What Is the Most Effective Medication for PTSD? 4 Options, Including Zoloft and Paxil

Post-traumatic stress disorder (PTSD) is a condition that causes persistent mental and emotional distress following a traumatic event. It can be debilitating and disrupt a person’s everyday life. If you or a loved one is living with PTSD, you’re not alone. It’s estimated that 1 in 11 people will be diagnosed with PTSD at some point in their lifetime.

First-choice treatments for PTSD can involve therapy, medication, or a combination of both. If you and your healthcare provider are considering medication as part of your treatment plan, your provider will work closely with you to find the right medication and dose to treat your symptoms.

In general, which PTSD medication is best for you will depend on your unique situation. But  there are four medications that are considered first-choice options for treating PTSD. Here’s what you need to know about each one.

1. Zoloft (sertraline)

Zoloft (sertraline) is a type of antidepressant called a selective serotonin reuptake inhibitor (SSRI). SSRIs work by raising serotonin levels in the brain. Serotonin is a chemical signal that helps deliver messages within the brain and nerves throughout the body. People with PTSD may have changes in these chemical signals that contribute to their symptoms.

Zoloft is an FDA-approved PTSD medication. In studies, it effectively reduced PTSD symptoms in over 50% of people taking it. And it’s generally well tolerated, with the most noticeable side effect being nausea.

Other common side effects of taking Zoloft for PTSD include:

• Insomnia (trouble sleeping)

• Diarrhea

• Dry mouth

• Fatigue

• Sexual side effects, such as erectile dysfunction and low sex drive

2. Paxil (paroxetine)

Paxil (paroxetine) is another SSRI that’s FDA approved to treat PTSD. Similar to Zoloft, Paxil improved PTSD symptoms in over 50% of the people taking it in clinical trials.

While it’s also generally well tolerated, Paxil does tend to cause more side effects than other SSRIs for many people. Common side effects reported by people taking Paxil for PTSD include:

• Nausea

• Dry mouth

• Drowsiness or insomnia

• Weakness

• Weight gain

• Sexual side effects

3. Prozac (fluoxetine)

Prozac (fluoxetine) is a SSRI antidepressant that’s prescribed off-label to treat PTSD. It has been shown to be helpful for symptoms of the condition, as well as for treating overlapping depression and anxiety symptoms. And it may also help prevent PTSD relapse (a worsening or return of symptoms). So even though it’s not FDA approved to treat the condition, there is strong evidence to support Prozac’s use as a treatment for PTSD.

The most common side effects reported by people taking Prozac include:

• Insomnia or drowsiness

• Headache

• Nervousness

• Nausea

• Sexual side effects

4. Effexor XR (venlafaxine)

Effexor XR (venlafaxine extended-release) is a type of antidepressant called a serotonin and norepinephrine reuptake inhibitor (SNRI). SNRIs work by raising the levels of both serotonin and norepinephrine in the brain. Like serotonin, norepinephrine is a chemical messenger in the body, and its imbalance may be related to worsening PTSD symptoms.

Effexor XR isn’t an FDA-approved PTSD medication, but it has strong evidence to support its off-label use. In a multinational clinical trial, Effexor XR lessened PTSD symptoms for over 50% of people who took it. It’s also considered to be similarly effective to SSRIs like Zoloft.

Effexor XR can sometimes raise blood pressure, so it should be used with caution if you have hypertension (high blood pressure). Other, more common side effects include:

• Nausea

• Dizziness or drowsiness

• Constipation

• Dry mouth

• Sweating

• Loss of appetite

• Sexual side effects

Other PTSD medications

The four antidepressants listed above have the most evidence supporting their effectiveness at treating PTSD. But it’s possible that your healthcare provider may prescribe a different medication off-label. Current guidelines just don’t recommend these alternatives as first-choice medications for PTSD.

Alternative off-label PTSD medications include:

• Serzone (nefazodone)

• Tofranil (imipramine)

• Nardil (phenelzine)

• Topamax (topiramate)

• Minipress (prazosin), which is sometimes prescribed off-label to treat nightmares associated with PTSD

What about medications like Seroquel and Risperdal?

Atypical antipsychotics are sometimes prescribed off-label to treat PTSD. This class of medication works by balancing brain chemicals like serotonin and dopamine.

Commonly prescribed atypical antipsychotics include:

• Seroquel (quetiapine)

• Risperdal (risperidone)

• Zyprexa (olanzapine)

• Abilify (aripiprazole)

Some studies have shown that atypical antipsychotics may be helpful for treating PTSD. According to these studies, these medications may be particularly beneficial for people who have psychosis or hypervigilance symptoms, which include irritability, fixating on potential threats, and a heightened state of awareness.

But it’s important to keep in mind that these studies were small and had some conflicting results. More clinical studies are needed to determine if the benefits of atypical antipsychotics outweigh the side effects for most people with PTSD. This is why they’re currently not recommended as first-choice treatment options by experts.

What medications should I avoid if I have PTSD?

Experts suggest healthcare providers avoid prescribing certain medications for PTSD, as they may worsen symptoms in the long term.

Benzodiazepines are commonly prescribed for anxiety conditions and panic attacks. Examples of well-known benzodiazepines are:

• Xanax (alprazolam)

• Valium (diazepam)

• Klonopin (clonazepam)

• Ativan (lorazepam)

Benzodiazepines are sometimes prescribed to temporarily treat symptoms of anxiety accompanying PTSD. However, research suggests that these medications are not effective at treating PTSD itself and can worsen symptoms over time.

Where can I find PTSD resources?

Symptoms of PTSD can be overwhelming, especially if left untreated. Research suggests that there is a strong connection between PTSD and suicide. One large study, for example, found that suicide rates were four to seven times higher for people with PTSD than for those without it.

There are several organizations and tools dedicated to helping people living with PTSD, including:

• National Center for PTSD: a research and educational center developed by the Department of Veterans Affairs that offers support and helpful resources for veterans

• PTSD Coach: a mobile application designed to provide information about PTSD and tools to help manage stress and PTSD symptoms

• Veterans Crisis Line: a telephone line for veterans to connect with trained responders, including fellow veterans

• PTSD Foundation of America: an organization committed to bringing hope and healing to veterans experiencing PTSD and their family members

• Sidran Institute: a nonprofit organization committed to helping people recover from PTSD and other associated conditions, such as substance use disorder

Why trust our experts?

Written by:

Tegan Smedley, PharmD, APh

Tegan Smedley, PharmD, APh, has 10 years of experience as a pharmacist. She has worked in a variety of settings, including retail, hospital, and ambulatory care.

Edited by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

Reviewed by:

Sarah Gupta, MD

Sarah Gupta, MD, is a licensed physician with a special interest in mental health, sex and gender, eating disorders, and the human microbiome. She is currently board certified by the American Board of Psychiatry and Neurology.

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