What are the medications for Post-Traumatic Stress Disorder (PTSD)?

From the Guidelines

Medications for PTSD should prioritize selective serotonin reuptake inhibitors (SSRIs) as first-line treatment, with sertraline and paroxetine being the only FDA-approved options specifically for PTSD, as recommended by the 2023 U.S. Department of Veterans Affairs and U.S. Department of Defense clinical practice guideline 1. The guideline suggests the use of specific manualized psychotherapies over pharmacotherapy, including prolonged exposure, cognitive processing therapy, or eye movement desensitization and reprocessing psychotherapy, in addition to medications like paroxetine, sertraline, or venlafaxine 1. Other commonly prescribed SSRIs include fluoxetine and escitalopram, which usually require 4-6 weeks to show full effectiveness and should be continued for at least 6-12 months after symptom improvement 1. For sleep disturbances or nightmares, prazosin may be added, although its efficacy has been downgraded due to contradictory study results 1. Benzodiazepines are generally avoided due to addiction potential and lack of efficacy for core PTSD symptoms 1. Medication should ideally be combined with trauma-focused psychotherapy for comprehensive treatment, as medications alone may not address all aspects of PTSD. Key considerations include:

• Selecting medications based on the patient's specific symptoms and medical history
• Monitoring for potential side effects and adjusting the treatment plan as needed
• Encouraging patients to adhere to their medication regimen and attend follow-up appointments
• Considering the use of psychotherapy in conjunction with medication for optimal treatment outcomes.

From the FDA Drug Label

Sertraline Hydrochloride Oral Concentrate is indicated for the treatment of posttraumatic stress disorder in adults The efficacy of sertraline in the treatment of PTSD was established in two 12-week placebo-controlled trials of adult outpatients whose diagnosis met criteria for the DSM-III-R category of PTSD PAXIL is indicated for the treatment of Posttraumatic Stress Disorder (PTSD) The efficacy of PAXIL in the treatment of PTSD was established in two 12-week placebo-controlled trials in adults with PTSD (DSM-IV)

Medications for PTSD include:

• Sertraline 2
• Paroxetine 3

These medications have been shown to be effective in the treatment of PTSD in adults.

From the Research

Medications for PTSD

• The most studied medications for PTSD are selective serotonin reuptake inhibitors (SSRIs), with sertraline, paroxetine, and fluoxetine being the most extensively studied 4.
• SSRIs have been shown to be effective in short-term trials (6-12 weeks) and continuation and maintenance treatment for 6-12 months can decrease relapse rates 4.
• Non-SSRIs, such as venlafaxine, nefazodone, trazodone, and mirtazapine, have been evaluated in PTSD and may be considered as second-line treatment 4.
• Monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs) have been evaluated in a small number of double-blind, placebo-controlled studies, but have significant adverse effects and safety issues 4.
• Anticonvulsants, such as carbamazepine, valproic acid, topiramate, and gabapentin, have been evaluated in PTSD and may be considered where co-morbidity of bipolar disorder exists, and where impulsivity and anger predominate 4.
• Atypical antipsychotics have been shown to be effective in PTSD, particularly in cases where paranoia or flashbacks are prominent, and may be used as an augmenter to SSRIs in refractory cases 4.

Evidence-Based Prescribing

• There is strong research evidence to support the pharmacological treatment of PTSD as a second line to trauma-focused psychological interventions 5.
• Fluoxetine, paroxetine, sertraline, and venlafaxine are the best-evidenced drugs for PTSD, with lower-level evidence for other medications 5.
• Prescribing for PTSD should be evidence-based, taking into account the individual patient's symptoms and medical history 5.

Predictors of Treatment Response

• Predictors of treatment response to SSRIs in patients with PTSD include gender, childhood sexual trauma, and sexual assault as index trauma 6.
• Latent class analysis has identified three classes of treatment response: fast responders, responders with low pretreatment symptom severity, and responders with high pretreatment symptom severity 6.
• Class membership can be predicted based on time since index trauma, severity of depression, and severity of anxiety 6.
• The study suggests that patients with longer time since index trauma may particularly benefit from treatment with sertraline or paroxetine 6.

Pharmacotherapy for PTSD

• A systematic review of 66 RCTs found that SSRIs improve PTSD symptoms and are first-line agents for the pharmacotherapy of PTSD, based on moderate-certainty evidence 7.
• The noradrenergic and specific serotonergic antidepressant (NaSSA) mirtazapine and the tricyclic antidepressant (TCA) amitriptyline may also improve PTSD symptoms, but this is based on low-certainty evidence 7.
• There is no evidence of benefit for the number of participants who improved following treatment with the antipsychotic group compared to placebo, based on very low-certainty evidence 7.