Carbamazepine Aripiprazole

Pharmacotherapy is the cornerstone of acute and maintenance treatment of bipolar disorder. Mood-stabilizing drugs are the usual first-choice treatments and include lithium, divalproex, carbamazepine, and lamotrigine. Atypical antipsychotics other than clozapine are also approved for treatment of acute mania. Lithium, lamotrigine, olanzapine, and aripiprazole are approved for maintenance therapy. Drugs used with less research support and without Food and Drug Administration (FDA) approval include topiramate and oxcarbazepine. Benzodiazepines are used adjunctively for mania. 

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. 

Among these choices, bnspirone is preferred if the patient is also experiencing anxiety. If the patient is depressed and agitated, a SSRI should be tried first. Second line choices inclnde carbamazepine (Tegretol) or one of the atypical antipsychot-ics—ziprasidone (Geodon), risperidone (Risperdal), olanzapine (Zyprexa), quetiap-ine (Seroquel), or aripiprazole (Abilify) can be tried. If psychotic symptoms are present, one of the atypical antipsychotics should be tried first. 

Concomitant use with potential CYP3A4 inducers - When a potential CYP3A4 inducer such as carbamazepine is added to aripiprazole therapy, double the... 

Drugs that may be affected by itraconazole include alfentanil, almotriptan, alprazolam, amphotericin B, aripiprazole, benzodiazepines, buspirone, busulfan, calcium blockers, carbamazepine, cilostazol, cisapride, corticosteroids, cyclosporine, digoxin, disopyramide, docetaxel, dofetilide, eletriptan, epierenone, ergot alkaloids, haloperidol, HMG-CoA reductase inhibitors, hydantoins (phenytoin), hypoglycemic agents, oral midazolam, phosphodiesterase type 5 inhibitors, pimozide, polyenes, protease inhibitors, quinidine, rifamycins, sirolimus, tacrolimus, tolterodine, triazolam, trimetrexate, vinca alkaloids, warfarin, and zolpidem. 

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. 

Modest elevations of aripiprazole serum concentration occur in the presence of ketoconazole or quinidine, which inhibit CYP 2D6 and 3A4, respectively. Carbamazepine has been reported to decrease aripiprazole serum concentrations. ... 

Carbamazepinewasfound to decrease the plasma levels of phenothiazines by as much as 50% (described with chlorpromazine, perphenazine, and fluphenazine). It has been reported to decrease the serum levels of clozapine by about60-85% due to its hepatic cytochrome P450 (CYP) enzyme-inducing properties. Loxapine may induce carbamazepine metabolism. Carbamazepine has been shown to reduce the plasma levels of risperidone by as much as 50%, while it increases olanzapine clearance by 44% and reduces its half-life by 20%. Carbamazepine increases aripiprazole metabolism through CYP3A4 induction. Thus, the aripiprazoie dose should be doubled. 

Thus, valproate is often used to reduce the risk for clozapine-induced seizures. Carbamazepine can potentially increase the risk for development of agranulocytosis when coadministered with clozapine, so this combination should be avoided. Carbamazepine increases renal clearance of olanzapine by about 45% and reduces its half-life by about 20%. To date, no pharmacokinetic interactions have been reported between aripiprazole and valproate. 

The manufacturers report that carbamazepine reduced the mean maximum plasma concentration and AUC of aripiprazole 30 mg by 68% and 73%, respectively. They recommend that the dose of aripiprazole is doubled when taken with carbamazepine. Other potent inducers of CYP3A4, such as efavirenz, nevirapine, phenytoin, phenobarbital, primidone, rifabutin, rifampicin and St John s wort are expected to have similar effects and an increase in the dose of aripiprazole may also be necessary if these drugs are given. ... 

Nakamura A, Mihara K, Nagai G, Suzuki T, Kondo T. Pharmacokinetic and pharmacodynamic interactions between carbamazepine and aripiprazole in... 

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