What medications are used to treat nightmares, particularly those associated with post-traumatic stress disorder (PTSD)?

Medications for Nightmares

For PTSD-associated nightmares, prazosin remains the most established first-line pharmacological option, starting at 1 mg at bedtime and titrating to 3-15 mg/day based on response, though Image Rehearsal Therapy should be attempted first when feasible. 1

First-Line Pharmacological Approach

Prazosin is the gold standard medication for nightmare treatment, particularly in PTSD contexts. 1, 2, 3 The dosing strategy requires careful titration:

• Start at 1 mg at bedtime 1
• Increase by 1-2 mg every few days until clinical response 1
• Target dose: 3-4 mg/day for civilians, 9.5-15.6 mg/day for military veterans 1
• Monitor blood pressure closely due to hypotensive effects 1, 4

The mechanism involves α1-adrenergic antagonism, reducing central norepinephrine activity that drives trauma-related nightmares. 2 Three of four randomized controlled trials showed significant improvement in nightmare frequency and severity. 3

Second-Line Options When Prazosin Fails or Is Not Tolerated

Clonidine is the recommended first replacement, with similar adrenergic-blocking mechanisms. 5, 4

• Dose: 0.1 mg twice daily initially, titrate to 0.2-0.6 mg/day in divided doses 5, 4
• Success rate: 85% (11/13 patients in case series) 4
• Requires blood pressure monitoring for orthostatic hypotension 4
• Particularly effective in female civilian PTSD patients 5

Trazodone represents a strong alternative with robust evidence:

• Average effective dose: 212 mg/day (range 25-600 mg) 1, 4
• Reduces nightmares from 3.3 to 1.3 nights/week (72% response rate) 1, 4
• Monitor for priapism risk—requires immediate discontinuation if occurs 4
• Blood pressure monitoring essential 4

Third-Line: Atypical Antipsychotics

When first and second-line agents fail, atypical antipsychotics may be considered, though evidence quality is lower. 1, 5

Risperidone has the strongest evidence in this class:

• Dose: 0.5-2.0 mg at bedtime 5, 6
• Success rate: 77-80% of patients report improvement 1, 6
• Most patients respond after first dose, with optimal benefit at 2 mg nightly 5
• By 6 weeks: statistically significant reductions in nightmare frequency 5
• Average maximum effective dose: 2.3 mg/day (range 1-3 mg) 7, 5

Olanzapine shows promise but limited data:

• Dose: 10-20 mg/day 7, 4
• 100% success rate in small case series (5/5 patients achieved full remission) 6
• Rapid improvement when added to existing regimens 7
• Consider for treatment-resistant cases 7

Aripiprazole is a third-line atypical antipsychotic:

• Dose: 15-30 mg/day 5
• Better tolerability profile than olanzapine 7
• 80% success rate (4/5 veterans showed substantial improvement at 4 weeks) 5
• American Academy of Sleep Medicine classifies as Level C evidence (low grade and sparse data) 1

Treatment Algorithm

1. Attempt Image Rehearsal Therapy first (non-pharmacological, 60-72% reduction in nightmares) 4
2. If pharmacotherapy needed: Start prazosin 1 mg, titrate to 3-15 mg/day 1
3. If prazosin fails/not tolerated: Switch to clonidine 0.1 mg BID, titrate to 0.2-0.6 mg/day 5, 4
4. If clonidine fails: Try trazodone, target 212 mg/day 5, 4
5. If all fail: Risperidone 0.5-2.0 mg at bedtime 5, 6
6. For treatment-resistant cases: Consider olanzapine 10-20 mg or aripiprazole 15-30 mg 5, 6

Medications to AVOID

Clonazepam shows no benefit over placebo in controlled trials—do not use. 1

Venlafaxine demonstrates no significant benefit for distressing dreams—avoid. 1

Benzodiazepines and sedative-hypnotics lack supporting evidence and carry dependency risks. 8

Critical Pitfalls and Monitoring

• Expect return of nightmares to baseline intensity if medication discontinued—this is not treatment failure but expected pharmacology 1, 5
• Blood pressure monitoring is mandatory with prazosin, clonidine, and trazodone due to orthostatic hypotension risk 1, 4
• Assess response after 2-8 weeks of adequate dosing before declaring treatment failure 4
• Nightmare treatment requires substantially lower antipsychotic doses (0.5-3 mg risperidone) than psychotic disorders—the mechanism operates at lower doses than dopamine blockade 5
• Monitor for extrapyramidal symptoms if risperidone doses approach or exceed 2 mg/day 5
• Combining Image Rehearsal Therapy with pharmacotherapy yields best outcomes—don't rely on medication alone 1

Emerging Options

Doxazosin (longer-acting α1-antagonist) shows promise as prazosin alternative:

• Dose: 4-8 mg at bedtime 9
• 8 mg produced 55.2% nightmare-free nights vs 4.3% without medication (OR=28.2) 9
• Well-tolerated except mild dizziness 9
• Longer half-life may provide more consistent coverage than prazosin 9