What is the recommended dose of Abilify (aripiprazole) for treating anhedonia and depression?

Aripiprazole Dosing for Anhedonia and Depression

For anhedonia and depression, start aripiprazole at 2-5 mg/day as adjunctive therapy to an antidepressant, with a typical effective range of 2-15 mg/day. 1

Primary Evidence for Depression and Anhedonia

The strongest evidence supports aripiprazole as augmentation therapy rather than monotherapy for depression:

• Aripiprazole 2-15 mg/day was efficacious and well tolerated as adjunctive therapy to antidepressants in patients who had not responded to antidepressant monotherapy in two identical placebo-controlled trials. 1

• The mechanism likely involves potent partial agonism of dopamine D2/D3 receptors, partial agonism of 5-HT1A receptors, and antagonism of 5-HT2A receptors, which may specifically address anhedonic symptoms. 1

Dosing Algorithm

Starting dose:

• Begin with 2-5 mg once daily when augmenting an existing antidepressant. 1
• No titration is necessary as the drug is effective within the first few weeks of treatment. 2

Maintenance dosing:

• The effective range is 2-15 mg/day for depression and anhedonia. 1
• For bipolar depression specifically, 5-15 mg once daily has demonstrated marked improvements in depressive symptoms including anhedonia. 3

Timing considerations:

• Steady-state plasma concentrations are achieved by 14 days due to the long elimination half-life of approximately 75 hours. 2
• Clinical response typically occurs within 6 weeks, with sustained benefits maintained up to 2 years. 3

Special Population Adjustments

Older patients and hepatic impairment:

• Use lower starting doses in older patients and those with hepatic impairment. 4, 5
• Consider starting at 5 mg daily in these populations. 4

CYP450 considerations:

• Reduce dose by 50% when coadministered with CYP3A4 or CYP2D6 inhibitors. 4, 2
• Double the dose when coadministered with CYP3A4 inducers. 2
• Use lower doses in poor metabolizers of CYP2D6. 4

Clinical Context and Caveats

Important considerations:

• Aripiprazole is FDA-approved as adjunctive therapy for major depressive disorder, making it the first atypical antipsychotic with this indication. 1
• The anti-anhedonic effects appear to be specific rather than pseudospecific (not simply due to overall mood improvement). 6
• In bipolar depression, all patients achieved complete functional recovery by 6 months to 1 year on aripiprazole 5-15 mg/day as adjunct therapy. 3

Tolerability profile:

• The drug has a placebo-level incidence of extrapyramidal symptoms at recommended doses. 2
• Low propensity for weight gain, hyperprolactinemia, and QT prolongation compared to other atypical antipsychotics. 2
• Most common adverse events include insomnia, anxiety, headache, and agitation, which typically decrease during continued therapy. 2, 3

Monitoring:

• Assess response by 6 weeks; if inadequate, consider dose adjustment within the 2-15 mg/day range. 1, 3
• Avoid exceeding 15 mg/day for depression/anhedonia as no additional therapeutic benefit is observed at higher doses. 2