What management approach is recommended for a patient with persistent anxiety on gabapentin 900mg PO TID, brexpiprazole 1mg PO QD, duloxetine 90mg PO QD, and alprazolam 0.5mg PO QD PRN, prior to their follow-up with a neurologist?

Management of Persistent Anxiety in a Patient on Complex Psychotropic Regimen

This patient requires optimization of their existing SSRI/SNRI therapy and structured CBT referral, while gabapentin should be evaluated as a potential contributor to heightened anxiety rather than a therapeutic agent. 1, 2

Immediate Assessment Priorities

Gabapentin may be causing or worsening the anxiety symptoms. Two case reports document that gabapentin 900mg daily caused heightened anxiety and restlessness in patients with cognitive impairment, with symptoms resolving within 48 hours of discontinuation. 2 Given this patient is taking gabapentin 900mg TID (2700mg daily total) for nerve pain, this represents a substantial dose that warrants evaluation as an iatrogenic contributor to anxiety symptoms. 2

Evaluate Current Medication Regimen

• The duloxetine 90mg daily dose is appropriate and within therapeutic range (60-120mg/day) for anxiety disorders. 1, 3 This SNRI represents guideline-concordant first-line therapy for generalized anxiety disorder. 1

• Assess adequacy of current SSRI/SNRI trial duration. Response to SSRIs/SNRIs follows a logarithmic pattern with statistically significant improvement by week 2, clinically significant improvement by week 6, and maximal benefit by week 12 or later. 1 If the patient has not completed 8-12 weeks at the current duloxetine 90mg dose, continue the medication and allow adequate time for response. 1, 4

• The alprazolam 0.5mg PRN represents suboptimal long-term management. Benzodiazepines should be reserved for short-term use only due to risks of dependence, tolerance, and withdrawal, and are not recommended for routine or chronic anxiety management. 1, 4, 5

Recommended Management Algorithm

Step 1: Address Potential Gabapentin-Induced Anxiety

Coordinate with the neurologist (prior to or at the scheduled follow-up) to evaluate whether gabapentin can be tapered or switched to an alternative for neuropathic pain. 2 Pregabalin represents an alternative gabapentinoid that may be better tolerated and has demonstrated efficacy in GAD, particularly for patients with comorbid pain conditions. 1

Step 2: Optimize Current Antidepressant Therapy

• If duloxetine has been at 90mg for <8-12 weeks, continue current dose and reassess response. 1, 4 Most adverse effects emerge within the first few weeks and typically resolve with continued treatment. 1

• If duloxetine has been at therapeutic dose for ≥8-12 weeks with inadequate response, consider switching to a different SSRI (escitalopram 10-20mg or sertraline 100-150mg). 1, 4 Escitalopram and sertraline are top-tier first-line agents with established efficacy and favorable side effect profiles. 1

• Do not add additional medications before ensuring adequate trial duration and addressing potential gabapentin contribution. 1, 4

Step 3: Initiate or Intensify Cognitive Behavioral Therapy

Refer for individual CBT specifically targeting anxiety patterns. 1, 4 Individual CBT is prioritized over group therapy due to superior clinical and cost-effectiveness, with large effect sizes for GAD (Hedges g = 1.01). 1 Combination treatment with SSRI/SNRI plus CBT provides superior outcomes compared to medication alone. 1, 4

• CBT should include 12-20 structured sessions incorporating: 1
  • Education on anxiety mechanisms
  • Cognitive restructuring to challenge distortions
  • Relaxation techniques (breathing exercises, progressive muscle relaxation)
  • Gradual exposure when appropriate

Step 4: Implement Adjunctive Non-Pharmacological Strategies

• Recommend regular cardiovascular exercise and structured physical activity. 1 Exercise provides moderate to large reduction in anxiety symptoms as adjunctive treatment. 1

• Teach specific anxiety management techniques: breathing techniques, progressive muscle relaxation, grounding strategies (noticing environmental details), visualization, mindfulness, and thought reframing. 1

Step 5: Plan Benzodiazepine Taper

Once anxiety improves with optimized SSRI/SNRI therapy and CBT, gradually taper alprazolam to discontinuation. 1, 4 Benzodiazepines are not recommended for long-term management due to dependence risk. 4

Critical Monitoring Considerations

• Monitor for suicidal thinking and behavior, especially if making medication changes. All SSRIs/SNRIs carry a boxed warning, with pooled absolute rates of 1% versus 0.2% for placebo. 1 Close monitoring is essential in the first months and following dose adjustments. 1

• Assess response using standardized anxiety rating scales (e.g., HAM-A) at each visit. 1

• Monitor for duloxetine side effects: nausea, sexual dysfunction, headache, insomnia, dry mouth, diarrhea, dizziness. 1, 3 Most adverse effects emerge within the first few weeks and typically resolve. 1

Important Clinical Pitfalls to Avoid

• Do not prematurely abandon duloxetine therapy before completing 12 weeks at therapeutic dose. 1 Full response may take 12+ weeks, and treatment should not be discontinued prematurely. 1

• Do not continue long-term benzodiazepine therapy. 1, 4 This perpetuates dependence risk without addressing underlying anxiety pathophysiology. 4

• Do not overlook gabapentin as a potential anxiety trigger. 2 The temporal relationship between gabapentin dosing and anxiety symptoms should be carefully evaluated. 2

• Screen for bipolar disorder before continuing or switching SSRIs/SNRIs. 4 Patients with bipolar disorder require mood stabilization first. 4 Note this patient is on divalproex 625mg daily, which may indicate bipolar disorder or seizure disorder—clarify diagnosis before medication adjustments.

• Do not add brexpiprazole (Rexulti) dose or additional augmentation agents before optimizing first-line therapy and addressing gabapentin. 1, 4