What is the best approach to manage a patient with complex post-traumatic stress disorder (cptsd) who is currently taking Sertraline, Esketamine (S-ketamine), and Rexulti (Brexpiprazole)?

Management of Complex PTSD on Current Medication Regimen

Prioritize trauma-focused psychotherapy immediately without requiring a prolonged stabilization phase, even with this complex medication regimen, as evidence demonstrates that 40-87% of patients with cPTSD no longer meet diagnostic criteria after 9-15 sessions of trauma-focused treatment, and delaying this definitive treatment is both demoralizing and therapeutically counterproductive. 1, 2

Immediate Treatment Restructuring Required

Trauma-Focused Psychotherapy as Primary Intervention

• Initiate Prolonged Exposure (PE), Cognitive Processing Therapy (CPT), or Eye Movement Desensitization and Reprocessing (EMDR) immediately without waiting for medication optimization or a stabilization phase 1, 2

• The evidence directly refutes the traditional phase-based approach for cPTSD—patients with childhood trauma histories, multiple comorbidities, and severe emotion dysregulation benefit from immediate trauma-focused treatment without adverse effects or increased dropout rates 3

• Emotion dysregulation, impulsivity, and negative self-concept improve through trauma processing itself, not through separate stabilization interventions, as these symptoms stem from unprocessed trauma-related stimuli and negative appraisals 2, 4

• Studies comparing patients with versus without childhood abuse histories found no differences in PTSD severity, emotion regulation, or treatment response when both groups received trauma-focused therapy (prolonged exposure or sertraline), with comparable outcomes at 6-month follow-up 3

Critical Medication Modifications

Sertraline (Current Medication):

• Continue sertraline as it is first-line pharmacotherapy with FDA approval for PTSD and demonstrates consistent efficacy across multiple placebo-controlled trials 1, 5, 6
• Plan to continue for minimum 6-12 months after symptom remission, as discontinuation leads to 26-52% relapse rates compared to only 5-16% when maintained on medication 1, 7
• Note that 92% of acute-phase sertraline responders maintained response during 6 months of continuation treatment, and 54% of initial non-responders converted to responder status with continued treatment 8

Esketamine (S-ketamine):

• This medication lacks evidence for cPTSD treatment in the provided guidelines and represents off-label use without established efficacy data for trauma-focused PTSD treatment 1, 2
• Consider discontinuation or re-evaluation of necessity, as trauma-focused psychotherapy provides more durable benefits than pharmacotherapy alone, with lower relapse rates after treatment completion 1

Rexulti (Brexpiprazole):

• Atypical antipsychotics show preliminary evidence as augmentation to SSRIs in treatment-refractory cases or when paranoia/flashbacks are prominent 5, 7
• However, this should be considered third-line augmentation after trauma-focused psychotherapy has been adequately trialed, not as primary treatment 5, 9
• Re-evaluate necessity after initiating trauma-focused psychotherapy, as affect dysregulation and dissociative symptoms typically improve with trauma processing 2, 4

Treatment Algorithm for This Patient

Step 1: Immediate Psychotherapy Referral

• Refer to trauma-focused psychotherapy (PE, CPT, or EMDR) within 1-2 weeks maximum 1, 2
• If in-person therapy unavailable, secure video teleconferencing produces equivalent outcomes 1
• Target 9-15 sessions as adequate dose for most patients with complex presentations 1, 2

Step 2: Medication Optimization During Psychotherapy

• Maintain sertraline at current therapeutic dose 5, 6, 7
• Taper and discontinue esketamine given lack of evidence base for cPTSD 1, 2
• Continue brexpiprazole temporarily but plan reassessment after 8-12 weeks of trauma-focused therapy 5, 9

Step 3: Reassessment at 12 Weeks

• If adequate response (≥30% symptom reduction), continue trauma-focused therapy to completion and maintain sertraline 8
• If partial response, continue therapy and consider whether brexpiprazole augmentation is providing additional benefit 5, 9
• If inadequate response, verify therapy is truly trauma-focused (not supportive counseling) and consider dose optimization of sertraline before adding additional medications 7, 8

Critical Pitfalls to Avoid

Never delay trauma-focused treatment by insisting on prolonged stabilization:

• This communicates to the patient that they cannot handle their traumatic memories, reducing self-confidence and motivation for active trauma processing 2, 4
• The assumption that affect dysregulation or dissociative symptoms require extensive pre-treatment stabilization is not evidence-based—these symptoms improve with trauma-focused treatment 3, 2

Avoid labeling this patient as "too complex" for standard trauma-focused treatment:

• This has iatrogenic effects by suggesting standard treatments will be ineffective 2, 4
• Evidence from patients with schizophrenia, psychotic disorders, and severe comorbidities demonstrates safety and efficacy of trauma-focused treatment without symptom exacerbation 3, 2

Do not add benzodiazepines for anxiety or sleep:

• Evidence shows 63% of patients receiving benzodiazepines developed PTSD at 6 months compared to only 23% receiving placebo 1, 2
• For PTSD-related nightmares or sleep disturbance, consider prazosin (1 mg at bedtime, titrate to 3 mg average effective dose) rather than sedative-hypnotics 1, 7

Recognize that dropout from trauma-focused treatment is typically due to practical factors:

• Travel time, childcare responsibilities, illness, or life stressors—not trauma characteristics or treatment intensity 3
• Address these barriers proactively rather than assuming the patient is "not ready" for trauma work 2, 4

Expected Outcomes

• With trauma-focused psychotherapy, 40-87% of patients no longer meet PTSD criteria after treatment completion 1, 2
• Relapse rates are significantly lower after completing trauma-focused psychotherapy compared to medication discontinuation 1
• Emotion dysregulation, interpersonal problems, and negative self-concept improve as core PTSD symptoms resolve through trauma processing 3, 2
• Depression symptoms generally improve following trauma-focused psychotherapy regardless of baseline severity 3