Medication Management for Treatment-Resistant PTSD and MDD
Immediate Next Step: Optimize Current Mirtazapine Dose
Increase mirtazapine from 15mg to 30-45mg daily, as the current dose is subtherapeutic and the patient has not yet received an adequate trial at therapeutic dosing. 1, 2
- Mirtazapine demonstrates efficacy at 15-45mg/day for major depression, with the current 15mg dose representing the lower end of the therapeutic range 3, 4
- An adequate antidepressant trial requires minimum licensed dosage for at least 4 weeks before considering treatment failure 1
- Mirtazapine has particular advantages for this patient: it is the only antidepressant with preliminary evidence for PTSD efficacy, shows rapid onset of action compared to SSRIs, and has the fewest gastrointestinal side effects among antidepressants 5, 3, 6
- Critical consideration: Given her recent total cholecystectomy for chronic constipation, mirtazapine is the optimal choice as it causes the fewest GI side effects and is only associated with increased appetite rather than constipation 6
If Inadequate Response After 4-6 Weeks at Therapeutic Dose
Primary Augmentation Strategy
Add aripiprazole 2-5mg daily as augmentation to optimized mirtazapine. 1
- The National Institute of Mental Health recommends augmentation with atypical antipsychotics (aripiprazole or quetiapine) for partial responders to antidepressants 1
- Aripiprazole augmentation shows superior remission rates compared to bupropion augmentation (55.4% vs 34.0%) 7
- Atypical antipsychotics are particularly effective when paranoia or flashbacks are prominent PTSD symptoms 5
Alternative Augmentation if Aripiprazole Not Tolerated
Consider lithium augmentation with careful monitoring. 1
- Lithium augmentation is one of the best-documented treatments for treatment-resistant depression 1
- Requires monitoring of blood levels, thyroid function, and renal function 1
Critical Medication to Avoid
Do not use bupropion in this patient. 5, 8
- Bupropion is ineffective for PTSD despite efficacy in depression 5
- Bupropion causes severe constipation and was associated with hemorrhoidectomy in case reports 8
- Given her recent cholecystectomy for chronic constipation, bupropion poses unacceptable GI risk 8
If Multiple Augmentation Strategies Fail
Consider non-pharmacological interventions including cognitive behavioral therapy or electroconvulsive therapy. 1
- Approximately 38% of patients do not achieve treatment response and 54% do not achieve remission with second-generation antidepressants alone 7
- CBT shows moderate certainty evidence for similar treatment effects as antidepressants across multiple outcomes 7
Monitoring Considerations
Monitor closely for suicidality, especially during dose adjustments. 2
- All antidepressant-treated patients require monitoring for clinical worsening and emergence of suicidal thoughts, particularly during initial months and dosage changes 2
- SSRIs (which she previously failed) are associated with increased risk for nonfatal suicide attempts 7
Monitor for agranulocytosis with mirtazapine. 2
- Discontinue mirtazapine immediately if sore throat, fever, stomatitis, or signs of infection develop with low WBC count 2
- Risk is highest in first 61 days of treatment 2
Monitor weight and appetite. 2