pharmacotherapy for post-traumatic stress disorder presented by: ann hamer, pharmd, bcpp date:...

Pharmacotherapy for Post-Traumatic Stress Disorder

Presented by: Ann Hamer, PharmD, BCPPDate: 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 PTSD Sx Remission Loss of PTSD Dx

Alpha Blocker Prazosin I I I

Anticonvulsant Divalproex I I I

Lamotrigine I I I

Tiagibine I I I

Topiramate M I I

Antipsychotic Olanzapine I I I

Risperidone L I I

SNRI Desvenlafaxine I I I

Duloxetine I I I

Venlafaxine M M I

Strength of Evidence: M=Moderate; L=Low; I=Insufficient


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

Benzodiazepines All I I I

Strength of Evidence: M=Moderate; L=Low; I=Insufficient


Outcome Measure Paroxetine Venlafaxine

Inducing remissionX

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://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




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 sedativeshttp://www.thecarlatreport.com/printpdf/5050



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




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




Adrenergic Agents

Medication Dosing Adverse Effects Monitoring

Propranolol(non-selectively antagonizes beta-1 and beta-2 adrenergic receptors)

10 - 40mg po TID-QID

Fatigue, dizzinessconstipation, bradycardia, hypotension, depression, insomnia, weakness, disorientation, nausea, diarrhea, hypersensitivity rxn, purpura, alopecia, impotence

BP, HRCYP 2D6 substrate

Clonidine(stimulates alpha-2 adrenergic receptors)

0.1 - 0.3 po qhs Somnolence, headacheHypotension, abdominal painFatigue, nightmares, nauseaURI, 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 Hypotension, first-dose asthenia, dizziness, nausea, palpitations, headache, somnolence, hypotension (orthostatic), impotence, priapism, urinary frequency, dyspnea, arthralgia, myalgia

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



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


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


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.


First-line• SSRIs

Second-line — examine symptomsSymptoms 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!

Obsessive-Compulsive

Disorder

02/5/15

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pharmacotherapy for post-traumatic stress disorder presented by: ann hamer, pharmd, bcpp date:...

Documents

insufficient slide

ptsd dose ssris

time slide

minimal evidence

treatment adherence

gold standard treatment

remission http

therapeutic response