What Medications Should Not Be Taken With Abilify? Understanding Drug Interactions

October 11, 2025 •

3 min read

According to the National Alliance on Mental Illness (NAMI), aripiprazole (the active ingredient in Abilify) is primarily metabolized by the liver's CYP2D6 and CYP3A4 enzymes, making it highly susceptible to interactions with other drugs that affect these enzyme systems. Understanding what medications should not be taken with Abilify? is crucial for preventing dangerous side effects and ensuring the drug's effectiveness.

Quick Summary

This guide outlines the critical drug-drug and substance interactions involving Abilify, detailing how certain medications can either raise or lower its concentration in the body or produce additive side effects. Learn about the risks posed by antidepressants, antifungal agents, sedatives, and other substances to maintain patient safety while on Abilify therapy.

Key Points

Enzyme Metabolism: Abilify is processed by CYP3A4 and CYP2D6 liver enzymes, which means many other drugs can interfere with its metabolism.
Medication Levels: Inhibitors of these enzymes (e.g., antifungals, some antidepressants) can increase Abilify levels, while inducers (e.g., anticonvulsants, St. John's Wort) can decrease them.
Additive Sedation: Combining Abilify with CNS depressants like benzodiazepines, opioids, or alcohol can intensify drowsiness, dizziness, and low blood pressure.
Cardiovascular Risks: Taking Abilify with blood pressure medications can increase the risk of orthostatic hypotension, and with certain heart drugs, it can raise the risk of abnormal heart rhythms.
Serotonin Syndrome: Using Abilify with other serotonergic medications requires caution due to the risk of a potentially severe condition called serotonin syndrome.
Grapefruit Caution: Consuming grapefruit or its juice should be avoided while on Abilify, as it can increase the drug's concentration in the body.
Crucial Communication: Patients should inform their healthcare providers about all medications, supplements, and substances they use to safely manage Abilify therapy.

The Mechanisms Behind Abilify Interactions

The human body uses a complex network of enzymes, primarily in the liver, to break down and eliminate medications. The cytochrome P450 (CYP450) enzyme system is a critical component of this process. Abilify (aripiprazole) is metabolized by two specific enzymes within this system: CYP3A4 and CYP2D6. Interactions occur when other drugs either inhibit (slow down) or induce (speed up) the activity of these enzymes, leading to potentially dangerous fluctuations in Abilify's concentration in the bloodstream. Inhibition can cause Abilify levels to rise too high, increasing the risk of side effects, while induction can cause levels to drop too low, reducing its therapeutic effectiveness.

Medications That Increase Abilify Levels

Taking Abilify with certain medications that inhibit the CYP2D6 and CYP3A4 enzymes can significantly increase the level of aripiprazole in the body, raising the risk of side effects like drowsiness, low blood pressure, or movement disorders. Strong inhibitors to be aware of include certain antifungal medications like itraconazole and ketoconazole, antibiotics such as clarithromycin, antidepressants including fluoxetine and paroxetine, the heart medication quinidine, and HIV medications like ritonavir. Additionally, consuming grapefruit and grapefruit juice can inhibit CYP3A4 and increase Abilify levels.

Medications That Decrease Abilify Levels

Conversely, medications that induce the CYP3A4 enzyme can accelerate Abilify's metabolism, causing its levels to fall and making it less effective. Potent inducers include seizure medications like carbamazepine and phenytoin, the antibiotic rifampin, and the herbal supplement St. John's Wort.

Additive Side Effect Risks

Some medications can increase specific side effects when taken with Abilify, even without affecting its metabolism. This can lead to increased sedation, low blood pressure, or other complications. Combining Abilify with benzodiazepines (e.g., lorazepam, alprazolam) can intensify sedative and blood pressure-lowering effects. Taking Abilify with blood pressure medications can increase the risk of orthostatic hypotension. Opioid pain relievers (e.g., morphine, tramadol) can increase sedative effects, and other CNS depressants like alcohol and certain antihistamines can amplify drowsiness and impair judgment. Combining Abilify with other serotonergic drugs can increase the risk of serotonin syndrome.

Comparison of Major Abilify Interactions


Interacting Drug Class	Example Drugs	Mechanism of Interaction	Potential Consequence	Action
CYP3A4 Inhibitors	Itraconazole, Clarithromycin, Grapefruit juice	Decreased Abilify metabolism; enzyme inhibition.	Increased Abilify levels, higher risk of side effects.	Avoid or require dose adjustment of Abilify.
CYP3A4 Inducers	Carbamazepine, Rifampin, St. John's Wort	Increased Abilify metabolism; enzyme induction.	Decreased Abilify levels, reduced effectiveness.	Avoid or require dose adjustment of Abilify.
CYP2D6 Inhibitors	Fluoxetine, Paroxetine, Quinidine	Decreased Abilify metabolism; enzyme inhibition.	Increased Abilify levels, higher risk of side effects.	Avoid or require dose adjustment of Abilify.
Benzodiazepines	Lorazepam, Diazepam	Additive CNS depressant effects.	Increased sedation, dizziness, low blood pressure.	Require close monitoring and potential dose reduction.
Blood Pressure Meds	Prazosin, Lisinopril, Metoprolol	Additive blood pressure-lowering effects.	Increased risk of orthostatic hypotension.	Require careful monitoring of blood pressure.
Alcohol	Ethanol	Additive CNS depressant effects.	Increased drowsiness, impaired judgment, mood instability.	Avoid consumption.

What to Discuss with Your Healthcare Provider

To ensure your safety while taking Abilify, discuss your complete medical history and all substances you use with your doctor or pharmacist. This includes prescription and over-the-counter medications, herbal supplements, vitamins, and recreational substances. Your healthcare provider can assess your risk for interactions and make necessary adjustments. Never stop taking any medication abruptly without consulting a professional.

Conclusion

Understanding potential interactions with Abilify is crucial for patient safety and effective treatment. Many substances can affect Abilify's levels or increase side effects. Always consult a medical professional before starting or stopping any medication to manage these risks safely. Open communication with your healthcare provider is the best way to prevent harmful drug interactions.

Frequently Asked Questions

Abilify is often taken with antidepressants, but some combinations can increase side effects or raise the risk of serotonin syndrome. Your doctor will carefully monitor you and may adjust the dosage of one or both medications to minimize risks.

You should generally avoid alcohol while taking Abilify. The combination can intensify nervous system side effects like dizziness, drowsiness, and impaired judgment.

Yes, grapefruit and grapefruit juice should be avoided. Grapefruit can inhibit the CYP3A4 enzyme, leading to higher levels of Abilify in your body and an increased risk of side effects.

Even non-prescription products can interact with Abilify. For instance, St. John's Wort can reduce Abilify's effectiveness. Always inform your doctor or pharmacist about any over-the-counter medication or supplement you take.

Combining Abilify with benzodiazepines, such as Ativan or Xanax, can increase sedation and lower your blood pressure. This can cause excessive drowsiness and increase the risk of falls.

Certain heart medications, particularly for blood pressure or rhythm, can interact with Abilify. Blood pressure medications may have an additive blood pressure-lowering effect, and heart rhythm drugs like quinidine can increase Abilify's levels.

Yes, some medications, particularly seizure drugs like carbamazepine and rifampin, can speed up Abilify's metabolism via the CYP3A4 enzyme, causing its levels to drop and making it less effective.