The medications conditionally recommended for the treatment of PTSD are sertraline, paroxetine, fluoxetine and venlafaxine. Each patient varies in their response and ability to tolerate a specific medication and dosage, so medications must be tailored to individual needs.


The current evidence base for PTSD psychopharmacology is strongest for the selective serotonin reuptake inhibitors (SSRIs): sertraline, paroxetine and fluoxetine as well as the selective serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine. Currently only sertraline (Zoloft) and paroxetine (Paxil) are approved by the Food and Drug Administration (FDA) for PTSD. From the FDA perspective, all other medication uses are “off label” (see footnote), though there are differing levels of evidence supporting their use.

Selective Serotonin Reuptake Inhibitors

The neurotransmitter serotonin has a well-recognized role in the experience of mood and anxiety disorders. The activity of this neurotransmitter in both the peripheral and central nervous systems can be modulated by SSRIs.

The SSRIs sertraline and paroxetine are the only medications approved by the FDA for PTSD. While SSRIs are typically the first class of medications used in PTSD treatment (Brady et al, 2001, Marshall, Beebe, Oldham & Zaninelli, 2001), exceptions may occur for patients based upon their individual histories of side effects, response, comorbidities and personal preferences.

Examples of an exception would be:

  • A patient with PTSD and co-occurring bipolar disorder where an antidepressant could cause mood instability that could be mitigated with a mood stabilizing medication (such as lithium or an anti-epileptic medication) before prescribing an SSRI.
  • Intolerable sexual dysfunction or gastrointestinal side effects due to the effects of increased serotonin levels in the peripheral nervous system.

Each patient varies in their response and ability to tolerate a specific medication and dosage, so medications must be tailored to individual needs. Research indicates that maximum benefit from SSRI treatment depends upon adequate dosages and duration of treatment. Ensuring treatment adherence is key to successful pharmacotherapy for PTSD. Some typical dosage ranges for medications:

  • Sertraline (Zoloft): 50 mg to 200 mg daily
  • Paroxetine (Paxil): 20 to 60 mg daily
  • Fluoxetine (Prozac): 20 mg to 60 mg daily

Other Antidepressants for PTSD

Antidepressants that affect the balance of serotonergic and noradrenergic neurotransmission, or which alter serotonin neurotransmission through other mechanisms of action, are also helpful in PTSD. Venlafaxine acts primarily as a serotonin reuptake inhibitor at lower dosages and as a combined serotonin and norepinephrine reuptake inhibitor at higher dosages. It is also a conditionally recommended treatment for PTSD. A typical dosage range is:

  • Venlafaxine (Effexor): 75 mg to 300 mg daily
All of the antidepressants described above are also effective in treating comorbid major depressive disorder (MDD) which, depending upon the study, accompanies PTSD about 50 percent of the time. Dose-related elevations in blood pressure have been noted with venlafaxine. It should be used with caution in patients with hypertension.

Other Medications for PTSD

Topiramate is in the anti-epileptic category of medications and is thought to modulate glutamate neurotransmission. There has been recent interest in its use for PTSD. The systematic review that served as the evidence base for the guideline development panel reported moderate strength of evidence for a medium to large magnitude effect for PTSD symptom reduction.

However, the panel concluded that there was insufficient evidence to make a recommendation because the potential side effects/harms for topiramate are greater than they are for SSRI antidepressants. It is not uncommon for patients taking topiramate to note side effects of cognitive dulling. Topiramate has also been found helpful in reducing alcohol consumption in those with an alcohol use disorder, which frequently accompanies PTSD.

Adapted from with original content written by Matt Jeffreys, MD. Matthew J. Friedman, MD, PhD, Thomas Mellman, MD and Jeffrey Sonis, MD, MPH also contributed.

The FDA regulates approval of medications, not prescribing of medications. An off-label use of a medication means that it is being used for an indication other than one for which is was approved by the FDA. It is estimated that 1 in 5 outpatient prescriptions are written off-label. According to the FDA, “From the FDA perspective, once the FDA approves a drug, healthcare providers generally may prescribe the drug for an unapproved use when they judge that it is medically appropriate for their patient.”


Journal Article

Brady, K., Pearlstein, T., Asnis, G. M., Baker, D., Rothbaum, B., Sikes, C. R., & Farfel, G. M. (2000). Efficacy and safety of sertraline treatment of posttraumatic stress disorder: A randomized controlled trial. Journal of the American Medical Association, 283, 1837-1844.

Journal Article

Marshall, R. D., Beebe, K. L., Oldham, M., & Zaninelli, R. (2001). Efficacy and safety of paroxetine treatment for chronic PTSD: A fixed-dose, placebo-controlled study. American Journal of Psychiatry, 158, 1982-1988.

Updated July 31, 2017

Conditionally Recommended

Medications are conditionally recommended by the APA Clinical Practice Guideline for the Treatment of PTSD (PDF, 1MB).