What are first-line treatments for PTSD?

Norma is a 70 yo woman with hypertension and post-traumatic stress disorder (PTSD). After the death of her husband, she experienced a severe major depressive episode and a resurgence of PTSD symptoms from a sexual assault she endured as a young woman. Knowing that trauma focused therapy is the first-line treatment for PTSD, you try to connect Norma with therapy. Unfortunately, she can’t find an available therapist who accepts her insurance. You then offer Norma a medication to treat both major depression and PTSD.

Which of the following are first-line medication treatments for PTSD (and MDD)?

  1. Escitalopram
  2. Sertraline
  3. Paroxetine
  4. Venlafaxine
  5. All of the above, except escitalopram

Medications are 2nd-line treatments for PTSD as their effects are smaller and not as durable as the effects of therapy. Medications should be considered when psychological interventions are not available, do not work, or are declined by the patient. The 2023 VA Clinical Practice guidelines recommend the SSRIs sertraline and paroxetine (both FDA approved for PTSD) as well as the SNRI venlafaxine (off-label) as the first-line medications for PTSD.  

Rather than listing individual medications, a 2022 systematic review from the Cochrane group, and several other clinical guidelines recommend the SSRIs as a class as the first line pharmacologic treatment of PTSD. I think that this is a mistake. Pooled data from RCTs of SSRIs for PTSD demonstrated efficacy for the class (58% of the SSRI group responded, compared with only 35% of the placebo group), but this positive finding was driven by the positive data from paroxetine and sertraline specifically. The Risk Ratio (RR) for a response from SSRIs as a class in PTSD was 0.66, with the 95% confidence interval (CI) 0.59-0.74. When the SSRIs were looked at individually on the same scale, only sertraline (RR = 0.68, 95% CI 0.56–0.81) and paroxetine (RR = 0.64, 95% CI 0.55–0.74) showed benefit (Williams 2022).   

What about the other SSRIs? Fluoxetine has some small positive studies in PTSD and is listed as a first-line treatment for PTSD in older clinical guidelines. Citalopram was included in 1 small study for PTSD and did not separate from placebo. In the 2023 VA guidelines, citalopram, escitalopram, and fluoxetine are all listed as having insufficient evidence to recommend for or against them in the treatment of PTSD.

Each medication in the SSRI class is an individual drug that is not interchangeable with other SSRIs (with the exception of citalopram and escitalopram). We have all had patients with depression who failed to respond to one SSRI but responded well to another one. In choosing a first-line pharmacologic treatment for PTSD, I recommend using the medications with the most robust evidence to support their use: sertraline, paroxetine, and venlafaxine.

When starting and titrating sertraline, paroxetine, or venlafaxine for PTSD (or anxiety disorders), start low and slowly increase the dose as tolerated. A full trial of sertraline, paroxetine, or venlafaxine for PTSD is 8 weeks of full-adherence at the FDA-max dose (sertraline 200mg, paroxetine 60mg, or venlafaxine XR 225mg) or the highest tolerated dose. If the medication is well-tolerated and there is a partial improvement on sertraline 200mg or venlafaxine XR 225mg, you can increase the dose above the FDA-max to sertraline 250mg daily or venlafaxine XR 300mg daily for a chance of additional benefit. 

Before starting a medication, you ask Norma to complete a PCL-5, so that you have a baseline measure of her PTSD symptoms. You choose sertraline, because paroxetine has a higher anticholinergic burden that can be troublesome in older adults and venlafaxine could raise her blood pressure. Norma starts sertraline 12.5mg daily, increasing the dose to 25mg daily after a week. She develops diarrhea while taking sertraline 25mg daily. The multiple loose stools per day are very bothersome and don’t resolve over 3 weeks. You stop the sertraline.  

Fortunately, in the interim, Norma was able to find a therapist trained in trauma focused therapy.   

What is trauma-focused therapy?
All trauma-focused therapies promote emotional regulation and include some emotional processing of a traumatic memory with the aim of integrating new corrective information into the memory. Not all licensed therapists are trained in this kind of work. Prolonged exposure (PE), EMDR (eye-movement desensitization and reprocessing), and cognitive processing therapy (CPT) are all evidence-based forms of trauma-focused therapy. 

Prolonged Exposure (PE) is a specific type of cognitive behavioral therapy (CBT) that helps patients gradually approach trauma-related memories, feelings and situations with the support of the therapist. Repeated exposures over time, initially through a trauma narrative and later by approaching triggering settings, help a person learn that the trauma cues are not currently dangerous and do not need to be avoided.

Eye-movement desensitization and reprocessing (EMDR) is a structured therapy in which patients briefly focus on a trauma memory while a therapist uses different forms of bilateral (i.e. both sides of the body) stimulation. By combining a dual awareness of the rhythmic movements (lateral eye movements, tones or taps) and an awareness of trauma memory, the vividness and emotion of the traumatic memory are reduced.

Cognitive Processing Therapy (CPT) is a specific type of cognitive behavioral therapy (CBT) that helps patients identify and challenge unhelpful beliefs related to the trauma and thereby reduce feelings of shame, guilt, and mistrust in the patient’s current life. The aim is to help the patient create a new understanding of the traumatic event that reduces its negative effects in their current life.

How to find an experienced practitioner:
Therapy provider registries for each of these forms of trauma-focused therapy can be used to identify local clinicians. The registries are not comprehensive. They are searchable by geographic location. EMDR, CPT, PE (UPenn), and PE (Emory)

After 12-weeks of EMDR with an individual therapist, Norma’s PTSD symptoms improved substantially. She then connected with a grief group and her depressive symptoms resolved over the next 6 months.

Which of the following are first-line medication treatments for PTSD (and MDD)?

  1. Escitalopram
  2. Sertraline
  3. Paroxetine
  4. Venlafaxine
  5. All of the above, except escitalopram

The answer is 5!

Look out for a future PsychSnap focused on the treatment of nightmares associated with PTSD.

Key Points

  1. Trauma focused therapies, including prolonged exposure (PE), EMDR (eye-movement desensitization and reprocessing), and cognitive processing therapy (CPT), are the first-line treatments for PTSD because their effect sizes are larger and more durable than those of medications. Therapy provider registries are are available here: EMDR, CPT, PE (UPenn), and PE (Emory).
  2. Sertraline, paroxetine, and venlafaxine are first-line medication treatments for PTSD. A full trial of these medications for PTSD is 8 weeks of full adherence to the FDA max dose.

Related PsychSnaps:
“How do you know when a patient has recovered from PTSD and you can consider de-prescribing medication?” Zoë Kopp, June 2024.
“Which SSRI should I choose?” Emma Samelson-Jones, February 2023.

Burback, Lisa, et al. “Treatment of posttraumatic stress disorder: a state-of-the-art review.” Current Neuropharmacology 22.4 (2024): 557.

VA/DoD Clinical Practice Guideline. (2023). Management of Posttraumatic Stress Disorder and Acute Stress Disorder Work Group. Washington, DC: U.S. Government Printing Office.

Williams, Taryn, et al. “Pharmacotherapy for post traumatic stress disorder (PTSD).” Cochrane Database of Systematic Reviews 3 (2022).

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