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Am Fam Physician. 2022;106(6):623-624

This clinical content conforms to AAFP criteria for CME.

Author disclosure: No relevant financial relationships.

Clinical Question

Is pharmacotherapy effective for reducing symptoms of posttraumatic stress disorder (PTSD) in adults?

Evidence-Based Answer

Selective serotonin reuptake inhibitors (SSRIs) improve symptoms of PTSD and are considered first-line pharmacologic agents. (Strength of Recommendation [SOR]: A, consistent, good-quality patient-oriented evidence.) Mirtazapine and amitriptyline also improve PTSD symptoms. (SOR: B, inconsistent or limited-quality patient-oriented evidence.) SSRI use is associated with an increased risk of treatment withdrawal because of adverse effects compared with placebo.1

Practice Pointers

PTSD is characterized by complex behavioral, somatic, and cognitive effects caused by a traumatic event. Psychotherapy and medications are used for treatment of PTSD. The lifetime prevalence of PTSD in North America is more than 9% for the general adult population and may be as high as 17% in U.S. veterans.2,3 The authors of the review sought to identify medications that are effective for reducing symptoms of PTSD in adults.

The Cochrane review included 66 randomized controlled trials and 7,442 participants ranging from 18 to 85 years of age with a primary diagnosis of PTSD.1 Doses of medications varied. Patients on concomitant medications were included, but those receiving psychotherapy were excluded. Pharmacotherapies were assessed for the patient-oriented outcomes of treatment efficacy and tolerability. Treatment efficacy was defined as improvement of PTSD symptoms compared with placebo and measured by the Clinical Global Impressions Scale–Improvement score. This scale ranges from a score of 1 (very much improved) to 7 (very much worse), and treatment was considered effective if participants scored 1 or 2.1 The studies lasted from 13 days to 28 weeks, and treatment tolerability was assessed using the surrogate measure of dropout secondary to adverse events.

SSRIs, including fluoxetine, paroxetine, and sertraline, improved PTSD symptoms compared with placebo (risk ratio [RR] = 0.66; 95% CI, 0.59 to 0.74) based on moderate-certainty evidence. These SSRIs improved symptoms across several PTSD symptom clusters (i.e., reexperiencing/intrusion, avoidance/numbing, and hyperarousal) determined by subscales. Treatment withdrawal due to adverse events increased among patients using SSRIs (RR = 1.41; 95% CI, 1.07 to 1.87; absolute risk of withdrawal overall was 9%).

Low-certainty evidence showed that mirtazapine (RR = 0.45; 95% CI, 0.22 to 0.94) and amitriptyline (RR = 0.60; 95% CI, 0.38 to 0.96) improved PTSD symptoms compared with placebo. There was no statistically significant increase in treatment withdrawal due to adverse events in those taking mirtazapine or amitriptyline compared with placebo. No evidence of benefit was found with the use of other medications such as anticonvulsants and antipsychotics; no studies reported the treatment efficacy of other potential therapies including alpha blockers, benzodiazepines, hypnotics, monoamine oxidase inhibitors, or serotonin-norepinephrine reuptake inhibitors. There were no adequate comparisons of medication types, such as an SSRI vs. amitriptyline.

The results are widely generalizable because the studies included adults with diverse trauma types, duration, severity, and comorbidities. The most common bias introduced in the reviewed studies was attrition bias. However, the lack of blinding for outcome assessors, selective reporting bias, and lack of clarity of randomization were also present.

Current clinical practice guidelines recommend offering fluoxetine, paroxetine, sertraline, and venlafaxine as first-line medications for PTSD.4,5 Family physicians should practice shared decision-making and discuss the potential value of SSRIs, amitriptyline, and mirtazapine for the treatment of PTSD. There is no evidence to support the use of other medications to treat PTSD.

The practice recommendations in this activity are available at

The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the U.S. Navy, the U.S. Marine Corps, or the U.S. Department of Defense.

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These are summaries of reviews from the Cochrane Library.

This series is coordinated by Corey D. Fogleman, MD, assistant medical editor.

A collection of Cochrane for Clinicians published in AFP is available at

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