What medications are used to treat nightmares?

Medication for Nightmares

Prazosin remains the first-line pharmacological treatment for PTSD-associated nightmares despite recent conflicting evidence, while Image Rehearsal Therapy should be prioritized for all nightmare disorder patients. 1

First-Line Approach

• Image Rehearsal Therapy (IRT) is the primary treatment for nightmare disorder, achieving 60-72% reduction in nightmare frequency and should be initiated before or alongside any medication. 1
• For patients requiring pharmacological intervention, prazosin is the most established medication option. 2

Prazosin: The Primary Pharmacological Option

Dosing Strategy

• Start at 1 mg at bedtime and titrate by 1-2 mg every few days until nightmares are controlled or side effects emerge. 2, 1
• Average effective dose is approximately 3 mg for civilians, though military veterans with combat-related PTSD often require higher doses (9.5-13.3 mg/day). 2
• Maximum recommended dose is 20 mg at bedtime. 3

Evidence Quality and Recent Controversy

• The American Academy of Sleep Medicine initially gave prazosin Level A evidence based on three randomized controlled trials showing significant reduction in PTSD-associated nightmares. 2
• However, a large 2018 VA study of 304 veterans found no benefit over placebo, leading to downgrading of the recommendation. 2
• Despite this, the American Academy of Sleep Medicine acknowledges that many patients respond very well to prazosin in clinical practice, and it remains the first pharmacological choice. 2

Critical Drug Interaction

• Concurrent use of SSRIs may reduce prazosin's effectiveness—one study showed 30.1-point CAPS reduction without SSRIs versus only 9.6 points with SSRIs. 2
• Consider this interaction when selecting or combining treatments. 2

Monitoring Requirements

• Monitor for orthostatic hypotension, especially after the first dose and with dose increases. 2, 1
• Blood pressure checks are essential during titration. 1

Alternative Pharmacological Options

Topiramate (Second-Line for PTSD Nightmares)

• Start at 12.5-25 mg daily and increase by 25-50 mg every 3-4 days. 2
• Effective dose for 91% of responders is ≤100 mg/day, though range extends to 400 mg/day. 2
• Achieved 79% reduction in nightmares with 50% complete suppression in one case series. 2
• Significant side effects include urticaria, nausea, acute narrow-angle glaucoma, severe headaches, panic, suicidal ideation, and memory problems. 2

Trazodone (Consider for Comorbid Insomnia)

• Dose range 25-600 mg (mean 212 mg) at bedtime. 2
• Reduced nightmare frequency from 3.3 to 1.3 nights per week in 72% of veterans. 2
• Major side effects: daytime sedation (most common), dizziness, headache, priapism (serious), orthostatic hypotension. 2, 1
• 19% discontinuation rate due to adverse effects. 2

Nabilone (Synthetic Cannabinoid)

• Start at 0.5 mg and titrate to maximum 3 mg based on efficacy and tolerability. 2
• Reduced CAPS nightmare scores by 3.6 points versus 1.0 for placebo in military personnel. 2
• 50% of patients were "much improved" versus 11% on placebo. 2
• Side effects: dry mouth and headache most common. 2

Clonidine (Alternative Alpha-Agonist)

• Dose 0.2-0.6 mg in divided doses. 1
• Level C evidence for PTSD-associated nightmares. 1
• Monitor blood pressure due to orthostatic hypotension risk. 1

Medications with Limited or Negative Evidence

Avoid or use with extreme caution:

• Clonazepam and venlafaxine show no benefit over placebo for nightmare disorder. 1
• Phenelzine (45-90 mg): eliminated nightmares in small case series but requires tyramine-restricted diet and has hypertensive crisis risk. 2
• Benzodiazepines (triazolam 0.5 mg, nitrazepam 5 mg): reduced unpleasant dreams equally but only studied for 3 days. 2
• Atypical antipsychotics (olanzapine, risperidone, aripiprazole): minimal evidence, reserve for refractory cases. 2

Critical Distinction: Night Terrors vs. Nightmares

• Night terrors occur during deep non-REM sleep with complete amnesia, while nightmares occur during REM sleep with full recall. 4
• Prazosin has NO role in night terrors—this is a common and dangerous prescribing error. 4
• For night terrors, clonazepam is considered only when episodes are frequent, severe, or causing functional impairment. 4

Clinical Algorithm

1. Initiate Image Rehearsal Therapy for all patients with nightmare disorder. 1

2. For PTSD-associated nightmares requiring medication:

   • Start prazosin 1 mg at bedtime, titrate every few days. 2, 1
   • Check if patient is on SSRIs—consider alternative if so. 2
   • Monitor blood pressure. 1

3. If prazosin fails or is not tolerated:

   • Consider topiramate (start 12.5-25 mg) if patient can tolerate cognitive side effects. 2
   • Consider trazodone (start 25-50 mg) if comorbid insomnia present. 2
   • Consider nabilone (start 0.5 mg) if available. 2

4. For non-PTSD nightmare disorder:

   • Prazosin, nitrazepam, or triazolam may be used. 1
   • Behavioral therapy remains first-line. 1

Common Pitfalls

• Do not confuse night terrors with nightmares—treatments differ completely. 4
• Do not ignore SSRI interactions with prazosin—they may significantly reduce efficacy. 2
• Do not use nefazodone as first-line due to hepatotoxicity risk. 2
• Do not expect immediate results—therapeutic benefit may take up to one week. 5
• Do not prescribe prazosin without blood pressure monitoring—orthostatic hypotension is the most common adverse effect. 2, 1