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

Recommended Medications for Post-Traumatic Stress Disorder (PTSD)

For PTSD treatment, selective serotonin reuptake inhibitors (SSRIs), specifically sertraline and paroxetine, are the first-line pharmacotherapy options as they have FDA approval and demonstrated efficacy in multiple controlled trials. 1, 2, 3

First-Line Medications

• Sertraline and paroxetine are FDA-approved for PTSD treatment, with consistent evidence showing 53-85% of participants classified as treatment responders compared to 32-62% with placebo 1
• These SSRIs have demonstrated efficacy in 12-week placebo-controlled trials for reducing core PTSD symptoms 2, 3, 2
• Fluoxetine has also shown efficacy in controlled trials but lacks FDA approval specifically for PTSD 1, 4
• SSRIs are preferred due to their favorable side effect profile compared to other medication classes 5

Medication for PTSD-Associated Nightmares

• Prazosin is recommended as first-line therapy for PTSD-associated nightmares with Level A evidence 6
• The mechanism involves reducing central nervous system noradrenergic activity that contributes to disruption of normal REM sleep 6
• Starting dose is typically 1 mg at bedtime, with gradual increases to an effective dose (average 3 mg, though military veterans may require 9.5-13.3 mg/day) 6
• Prazosin significantly reduces trauma-related nightmares as measured by standardized scales 6

Second-Line Options

• If SSRIs are ineffective or not tolerated, consider serotonin-potentiating non-SSRIs such as venlafaxine, nefazodone, trazodone, or mirtazapine 5
• For PTSD-associated nightmares that don't respond to prazosin, consider:
  • Clonidine (0.2-0.6 mg in divided doses) 1, 6
  • Topiramate (starting at 25 mg/day, titrating up to effect or maximum 400 mg/day) 1, 6
  • Trazodone (mean effective dose 212 mg/day) 1, 6

Third-Line Options

• Tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) have shown some efficacy but have significant adverse effects and safety concerns 5
• Atypical antipsychotics may be considered as monotherapy or augmentation to SSRIs in refractory cases 5
• Other options with limited evidence include:
  • Low-dose cortisol 1
  • Anticonvulsants (lamotrigine, valproic acid, gabapentin) 5

Important Considerations

• Relapse is common with medication discontinuation; studies show 26-52% of patients relapse when shifted from sertraline to placebo, compared to 5-16% maintained on medication 1
• Continuation and maintenance treatment for 6-12 months decreases relapse rates 5
• Benzodiazepines should be avoided or used only short-term due to potential depressogenic effects and possibility of worsening PTSD 5
• Psychological debriefing should not be used for recent traumatic events 1

Treatment Algorithm

1. Start with an SSRI (sertraline or paroxetine) as first-line therapy 1, 2, 3
2. If nightmares are prominent, add prazosin 6
3. If inadequate response after 8-12 weeks of optimal dosing:
   • Switch to another SSRI or venlafaxine 5, 4
   • Consider augmentation with atypical antipsychotics for refractory symptoms 5
4. For persistent nightmares despite prazosin, consider topiramate or trazodone 1, 6
5. For treatment-resistant cases, consider TCAs or MAOIs as third-line options 5

Remember that psychotherapy, particularly trauma-focused cognitive behavioral therapy, is considered first-line treatment for PTSD, with medication often used as an adjunct or when psychotherapy is not available or effective 4.