Medication Options to Add to Prazosin for Extreme Nightmares in PTSD
Topiramate is the most effective medication to add to prazosin for treating extreme nightmares in PTSD patients who have an inadequate response to prazosin alone. 1
First-Line Augmentation: Topiramate
Topiramate has demonstrated significant efficacy in reducing PTSD-associated nightmares with substantial evidence supporting its use:
- Mechanism of action: Works by inhibiting sodium and calcium channels, stimulating GABA-A receptors, inhibiting glutamate, and affecting carbonic anhydrase isoenzymes 1
- Efficacy data:
- Dosing:
- Start at 12.5-25 mg daily
- Increase by 25-50 mg every 3-4 days until therapeutic response
- Most responders (91%) require ≤100 mg/day, though effective dosing ranges from 12.5-500 mg/day 1
Alternative Augmentation Options
If topiramate is contraindicated or not tolerated, consider these alternatives:
1. Clonidine
- Evidence level: C (lower than prazosin but established use) 1
- Mechanism: α2-adrenergic receptor agonist that suppresses CNS sympathetic outflow
- Dosing: 0.2-0.6 mg in divided doses
- Efficacy: Effective in 11/13 patients in case series 1
- Caution: Monitor for hypotension; may have synergistic effects with prazosin
2. Atypical Antipsychotics
- Options: Olanzapine, risperidone, or aripiprazole 1
- Efficacy:
- Caution: Monitor for metabolic side effects and extrapyramidal symptoms
3. Trazodone
- Evidence level: C 1
- Efficacy: Decreased nightmares from 3.3 to 1.3 nights/week (p<0.005) in 72% of veterans 1
- Dosing: 25-600 mg (mean 212 mg)
- Caution: High rate of side effects (60%), including sedation, dizziness, and priapism 1
Important Clinical Considerations
Prazosin Optimization First
Before adding a second agent, ensure prazosin is optimally dosed:
- Civilian patients: Average maintenance dose ~3 mg (range 1-10 mg) 2
- Military veterans: May require higher doses (9.5-15.6 mg/day) 2
- Women: May respond to lower doses than men (7.0 mg vs 15.6 mg) 2
- Consider 3-times-daily dosing: Due to prazosin's short half-life (2-3 hours), multiple daily doses may provide better symptom control 3
Potential Drug Interactions
- SSRIs: May decrease prazosin efficacy for PTSD treatment 2
- PDE-5 inhibitors: Can cause additive hypotensive effects 2
Monitoring Parameters
- Blood pressure: Monitor for orthostatic hypotension, especially when initiating therapy
- Nightmare frequency and intensity: Use standardized measures like CAPS or sleep diaries
- Side effects: Dizziness is common with prazosin 2
Treatment Algorithm
- Optimize prazosin dosing first (up to 15 mg/day for veterans, lower for civilians)
- If inadequate response after 4 weeks of optimal prazosin dosing:
- First choice: Add topiramate starting at 25 mg daily, titrating up to 100 mg/day
- If topiramate contraindicated/not tolerated: Try clonidine 0.1 mg twice daily, titrating to 0.2-0.6 mg/day
- Third option: Consider atypical antipsychotics (risperidone 1-3 mg or olanzapine 5-20 mg)
Common Pitfalls to Avoid
- Inadequate prazosin dosing: Many patients require higher doses than initially prescribed
- Ignoring timing of nightmares: Consider multiple daily dosing of prazosin if daytime flashbacks or early evening nightmares occur 3
- Overlooking non-PTSD causes: Some nightmares may be due to other medications or medical conditions
- Neglecting non-pharmacological approaches: Consider adding Imagery Rehearsal Therapy (IRT), which has Level A evidence 1
- Failure to monitor for side effects: Both prazosin and augmenting agents can cause significant adverse effects
Remember that medication adjustments should be made gradually with careful monitoring for both efficacy and side effects.