1. Pharmacotherapy for Post-Traumatic Stress Disorder
Presented by: Ann Wheeler, PharmD, BCPP
Date: 01/26/2017 1 1

2. Learning Objectives: Disclosures and 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. 2 2

3. Discuss step-wise approach in treatment of PTSD Gold standard
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 3 3

4. 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
International Society for Traumatic Stress Studies

5. 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

6. Pharmacotherapy: Strength of Evidence
Drug Class
Drug
PTSD Sx
Remission
Loss of PTSD Dx
Alpha Blockers
Prazosin --
Anticonvulsants
Divalproex
Lamotrigine
Tiagibine
Topiramate M
Antipsychotics
Olanzapine
Risperidone L
SNRIs
Desvenlafaxine
Duloxetine
Venlafaxine
Strength of Evidence: M=Moderate; L=Low; -- =Insufficient

7. Pharmacotherapy: Strength of Evidence
Drug Class
Drug
PTSD Sx
Remission
Loss of PTSD Dx
SSRIs
Citalopram --
Fluoxetine M
Paroxetine
Sertraline
TCAs
All
Other ATDs
Bupropion
Mirtazapine
Nefazodone
Trazodone
Benzodiazepines
Strength of Evidence: M=Moderate; L=Low; -- =Insufficient

8. Pharmacotherapy: Strength of Evidence
Outcome Measure
Paroxetine
Venlafaxine
Inducing remission X
Improving depressive symptoms
Improving functional impairment
Improving quality of life
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.

9. 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 mg/d
Response
Most studies show a modest response (60% response, 40% remission)
A deficiency in amygdala serotonin transport has been identified in some individuals with PTSD

10. 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

11. SSRI/SNRI Dosing Recommendations
Antidepressant
Usual Starting Dose (mg)
Low Starting Dose (mg)
Therapeutic Daily Dose (mg)
Paroxetine 20
5 to 10
20 to 60
Sertraline 50
12.5 to 25
50 to 200
Fluoxetine 5
Escitalopram 10
20 to 30
Venlafaxine
37.5
37.5 to 300

12. Pharmacology for PTSD: Antipsychotics
Should not be used first-line; exception is use for psychotic sx
Sedating atypicals most likely to show benefit
Quetiapine and risperidone are 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

13. 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.

14. 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 mg po 3-4x/day
Clonidine mg po bedtime and PRN
Prazosin 1 - 3mg po bedtime
Guanfacine not supported in studies
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 alpha-adrenergic antagonist.

15. Adrenergic Agents Medication Dosing Adverse Effects Monitoring
Propranolol
(non-selectively antagonizes beta-1 and beta-2 adrenergic receptors)
mg po TID-QID
Fatigue, dizziness
constipation, bradycardia, hypotension, depression, insomnia, weakness, disorientation, nausea, diarrhea, hypersensitivity reaction, purpura, alopecia, impotence
BP, HR
CYP 2D6 substrate
Clonidine
(stimulates alpha-2 adrenergic receptors)
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
Cr at baseline; vital signs frequently if cardiac conduction disturbance; HR, BP at baseline, after dose increases, then periodically
Prazosin
(antagonizes peripheral alpha-1 adrenergic receptors)
1 - 3mg po qhs (doses up to 15 mg have been studied)
Hypotension, first-dose asthenia, dizziness, nausea, palpitations, headache, somnolence, hypotension (orthostatic), impotence, priapism, urinary frequency, dyspnea, arthralgia, myalgia
BP; abrupt d/c is not recommended

16. 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
Data suggest benzodiazepine may impair therapeutic effects of treatments such as exposure therapy that rely on extinction learning
Minimal evidence for actual benefit
Little evidence for or against buspirone

17. 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.

18. 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

19. 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”

20. General Considerations
When to discontinue treatment:
Effective treatments (treatment goals have been met) should be continued for a significant period of time
At least 6 months and generally >1 year
Those with early robust response may consider shorter duration

21. 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.

22. General Considerations
First-line
SSRIs
Second-line — examine symptoms
Symptoms
Drug Class Selection
Excessively aroused, hyperreactive, dissociative episodes, nightmares
Adrenergic agent
Fearful hypervigilant, paranoid, psychotic
Atypical antipsychotic
Comorbid major depression
Alternative antidepressant (venlafaxine)
Labile, impulsive, aggressive
Mood stabilizer
Olanzapine helpful in some studies, esp as adjunct
Quetiapine supported, though research lags
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

23. 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

24. Personality Disorders in the Primary Care Setting
The End
Personality Disorders in the Primary Care Setting
2/2/17 24 24