Are Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) recommended for the treatment of Post-Traumatic Stress Disorder (PTSD)?

SNRIs for PTSD Treatment

SNRIs are recommended as second-line pharmacotherapy for PTSD when SSRIs are ineffective or not tolerated, though they lack the robust evidence base and FDA approval that SSRIs possess for this indication. 1, 2

First-Line Treatment: SSRIs, Not SNRIs

• SSRIs remain the established first-line pharmacological treatment for PTSD, with sertraline and paroxetine holding FDA approval for this indication 3, 1, 2
• SSRIs have the most extensive evidence base, with the largest number of double-blind, placebo-controlled trials demonstrating efficacy in reducing PTSD symptoms 1, 4
• Response rates with SSRIs reach 53-85% in clinical trials, significantly outperforming placebo (32-62%) 3
• SSRIs offer the additional advantage of treating common PTSD comorbidities including depression, panic disorder, and social anxiety disorder 4

SNRIs as Second-Line Treatment

When SSRIs fail or are not tolerated, SNRIs represent a reasonable next step based on the following evidence:

Supporting Evidence for SNRIs in PTSD

• Venlafaxine (an SNRI) has been evaluated in open-label studies and case reports with promising results, though it lacks the rigorous double-blind, placebo-controlled trial data that SSRIs possess 1
• SNRIs are classified as "serotonin-potentiating non-SSRIs" and should be considered as second-line treatment due to their promising results and relatively good safety profile 1
• The theoretical mechanism supports efficacy: SNRIs inhibit reuptake of both serotonin and norepinephrine, potentially addressing the noradrenergic dysregulation seen in PTSD 5

Clinical Context

• The evidence gap is significant: No SNRI has achieved FDA approval for PTSD, and no large-scale randomized controlled trials have been published specifically for SNRIs in PTSD 1, 6
• SNRIs have demonstrated efficacy in other anxiety disorders and chronic pain conditions, which provides indirect support for their use in PTSD 3, 5
• In anxiety disorders more broadly, SNRIs show comparable efficacy to SSRIs with similar response rates and dropout rates 7

Treatment Algorithm for PTSD Pharmacotherapy

Follow this stepwise approach:

1. First-line: Initiate SSRI therapy (sertraline or paroxetine preferred due to FDA approval) 1, 2
2. Second-line: If SSRI is ineffective after adequate trial (6-12 weeks at therapeutic dose) or not tolerated, switch to an SNRI (venlafaxine) or alternative SSRI 1, 5
3. Third-line: Consider MAOIs or tricyclic antidepressants, though these have significant adverse effects and safety concerns 1
4. Augmentation: For partial responders, consider adding atypical antipsychotics (risperidone has strongest evidence) or prazosin for nightmares 3, 6

Critical Safety Considerations for SNRIs

• Monitor blood pressure and pulse regularly, as SNRIs are associated with sustained hypertension and increased pulse 7
• Never discontinue abruptly—SNRIs require slow taper due to significant discontinuation syndrome, particularly with venlafaxine 7
• SNRIs increase bleeding risk, especially when combined with NSAIDs, aspirin, or anticoagulants 7
• Common adverse effects include fatigue/somnolence, diaphoresis, dry mouth, nausea, dizziness, and insomnia 7
• Venlafaxine and desvenlafaxine are associated with overdose fatalities 7

Duration of Treatment

• Acute treatment: 6-12 weeks minimum to assess response 1, 2
• Continuation/maintenance: 6-12 months of treatment decreases relapse rates significantly 1
• Relapse rates are higher with medication discontinuation (26-52% for sertraline) compared to completion of cognitive behavioral therapy 3

Common Pitfall to Avoid

Do not use SNRIs as first-line therapy for PTSD. Despite their efficacy in other anxiety disorders and theoretical mechanistic support, the evidence base for SNRIs in PTSD consists primarily of open-label studies and case reports, not the rigorous controlled trials that support SSRI use 1, 5. Reserve SNRIs for patients who have failed or cannot tolerate SSRIs.