Is Abilify (aripiprazole) effective for treating anxiety and depression?

Abilify (Aripiprazole) for Anxiety and Depression

Abilify (aripiprazole) is not FDA-approved as a first-line treatment for anxiety or depression, but it can be effective as an augmentation strategy for patients with depression who have had an inadequate response to antidepressants. 1

Mechanism and Indications

Aripiprazole is an atypical antipsychotic that works as a partial agonist at dopamine D2/D3 and serotonin 5-HT1A receptors, and as an antagonist at 5-HT2A receptors. While primarily approved for schizophrenia and bipolar disorder, its use in depression is as an adjunctive (add-on) therapy.

Evidence for Depression

• As First-Line Treatment: Not recommended. The American College of Physicians recommends selecting second-generation antidepressants (SSRIs, SNRIs) as first-line pharmacologic therapy for major depression 2
• As Augmentation Therapy: Aripiprazole has demonstrated efficacy as an adjunctive treatment for patients with major depressive disorder who have had an inadequate response to antidepressant therapy 3
• Core Depression Symptoms: Studies show aripiprazole augmentation significantly improves core symptoms of depression including depressed mood, work and activities, guilt, and psychic anxiety compared to placebo 4

Evidence for Anxiety

• As First-Line Treatment: Not recommended. SSRIs and SNRIs remain the first-line pharmacological treatments for anxiety disorders 5
• As Augmentation Therapy: Open-label studies suggest aripiprazole may be effective as augmentation for patients with persistent anxiety symptoms despite SSRI treatment 6, 7
• Response Rate: In one retrospective study, 59% of patients with treatment-resistant depression and anxiety showed significant improvement when aripiprazole was added to their SSRI regimen 6

Dosing for Augmentation

• Starting dose: 2-5 mg/day
• Typical effective dose range: 5-15 mg/day
• Maximum dose: 15-30 mg/day
• Response may be seen as early as 1-5 weeks after initiation 6

Side Effects and Monitoring

• Common side effects: Akathisia (restlessness), insomnia, headache, nausea, weight gain
• Serious concerns: Increased risk for suicidal thinking and behavior, especially early in treatment or with dose adjustments 1
• Behavioral changes: Monitor for emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, and other unusual changes in behavior 1
• Compulsive behaviors: Patients should be monitored for pathological gambling, compulsive shopping, sexual urges, and binge eating 1

Treatment Algorithm

1. First-line treatment for depression/anxiety: Start with an SSRI (e.g., sertraline, escitalopram) or SNRI (e.g., venlafaxine, duloxetine)
2. Evaluate response: After 6-8 weeks at an adequate dose 2
3. If inadequate response:
   • Consider switching to another antidepressant
   • OR add aripiprazole as augmentation therapy
4. When adding aripiprazole:
   • Start at 2-5 mg daily
   • Titrate based on response and tolerability
   • Monitor closely for akathisia and other side effects
   • Assess response after 4-6 weeks

Cautions and Contraindications

• Aripiprazole carries a boxed warning regarding increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults 1
• Not recommended as monotherapy for depression 1
• Use with caution in patients with bipolar disorder as antidepressants may trigger manic episodes 5
• Monitor for extrapyramidal symptoms, particularly akathisia, which occurs more frequently than in schizophrenia treatment 3

Bottom Line

While aripiprazole is not a first-line treatment for either depression or anxiety, it has demonstrated efficacy as an augmentation strategy for patients who have had an inadequate response to standard antidepressant therapy. The decision to use aripiprazole should be based on careful consideration of potential benefits versus risks, with close monitoring for side effects.