Can I add Abilify (aripiprazole) to my treatment regimen?

Can I Add Abilify (Aripiprazole)?

Yes, adding Abilify (aripiprazole) is a well-established augmentation strategy, particularly for treatment-resistant depression or schizophrenia with persistent symptoms, and is recommended as a first-line augmentation option by major guidelines. 1

Primary Indication for Adding Aripiprazole

For Depression Augmentation:

• The American College of Physicians recommends aripiprazole as the most preferred augmentation strategy for patients with partial response to an antidepressant, over switching medications or augmenting with brexpiprazole. 1
• Aripiprazole augmentation should be considered after inadequate response to at least one antidepressant treatment at adequate dose for at least 4 weeks. 1
• Aripiprazole has demonstrated significant efficacy as an augmentation strategy, doubling remission rates compared to placebo, with efficacy and tolerability at low doses (mean dose of 6.9 mg/day). 1

For Schizophrenia:

• If positive symptoms persist despite adequate antipsychotic monotherapy, aripiprazole augmentation can be considered, particularly for clozapine-treated patients with ongoing positive symptoms. 2
• For persistent negative symptoms in schizophrenia where positive symptoms are well controlled, switching to aripiprazole or adding it as augmentation may be beneficial. 2
• Aripiprazole augmentation may also help reduce negative symptoms when added to existing antipsychotic therapy. 2

Dosing Strategy

Initiation:

• For depression augmentation, start with low doses (mean effective dose 6.9 mg/day). 1
• For schizophrenia, aripiprazole 10 or 15 mg once daily is effective and well tolerated. 3
• Dosage titration is not necessary, and the drug is effective in the first few weeks of treatment. 3
• Steady-state plasma concentrations are achieved by 14 days. 3

Critical Monitoring Requirements

Before Starting:

• Obtain BMI, waist circumference, blood pressure, HbA1c, glucose, lipids, prolactin, liver function tests, urea and electrolytes, full blood count, and electrocardiogram. 2

During Treatment:

• Check fasting glucose at 4 weeks following initiation. 2
• Monitor BMI, waist circumference, and blood pressure weekly for 6 weeks. 2
• Repeat all baseline measures at 3 months and annually thereafter. 2
• Weight should be monitored regularly; if weight loss occurs (>5% from baseline), discontinuation should be considered. 2

Important Safety Considerations

Depression Risk:

• Aripiprazole may be associated with the emergence or worsening of depression. 2
• Discuss the risk of depression with patients in advance of therapy. 2
• Appropriate discussion and patient counseling are recommended before therapy initiation to prevent worsening of pre-existing depression or suicidality. 2

Common Adverse Effects:

• The most common adverse events include insomnia, anxiety, headache, and agitation. 3
• Extrapyramidal symptoms (EPS) occur in up to 28% of recipients, though aripiprazole is associated with a placebo-level incidence of EPS-related adverse events. 3, 4
• Akathisia may occur; the Barnes Akathisia Scale showed slight differences from placebo in some trials. 5

Metabolic Profile:

• Aripiprazole has a low propensity to cause clinically significant bodyweight gain, hyperprolactinaemia, or corrected QT interval prolongation. 3
• However, more patients receiving aripiprazole monotherapy than placebo had clinically significant bodyweight gain during 100 weeks' treatment. 4
• Decreases of 5% to 10% in body weight occurred in 12% of patients treated with aripiprazole compared with 5% treated with placebo. 2

Drug Interactions

Critical Interactions:

• Use with strong inducers of cytochrome P450 (rifampin, phenobarbital, carbamazepine, phenytoin) may result in decreased efficacy and is not recommended. 2
• Dosage adjustment of aripiprazole is necessary when coadministered with CYP3A4 and CYP2D6 inhibitors (aripiprazole concentration increases) and with inducers of CYP3A4 (aripiprazole concentration decreases). 3

Special Populations

Renal Impairment:

• Aripiprazole should be reduced to 30 mg once daily in patients with severe renal impairment (creatinine clearance <30 mL/min). 2

Elderly Patients:

• No dosage adjustment is recommended for elderly patients. 5
• Patients prone to dehydration (the elderly) should be aware that gastrointestinal adverse effects may be more severe and could result in hospitalization. 2

Pregnancy and Lactation:

• Pregnancy should only be used if benefit justifies potential risk to fetus. 2
• Limited data report presence of aripiprazole in human breast milk; there are reports of poor weight gain in breastfed infants and inadequate milk supply in lactating women. 5

When NOT to Add Aripiprazole

Consider Clozapine First:

• For patients with refractory schizophrenia who have failed two antipsychotics (including one atypical), clozapine should be considered before aripiprazole. 6

Anticholinergic Burden:

• Review the anticholinergic burden of the patient's medication regimen before adding aripiprazole, as minimizing this burden is important for cognitive symptoms. 2