If you have post-traumatic stress disorder (PTSD), getting symptoms under control may require a combination of trauma-based therapy and medications. Though trauma-based therapy is the preferred first-line treatment, prescribed medications can provide additional support if therapy alone is not working.

A medication that works best for PTSD will be personalized to the symptoms that are limiting your day-to-day activities. Medications will often help target and control symptoms such as depression, anxiety, sleep problems, or psychosis.

Medications for Depression and Anxiety Associated With PTSD

When someone starts a medication for PTSD, the first medication they usually try is an antidepressant. There are two classes of antidepressants recommended for PTSD: selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).

The most common antidepressants for PTSD include:

• Sertraline
• Paxil (paroxetine)
• Fluoxetine
• Effexor XR (venlafaxine)

A review of multiple studies examined each SSRI or SNRI’s effectiveness at reducing PTSD symptoms:

• Fluoxetine: Despite a modest 28% reduction in PTSD symptoms, fluoxetine is often preferred due to its minimal side effects and good tolerability after stopping the medication.
• Sertraline: Sertraline, while well-tolerated and shown to reduce PTSD symptoms by 20%, should be avoided by those with heart rhythm issues due to the increased risk of QT prolongation. 
• Paroxetine: Paroxetine, though the most effective SSRI for PTSD with a 44% to 56% reduction in symptoms, has the most side effects and poorest tolerability upon discontinuation.
• Venlafaxine: Venlafaxine, an SNRI with a 26% to 35% PTSD symptom reduction, has more side effects than SSRIs, including increased blood pressure and insomnia.

Generally, SSRIs and SNRIs have similar effectiveness; however, people can respond differently between the various medications within the same class. 

Medications for Sleep Issues Associated With PTSD

Research has shown that a medication called prazosin can effectively reduce nightmares and promote better sleep among those with trauma-related nightmares or sleep disturbances.

Prazosin is classified as an alpha-adrenergic receptor blocker. It can inhibit alpha receptors on the walls of blood vessels and in the brain. When prazosin enters the brain, it can block the release of stress hormones and enhance sleep quality. If you are having difficulty sleeping, prazosin can be used alone or in addition to an SSRI or SNRI.

Medications for Psychosis Associated With PTSD

Those who experience PTSD-related psychosis symptoms, such as dissociation, hallucinations, or delusions, can take second-generation antipsychotics.

Common antipsychotics used in PTSD include:

• Seroquel (quetiapine)
• Risperdal (risperidone)
• Zyprexa (olanzapine)

From a collection of limited studies available, second-generation antipsychotics showed a minimal reduction of PTSD symptoms, ranging from 1.5% to 26%. Antipsychotics are usually recommended when antidepressants do not work. They can be taken alone or in combination with an SSRI or SNRI.

Medications to Avoid

Some medications should be avoided due to the lack of supporting evidence for their safety and efficacy. In addition, these medications may intensify the fear response associated with PTSD.

Medications that are not recommended to treat PTSD are:

• Benzodiazepines: Xanax (alprazolam), Ativan (lorazepam), Valium (diazepam), Klonopin (clonazepam)
• Cannabis or cannabis derivatives: tetrahydrocannabinol, cannabidiol

There is not enough evidence to recommend for or against the use of:

• Tricyclic antidepressants: amitriptyline, Pamelor (nortriptyline), Silenor (doxepin)
• Psychedelics: 3,4-methylenedioxymethamphetamine (MDMA)

Other Treatment Options

Other than medications, trauma-based therapy is a common method for managing and reducing PTSD symptoms. There are three types of trauma-based therapy:

• Prolonged exposure (PE): Teaches you how to slowly approach memories and feelings that you have been avoiding since your trauma. It involves talking about your experience to a therapist and exposing yourself to activities that you have been avoiding since the traumatic event.
• Cognitive processing therapy (CPT): Helps you recognize and challenge negative thoughts. It teaches people how to evaluate their thoughts and develop more helpful ways of thinking.
• Eye-movement desensitization and reprocessing (EMDR): Involves recalling a traumatic memory while paying attention to back-and-forth movement, such as moving your eyes from side to side or listening to tones. The stimulation is believed to help process the traumatic memories and reduce their vividness and emotional impact.

It is recommended to try any of these forms of therapy before starting medications. However, if therapy is still not working out for you, your provider may start combining medications with therapy to provide the best chance of managing your symptoms.

Summary

If you have PTSD, trying trauma-based therapy first before starting medications is best. However, medications can provide added support for managing symptoms if therapy alone does not work.

First-line medications such as fluoxetine, sertraline, paroxetine, or venlafaxine are recommended. For sleep-related symptoms, you might also benefit from taking prazosin. You may add other medications, such as antipsychotics, if antidepressants don’t work for you.

Choosing the right medication for PTSD is a personal decision that you should discuss with your healthcare provider. They can assess your specific symptoms, medical history, and other factors to determine the most appropriate and effective treatment plan for you.