Can Aripiprazole (Abilify) help with anxiety?

Can Aripiprazole (Abilify) Help with Anxiety?

Aripiprazole is not a first-line treatment for primary anxiety disorders and lacks FDA approval for this indication, but it may serve as an augmentation strategy when SSRIs or SNRIs fail to adequately control anxiety symptoms. 1

FDA-Approved Indications and Anxiety

• Aripiprazole has no FDA approval for treating anxiety disorders as a primary indication 1
• The FDA label explicitly warns that aripiprazole can cause anxiety as an adverse effect (17% incidence in clinical trials vs. 13% with placebo) 1
• Patients and caregivers should be counseled about the emergence of anxiety, agitation, panic attacks, and restlessness, particularly early in treatment 1

First-Line Treatment Recommendations

• SSRIs (escitalopram, sertraline, paroxetine, fluoxetine) and SNRIs (venlafaxine, duloxetine) are the established first-line pharmacologic treatments for anxiety disorders including generalized anxiety disorder, social anxiety disorder, panic disorder, and separation anxiety disorder 2, 3
• Cognitive-behavioral therapy, particularly exposure therapy, should be considered alongside or before pharmacotherapy 3
• For cancer-related anxiety, psychotherapy with or without anxiolytics or antidepressants is recommended as first-line treatment 2

Role as Augmentation Strategy

When first-line treatments fail, aripiprazole may be considered as augmentation therapy, though evidence quality is limited:

Supporting Evidence for Augmentation:

• Open-label studies suggest aripiprazole (15-30 mg/day) augmentation of SSRIs resulted in 59% of treatment-resistant depression and anxiety patients achieving "much improved" or "very much improved" status by 12 weeks 4
• A prospective 8-week study in generalized anxiety disorder and panic disorder patients showed significant reduction in symptom severity when aripiprazole was added to existing pharmacotherapy 5
• Eighty percent of patients with persistent anxiety symptoms on SSRIs showed >50% symptom reduction by week 2 when aripiprazole was added 6

Limitations of Augmentation Evidence:

• All supporting studies are open-label, uncontrolled, or retrospective with small sample sizes 4, 5, 6
• A randomized controlled trial in treatment-resistant depression found aripiprazole improved depression subscale scores but did not significantly improve anxiety subscale scores compared to placebo 7
• The low doses used (2-5 mg/day) in controlled trials may have been insufficient to impact anxiety symptoms 7

Clinical Algorithm for Use

If considering aripiprazole for anxiety:

1. Ensure adequate trials of first-line agents first: Minimum 8-12 weeks of therapeutic-dose SSRI or SNRI 4, 5
2. Consider alternative augmentation strategies with stronger evidence: For depression with anxiety, bupropion or cognitive therapy augmentation have similar efficacy profiles in controlled trials 2
3. If proceeding with aripiprazole augmentation: Start at 2-5 mg/day and titrate to 15-30 mg/day based on response and tolerability 4, 6
4. Monitor closely for worsening anxiety: 13-17% of patients experience treatment-emergent anxiety or restlessness 1, 5

Critical Safety Considerations

• Discontinuation rates due to adverse effects: 13% in anxiety augmentation studies, primarily due to sedation, chest discomfort, and restlessness 5
• Common adverse effects include akathisia (10%), sedation (7-16% in pediatrics), somnolence, and extrapyramidal symptoms 1
• Weight gain and metabolic effects are concerns with longer-term use 1
• Aripiprazole carries a boxed warning for increased suicidal thinking in young adults (though studied primarily in depression) 1

Bottom Line

Reserve aripiprazole for treatment-resistant anxiety cases where multiple first-line agents have failed, recognizing that controlled trial evidence for anxiety-specific benefits is lacking and the medication may paradoxically worsen anxiety in some patients. 1, 4, 7 The strongest evidence supports its use as augmentation in depression with comorbid anxiety rather than primary anxiety disorders.