What adjustments can be made to the medication regimen of a patient with schizoaffective disorder, bipolar type, and post-traumatic stress disorder (PTSD), currently taking topiramate (100 mg twice a day (BID)), metformin (500 mg BID), Abilify (aripiprazole) (5 mg), prazosin (1 mg), and olanzapine (15 mg BID), who experiences sleep disturbances, nightmares, and nocturnal fear?

Medication Adjustments for Sleep Disturbances and Nightmares in Schizoaffective Disorder with PTSD

Primary Recommendation

Increase prazosin from 1 mg to a target dose of 10-16 mg at bedtime, and add trazodone 50-100 mg at bedtime for persistent insomnia and PTSD-related nightmares. 1

Rationale and Stepwise Approach

Step 1: Optimize Prazosin Dosing

Your patient is significantly underdosed on prazosin at only 1 mg. The evidence strongly supports much higher dosing:

• Target prazosin dose: 10-16 mg at bedtime for military/combat-related PTSD, with some studies using up to 20 mg daily 1, 2
• Start by increasing prazosin by 1-2 mg every 3-7 days, monitoring for orthostatic hypotension after each dose increase 2, 3
• The mean effective dose in PTSD studies is 2-6 mg for civilians, but military populations often require 10-16 mg 2
• Prazosin reduces nightmare frequency from approximately 4 nights/week to 1-2 nights/week when adequately dosed 4, 3
• Monitor blood pressure before each dose increase, particularly the first-dose effect 2

Common pitfall: Clinicians often keep prazosin at 1-2 mg due to hypotension concerns, but this dose is therapeutically inadequate for PTSD nightmares. Most patients tolerate gradual titration to 10-16 mg without significant adverse effects 5, 2

Step 2: Add Trazodone for Insomnia and Nightmares

Since prazosin alone may not fully resolve sleep disturbances:

• Add trazodone 50-100 mg at bedtime, titrating to a target of 200-212 mg if needed 1
• Trazodone reduced nightmare frequency from 3.3 nights/week to 1.3 nights/week in PTSD patients 1
• Start at 25-50 mg and increase by 25-50 mg every 3-7 days based on response 1
• Watch for: daytime sedation (most common), dizziness, and rarely priapism (5/74 patients in one study discontinued for this reason) 1

Step 3: Consider Topiramate Dose Optimization

Your patient is already on topiramate 100 mg BID (200 mg total daily):

• This is at the target dose range of 200 mg/day used in PTSD nightmare studies 1
• Topiramate reduced nightmare prevalence from 100% to 60% and frequency from 4 nights/week to 2 nights/week 1
• Do not increase further as 91% of responders achieved benefit at ≤100 mg/day, and higher doses increase side effects without additional benefit 1

Step 4: Evaluate Antipsychotic Regimen

The current regimen is problematic:

• Olanzapine 15 mg BID (30 mg total daily) is excessive and likely contributing to sedation issues and metabolic concerns 6
• Olanzapine at 10-20 mg at bedtime has been used for PTSD-related sleep disturbances 1
• Consider consolidating to olanzapine 15-20 mg once at bedtime rather than BID dosing 6
• Aripiprazole 5 mg is a reasonable adjunct dose for schizoaffective disorder 7

Alternative consideration: The NCCN guidelines suggest olanzapine 2.5-5 mg at bedtime specifically for insomnia, or quetiapine 25-50 mg at bedtime 1, 8. However, given your patient's schizoaffective disorder requiring antipsychotic coverage, maintaining therapeutic antipsychotic dosing is appropriate.

Step 5: Address Nocturnal Enuresis

The bedwetting history may be related to:

• Deep sleep induced by high-dose olanzapine 6
• Consider reducing total daily olanzapine dose as suggested above
• Prazosin at higher doses may paradoxically help by improving sleep architecture and reducing trauma-related arousal 2, 4

Medications to Avoid

• Do not add benzodiazepines (clonazepam showed no benefit for PTSD nightmares in controlled trials) 1
• Avoid further dose increases of olanzapine given metabolic risks and current excessive dosing 6

Monitoring Plan

• Week 1-4: Increase prazosin by 1-2 mg every 3-7 days, checking orthostatic blood pressure before each increase
• Week 2: Add trazodone 50 mg at bedtime if insomnia persists
• Week 4-8: Titrate trazodone to 100-200 mg based on response and tolerability
• Ongoing: Monitor for daytime sedation, nightmare frequency (use sleep diary), and quality of life improvements

Expected Timeline

• Prazosin response: Within 2-4 weeks of reaching therapeutic dose 2, 3
• Trazodone response: Within 1-2 weeks 1
• Full benefit: 6-8 weeks after optimization 1, 4