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

Medication Treatment for PTSD and Nightmare Disorder

First-Line Treatment Approach

For PTSD-associated nightmares, start with Image Rehearsal Therapy (IRT) as first-line treatment, and if pharmacotherapy is needed, prazosin remains the most established medication option despite recent controversies, with alternative agents including clonidine, risperidone, and trazodone as viable second-line choices. 1, 2, 3

Pharmacological Treatment Algorithm

For PTSD-Associated Nightmares

First-Line Medication:

• Prazosin (alpha-1 adrenergic antagonist) is the most established pharmacological option 1, 2
  • Starting dose: 1 mg at bedtime 2, 3
  • Titrate by 1-2 mg every few days until clinical response 2, 3
  • Effective doses: 3-4 mg/day for civilians, 9.5-15.6 mg/day for military veterans 2, 3
  • Monitor blood pressure after initial dose and with each significant increase 2, 3
  • Note: Recent evidence has downgraded prazosin's recommendation level, but it remains widely used in absence of superior alternatives 4

Second-Line Medications (when prazosin fails or is contraindicated):

• Clonidine (alpha-2 adrenergic agonist) 1, 3

  • Dose: 0.2-0.6 mg in divided doses 1, 3
  • Reduced nightmares in 11/13 patients in case series 1, 3
  • Monitor for postural hypotension and sedation 1
  • 63% success rate in clinical practice 5

• Atypical Antipsychotics 1

  • Risperidone: 0.5-3 mg/day; 77% success rate in clinical trials 1, 5
  • Olanzapine: 2.5-20 mg; 100% success rate in small case series (5/5 patients) 1, 5
  • Quetiapine: 12.5-800 mg; 50% success rate 5
  • Aripiprazole: also recommended but less data 1
  • Consider particularly when psychotic symptoms, severe agitation, or treatment resistance present 1

• Trazodone 1

  • Dose: 25-600 mg (mean effective dose 212 mg) 1
  • Reduced nightmares from 3.3 to 1.3 nights/week (72% response rate) 1
  • Common side effects (60% of patients): daytime sedation, dizziness, headache, priapism, orthostatic hypotension 1
  • 19% discontinuation rate due to side effects 1

Third-Line Options:

• Topiramate: Start 25 mg/day, titrate to effect (max 400 mg/day); 79% response rate with 50% achieving complete suppression 1, 6
• Gabapentin: Limited evidence but may be considered 1
• Phenelzine (MAOI): 30-90 mg; eliminated nightmares in small studies but requires dietary restrictions 1
• Tricyclic antidepressants: May be considered but less favorable side effect profile 1
• Cyproheptadine: Limited evidence 1
• Fluvoxamine: May be used 1
• Nabilone (synthetic cannabinoid): Emerging evidence, particularly in Canada 4

For Nightmare Disorder (Non-PTSD)

Medication Options:

• Prazosin: Same dosing as PTSD-associated nightmares 1
• Nitrazepam: 5 mg; equally effective as triazolam for reducing unpleasant dreams 1
• Triazolam: 0.5 mg; superior to nitrazepam for sleep duration but equal for nightmare reduction 1

Medications NOT Recommended

Avoid these agents:

• Clonazepam: No improvement over placebo in controlled trials 1, 6
• Venlafaxine: No significant benefit over placebo for distressing dreams 1, 6
• Nefazodone: Not first-line due to hepatotoxicity risk 1
• Benzodiazepines (general): May worsen PTSD symptoms 7

PTSD Core Symptoms (Beyond Nightmares)

First-Line Pharmacotherapy for Overall PTSD:

• SSRIs are first-line for core PTSD symptoms 8, 7, 9
  • Sertraline: FDA-approved for PTSD 8, 7
  • Paroxetine: FDA-approved for PTSD 7
  • Fluoxetine: Extensively studied 7
• Continue treatment for 6-12 months to decrease relapse rates 7
• Note: SSRIs have modest effects on nightmares specifically, requiring targeted nightmare treatment 10

Critical Clinical Considerations

Monitoring Requirements:

• Blood pressure monitoring essential with prazosin, clonidine, and trazodone due to hypotensive effects 2, 3
• Discontinuation of medications may cause return of nightmares to baseline intensity 2, 3
• Liver function monitoring if using nefazodone 1

Common Pitfalls to Avoid:

• Do not use benzodiazepines long-term; they may promote or worsen PTSD 7
• Do not prescribe clonazepam or venlafaxine specifically for nightmares—evidence shows no benefit 1, 6
• Do not overlook non-pharmacological treatments; IRT is highly effective and should be offered alongside or before medications 1, 2, 3, 6
• Do not assume SSRI treatment of core PTSD symptoms will adequately address nightmares—targeted treatment is often necessary 10, 9

Quality of Life Impact:

• Untreated nightmares significantly impair quality of life, cause sleep avoidance, and are an independent suicide risk factor 6, 10, 4
• Nightmare cessation leads to improved quality of life, fewer hospitalizations, lower healthcare costs, and reduced all-cause mortality 10

Combination Therapy Approach

Optimal Strategy:

• Combine IRT with pharmacotherapy for best outcomes 1, 2, 3, 6
• Consider adding CBT for insomnia (CBT-I) when both insomnia and nightmares present 6, 4
• SSRIs for core PTSD symptoms plus targeted nightmare treatment (IRT and/or prazosin/alternatives) addresses both issues 7, 9