Key points
- The VA/DoD guideline states: "We recommend paroxetine, sertraline, or venlafaxine for the treatment of PTSD" (Strong for).
- NIMH says the FDA has approved two SSRIs for PTSD; the National Center for PTSD names them as sertraline and paroxetine.
- Many other medicines have too little evidence for a recommendation either way, which is different from being proven not to work.
- The guideline recommends against benzodiazepines and against cannabis or cannabis derivatives for PTSD (Strong against).
- Antidepressant labels carry a boxed warning, and a medicine should not be stopped suddenly without talking to your prescriber.
How to read the guideline's wording
The VA/DoD Clinical Practice Guideline is written by the U.S. Departments of Veterans Affairs and Defense. Its current version is from 2023. Each recommendation has a fixed form of words, so the exact phrase tells you how firm it is.
"We recommend" means Strong for. "We suggest" means Weak for. "We suggest against" means Weak against. "We recommend against" means Strong against. "There is insufficient evidence to recommend for or against" means the panel took neither side. The guideline points out that a Weak recommendation is still evidence-based and important to care.
One more statement frames all of this. The guideline says: "We recommend individual psychotherapies, listed in Recommendation 8, over pharmacologic interventions for the treatment of PTSD." Medicine still has a place. The National Center for PTSD says medications are an effective option when those therapies are not available or feasible, or when a person prefers medication.
Antidepressants the guideline recommends
The three recommended medicines are antidepressants. Sertraline and paroxetine are selective serotonin reuptake inhibitors (SSRIs). Venlafaxine is a serotonin and norepinephrine reuptake inhibitor (SNRI), and its use for PTSD is off-label. The National Center for PTSD says these medicines are believed to act on brain chemicals tied to how we manage stress.
It also says you may need a few weeks to notice an effect, and that you need to keep taking the medicine to keep getting the benefits. Side effects it names include upset stomach, sweating, headache, dizziness and sexual side effects.
For a closer look at what the guideline and labels say about each of the three, read our guide to SSRIs and venlafaxine for PTSD.
Medicines with too little evidence either way
The guideline says there is insufficient evidence to recommend for or against this group for PTSD. A prescriber may use some of them for another condition a person has alongside PTSD. Any use of these for PTSD itself is off-label.
- Other SSRIs: citalopram, escitalopram and fluoxetine. The guideline notes the 2017 edition had recommended fluoxetine and a newer review found no benefit.
- Other antidepressants: amitriptyline, bupropion, desvenlafaxine, duloxetine, imipramine, mirtazapine, nefazodone and phenelzine.
- Others in the same statement: buspirone, eszopiclone, lamotrigine, olanzapine, pregabalin, quetiapine, rivastigmine and topiramate.
Medicines the guideline suggests or recommends against
"We suggest against divalproex, guanfacine, ketamine, prazosin, risperidone, tiagabine, or vortioxetine for the treatment of PTSD" (Weak against). The guideline notes these medicines are known to be effective for other conditions, so this statement is only about treating PTSD.
Prazosin appears twice, which can be confusing. It is suggested against for PTSD overall, yet a separate statement reads: "We suggest prazosin for the treatment of nightmares associated with PTSD" (Weak for). The guideline describes it as a blood pressure medicine, and either use for PTSD is off-label.
Two statements are firmer: "We recommend against benzodiazepines for the treatment of PTSD," and "We recommend against cannabis or cannabis derivatives for the treatment of PTSD" (both Strong against). The guideline's reasoning covers harms such as misuse and cognitive changes for benzodiazepines. People who take a benzodiazepine should not stop suddenly and should talk with their prescriber.
The guideline also suggests against adding a group of antipsychotics, including aripiprazole, brexpiprazole and quetiapine, to medications for PTSD (Weak against).
Safety points that apply widely
The Zoloft and Paxil labels carry a boxed warning: antidepressants increased the risk of suicidal thoughts and behaviors in children, teens and young adults, and anyone taking them should be closely monitored for worsening or new suicidal thoughts. Those labels also say these medicines must not be taken with, or within 14 days of, MAOIs. Both labels advise reducing the dose gradually rather than stopping abruptly whenever possible.
If you or someone you know is in crisis, call or text 988, or call 911. Locascio Wellness does not provide emergency services. If you are pregnant, planning to become pregnant or breastfeeding, tell your prescriber.
Getting care with us online
A licensed psychiatrist on our team treats trauma by secure video for people physically located in Pennsylvania or New York during each visit. Whether any medicine is an option for you is a decision for you and your prescriber. Ask us whether our psychiatrist can help through our medication care contact form, or read about online trauma treatment.
Our therapists do not prescribe. Trauma therapy with our team is available in Pennsylvania, West Virginia, Arizona and Colorado, not New York. Our trauma and PTSD therapy page explains that option. Learning your options is a good first step, and NIMH says you can get better with treatment.
Common questions
Is there one medicine that works for everyone with PTSD?
No. NIMH says people should work with their health care providers to find the right medication or combination and the right dose. The National Center for PTSD says that in general the three recommended medicines appear to work about equally well.
Why would someone take a medicine with insufficient evidence for PTSD?
A prescriber may be treating another condition. The National Center for PTSD notes that PTSD often comes with conditions such as depression, and that antidepressants other than the three recommended may be warranted to treat depression. Insufficient evidence means the guideline took no side for PTSD. Ask your prescriber why a medicine was chosen for you.
Can a medicine help with specific symptoms?
NIMH says some medications may help treat specific PTSD symptoms, such as sleep problems and nightmares, and that SSRIs may help people manage sadness, worry, anger and feeling emotionally numb. A prescriber can talk through which symptoms matter most to you and the possible risks and benefits of any option.
Does your psychiatrist prescribe these medicines?
Any medicine decision depends on your history and a prescriber's judgment, and a visit may not end in a prescription. Whether it is an option for you is a decision for you and your prescriber. Ask us whether our psychiatrist can help.
Sources
- VA/DoD Clinical Practice Guideline for the Management of Posttraumatic Stress Disorder and Acute Stress Disorder (2023)
- National Center for PTSD: Clinician's Guide to Medications for PTSD
- National Center for PTSD: Medications for PTSD
- National Institute of Mental Health: Post-Traumatic Stress Disorder
- DailyMed: Zoloft (sertraline) prescribing information
- DailyMed: Paxil (paroxetine) prescribing information
Published by Locascio Wellness. Published November 5, 2026. Clinically reviewed by Kenneth M. Levy, DO, Psychiatrist (Pennsylvania license OS007464L). This page is general information, not medical advice or a diagnosis.