Pharmacotherapy for Post-Traumatic
Stress Disorder
Presented by: Ann Wheeler, PharmD, BCPP
Date: 01/14/2016
Disclosures and Learning Objectives
Learning Objectives:
• Know the two classes of medications most
helpful for PTSD
• Be able to discuss the benefits of second-line
treatment alternatives
Disclosures: Dr. Ann Wheeler 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 Blockers
Anticonvulsants
Antipsychotics
SNRIs
PTSD Sx
Remission
Loss of PTSD Dx
Prazosin
--
--
--
Divalproex
--
--
--
Lamotrigine
--
--
--
Tiagibine
--
--
--
Topiramate
M
--
--
Olanzapine
--
--
--
Risperidone
L
--
--
Desvenlafaxine
--
--
--
Duloxetine
--
--
--
Venlafaxine
M
M
--
Strength of Evidence: M=Moderate; L=Low; -- =Insufficient
Pharmacotherapy: Strength of Evidence
Drug Class
Drug
PTSD Sx
Remission
Loss of PTSD Dx
SSRIs
Citalopram
--
--
--
Fluoxetine
M
--
--
Paroxetine
M
M
--
Sertraline
M
--
--
TCAs
All
--
--
--
Other ATDs
Bupropion
--
--
--
Mirtazapine
--
--
--
Nefazodone
--
--
--
Trazodone
--
--
--
All
--
--
--
Benzodiazepines
Strength of Evidence: M=Moderate; L=Low; -- =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. Ideal for comorbid MDD.
•
Sertraline and paroxetine are the only SSRIs with FDA
approval for PTSD
•
Dosing sertraline 50 – 200mg/d, paroxetine 20 - 60mg/d
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 with other antidepressants are mixed
•
•
•
Evidence supports use of venlafaxine (75 – 300mg/d)
NICE recommends mirtazapine, amitriptyline and
phenelzine first-line; however 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; exception is use for psychotic sx
•
•
Sedating atypicals most likely to show benefit
Risperidone is the most researched. VA revised
guideline:
•
•
CI for use an adjunctive agent—potential harm exceeds
benefits.
There is insufficient evidence to recommend any other AAP
as an adjunctive agent for PTSD.
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.
•
Indicated for bipolar disorder w/ or w/o PTSD.
•
Trials showing effectiveness are typically open-label
•
Notably, valproate (Depakote) no better than placebo.
•
Topiramate may be helpful for nightmares and
flashbacks. Currently listed as having no demonstrated
benefit in VA/DoD Practice Guideline. May be helpful in
those dually diagnosed with an alcohol use disorder.
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, sleep
disturbance (nightmares) 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
Central alpha-adrenergic
agonists (e.g. clonidine) reduce
sympathetic outflow from the
alpha-2 receptor sites in the
CNS, thus decreasing
peripheral vascular resistance
and slowing the surge of
catecholamines. Prazosin is a
central and peripheral alphaadrenergic antagonist.
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 reaction,
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 in the short-term (≤5 days), BUT…
Avoid in active or recent substance abuse
•
SA in 40% of PTSD (75% if combat-related)
Risks:
•
Potential disinhibition, difficulty integrating the traumatic experience,
interfering with the mental processes needed to benefit from
psychotherapy, increased falls and mental clouding in the elderly,
psychomotor and cognitive impairment, and dependence/addiction
Minimal 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
Future Research
•
Glucocorticoid receptors—modulate the effects of stress and
development of PTSD
•
Neuropeptides: corticotropin releasing factor (CRF),
adrenocorticotropin hormone (ACTH), substance P, neuropeptide
Y—improve resiliency of the brain to the effects of trauma. BBB is
a challenge. Intranasal oxytocin has demonstrated some benefit in
decreasing hyperarousal symptoms.
•
D-cycloserine may facilitate extinction of conditioned fear
•
Memantine (Namenda)—prevents neurodegeneration by protecting
against glutamatergic destruction of neurons through its
antagonism of the NMDA receptor. May be useful in preventing
hypothesized neurodegeneration in the hypothalamus and memory
loss in PTSD.
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
Common clinical barriers
• Fear of possible side effects (e.g. sexual side effects)
• Feeling medication is a “crutch” and that taking it is a
weakness
• Fear of being addicted
• Taking only occasionally when symptoms get severe
• Using “self medication”
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.
Pharmacologic Treatment of PTSD
Treatment Considerations
First-line treatment recommendation
Psychotherapy (CBT)
First-line pharmacologic treatment options
SSRIs (dosing is similar to depression)
• Best evidence with paroxetine
Second-line pharmacologic treatment options
Define realistic treatment goals and monitor for
improvement
•
•
•
•
•
•
Reduction in PTSD symptom severity
Suicidal behavior
Substance misuse
Social isolation
Comorbid psychopathology
Global function/quality of life
The End
Somatic
Symptom
Disorder
1/21/16