What medication is recommended for a patient with post-traumatic stress disorder (PTSD) experiencing nightmares?

Medication for PTSD Nightmares

Prazosin remains the first-choice pharmacologic agent for PTSD-related nightmares despite recent contradictory evidence, with image rehearsal therapy as the primary non-pharmacologic recommendation. 1

Primary Pharmacologic Recommendation: Prazosin

The American Academy of Sleep Medicine identifies prazosin as the first choice for pharmacologic therapy of PTSD nightmares, though the recommendation was downgraded from "recommended" to "may be used" following a large negative trial. 1

Dosing Strategy

• Start at 1 mg at bedtime, monitoring for orthostatic hypotension after the first dose 1
• Titrate gradually to maintenance levels of 2-6 mg nightly for civilians 1
• Military/combat PTSD may require higher doses: mean effective dose 14.8-15.6 mg for men, 7.0 mg for women 1
• Maximum recommended dose is 20 mg at bedtime, with optional 5 mg mid-morning dose 1

Evidence Nuances and Critical Caveats

A major 2018 VA study of 304 patients found no benefit of prazosin over placebo at 10 or 26 weeks, leading to the recommendation downgrade. 1 However, this must be interpreted carefully:

• 78% of patients in both groups were on maintenance antidepressants, which appears to reduce prazosin efficacy 1
• Earlier positive trials showed prazosin reduced CAPS nightmare scores by 3.1 vs 1.2 for placebo (p<0.001) 1
• Patients on SSRIs showed markedly reduced prazosin response: total CAPS decreased 30.1 vs only 9.6 in those on SSRIs 1

Clinical reality: Many patients respond very well to prazosin, making it the first-line choice despite mixed trial data. 1

Alternative First-Line Options When Prazosin Fails or Is Contraindicated

Clonidine (Preferred Alternative)

The American Academy of Sleep Medicine recommends clonidine as the first-line replacement for prazosin, starting at 0.1 mg twice daily, with average effective dose of 0.2 mg/day. 2

• Similar mechanism to prazosin (reduces CNS adrenergic activity) 2
• Demonstrated specific efficacy in female civilian PTSD patients 2
• Monitor blood pressure carefully for orthostatic hypotension 2

Risperidone (Second-Line Alternative)

Start risperidone at 0.5-2.0 mg at bedtime, with 80% of patients reporting improvement after the first dose. 2

• Most patients achieve optimal benefit at 2 mg nightly 2
• Total cessation of nightmare recall often occurs within 1-2 days 2
• Average maximum effective dose is 2.3 mg/day (range 1-3 mg) over 12 weeks 2
• Nightmare treatment requires substantially lower doses than psychotic disorders 2
• No significant side effects reported at doses of 0.5-3 mg/day, but monitor for extrapyramidal symptoms if approaching 2 mg/day 2

Aripiprazole (Third-Line Alternative)

Use aripiprazole 15-30 mg/day if clonidine and risperidone are ineffective or not tolerated, with better tolerability profile than olanzapine. 2

• Four of five veterans showed substantial improvement at 4 weeks 2

Additional Pharmacologic Options

Topiramate

Topiramate may be used for PTSD nightmares, starting at 12.5-25 mg daily and titrating every 3-4 days. 1

• 91% of full responders achieved benefit at ≤100 mg/day 1
• Reduced nightmares in 79% of patients, with full suppression in 50% 1
• Significant side effects include acute narrow-angle glaucoma, severe headaches, emergent suicidal ideation, and memory concerns 1

Other Options Listed by AASM

The following may be used but have less robust evidence: olanzapine, clonidine, cyproheptadine, fluvoxamine, gabapentin, nabilone, phenelzine, trazodone, and tricyclic antidepressants 1

Trazodone

• Mean effective dose 212 mg/day for nightmares 1
• Decreased nightmare frequency from 3.3 to 1.3 nights/week 1
• 60% experienced side effects, particularly daytime sedation or dizziness 1

Medications NOT Recommended

Clonazepam and venlafaxine are not recommended for nightmare disorder. 1

Recommended Treatment Algorithm

1. First-line: Prazosin 1 mg at bedtime, titrate to 2-6 mg (civilians) or up to 20 mg (military/combat PTSD) 1, 2

   • If patient is on SSRI, consider alternative first-line agent due to reduced efficacy 1

2. If prazosin ineffective or not tolerated: Clonidine 0.1 mg twice daily, titrate to 0.2 mg/day average 2

3. If clonidine ineffective or not tolerated: Risperidone 0.5-2.0 mg at bedtime 2

4. If risperidone ineffective or not tolerated: Aripiprazole 15-30 mg/day 2

5. Consider topiramate as adjunctive or alternative option, starting 12.5-25 mg daily 1

Non-Pharmacologic First-Line Treatment

Image rehearsal therapy is the recommended primary treatment for PTSD-associated nightmares and nightmare disorder. 1

• Other behavioral options include CBT, CBT for insomnia, EMDR, and exposure/relaxation/rescripting therapy 1

Critical Pitfalls to Avoid

• Do not ignore the SSRI interaction with prazosin—efficacy drops dramatically in patients on SSRIs 1
• Monitor blood pressure carefully with both prazosin and clonidine for orthostatic hypotension 1, 2
• Avoid nefazodone as first-line due to hepatotoxicity risk 2
• Expect return of nightmares if medication is discontinued 2
• Do not confuse night terrors (non-REM, no recall) with nightmares (REM, full recall)—treatments differ completely 3
• Risperidone dosing for nightmares is much lower than for psychosis; do not overdose 2