What is the first-line medication for Post-Traumatic Stress Disorder (PTSD)?

From the Guidelines

The first-line medication treatment for PTSD is selective serotonin reuptake inhibitors (SSRIs), specifically sertraline (Zoloft) and paroxetine (Paxil), as well as the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine, as recommended by the 2023 U.S. Department of Veterans Affairs and U.S. Department of Defense clinical practice guideline 1.

Key Points

• Typical starting doses are sertraline 25-50mg daily or paroxetine 10-20mg daily, gradually increasing as needed to therapeutic doses (sertraline 50-200mg daily; paroxetine 20-60mg daily) 1.
• Treatment should continue for at least 6-12 months after symptom improvement, with some patients requiring longer treatment 1.
• Other SSRIs like fluoxetine and escitalopram, though not FDA-approved specifically for PTSD, are also commonly used 1.
• These medications work by increasing serotonin levels in the brain, which helps regulate mood, anxiety, and stress responses that are dysregulated in PTSD 1.
• Patients should be aware that full benefits may take 4-6 weeks to appear, and side effects like nausea, headache, and sexual dysfunction may occur initially but often improve with time 1.
• Medication should ideally be combined with trauma-focused psychotherapy for optimal outcomes 1.
• If SSRIs are ineffective or poorly tolerated, SNRIs like venlafaxine may be considered as alternative first-line options 1.

From the FDA Drug Label

Posttraumatic Stress Disorder (PTSD) 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

First line medication for PTSD is sertraline 2.

• Sertraline 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. Alternatively, paroxetine 3 is also effective for the treatment of PTSD, as demonstrated in two 12-week, multicenter, placebo-controlled studies.

From the Research

First-Line Medication for PTSD

The first-line medication for post-traumatic stress disorder (PTSD) is selective serotonin reuptake inhibitors (SSRIs) 4, 5, 6, 7, 8.

• SSRIs have been extensively studied and have demonstrated efficacy in short-term trials (6-12 weeks) 4.
• They have a favorable adverse effect profile, making them a preferred choice for treating PTSD 4, 5.
• Examples of SSRIs that are US FDA-approved for PTSD include sertraline and paroxetine 4.
• Continuation and maintenance treatment with SSRIs for 6-12 months can decrease relapse rates 4.

Alternative Medications

If SSRIs are not tolerated or are ineffective, other medications can be considered, including:

• Non-SSRIs, such as venlafaxine, nefazodone, trazodone, and mirtazapine 4.
• Monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs), although they have significant adverse effects and safety issues 4.
• Anticonvulsants, such as carbamazepine, valproic acid, topiramate, and gabapentin, which may be effective in patients with co-morbid bipolar disorder or impulsivity and anger 4.
• Atypical antipsychotics, which may be effective as monotherapy or as an augmenter to SSRIs in patients with prominent paranoia or flashbacks 4.

Evidence Summary

Multiple studies have demonstrated the efficacy of SSRIs in treating PTSD, with response rates ranging from 58% to 65% compared to 22% to 35% for placebo 6, 7. The evidence supports the use of SSRIs as first-line agents for the pharmacotherapy of PTSD, with the NaSSA mirtazapine and the TCA amitriptyline also showing promise, although with lower certainty 7.