What is the best course of action to manage severe anxiety in a patient recently discontinued from lamotrigine and brexpiprazole?

Management of Severe Anxiety After Discontinuation of Lamotrigine and Brexpiprazole

Continue and optimize the current Celexa (citalopram) 40mg regimen while adding cognitive behavioral therapy (CBT), as this combination demonstrates superior outcomes compared to medication alone for severe anxiety. 1, 2

Immediate Treatment Strategy

Step 1: Optimize Current SSRI Therapy

• Maintain Celexa at 40mg daily, as this is the maximum recommended dose (higher doses increase QT prolongation risk without additional benefit) 2
• Allow 8-12 weeks at this therapeutic dose before considering medication changes, as full response may take this long 2, 3
• Monitor treatment response every 2-4 weeks using standardized anxiety rating scales 2

Step 2: Add Evidence-Based Psychotherapy

• Initiate CBT immediately - the combination of SSRI plus CBT shows superior efficacy compared to medication monotherapy for anxiety disorders 1, 2
• Structure CBT as approximately 14 sessions over 4 months, with each session lasting 60-90 minutes 1
• CBT addresses both neurobiological and psychological components of anxiety disorders simultaneously 2

Step 3: Continue Supportive Medications

• Maintain gabapentin 300mg daily - this is listed as a second-line agent for anxiety disorders in Canadian guidelines 1
• Continue alprazolam PRN for acute anxiety episodes, though benzodiazepines should not be used routinely long-term 3
• Continue Ritalin if ADHD symptoms are present and contributing to functional impairment

If Inadequate Response After 8-12 Weeks

Option A: Switch to SNRI (Preferred)

• Switch to venlafaxine extended-release, which demonstrates statistically significantly better response and remission rates than SSRIs in patients with depression and anxiety symptoms 2
• SNRIs have dual action on serotonin and norepinephrine, potentially providing greater efficacy for both depression and anxiety 2
• Start venlafaxine at 37.5-75mg daily and titrate to 150-225mg daily based on response 3

Option B: Augmentation Strategy

• Add buspirone only after confirming adequate SSRI trial duration and dose optimization 2
• Start buspirone at 7.5mg twice daily, titrate to 15-30mg twice daily (maximum 60mg/day) 3
• Note: Buspirone augmentation has higher discontinuation rates (20.6%) due to adverse events compared to other strategies 2

Option C: Switch to Alternative SSRI

• Consider switching to sertraline or escitalopram, which have extensive evidence for anxiety disorders 1, 2
• Escitalopram has favorable drug interaction profile with minimal CYP450 effects 2
• Allow 2-week washout when switching between SSRIs to minimize serotonin syndrome risk 2

Critical Safety Considerations

Avoid Medication Combinations That Increase Risk

• Do not combine multiple serotonergic agents (SSRI + SNRI, SSRI + tricyclic) due to serotonin syndrome risk 2
• Do not restart lamotrigine or brexpiprazole at this time - the case report literature documents severe akathisia, increased anxiety, and suicidal ideation when aripiprazole (similar mechanism to brexpiprazole) is combined with lamotrigine and antidepressants 4
• Do not exceed citalopram 40mg daily due to dose-dependent QT prolongation 2

Monitor for Adverse Effects

• Assess for suicidal thoughts and behaviors, particularly during the first 1-2 months and after any dose changes 2
• Watch for behavioral activation/agitation, especially early in treatment or after dose increases 5
• Monitor for serotonin syndrome signs: mental status changes, neuromuscular hyperactivity, autonomic hyperactivity 2

Rationale for Discontinuing Lamotrigine and Brexpiprazole

The discontinuation of these medications was appropriate because:

• Lamotrigine combined with antipsychotics and antidepressants increases risk of severe akathisia, anxiety, and suicidal ideation in mood disorder patients 4
• Brexpiprazole (similar to aripiprazole) can worsen anxiety when combined with mood stabilizers and antidepressants 4
• Neither medication is first-line for primary anxiety disorders 1, 3

Duration of Treatment

• Continue SSRI therapy for 6-12 months after achieving remission of anxiety symptoms 3
• For patients with recurrent anxiety episodes, longer duration therapy (years) may be beneficial 2
• Maintain CBT skills practice even after symptom remission to prevent relapse 1

Common Pitfalls to Avoid

• Premature medication switching: Do not switch before allowing 8-12 weeks at therapeutic SSRI dose 2
• Polypharmacy without rationale: Adding multiple medications simultaneously makes it impossible to determine which is effective or causing side effects 4
• Neglecting psychotherapy: Medication alone is less effective than combination treatment for anxiety disorders 1, 2
• Inadequate monitoring: Failure to assess response systematically leads to prolonged ineffective treatment 2