Pharmacotherapy for Post-Traumatic
Stress Disorder
Presented by: Ann Hamer, PharmD, BCPP
Date: 01/29/2015
Disclosures and Learning Objectives
Learning Objectives:
• Know the two classes of medications most
helpful for PTSD
• Know how to select a second-line treatment
alternative
Disclosures: Dr. Ann Hamer has nothing to disclose.
PTSD in the Primary Care Setting
• Discuss step-wise approach in treatment
of PTSD
• Gold standard
• Indicated medications
• Strength of evidence
• Second-line treatment recommendations
• Topic for next time
Pharmacologic Interventions
Psychotherapy (CBT) remains the gold standard treatment
for PTSD
•
All of the existing guidelines (6 out of 6) agree that
trauma-focused psychological interventions are
effective, empirically supported first-line treatments for
PTSD
•
Less agreement among guidelines in regards to
pharmacologic interventions.
•
50% agree that SSRIs are first-line (VA/DoD, APA, ISTSS)
•
IOM guidelines found minimal evidence for all pharmacologic
treatment options
Pharmacologic Interventions
General Considerations for Pharmacotherapy:
•
Main goal is to minimize symptoms rather than cure
PTSD
•
Hyperarousal symptoms (nightmares, etc) are the most
likely to respond
•
Medications should never replace therapy unless it is
ineffective or declined
•
Patient preferences need to be incorporated into shared
decision-making because they can influence treatment
adherence and therapeutic response
http://www.thecarlatreport.com/printpdf/5050
http://www.publichealth.va.gov/docs/vhi/posttraumatic.pdf
http://www.nice.org.uk/guidance/cg26/resources/guidance-posttraumatic-stress-disorder-ptsd-pdf
Pharmacotherapy: Strength of Evidence
Drug Class
Drug
Alpha Blocker
Anticonvulsant
Antipsychotic
SNRI
PTSD Sx
Remission
Loss of PTSD Dx
Prazosin
I
I
I
Divalproex
I
I
I
Lamotrigine
I
I
I
Tiagibine
I
I
I
Topiramate
M
I
I
Olanzapine
I
I
I
Risperidone
L
I
I
Desvenlafaxine
I
I
I
Duloxetine
I
I
I
Venlafaxine
M
M
I
Strength of Evidence: M=Moderate; L=Low; I=Insufficient
Pharmacotherapy: Strength of Evidence
Drug Class
Drug
PTSD Sx
Remission
Loss of PTSD Dx
SSRI
Citalopram
I
I
I
Fluoxetine
M
I
I
Paroxetine
M
M
I
Sertraline
M
I
I
TCAs
All
I
I
I
Other SGAs
Bupropion
I
I
I
Mirtazapine
I
I
I
Nefazodone
I
I
I
Trazodone
I
I
I
All
I
I
I
Benzodiazepines
Strength of Evidence: M=Moderate; L=Low; I=Insufficient
Pharmacotherapy: Strength of Evidence
Outcome Measure
Inducing remission
Paroxetine
X
Venlafaxine
X
Improving depressive
symptoms
X
X
Improving functional
impairment
X
X
Improving quality of life
X
Psychological and Pharmacological Treatments for Adults With Posttraumatic Stress Disorder (PTSD). Comparative
Effectiveness Review No. 92. AHRQ Publication No. 13-EHC011-EF. Rockville, MD: Agency for Healthcare
Research and Quality; April 2013.
www.effectivehealthcare.ahrq.gov/reports/final.cfm.
Pharmacology for PTSD: Antidepressants
Treatment Recommendations
•
APA and VA recommend SSRIs as first choice when
medications are indicated
•
Sertraline and paroxetine remain the only SSRIs with
FDA approval for PTSD
•
Dose SSRIs the same as for depression
Response
•
Most studies show a modest response (60% response,
40% remission)
http://www.thecarlatreport.com/printpdf/5050
http://www.publichealth.va.gov/docs/vhi/posttraumatic.pdf
http://www.nice.org.uk/guidance/cg26/resources/guidance-posttraumatic-stress-disorder-ptsd-pdf
http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/acutestressdisorderptsd-watch.pdf
Pharmacology for PTSD: Other ATDs
Studies on other antidepressants are mixed
•
•
•
Evidence supports use of venlafaxine
NICE recommends mirtazapine, amitriptyline and
phenelzine first-line; less evidence supporting use
No evidence for use of bupropion
Sleep may be least likely to respond to SSRI
•
Consider adding mirtazapine (low dose), trazodone,
or a low dose sedating TCA like amitriptyline/doxepin
http://www.thecarlatreport.com/printpdf/5050
http://www.publichealth.va.gov/docs/vhi/posttraumatic.pdf
http://www.nice.org.uk/guidance/cg26/resources/guidance-posttraumatic-stress-disorder-ptsd-pdf
http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/acutestressdisorderptsd-watch.pdf
Pharmacology for PTSD: Antipsychotics
Should not be used first-line; should not be used as
monotherapy; no studies support use of typicals
Sedating atypicals most likely to show benefit
•
•
•
Risperidone is the most researched, and may be a
helpful adjunct to SSRIs
Olanzapine helpful in some studies, esp as adjunct
Quetiapine supported, though research is lacking
Other medications are better choices as sedatives
http://www.thecarlatreport.com/printpdf/5050
http://www.publichealth.va.gov/docs/vhi/posttraumatic.pdf
http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/acutestressdisorderptsd-watch.pdf
Pharmacology for PTSD: Mood Stabilizers
Often shown to be ineffective, especially as
monotherapy
•
Trials showing effectiveness are typically open-label
•
Notably, valproate (Depakote) no better than placebo.
•
Topiramate may be helpful for nightmares and
flashbacks
http://www.thecarlatreport.com/printpdf/5050
http://www.publichealth.va.gov/docs/vhi/posttraumatic.pdf
http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/acutestressdisorderptsd-watch.pdf
Pharmacology for PTSD: Anti-Adrenergics
More helpful in the short term
Typically associated with less stigma
May help with hypervigilance and activation
•
Propranolol 10 - 40mg po 3-4x/day
•
Clonidine 0.1 - 0.3mg po bedtime and PRN
•
Prazosin 1 - 3mg po bedtime
•
Guanfacine not supported in studies
http://www.thecarlatreport.com/printpdf/5050
http://www.publichealth.va.gov/docs/vhi/posttraumatic.pdf
http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/acutestressdisorderptsd-watch.pdf
Adrenergic Agents
Medication
Dosing
Adverse Effects
Monitoring
Propranolol
10 - 40mg po
TID-QID
Fatigue, dizziness
constipation, bradycardia,
hypotension, depression, insomnia,
weakness, disorientation, nausea,
diarrhea, hypersensitivity rxn,
purpura, alopecia, impotence
BP, HR
CYP 2D6 substrate
(non-selectively
antagonizes
beta-1 and
beta-2
adrenergic
receptors)
Clonidine
0.1 - 0.3 po qhs Somnolence, headache
Hypotension, abdominal pain
Fatigue, nightmares, nausea
URI, irritability, throat pain, insomnia,
constipation, emotional disturbance,
xerostomia, bradycardia, dizziness,
temperature elevated, diarrhea,
otalgia, sexual dysfxn, withdrawal sx
(stimulates
alpha-2
adrenergic
receptors)
Prazosin
(antagonizes
peripheral
alpha-1
adrenergic
receptors)
1 - 3mg po qhs
Hypotension, first-dose asthenia,
dizziness, nausea, palpitations,
headache, somnolence, hypotension
(orthostatic), impotence, priapism,
urinary frequency, dyspnea,
arthralgia, myalgia
Cr at baseline; vital
signs frequently if
cardiac conduction
disturbance; HR, BP at
baseline, after dose
increases, then
periodically
BP
Pharmacology for PTSD: Benzodiazepines
May be helpful for sleep, BUT…
Avoid in active or recent substance abuse
•
SA in 40% of PTSD (75% if combat-related)
Benzos may contribute to emotional numbing
•
This may interfere with recovery
Scant evidence for actual benefit
Little evidence for or against buspirone
http://www.thecarlatreport.com/printpdf/5050
http://www.publichealth.va.gov/docs/vhi/posttraumatic.pdf
General Considerations
Define realistic treatment goals:
•
Reduction in PTSD symptom severity
•
Suicidal behavior
•
Substance misuse
•
Social isolation
•
Comorbid psychopathology
•
Global function/quality of life
Assess response using validated scales
General Considerations
When to discontinue treatment:
•
Effective treatments (treatment goals have been met)
should be continued for a significant period of time
•
Generally >1 year
•
Those with early robust response may consider shorter duration
General Considerations
When to discontinue treatment:
•
Intolerable side effects
•
Lack of treatment effectiveness
•
Partial effectiveness
•
Switch vs. augmentation strategies
•
Augmentation—difficult to determine if effectiveness is from 2nd
agent or from a combination of the two. Only way to determine
is to slowly taper first agent.
General Considerations
First-line
•
SSRIs
Second-line — examine symptoms
Symptoms
Drug Class Selection
Excessively aroused, hyperreactive,
dissociative episodes
Adrenergic agent
Fearful hypervigilant, paranoid, psychotic
Atypical antipsychotic
Comorbid major depression
Other antidepressant
(venlafaxine)
Labile, impulsive, aggressive
Mood stabilizer
Psychological and Pharmacological Treatments for Adults With Posttraumatic Stress Disorder (PTSD). Comparative
Effectiveness Review No. 92. AHRQ Publication No. 13-EHC011-EF. Rockville, MD: Agency for Healthcare
Research and Quality; April 2013. www.effectivehealthcare.ahrq.gov/reports/final.cfm.
Summary
•
•
•
•
•
•
PTSD occurs in 8.6% of primary care patients
DSM-V has shifted PTSD diagnostic criteria to 6
categories (think TRAUMA)
Tools like the PC-PTSD and PCL-C accurately detect
PTSD in the primary care setting
Good treatment avoids retraumatization
CBT and EMDR are treatments of choice in PTSD
Antidepressants (SSRIs) and anti-adrenergics are the
most supported/commonly used medications for
PTSD
The End!
ObsessiveCompulsive
Disorder
02/5/15
http://proof.nationalgeographic.com/2014/11/05/musings-corey-arnold-looks-wildlife-straight-in-theeye/?source=photoeditorspicks