Should Rexulti (brexpiprazole) be considered for a 23-year-old female with ongoing anxiety, panic attacks, post-traumatic stress disorder (PTSD), and a history of substance abuse, currently taking escitalopram (20mg/day) and trazodone (150mg at bedtime) while weaning off benzodiazepines?

Management of Anxiety with Comorbid PTSD and Substance Abuse History

Rexulti (brexpiprazole) is not recommended as an adjunctive treatment for this 23-year-old female patient with anxiety, panic attacks, PTSD, and substance abuse history who is currently on escitalopram and trazodone while weaning off benzodiazepines.

Current Treatment Assessment

The patient is currently on:

• Escitalopram 20mg daily (maximum recommended dose) with slight improvement
• Trazodone 150mg at bedtime
• In process of weaning off benzodiazepines

Rationale Against Adding Brexpiprazole

1. Lack of FDA approval for anxiety disorders

   • Brexpiprazole is only FDA-approved for adjunctive treatment of major depressive disorder and schizophrenia 1
   • Not indicated for anxiety disorders, panic attacks, or PTSD

2. Risk considerations in substance abuse history

   • Patients with substance use history should avoid medications with potential for dependence
   • The current guideline recommends buspirone or SSRIs for patients with substance use history rather than atypical antipsychotics 2

3. Alternative evidence-based options available

   • Current guidelines recommend optimizing SSRI therapy before considering atypical antipsychotics
   • Escitalopram may require higher doses for anxiety disorders than for depression (10-20mg daily) 2

Recommended Treatment Approach

Step 1: Optimize Current Therapy

• Continue escitalopram 20mg daily as the patient is showing slight improvement
• Continue trazodone 150mg at bedtime for sleep support
• Complete benzodiazepine taper as planned due to substance abuse history

Step 2: Consider Evidence-Based Alternatives

If response remains inadequate after 4-6 weeks of optimized therapy:

1. First-line alternative medication options:

   • Switch to sertraline (50-200mg daily), which shows superior efficacy for psychomotor agitation often accompanying panic attacks 2
   • Consider buspirone (starting at 5mg twice daily, maximum 60mg daily) as an alternative to benzodiazepines 2
   • Consider venlafaxine (37.5-225mg daily) which has strong evidence for generalized anxiety disorder 2

2. Add cognitive behavioral therapy (CBT):

   • Highly effective as an adjunct to medication for anxiety disorders
   • Recommended components include cognitive restructuring, gradual exposure, relaxation techniques, and education about anxiety 2
   • Optimal structure: approximately 14 individual sessions over 4 months, each lasting 60-90 minutes

Monitoring and Follow-up

• Reassess symptoms every 2-4 weeks during medication changes
• Evaluate for side effects and monitor for emergence of suicidal ideation
• Use GAD-7 scale to assess anxiety severity (0-4: mild; 5-9: moderate; 10-21: moderate to severe)
• Follow up within 1-2 weeks of any medication changes

Important Considerations and Cautions

• Substance abuse history: Avoid benzodiazepines and consider alternatives like buspirone or SSRIs 2
• Young adult status: This 23-year-old patient falls in an age group requiring careful monitoring for behavioral activation/agitation and suicidal ideation with antidepressants
• Treatment duration: Continue treatment for at least 9-12 months after symptom remission 2
• Antipsychotic risks: Atypical antipsychotics like brexpiprazole carry risks including metabolic changes, tardive dyskinesia, and neuroleptic malignant syndrome that outweigh potential benefits in this clinical scenario 1

Remember that the primary goal is to achieve remission of anxiety symptoms while supporting the patient through benzodiazepine withdrawal, using evidence-based approaches that minimize risk given her substance abuse history.