Medications for PTSD Treatment
Prazosin is the first-line pharmacotherapy for PTSD-associated nightmares with Level A evidence, while SSRIs (sertraline and paroxetine) are FDA-approved first-line medications for overall PTSD treatment. 1, 2, 3
First-Line Medications
SSRIs
- Sertraline and paroxetine are FDA-approved for PTSD treatment and have the most extensive evidence supporting their use 2, 3
- SSRIs have demonstrated efficacy in short-term trials (6-12 weeks) with continuation and maintenance treatment for 6-12 months decreasing relapse rates 4
- Sertraline has shown a 60% responder rate compared to 38% for placebo in clinical trials 5
- Typical side effects include insomnia, diarrhea, nausea, fatigue, and decreased appetite 5
Prazosin
- Recommended specifically for PTSD-associated nightmares with Level A evidence 1
- Works by reducing elevated CNS noradrenergic activity that contributes to disruption of normal REM sleep 1
- Starting dose is 1 mg at bedtime, with gradual increases by 1-2 mg every few days until an effective dose is reached (average effective dose is 3 mg) 1
- Higher doses (9.5-13.3 mg/day) may be needed for military veterans 1
- Main side effect concern is orthostatic hypotension, requiring blood pressure monitoring 1
Second-Line Medications
Clonidine
- May be considered (Level C evidence) for PTSD-associated symptoms 6, 1
- Alpha-2 adrenergic receptor agonist that suppresses sympathetic nervous system outflow 6
- Dosage of 0.2-0.6 mg in divided doses 6
- Has been shown to decrease frequency of nightmares in multiple studies 6
- Monitor for blood pressure changes 7
Trazodone
- Effective for PTSD symptoms and associated sleep disturbances 6, 1
- Dosage range of 25-600 mg (mean effective dose 212 mg) 1
- 72% of veterans experienced decreased nightmares in one study 7
- Side effects include daytime sedation, dizziness, headache, priapism, and orthostatic hypotension 6, 1
Third-Line/Adjunctive Medications
Atypical Antipsychotics
- Olanzapine, risperidone, and aripiprazole may be used for PTSD-associated symptoms 6, 1
- Risperidone (0.5-2.0 mg/day) has shown 80% improvement in symptoms including nightmares 6
- Aripiprazole (15-30 mg/day) has shown substantial improvement in nightmares in 4 out of 5 veterans 6
- Consider when paranoia or flashbacks are prominent or as augmentation to SSRIs in refractory cases 4
Topiramate
- May be beneficial for PTSD symptoms including irritability and anger 1, 7
- Starting dose of 25 mg/day with titration up to effect or maximum 400 mg/day 1
- Reduced nightmares in 79% of patients in one study, with full suppression in 50% 1
- Monitor for side effects including cognitive impairment, weight loss, and paresthesias 7
Other Options
- Cyproheptadine (serotonin receptor antagonist) has shown some efficacy in case series 6, 1
- Low-dose cortisol (10 mg/day) has shown medium-to-high benefit with low side effects 6
- Anticonvulsants (lamotrigine, valproic acid, gabapentin) may be considered, especially with comorbid bipolar disorder or when impulsivity and anger predominate 4
Medications to Avoid
- Clonazepam and other benzodiazepines are not recommended as they show no improvement in nightmares and may worsen PTSD 1, 4
- Venlafaxine has shown no significant benefit over placebo for PTSD-related distressing dreams 1
Treatment Algorithm
- Start with an SSRI (sertraline or paroxetine) for overall PTSD symptoms 2, 3
- Add prazosin if nightmares are prominent 1
- If inadequate response after 8-12 weeks of optimal dosing, consider:
- For treatment-resistant cases, consider topiramate, anticonvulsants, or other third-line options 1, 4
Important Clinical Considerations
- Untreated PTSD-associated symptoms significantly impair quality of life, causing sleep avoidance, sleep deprivation, and daytime fatigue 1
- Treatment duration should be at least 9-12 months after symptom improvement 7
- Regular monitoring for side effects and periodic reevaluation of medication effectiveness is essential 1, 7