Post on 19-Dec-2015
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
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
Benzodiazepines All I I I
Strength of Evidence: M=Moderate; L=Low; I=Insufficient
Pharmacotherapy: Strength of Evidence
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://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 sedativeshttp://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(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
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 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