What to do for an adult patient with a history of trauma or mental health conditions, experiencing nightmares, while taking Remeron (mirtazapine) 45mg, prazosin 2mg, Zyprexa (olanzapine) 15mg, Buspar (buspirone) 10mg three times a day (TID), and clonidine 0.1mg twice a day (BID)?

Management of Persistent Nightmares Despite Polypharmacy

The prazosin dose is critically subtherapeutic at 2mg—increase it to 9-15mg/day for veterans or 3-4mg/day minimum for civilians, while simultaneously initiating Image Rehearsal Therapy as the only evidence-based first-line treatment. 1

Immediate Medication Optimization

Prazosin Dose Escalation (Priority Action)

• The current 2mg dose is far below therapeutic range—effective dosing requires 3-4mg/day for civilians or 9.5-15.6mg/day for veterans with PTSD-related nightmares 1
• Titrate by 1-2mg every few days, monitoring blood pressure after each significant increase to avoid orthostatic hypotension 1
• The American Academy of Sleep Medicine identifies prazosin as the most established medication for nightmare disorder, with doses ranging from 1-16mg/day showing efficacy 2, 3

Clonidine Dose Assessment

• The current 0.1mg BID (0.2mg/day total) is at the lower end of the therapeutic range for PTSD nightmares 2, 1
• Evidence supports 0.2-0.6mg/day in divided doses, with most patients responding to 0.2mg/day average 2, 4
• However, clonidine is redundant with prazosin—both are alpha-adrenergic agents targeting the same mechanism 1, 5
• Consider discontinuing clonidine once prazosin reaches therapeutic dosing to avoid excessive alpha-blockade and hypotension risk 4

Medication Regimen Concerns

Olanzapine (Zyprexa) 15mg

• The American Academy of Sleep Medicine supports olanzapine for PTSD-associated nightmares, with case series showing rapid improvement at 10-20mg/day 2
• This dose is appropriate and evidence-based for nightmare treatment 2
• Monitor for metabolic side effects given the high dose 2

Mirtazapine (Remeron) 45mg

• While mirtazapine has serotonergic effects, there is no high-quality evidence supporting its efficacy for nightmares specifically 6
• The 45mg dose is at maximum for depression/anxiety but not specifically targeting nightmares 6
• Consider whether this medication is providing benefit beyond sedation 6

Buspirone 10mg TID

• Buspirone has no established role in nightmare treatment—it is not mentioned in any American Academy of Sleep Medicine guidelines for nightmare disorder 2
• This medication appears to be targeting anxiety rather than nightmares specifically 2

Critical Treatment Algorithm

Step 1: Optimize Prazosin (Immediate)

• Increase prazosin from 2mg to 4-6mg over 1-2 weeks, monitoring blood pressure 1
• Target dose: 9-15mg/day if veteran, 3-6mg/day if civilian 1
• This single intervention has the strongest evidence base 2, 3

Step 2: Initiate Image Rehearsal Therapy (Within 1-2 Weeks)

• Image Rehearsal Therapy is the only "recommended" (not just "may be used") treatment by the American Academy of Sleep Medicine 2
• Involves rewriting nightmare content into positive scenarios and rehearsing 10-20 minutes daily while awake 2, 1
• Three sessions (two 3-hour sessions one week apart, with 1-hour follow-up 3 weeks later) show significant efficacy 2

Step 3: Simplify Polypharmacy (After Prazosin Optimization)

• Taper clonidine gradually over 2-4 weeks once prazosin reaches therapeutic dose to avoid redundant alpha-blockade 4, 5
• Reduce by 10-20% every 24-48 hours while monitoring for rebound hypertension 4
• Consider whether buspirone is providing benefit—if not, taper and discontinue 2

Step 4: If Nightmares Persist After Prazosin Optimization

• Switch from prazosin to risperidone 0.5-2.0mg at bedtime (80% response rate after first dose) 2, 1, 5
• Alternative: aripiprazole 15-30mg/day (better tolerability than olanzapine, though patient already on olanzapine) 2, 1

Critical Pitfalls to Avoid

Medication-Specific Warnings

• Never use clonazepam or venlafaxine—the American Academy of Sleep Medicine specifically recommends against these for nightmare disorder 2
• Monitor blood pressure carefully with both prazosin and clonidine—orthostatic hypotension is the primary safety concern 1, 4, 7
• Expect return of nightmares if medications are discontinued—symptoms typically return to baseline intensity 1

Polypharmacy Risks

• This patient is on five psychotropic medications, creating significant drug interaction and side effect burden 2
• The combination of olanzapine 15mg + mirtazapine 45mg creates substantial sedation and metabolic risk 2, 6
• Two alpha-adrenergic agents (prazosin + clonidine) is redundant and increases hypotension risk 1, 4, 5

Evidence Quality Context

The American Academy of Sleep Medicine 2018 position paper provides the most authoritative guidance, distinguishing between "recommended" (Image Rehearsal Therapy only), "may be used" (prazosin, olanzapine, risperidone, aripiprazole, clonidine), and "not recommended" (clonazepam, venlafaxine) interventions 2. The fundamental problem here is undertreated prazosin combined with excessive polypharmacy—the patient has multiple medications with weak or no evidence for nightmares while the one medication with the strongest evidence (prazosin) is dosed at only 13-20% of the therapeutic target 1, 3.