Can Abilify (Aripiprazole) Worsen Depression?
Yes, Abilify (aripiprazole) can potentially worsen depression in some patients, particularly during the early stages of treatment or with dosage adjustments. According to the FDA drug label, patients, families, and caregivers should be alert to the emergence of symptoms including worsening of depression, especially early during antidepressant treatment and when the dose is adjusted up or down 1.
Mechanism and Risk Factors
Aripiprazole works as a partial agonist at dopamine D2 and D3 receptors, which means it can:
- Act as a dopamine blocker in high-dopamine states
- Act as a dopamine stimulator in low-dopamine states
This unique mechanism explains why some patients may experience:
- Improvement in depression symptoms (as seen in augmentation studies)
- Worsening of depression in others (particularly those with certain neurochemical profiles)
Warning Signs to Monitor
The FDA drug label specifically warns about monitoring for 1:
- Anxiety
- Agitation
- Panic attacks
- Insomnia
- Irritability
- Hostility
- Aggressiveness
- Impulsivity
- Akathisia (psychomotor restlessness)
- Hypomania/mania
- Worsening of depression
- Suicidal ideation
These symptoms may be associated with an increased risk for suicidal thinking and behavior, particularly during:
- Early treatment initiation
- Dose adjustments (either increasing or decreasing)
Clinical Implications and Management
If depression worsens on aripiprazole:
Report symptoms promptly: Patients should report any worsening symptoms to their healthcare provider immediately, especially if severe or abrupt in onset 1.
Close monitoring: Healthcare providers should closely monitor patients, particularly during the first few weeks of treatment and with any dose changes 1.
Potential medication changes: Worsening depression may indicate a need for very close monitoring and possibly changes in medication 1.
Important context: Aripiprazole is not approved as a single agent for depression treatment but rather as an adjunctive therapy 1.
Evidence in Special Populations
While the primary evidence focuses on aripiprazole's potential to worsen depression, it's worth noting that in patients with psoriasis, depression was reported in approximately 1% of patients taking apremilast (a different medication) 2. This highlights the importance of monitoring mental health symptoms with various medications that may affect neurotransmitter systems.
Clinical Recommendation
For patients starting aripiprazole:
- Begin with low doses and titrate slowly
- Educate patients and families about warning signs of worsening depression
- Schedule more frequent follow-ups during the initial treatment period and dose adjustments
- Consider alternative treatments if depression symptoms worsen significantly
Remember that while aripiprazole can be an effective augmentation strategy for treatment-resistant depression in many patients, its unique pharmacological profile means that individual responses can vary significantly, and worsening depression is a recognized risk that requires vigilant monitoring.