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Managing Post-traumatic Stress Disorder: The Pharmacotherapy Option


First-line agents include selective serotonin reuptake inhibitors and venlafaxine.

Although psychotherapy is the preferred treatment for patients with post-traumatic stress disorder (PTSD), pharmacotherapy presents another good option.1 First-line agents include selective serotonin reuptake inhibitors (SSRIs) and the selective serotonin-norepinephrine reuptake inhibitor venlafaxine. Patients who choose pharmacotherapy with these agents might approach their primary care physician for treatment.

Risk Factors and Comorbidities
Any person exposed to the threat of death, injury, or serious harm to self or others is at risk for PTSD. Common risk factors include natural disasters, serious motor vehicle accidents, physical assault, and rape. Natural disasters carry the lowest risk of PTSD and sexual assault the highest. The risk also varies with other factors, such as one’s sex and the intensity, frequency, and duration of the trauma.

PTSD is twice as likely to develop in women as in men. Patients who have experienced life-threatening trauma and those working in occupations that involve frequent trauma exposures, such as police and firefighters, are at risk. PTSD does not develop in most of those who are exposed to trauma, and they maintain normal functioning.

The rates of comorbidity with PTSD are high for major depressive disorder and alcohol dependence. Depression appears to be the most common comorbidity in women; alcohol dependence is the second most common. An estimated 50% or more of patients with PTSD have major depressive disorder. The rates of alcohol dependence and abuse range from 25% to 50%. Patients who have PTSD also are at increased risk for dementia and an increased number of medical conditions compared with patients who do not.  

Evidence-Based Recommendations
The Pharmacotherapy Work Group that revised the Department of Veterans Affairs/Department of Defense Clinical Practice Guideline for PTSD reviewed randomized controlled trials and meta-analyses on the effectiveness of pharmacotherapy for PTSD. SSRIs and venlafaxine were strongly recommended as first-line agents.

Other medications that have some evidence of effectiveness include tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), mirtazapine, and nefazodone; prazosin may be used for nightmares. Nefazodone carries a small but serious risk of liver failure. TCAs and MAOIs carry serious adverse effects and should be prescribed only by a clinician who is experienced with these medications. Atypical antipsychotics and benzodiazepines were not recommended as treatments.

Randomized controlled trials showed the strongest evidence for SSRIs; sertraline and paroxetine are the only ones currently FDA-approved for the treatment of patients with PTSD. These studies found significant reductions in PTSD symptoms with active treatment compared with placebo, based on the Clinician Administered PTSD Scale and other objective measures. In a large multicenter, placebo-controlled trial, venlafaxine was recommended as a first-line agent because of its beneficial effects on PTSD symptoms.

Benzodiazepines are not recommended for several reasons. They have no proven efficacy for management of the core PTSD symptoms, and they may actually interfere with trauma-focused psychotherapy, such as prolonged exposure therapy, by decreasing the habituation of the anxiety response. Other concerns are that benzodiazepines enhance avoidance and that the rate of comorbidity of substance abuse and dependence with PTSD is high.

Evidence for the efficacy of antipsychotics in PTSD management is lacking. The guideline originally endorsed risperidone as adjunctive treatment, based on smaller studies showing some benefit, but shortly after the guideline was published, a large placebo-controlled multisite trial of risperidone showed no benefit. The guideline was revised to reflect no benefit for adjunctive use of risperidone in PTSD. One of 2 published randomized controlled trials for olanzapine showed negative results for monotherapy, and the other demonstrated positive results as adjunctive therapy. Based on the current evidence and the potential for adverse effects, antipsychotics are not recommended for PTSD.

Essentials for Managing Co-Occurring Disorders
These disorders influence one another and complicate treatment. They also interfere with the management of medical problems in primary care. Substance abuse has many potential negative effects on symptoms, treatment, and social functioning. Prescribing medications in this context may lead to unintended adverse effects or decreased response.

Suicidal ideations would be one of the most concerning symptoms of comorbid depression and must be monitored closely. Lack of energy, concentration, and motivation also impair treatment response and occupational and social functioning. All of these comorbid disorders must be considered in developing an effective treatment plan.

One of the most important things for primary care physicians is to open a dialogue about symptoms, diagnosis, and potential treatment options. Patients with PTSD often are reluctant to disclose their symptoms and trauma history. Gaining their trust and knowing when to make a referral are important interventions. Some physicians may be concerned about dealing with an area they are unfamiliar with, but patients often feel relief when they disclose having PTSD and the physician helps them develop initial plans for treatment.

Take-Home Message
Patients may first approach their primary care physician about treatment. Developing a rapport and dialogue with the patient about treatment options is important. Pharmacotherapy is an effective intervention for PTSD; SSRIs and venlafaxine are the first-line agents. An emergent mental health referral would be indicated if there is an acute safety concern, such as suicidal ideation. Trauma-focused psychotherapy is highly effective. Primary care physicians should discuss this option and have some referral sources in mind.


1. Jeffreys M, Capehart B, Friedman MJ. Pharmacotherapy for posttraumatic stress disorder: review with clinical applications. J Rehabil Res Dev. 2012;49:703-716.

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