Fluoxetine Aripiprazole

Conventional antipsychotic drugs such as chlorpromazine and haloperidol have long been used in the treatment of acute mania. More recently, atypical antipsychotic drugs including aripiprazole, olanzapine, quetiapine, risperidone, and ziprasi-done have been approved for the treatment of bipolar mania or mixed mood episodes as monotherapy or in combination with mood-stabilizing drugs.25 Aripiprazole and olanzapine are also approved for maintenance therapy. The combination of olanzapine and fluoxetine is approved for treatment of bipolar depression. Quetiapine is approved for treatment of... 

Risperidone Aripiprazole 2D6 > 3A4 2D6, 3A4 Carbamazepine and phenytoin topiramate hypericum (St. John s Wort). Paroxetine, fluoxetine, sertraline (high dose) grapefruit juice 2D6 or 3A4 substrates acting as competitive inhibitors. 

Concomitant use with potential CYP2D6 inhibitors - During coadministration of potential CYP2D6 inhibitors such as quinidine, fluoxetine, or paroxetine with aripiprazole, reduce the aripiprazole dose to at least one-half of its normal dose. 

Aripiprazole is hepatically metabolized, mainly by two cytochrome P450 enzymes CYP 2D6 and CYP 3A4. Therefore, dosage adjustments are necessary when this medication is given with other medications that either inhibit or induce these enzymes. For example, the dose of aripiprazole should be halved when this medication is given with ketoconazole, a CYP 3A4 inhibitor, or at least decreased when given with fluoxetine, a CYP 2D6 inhibitor. When aripiprazole is given with CYP 3A4 inducers such as carbamazepine, the dose should be doubled. 

Another group of mood-stabilizing drugs that are also anticonvulsant agents have become more widely used than lithium. These include carbamazepine and valproic acid for the treatment of acute mania and for prevention of its recurrence. Lamotrigine is approved for prevention of recurrence. Gabapentin, oxcarbazepine, and topiramate are sometimes used to treat bipolar disorder but are not approved by FDA for this indication. Aripiprazole, chlorpromazine, olanzapine, quetiapine, risperidone, and ziprasidone are approved by FDA for the treatment of manic phase of bipolar disorder. Olanzapine plus fluoxetine in combination and quetiapine are approved for the treatment of bipolar depression. 

Fluoxetine (Prozac) PHENOTHIAZINES Risperidone, Aripiprazole Clozapine, Quetiapine, Ziprasidone ... 

Fluoxetine and probably paroxetine may cause clinically significant increases in aripiprazole levels. The concurrent use of aripiprazole with SSRIs or venlafaxine has led to adverse effects such as the neuroleptic malignant syndrome and extrapyramidal symptoms. 

The manufacturers suggest that potent inhibitors of CYP2D6, such as fluoxetine and paroxetine would be expected to increase aripiprazole levels, and they recommend that the dose of aripiprazole should be halved if these drugs are given. The UK manufacturer suggests that weaker inhibitors of this isoenzyme (they name escitalopram) would only be expected to cause modest increases in aripiprazole levels, and therefore no dosage adjustment would expected to be required. ... 

The concurrent use of aripiprazole and SSRIs can be useful, but it is important to remember to adjust the dose if paroxetine or fluoxetine are started or stopped, and be aware that, rarely, adverse effects such as extrapyramidal symptoms and the neuroleptic malignant syndrome may develop. 

Duggal HS, Kithas J. Possible neuroleptic malignant syndrome with aripiprazole and fluoxetine./I (2005) 162, 397-8. 

Drug-drug interactions SSRIs Aripiprazole had no effects on the pharmacokinetics of escitalopram, fluoxetine, paroxetine, sertraline, or venlafaxine either in healthy subjects ( =63) or in patients with major depressive disorder ( =498) [69. Point estimates for mean plasma concentration ratios indicated no substantial effect of aripiprazole on any antidepressant escitalopram 0.97 (0.91-1.03), fluoxetine 1.18 (1.05-1.32), paroxetine 0.73 (0.60-0.89), sertraline 0.96 (0.89-1.04), or venlafaxine 0.97 (0.89-1.05). 

Metabolism A 6-month, retrospective chart review compared patients on aripiprazole alone to aripiprazole and an SSRI (citalopram, fluoxetine, paroxetine, sertraline, venlafaxine) or aripiprazole and bupropion [92 ]. Only the combination of aripiprazole and an SSRI had statistically significant weight gain, thus it was hypothesised that in the presence of high serotonergic activity, aripiprazole acts as an antagonist at the 5-HT2c receptor. 

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