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

Medications for PTSD Treatment

Selective serotonin reuptake inhibitors (SSRIs), particularly sertraline and paroxetine, are the first-line pharmacological treatments for PTSD, with venlafaxine (an SNRI) as another effective option. 1, 2, 3

First-Line Medications

SSRIs

• Sertraline (50-200 mg/day): FDA-approved for PTSD with demonstrated efficacy in multiple 12-week trials 2
• Paroxetine (20-60 mg/day): FDA-approved for PTSD with established efficacy in 12-week placebo-controlled trials 3
• Fluoxetine: Shown effectiveness in clinical trials though not FDA-approved specifically for PTSD 4

SNRIs

• Venlafaxine: Effective for PTSD symptoms with evidence supporting its use as a second-line option 1, 4

Second-Line Medications

When SSRIs/SNRIs are ineffective or not tolerated:

• Mirtazapine: Promising results in open-label studies 4
• Trazodone: Particularly helpful for PTSD-related sleep disturbances, though may cause side effects including daytime sedation 5
• Nefazodone: Effective in some studies but not recommended as first-line due to hepatotoxicity risk 5, 4

Add-on Therapies for Specific Symptoms

For Nightmares/Sleep Disturbances

• Prazosin: Particularly effective for PTSD-related nightmares and sleep disturbances 1, 6, 7

For Treatment-Resistant Cases

• Atypical antipsychotics: Risperidone shows the strongest evidence as an effective add-on therapy when SSRIs provide insufficient benefit 6, 7
• Anticonvulsants: Consider topiramate, lamotrigine, or valproic acid, especially when impulsivity and anger are prominent 4, 7

Medications to Avoid or Use with Caution

• Benzodiazepines: Not recommended for PTSD treatment as they may worsen outcomes and lack consistent empirical support 5, 1, 6
• Beta-blockers: May provide dual benefits for PTSD patients with comorbid hypertension, anxiety, tremor, and increased heart rate 1

Treatment Algorithm

1. Initial Treatment: Start with sertraline (50-200 mg/day) or paroxetine (20-60 mg/day) for 12 weeks
2. Inadequate response:
   • Switch to the other SSRI or venlafaxine
   • Consider adding prazosin if nightmares/sleep disturbances are prominent
3. Still inadequate response:
   • Add risperidone as augmentation therapy
   • Consider anticonvulsants if anger/impulsivity are prominent symptoms

Monitoring Treatment Response

• Use standardized PTSD measures (PCL-5) to track progress weekly
• A "good end-state" is considered as PCL-5 score ≤19 1
• Continue effective medication for at least 6-12 months to decrease relapse rates 4

Important Considerations

• Response rates to SSRIs rarely exceed 60%, and less than 20-30% of patients achieve full remission 6
• Higher severity of comorbid disorders does not necessarily result in inferior response to SSRI treatment 8
• Patients with longer time since index trauma might particularly benefit from treatment with sertraline or paroxetine 8
• Gender, childhood sexual trauma, and sexual assault as index trauma may moderate treatment response 8

While psychotherapy (particularly trauma-focused cognitive behavioral therapy) is considered first-line treatment for PTSD, pharmacotherapy is essential for patients who have residual symptoms after psychotherapy or are unable/unwilling to access psychotherapy 7.