What is the best course of action for a patient on Abilify (aripiprazole) 5mg and Depakote (valproate) 500mg who reports manageable depression but persistent anxiety?

Management of Persistent Anxiety in a Patient on Aripiprazole and Valproate

Optimize the current antidepressant/anxiolytic regimen first by adding an SSRI to address the persistent anxiety, as SSRIs are first-line pharmacotherapy for generalized anxiety disorder and the current regimen lacks a proven anxiolytic agent. 1

Immediate Assessment Required

Reassess the clinical picture with validated screening tools before making medication changes:

• Administer the GAD-7 (Generalized Anxiety Disorder 7-item scale) where scores ≥5 indicate mild anxiety, ≥10 moderate anxiety, and ≥15 severe anxiety 2
• Use the PHQ-9 (Patient Health Questionnaire-9) to objectively quantify current depressive symptoms 2, 3
• Screen for suicidal ideation immediately, as suicide risk is elevated in patients with comorbid depression and anxiety 2
• Rule out medical causes: unrelieved pain, delirium from infection or electrolyte imbalance, endocrine disorders, and medication side effects 2

Critical Problem with Current Regimen

The current medication combination lacks a proven anxiolytic agent:

• Aripiprazole 5mg is FDA-approved for acute mania in bipolar disorder but has no established efficacy for anxiety disorders 1
• Valproate (Depakote) 500mg is approved for acute mania but not for anxiety treatment 1
• Neither medication addresses the generalized anxiety disorder that appears to be the primary residual symptom 1

Recommended Treatment Algorithm

Step 1: Add an SSRI for Anxiety

Initiate an SSRI as the primary anxiolytic intervention:

• SSRIs are physician-prescribed first-line treatment for generalized anxiety disorder with choice informed by side effect profiles, drug interactions, patient age and preference 1
• Monitor regularly for adherence, side effects, and adverse events 1
• Common options include sertraline, escitalopram, or paroxetine, all with established efficacy for GAD 1

Step 2: Consider Aripiprazole Dose and Tolerability

Evaluate whether aripiprazole is contributing to or exacerbating anxiety:

• Aripiprazole can cause akathisia in approximately 18% of patients with bipolar disorder, which manifests as severe restlessness and anxiety 4
• The combination of aripiprazole with mood stabilizers (like valproate) may worsen akathisia and anxiety symptoms 4
• If akathisia is present, discontinue aripiprazole immediately as it can lead to increased anxiety and suicidal ideation 4
• If aripiprazole is continued, use the lowest effective dose and monitor closely for akathisia development 4

Step 3: Reassess After 8 Weeks

Schedule monthly follow-up until symptoms subside:

• Assess compliance with SSRI treatment, patient concerns about side effects, and satisfaction with symptom relief 1
• After 8 weeks of treatment, if symptom reduction is poor despite good compliance, alter the treatment course by adding psychological intervention or changing the specific medication 1
• Consider tapering antidepressant medications only if anxiety symptoms are under control and primary environmental sources of anxiety are no longer present 1

Non-Pharmacologic Interventions (Essential Adjunct)

Refer for cognitive-behavioral therapy (CBT) as first-line treatment:

• CBT has efficacy comparable to or superior to pharmacotherapy for moderate anxiety symptoms 2, 3
• All trials of CBT showed significant effects on anxiety in patients with comorbid depression and anxiety 1
• Structured CBT should include cognitive change, behavioral activation, biobehavioral strategies, education, and relaxation strategies 1

Provide psychoeducation and supportive care:

• Education on stress reduction strategies (progressive muscle relaxation) 1
• Information on sleep hygiene and self-management of fatigue 1
• Information about signs and symptoms of anxiety disorders and their treatment 1

Common Pitfalls to Avoid

Do not use PRN benzodiazepines or clonidine for chronic anxiety management:

• Guidelines specifically caution against benzodiazepines due to abuse potential, dependence, and cognitive impairment 3
• These should only be used for time-limited periods during acute agitation 1

Do not assume aripiprazole will treat anxiety:

• Despite some retrospective case series suggesting aripiprazole augmentation may help treatment-resistant anxiety 5, 6, these are low-quality studies
• Controlled trials show aripiprazole does not prevent depressive relapse in bipolar disorder and may worsen anxiety through akathisia 4, 7
• A randomized controlled trial found no benefit of adjunctive aripiprazole for bipolar depression compared to placebo 8

Monitor for treatment non-compliance:

• Patients with anxiety commonly avoid threatening stimuli and may not follow through on referrals or treatment recommendations 1
• Assess and construct a plan to circumvent obstacles to compliance, or discuss alternative interventions that present fewer obstacles 1

Specific Monitoring Parameters

Establish a structured follow-up schedule:

• Reassess in 2-4 weeks after initiating SSRI to evaluate early treatment response using GAD-7 and PHQ-9 3
• Monthly assessment until symptoms subside, including compliance monitoring and adverse effect assessment 3
• Document functional impairment in work, social interactions, and activities of daily living at each visit 2