EBM Consult

Carbamazepine (Carbatrol; Equetro; Tegretol) and Quetiapine (Seroquel) Drug Interaction

Summary:

  • Carbamazepine (Carbatrol; Equetro; Tegretol) is an anticonvulsant historically known for its use in the treatment of epilepsy, but it is also commonly used as a mood stabilizer for the treatment of bipolar disorder and pain associated with trigeminal neuralgia.
  • Quetiapine (Seroquel) is a well-known atypical antipsychotic that is used in patients with a number of psychiatric conditions including: schizophrenia, bipolar disorder, ICU-associated delirium, and as adjunct in the treatment of major depressive disorder.
  • Unfortunately, carbamazepine is one of a few anticonvulsants known to cause clinically relevant drug-drug interactions, due to its ability to induce several of the cytochrome P450 (CYP) enzymes such as CYP1A2, 2B6, 2C9, 2C19, and 3A4.
  • This is relevant given that quetiapine's metabolism is predominately via CYP3A4 and a minor amount is via CYP2D6.  Pharmacokinetic studies have shown that carmazepine can reduce quetiapine's mean area under the curve (AUC) by 87%, Cmax by 80%, and increase the clearance overall by 7-fold.

Editor-in-Chief: Anthony J. Busti, MD, PharmD, FNLA, FAHA
Last Reviewed:
August 2015

Explanation

  • Carbamazepine (Carbatrol; Equetro; Tegretol) is an anticonvulsant historically known for its use in the treatment of epilepsy, but it is also commonly used as a mood stabilizer for the treatment of bipolar disorder and pain associated with trigeminal neuralgia.  Quetiapine (Seroquel) is a well-known atypical antipsychotic that is used in patients with a number of psychiatric conditions including: schizophrenia, bipolar disorder, ICU-associated delirium, and as adjunct in the treatment of major depressive disorder.  Unfortunately, carbamazepine is one of a few anticonvulsants known to cause clinically relevant drug-drug interactions, due to its ability to induce several of the cytochrome P450 (CYP) enzymes such as CYP1A2, 2B6, 2C9, 2C19, and 3A4.  Therefore, any medication known to be a major substrate of any of these CYP enzymes may experience lower concentrations in the body if carbamazepine is being initiated or coadministered. 

     

    This is relevant given that quetiapine's metabolism is predominately via CYP3A4 and a minor amount is via CYP2D6.1  As such anything that induces the activity of CYP3A4, can increase the metabolism of quetiapine to its main metabolites (Sulfoxide-quetiapine, O-desalkyl-quetiapine, N-desalkyl-quetiapine). Based on the inductive properties of carbamazepine on CYP3A4 as well as other enzymes, this explains part of the reason for the drug-drug interaction associated with quetiapine. 

    Pharmacokinetic studies have shown that carbamazepine can reduce quetiapine's mean area under the curve (AUC) by 87%, Cmax by 80%, and increase the clearance overall by 7-fold.  As such, it is plausible that the plasma concentrations or total quetiapine exposure will be lowered to the extent that there is a possibility for a reduced efficacy of quetiapine.  Therefore, patients on stable doses of quetiapine who begin treatment with carbamazepine (regardless of the indication) should be monitored for changes in the psychiatric condition for which quetiapine is being used to manage.

    References:

    1. Grimm SW, Richtand NM, Winter HR et al.  effects of cytochrome P450 3A modulators ketoconazole and carbamazepine on quetiapine pharmacokinetics.  Br J Clin Pharmacol  2006;61:58-69.

MESH Terms & Keywords

  • Carbamazepine (Tegretol) and Quetiapine (Seroquel) Drug Interaction