MA, et al. J Clin Psychiatry. 2000; 61:129–33.




This change from the last guidelines is chiefly based on a

large, negative (but until recently unpublished) trial

which was completed 3 years ago

The PACT Trial (Prazosin and Combat Trauma)

Started in 2007

Completed in 2014

Published 2/8/18

Caution advised

CSP No. 563, Prazosin and Combat Trauma PTSD (PACT) Study. https://clinicaltrials.gov/ct2/show/NCT00532493. Accessed 5/15/18.


Raskind MA, et al N Engl J Med. 2018;378:507-17.


Represented the largest study of prazosin every

conducted in regards to PTSD management

304 participants randomized to prazosin or placebo for 10

weeks

Average daily prazosin dose of 14.8mg

70% reached maximum allowed dose (20mg/day for males;

12mg/day for females)

Caution advised



No significant difference from placebo in any of the 3 primary outcomes (recurrent distressing dreams, sleep quality, clinician global impression of change)

No significant difference in any of the secondary outcomes (total PTSD symptoms, depressive symptoms, quality of life alcohol use)

Did note a difference in rate of new or worsening suicidal ideation (8% prazosin; 15% placebo, P = 0.048)

Clinical relevance not certain

Stop right here



CAPS: recurrent distressing

dreams

Baseline Week 10

Prazosin 6.3±0.9 4.4±2.1

Placebo 6.3±0.9 4.6±2.3P = 0.38

78% in the prazosin group were currently maintained on

an antidepressant, compared to 31% in the 2013 trial

Strict exclusion criteria prevented anyone with

“psychosocial instability” from entering the trial

Defined as a short-term or long-term situational life crisis

Low baseline blood pressure may have indicated lower

levels of arousal

Low alcohol use may also reflect difference in symptom

severity as compared to other trials

Stop right…here?



Despite the shift in the guidelines, there is likely still a

role for prazosin moving forward

Further research necessary to identify patients who may

benefit from this medication

New trials are necessary to identify other agents with

benefit

Moving forward




“No, there is another.”

“That alpha blocker

is our last hope”

Kennejima. Creative Commons License. 2012.

William Cromar. Creative Commons License. 2010.

https://www.flickr.com/photos/williamcromar/499

9817761

Newer data shows prazosin may not be the only alpha1

antagonist with CNS penetration

Doxazosin also appears to have effects on PTSD-related

nightmares

Longer half-life (2-3 hrs vs ~22hrs) may lead to less

frequent dosing and less fluctuation in blood pressure

Half the potency of prazosin and available in IR tablets

May be halved

Doxazosin

Smith C and Koola MM. Psychiatr Ann. 2016; 46(9): 553–5.

Richards A, Inslicht S, Ruoff LM, et al. Focus. 2018; 16: 67-73.

Elliott HL, Meredith PA, Reid JL. The American Journal of Cardiology. 1987; 59(14): G78-81.

PL Detail-Document #280228. Comparison of alpha blockers. Pharmacist’s Letter. February 2012.

May be useful for patients who develop orthostasis on

prazosin 1mg

Dosing

IR: Initiate at 1mg at bedtime

Increase to 2mg at day 3 and by 2mg per week thereafter, up

to 8mg per day

ER: Initiate at 4mg at bedtime

Increase to 8mg per day after at least 2 weeks

Doxazosin

De Jong J, Wauben P, Hujibrechts I, Oolders H, Haffmans J. J Clin Psychopharmacol. 2010 ; 30(1): 84-5.

Richards A, Inslicht S, Ruoff LM, et al. Focus. 2018; 16: 67-73.

Roepke S, Danker-Hopfe H, Repantis D, et al. Pharmacopsychiatry. 2017; 50: 26–31.

Smith C and Koola MM. Psychiatr Ann. 2016; 46(9): 553–5.

Upon recall of a traumatic memory, propranolol may

decrease hyperarousal symptoms

Doses ranged from 40mg/day-1mg/kg/day and were

administered either before or immediately after memory

reactivation

PTSD symptoms were then re-assessed one week later

Results are mixed, with two researchers noting response

and one unable to replicate these positive findings

Propranolol

Brunet A, et al. J Psychiatr Res. 2008; 42(6): 503-6.

Wood NE, et al. Psychiatry Res. 2015; 225(1-2): 31-9.

Kindt M, van Emmerik A. Ther Adv Psychopharmacol. 2016; 6(4): 283-95.

Brunet A, et al. Am J Psychiatry. 2018; 175(5): 427-33.

What else can I do for

my patients?

Have limited benefit on core PTSD symptoms

Increased symptoms in some cases

Concern for risk of falls, agitation, and CNS depressant effects,

particularly in combination with opioids

May contribute to cognitive impairment, interfering with fear

extinction process that should take place during psychotherapy

Benefit may be seen in patients with insomnia or acute panic

symptoms

If so, recommend duration is no more than 2-4 weeks

Caution against benzodiazepine use

Bernardy NC. PTSD Research Quarterly. 2013; 23: 1-9.

Guina J, Rossetter SR, DeRhodes BJ, Nahhas RW, Welton RS. Journal of Psychiatric Practice. 2015; 21(4): 281-303.

Trauma-informed care (TIC)

Delivering services in a way that is “grounded in an

understanding of and responsiveness to the impact of

trauma, that emphasizes physical, psychological, and

emotional safety for both providers and survivors, and that

creates opportunities for survivors to rebuild a sense of

control and empowerment”

Ensuring that the treatment environment itself is not a

barrier to recovery and does not retraumatize your

patient/customer

Even if you’re not trained in

psychotherapy, you can still

help

Substance Abuse and Mental Health Services Administration. Trauma-Informed Care in Behavioral Health Services. Treatment Improvement Protocol (TIP)

Series 57. HHS Publication No. (SMA) 13-4801. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2014.

See resilience not pathology

Establish safety

Build routine

Same provider, same time each month

Cultivate trust

Avoid reinforcing the trauma

Features of Trauma Informed Care



Cannot always prevent

Ex: anniversary month of an index trauma

Body language can be telling

Avoid reinforcing the trauma



Trigger Method of avoidance

Fear of

revictimization

Ensure adequate lighting, minimize feeling of isolation, allow

patient/client access to exit points, be careful with physical

contact and ask permission before any physical exam

Visual reminders of

trauma

Remove related items from office (i.e., military paraphernalia)

Power dynamics Avoid authoritarian statements (“because I told you so”)

Sit next to patient, not across desk

Making the office space work

for your patients

Questions??

All of the following are considered core symptoms of PTSD, except _________.

A. Exaggerated startle response

B. Vivid nightmares


D. Altered patterns of thinking

Post Test Question #1


While depersonalization (losing sense of self) and other dissociative features are

possible with PTSD, it is not required for diagnosis.

Such symptoms are more commonly seen with panic disorder


Which of the following is classified as having a significant level of benefit in


A. Venlafaxine

B. Amitriptyline

C. Mirtazapine

D. Prazosin


A. Venlafaxine

Venlafaxine retained its high level of evidence supporting use in PTSD

management.

Amitriptyline is given a lower level of evidence, due in part to its side effect

profile

Prazosin and mirtazapine were both downgraded based on the more recent

guidelines


Which medication results in negative therapeutic outcomes when used in


A. Lorazepam

B. Propranolol

C. Paroxetine

D. Nefazodone


A. Lorazepam

As a benzodiazepine, lorazepam may interfere with the cognitive processing

necessary to complete psychotherapy and may worsen overall cognitive function

Propranolol is not mentioned at all in the more recent guidelines but there is

growing evidence supporting its use as augmentation to psychotherapy

Paroxetine is still considered efficacious but use is limited by sexual side effects

and weight gain

Nefazodone is rarely used due to concerns of hepatotoxicity, though it is

considered to have good efficacy


Which of the following represents appropriate application of Trauma Informed

Care (TIC)?

A. Assuming that PTSD is rare and probably doesn’t affect your patients

B. Explaining the rationale behind a clinical decision as “because I said so”

C. Interrupting patients who “never get to the point”

D. Informing a patient beforehand if he or she will be seeing a different

provider at next follow-up


D. Informing a patient beforehand if he or she will be seeing a different provider at next follow-up. Trust is a MAJOR concern in PTSD and it takes time to earn from your patient. Seeing a new face without understanding beforehand that it may occur can bring back past mistrust (commanding officers in Vietnam were moved in and out frequently, leading to lack of cohesion in fighting units)

Trauma is, unfortunately, highly prevalent. One need only read about the #MeToo movement to see this in action

Power imbalance is another concept that resonates with those with those who experienced trauma, whether sexual or combat related. Authoritarian statements may reinforce this and re-trigger the individual

Many individuals simply want to be validated and feel that they are being heard. While patients may sometimes need redirection, it is important to make the individual know their concerns are important. If you must intervene, make sure to restate the individual’s concerns and allow them to tell you whether or not you as a clinician are understanding the situation correctly


The role of psychotherapy in management of PTSD has been understated in the past and is now being increasingly emphasized

Large trials fail to replicate results from case series of pilot studies

Prazosin may have role for certain individuals on a case-by-case basis; less restrictive studies in a more realistic patient population may be beneficial

Similarly, the decision to discontinue prazosin must also be made on a case-by-case basis

Other alpha adrenergic modulators with more favorable pharmacokinetic profiles may have a role in management of PTSD symptoms

TAKE HOME POINTS

Bernardy NC. The role of benzodiazepines in the treatment of Posttraumatic Stress Disorder (PTSD). PTSD Research Quarterly. 2013; 23: 1-9.

Brunet A, Saumier D, Liu A, et al. Reduction of PTSD symptoms with pre-reactivation propranolol therapy: a randomized controlled trial. Am J Psychiatry. 2018; 175(5): 427-33.

Brunet A, Orr SP, Tremblay J, Robertson K, Nader K, Pitman RK. Effect of post-retrieval propranolol on psychophysiologic responding during subsequent script-driven traumatic imagery in post-traumatic stress disorder. J Psychiatr Res. 2008; 42(6): 503-6.

De Jong J, Wauben P, Hujibrechts I, Oolders H, Haffmans J. Doxazosin treatment for posttraumatic stress disorder. J Clin Psychopharmacol. 2010 ; 30(1): 84-5.

Diagnostic and Statistical Manual of Mental Disorders, 5th edition. American Psychiatric Association: Washington, DC; 2013.

Elliott HL, Meredith PA, Reid JL. Pharmacokinetic overview of doxazosin. The American Journal of Cardiology. 1987; 59(14): G78-81.

Guina J, Rossetter SR, DeRhodes BJ, Nahhas RW, Welton RS. Benzodiazepines for PTSD: A systematic review and meta-analysis. Journal of Psychiatric Practice. 2015; 21(4): 281-303.

Resources & References

Gray EN, Shuman MD, McGrane IR. The role of prepulse inhibition in medication

management of PTSD: A case report. Ment Health Clin. 2013; 2:18.

Kindt M, van Emmerik A. New avenues for treating emotional memory disorders:

towards a reconsolidation intervention for posttraumatic stress disorder. Ther

Adv Psychopharmacol. 2016; 6(4): 283-95.

Koola MM, Varghese SP, Fawcett JA. High-dose prazosin for the treatment of post-

traumatic stress disorder. Ther Adv Psychopharmacol. 2014; 4(1): 43-7.

Kung S, Espinel Z, Lapid MI. Treatment of nightmares with prazosin: A systematic

review. Mayo Clin Proc. 2012; 87(9): 890–900.

The Management of Post-Traumatic Stress Working Group. VA/DoD clinical

practice guideline for management of post-traumatic stress. 2010. Online.

Available: https://www.healthquality.va.gov/ptsd-full-2010c.pdf. Accessed

5/15/18.


The Management of Posttraumatic Stress Disorder Work Group. VA/DoD clinical practice guideline for the management of posttraumatic stress disorder and acute stress disorder. 2017. Online. Available: https://www.healthquality.va.gov/guidelines/MH/ptsd/VADoDPTSDCPGFinal012418.pdf. Accessed 5/15/18.

Marmar CR, Schlenger W, Henn-Haase C, et al. Course of posttraumatic stress disorder 40 Years after the Vietnam War: findings from the National Vietnam Veterans Longitudinal Study. JAMA Psychiatry. 2015; 72(9): 875-81.

PL Detail-Document #280228. Comparison of alpha blockers. Pharmacist’s Letter.2012.

Raskind MA, Dobie DJ, Kanter ED, et al. The alpha1-adrenergic antagonist prazosin ameliorates combat trauma nightmares in veterans with posttraumatic stress disorder: a report of 4 cases. J Clin Psychiatry. 2000; 61:129–33.

Raskind MA, Peskind ER, Kanter ED, et al. Reduction of nightmares and other PTSD symptoms in combat veterans by prazosin: a placebo-controlled study. Am J Psychiatry. 2003; 160:371–3.


Raskind MA, Peterson K, Williams T, et al. A trial of prazosin for combat trauma PTSD with nightmares in active-duty soldiers returned from Iraq and Afghanistan. Am J Psychiatry. 2013; 170:1003–10.

Raskind MA, Peskind ER, Chow B, et al. Trial of Prazosin for Post-Traumatic Stress Disorder in Military Veterans. N Engl J Med. 2018; 378: 507-17.

Richards A, Inslicht S, Ruoff LM, et al. An open-label study of doxazosin extended-release for PTSD: findings and recommendations for future research on doxazosin. Focus. 2018; 16: 67-73.

Roepke S, Danker-Hopfe H, Repantis D, et al. Doxazosin, an α-1-adrenergic-receptor antagonist, for nightmares in patients with posttraumatic stress disorder and/or borderline personality disorder: A chart review. Pharmacopsychiatry. 2017; 50: 26–31.

Rothbaum BO, Killeen TK, Davidson JR, et al. Placebo-controlled trial of risperidone augmentation for selective serotonin reuptake inhibitor-resistant civilian posttraumatic stress disorder. J Clin Psychiatry 2008; 69: 520-5.

Shay J. Odysseus in America: combat trauma and the trials of homecoming. 2nd ed. New York: Scribner; 2002.


Smith C and Koola MM. Evidence for using doxazosin in the treatment of posttraumatic stress disorder. Psychiatr Ann. 2016; 46(9): 553–5.

Substance Abuse and Mental Health Services Administration. Trauma-Informed Care in Behavioral Health Services. Treatment Improvement Protocol (TIP) Series 57. HHS Publication No. (SMA) 13-4801. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2014.

Taylor FB, Martin P, Thompson C, et al. Prazosin effects on objective sleep measures and clinical symptoms in civilian trauma posttraumatic stress disorder: a placebo-controlled study. Biol Psychiatry. 2008; 63(6): 629–32.

VA Office of Research and Development. Cooperative Studies Program #563 - Prazosin and Combat Trauma PTSD (PACT). 2018. Online. Available: https://clinicaltrials.gov/ct2/show/NCT00532493. Accessed 5/15/18.

Wood NE, Rosasco ML, Suris AM, et al. Pharmacological blockade of memory reconsolidation in posttraumatic stress disorder: Three negative psychophysiological studies. Psychiatry Res. 2015; 225(1-2): 31-9.


Speaker Contact InformationMichael Shuman, PharmD, BCPP

[email protected]

HelixTalk Podcast (http://helixtalk.com)

Episode 72: Drop It Like It’s Hot:

Prazosin and the 2017 VA/DoD PTSD

Guidelines

For more

information

https://www.rosalindfranklin.edu/academics/college-of-pharmacy/helixtalk/helixtalk-episode-72--drop-it-like-its-hot-prazosin-and-the-2017-va-dod-ptsd-guidelines

Documents

Post-Traumatic Stress Disorder (PTSD) symptoms in your ... · Prevalence rates for PTSD in the general population have been estimated at 6.1-12.3% A 2008 study of 11,441 veterans