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

Recommended Medications for PTSD

Sertraline and paroxetine are the first-line medications for PTSD, as both are FDA-approved for this indication and have the strongest evidence base from multiple placebo-controlled trials. 1, 2

First-Line Treatment: SSRIs

Start with either sertraline or paroxetine as initial pharmacotherapy for PTSD. These agents have demonstrated:

• 53-85% treatment response rates compared to 32-62% with placebo across multiple trials 3
• FDA approval specifically for PTSD treatment 3, 1, 2
• Efficacy across all three PTSD symptom clusters: reexperiencing, avoidance/numbing, and hyperarousal 1
• Superior tolerability compared to older antidepressants 4, 5

Sertraline Dosing and Evidence

• Established efficacy in two 12-week placebo-controlled trials 1
• 60% responder rate versus 38% with placebo 6
• Maintains response for up to 28 weeks following initial treatment 1
• Well-tolerated with only 9% discontinuation rate due to adverse events 6
• Common side effects: insomnia (35%), diarrhea (28%), nausea (23%), fatigue (13%), decreased appetite (12%) 6

Paroxetine Evidence

• Proven efficacy in 12-week placebo-controlled trials 2
• FDA-approved for PTSD with demonstrated effectiveness across trauma types 3, 2
• Addresses core PTSD symptoms including intrusive thoughts, avoidance behaviors, and hyperarousal 2

Fluoxetine as Alternative

• Effective in multiple trials but lacks FDA indication for PTSD 3
• Consider when sertraline or paroxetine are not tolerated 3

Critical Treatment Duration Considerations

Continue SSRI treatment for at least 6-12 months after symptom improvement to prevent relapse. 3, 4

• 26-52% of patients relapse when sertraline is discontinued versus 5-16% who continue medication 3
• 34% relapse rate with fluoxetine discontinuation versus 17% who continue 3
• Relapse after medication discontinuation is significantly more common than after completing CBT 3

Adjunctive Treatment for Specific PTSD Symptoms

For Nightmares and Sleep Disturbances

Prazosin is the recommended medication for PTSD-associated nightmares (Level A evidence). 3, 7

• Start at 1 mg at bedtime, increase by 1-2 mg every few days 3, 7
• Average effective dose: 3 mg (range 1-10 mg) 3
• Higher doses (9.5-13.3 mg/day) used in some veteran populations 3
• Reduces CAPS nightmare scores from 4.8-6.9 to 3.2-3.6 3
• Monitor for orthostatic hypotension 3, 7
• Mechanism: reduces elevated CNS noradrenergic activity contributing to arousal and nightmares 3, 7

For Irritability and Anger

Prazosin addresses irritability and anger symptoms in addition to nightmares. 7

Topiramate may be beneficial for irritability and anger when prazosin is insufficient: 7

• Start 12.5-25 mg daily, increase in 25-50 mg increments every 3-4 days 7
• Most responders achieve benefit at ≤100 mg/day 7
• 79% reduction in nightmares, with 50% achieving complete suppression 7
• Monitor for cognitive impairment, weight loss, and paresthesias 7

Second-Line Options

If SSRIs are ineffective or not tolerated:

Venlafaxine, nefazodone, trazodone, and mirtazapine are serotonin-potentiating alternatives with promising open-label results 4

Trazodone for sleep disturbances: 3

• Dosage range: 25-600 mg (mean effective dose 212 mg) 3
• 72% of veterans experienced decreased nightmares 3, 7
• Side effects: daytime sedation (most common), dizziness, headache, priapism, orthostatic hypotension 3
• 19% discontinuation rate due to adverse effects 3

Clonidine (Level C evidence): 3

• Dosage: 0.2-0.6 mg in divided doses 3, 7
• Monitor blood pressure changes 3, 7
• Less rigorously studied than prazosin despite long clinical use 3

Third-Line Treatments

MAOIs and tricyclic antidepressants showed inconsistent results in limited trials and have significant cardiovascular complications and overdose risk 4

Atypical antipsychotics should be considered when paranoia or flashbacks are prominent, or as augmentation in refractory cases 4

Anticonvulsants (carbamazepine, valproic acid, gabapentin) may be useful when bipolar comorbidity exists or impulsivity/anger predominate 4

Critical Pitfalls to Avoid

• Do not use benzodiazepines: ineffective in controlled trials despite case reports, with potential depressogenic effects and possible PTSD worsening 4
• Avoid premature discontinuation: relapse rates are high when medications are stopped before 6-12 months 3, 4
• Do not rely on medication alone: concurrent trauma-focused CBT is recommended alongside pharmacotherapy 3, 7

Treatment Algorithm

1. Initiate sertraline or paroxetine as first-line treatment 3, 1, 2, 4, 8
2. Add prazosin if nightmares, sleep disturbances, or hyperarousal symptoms persist 3, 7
3. Consider topiramate for refractory irritability and anger 7
4. Switch to alternative SSRI (fluoxetine) or serotonin-potentiating agent (venlafaxine, mirtazapine) if initial SSRI fails 3, 4
5. Augment with atypical antipsychotic for prominent psychotic features or treatment-resistant cases 4
6. Continue successful treatment for minimum 6-12 months before considering discontinuation 3, 4