Abilify in combination with fluoxetine

[sarek]

A friend of mine has recently had Abilify prescribed. She is on fluoxetine as well.
The doc noted there could be an interaction yet went ahead anyway.
She is also on Effexor though there do not seem to be known interactions with that.

So far signs of worsening depression and fatigue are the most obvious side effects. These effects started almost instantaneously.

Is this to be expected? What exactly is known about the mechanism of the interaction between these two meds?

[David Baxter]

Abilify and fluoxetine are not in the same family and will not necessarily interact in an adverse way, depending on the doses and diagnosis.

Abilify is in the family known as "atypical antipsychotics" while fuoxetine (Prozac) and Effexor are in the family of SSRI and SNRI medications.

Your friend may have been prescribed the Abilify for

1. schizoaffective disorder (like schizophrenia but with an added mood disorder),
2. bipolar disorder, or
3. in small doses as an adjunct to SSRI and SNRI medications to boost the antidepressant properties of those medications.

Given that two antidepressants are prescribed, my guess would be #2 or #3. With bipolar disorder, sometimes use of an SSRI like Prozac can induce mania or rapid cycling bipolar so that the patient needs to be monitored for this. That's probably what the pharmacist was referring to.

[TSOW]

What exactly is known about the mechanism of the interaction between these two meds?

The Medscape Drug Interaction Checker returned the following interaction warning. CYP P-450-2D6 refers to the cytochrome P-450 enzyme system in the liver and is the site of many drug/drug interactions where one medication delays the clearance of another, resulting in an accumulation of the unmetabolized drug in the bloodstream.

If you have concerns about this, the prescribing physician or pharmacist should be consulted.

Not only prescribed medications cause concern over this particular metabolic pathway, but numerous over the counter medications compete for this liver enzyme as well such as some cold and cough medications and stomach acid blockers like cimetidine (Tagamet) as well. In women, sometimes there can be effects on oral contraceptives as as a result of this drug/drug interaction.

Several postings discussion drug interactions and cytochrome P-450 can be seen in the "sticky" posts in the Psychlinks section on Medication Interactions

Effexor (venlafaxine) bypasses the liver, does not require nor interfere with cytochrome P-450 for metabolization, so this medication would not be implicated.

Moderate Interaction
ARIPIPRAZOLE/FLUOXETINE; PAROXETINE
Abilify Oral and Prozac Oral may interact based on the potential interaction between ARIPIPRAZOLE and FLUOXETINE; PAROXETINE.

Aripiprazole/Fluoxetine; Paroxetine
This information is generalized and not intended as specific medical advice. Consult your healthcare professional before taking or discontinuing any drug or commencing any course of treatment.

MONOGRAPH TITLE: Aripiprazole/Fluoxetine; Paroxetine

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Fluoxetine and paroxetine may inhibit the metabolism of aripiprazole by CYP P-450-2D6.(1)

CLINICAL EFFECTS: Concurrent administration of fluoxetine or paroxetine with aripiprazole may result in elevated levels of aripiprazole and signs of toxicity.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of aripiprazole states that the dose of aripiprazole should be reduced to one-half of its normal dose when fluoxetine or paroxetine are coadministered, unless aripiprazole is being administered as adjunctive therapy for Major Depressive Disorder. If fluoxetine or paroxetine therapy is discontinued, the dose of aripiprazole should be increased.(1)

DISCUSSION: The administration of quinidine (166 mg daily for 13 days) with a single dose of aripiprazole (10 mg) resulted in a 112% increase in the area-under-curve (AUC) of aripiprazole and a 35% decrease in the AUC of dehydro-aripiprazole, the active metabolite of aripiprazole. Fluoxetine and paroxetine, which are also potent inhibitors of CYP P-450-2D6, are expected to interact similarly.(1)

REFERENCE:
1.Abilify (aripiprazole) US prescribing information. Otsuka America Pharmaceutical, Inc. July, 2009.

[sarek]

Thank you for the information. This is most helpful. There was also mention of interaction with cold and cough meds. Are these the ones based on codeine or pseudoephedrine?