Can Abilify (aripiprazole) be used to treat anxiety and depression?

Aripiprazole (Abilify) for Anxiety and Depression

Aripiprazole is FDA-approved as adjunctive (add-on) therapy for major depressive disorder when combined with an antidepressant, but it is NOT approved as monotherapy for depression or for any primary anxiety disorder. 1

FDA-Approved Indication

Use aripiprazole only as augmentation therapy when a patient has failed to respond adequately to standard antidepressant treatment (SSRIs or SNRIs), not as a first-line agent. 1 The FDA label specifically states that aripiprazole "is not approved as a single agent for treatment of depression." 1

When to Consider Aripiprazole Augmentation

Start with first-line SSRI therapy (sertraline, escitalopram, or fluoxetine) for patients with depression and anxiety, allowing 6-8 weeks for adequate trial at therapeutic doses. 2 If patients show inadequate response after this period despite good adherence, consider the following sequence:

• First option: Switch to another SSRI or SNRI (venlafaxine may have better response rates for depression with prominent anxiety). 2
• Second option: Add cognitive behavioral therapy to ongoing pharmacotherapy. 2
• Third option: Consider aripiprazole augmentation if the above strategies fail. 3, 4

Evidence for Efficacy in Residual Symptoms

When used as augmentation, aripiprazole demonstrates significant benefit for both depressive and anxiety symptoms:

• Core depression symptoms: Aripiprazole augmentation produces significant improvement in depressed mood, loss of interest/activities, guilt, and psychic anxiety compared to placebo (all p<0.01). 5
• Anxious depression subtype: Patients with anxious features (Hamilton anxiety/somatization factor score ≥7) showed significantly greater MADRS improvement with aripiprazole augmentation (-8.72) versus placebo (-6.17, p≤0.001). 6
• Residual anxiety symptoms: In open-label studies, 80% of patients with persistent anxiety despite SSRI treatment showed >50% symptom reduction by week 2 of aripiprazole augmentation. 3
• Response rates: 59% of treatment-resistant patients achieved "much improved" or "very much improved" status with aripiprazole augmentation at doses of 15-30 mg/day. 4

Practical Dosing Strategy

When augmenting with aripiprazole for treatment-resistant depression with anxiety:

• Start with 2-5 mg/day initially to assess tolerability. 7
• Titrate to 15-30 mg/day based on response and tolerability, as this range showed optimal efficacy in clinical studies. 4
• Assess response as early as week 1-2, as some patients show rapid improvement. 4, 6
• Continue for at least 6 weeks to evaluate full therapeutic benefit. 5, 6

Critical Safety Monitoring

Monitor closely for treatment-emergent suicidality, particularly in the first 1-2 weeks after initiation or dose changes, as aripiprazole carries an FDA black box warning for this risk. 1 Patients and families should be instructed to watch for emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, or worsening depression. 1

Common adverse effects include:

• Akathisia (restlessness): Most common reason for discontinuation; occurs in approximately 10% of patients versus 4% with placebo. 1
• Weight gain: Monitor weight regularly, though reporting rates did not differ significantly between anxious and non-anxious subgroups. 6
• Sedation/somnolence: Occurs in 5-16% depending on population (higher in pediatric patients). 1
• Extrapyramidal symptoms: Including tremor and muscle stiffness. 1

Common Pitfalls to Avoid

Do not use aripiprazole as monotherapy for depression or anxiety disorders—it must be combined with an ongoing antidepressant. 1 The FDA label explicitly states it is not approved as a single agent for depression treatment.

Do not prescribe aripiprazole before ensuring an adequate trial of first-line SSRI therapy (6-8 weeks at therapeutic doses). 2 Approximately 38% of patients don't respond to initial SSRI treatment, but switching to another SSRI or adding CBT should be attempted before atypical antipsychotic augmentation. 2

Avoid using aripiprazole for primary anxiety disorders without comorbid depression, as it lacks FDA approval for generalized anxiety disorder, panic disorder, social anxiety disorder, or PTSD. 1 SSRIs remain the first-line pharmacologic treatment for these conditions. 2

Do not overlook the need for cognitive behavioral therapy, which remains a first-line treatment for both depression and anxiety and should be offered alongside or before pharmacotherapy when feasible. 2

Alternative Augmentation Strategies

If aripiprazole is not tolerated or contraindicated, consider:

• Switching to a different SSRI (one in four patients becomes symptom-free after switching). 2
• Adding mirtazapine, which has faster onset than SSRIs though response rates equalize after 4 weeks. 2
• Combining SSRI with cognitive behavioral therapy, which addresses both depression and comorbid anxiety symptoms. 2