Does carbamazepine (CBZ) induce or interact with stimulants?

From the Guidelines

Carbazepine induces stimulants by accelerating their metabolism through its enzyme-inducing properties, particularly as a CYP3A4 inducer, which can lead to reduced effectiveness of stimulant medications. This interaction is a result of carbamazepine's ability to induce cytochrome P450 enzymes, specifically CYP3A4, as noted in the context of other medications like aprepitant 1. When considering the use of carbamazepine with stimulants, it's crucial to understand that this induction can lead to decreased plasma concentrations of the stimulants, potentially requiring dose adjustments to maintain therapeutic efficacy. Key points to consider include:

• The interaction affects various stimulants, including methylphenidate and amphetamine-based medications.
• The onset of this interaction typically occurs within 3-5 days of starting carbamazepine.
• The effects can persist for 2-4 weeks after carbamazepine is discontinued, due to the time required for enzyme induction and normalization.
• Monitoring for changes in stimulant effectiveness is essential, and healthcare providers may need to adjust stimulant doses or consider alternative anticonvulsants with fewer enzyme-inducing properties, such as lamotrigine or levetiracetam, for patients requiring both anticonvulsant and stimulant therapy, as guided by the principles of managing drug interactions similar to those described with aprepitant 1.

From the FDA Drug Label

Agents That Increase Carbamazepine Levels CYP3A4 inhibitors inhibit carbamazepine metabolism and can thus increase plasma carbamazepine levels. Agents That Decrease Carbamazepine Levels CYP3A4 inducers can increase the rate of carbamazepine metabolism. Effect of Carbamazepine on Plasma Levels of Concomitant Agents Decreased Levels of Concomitant Medications Carbamazepine is a potent inducer of hepatic 3A4 and is also known to be an inducer of CYP1A2, 2B6, 2C8/9/19 and may therefore reduce plasma concentrations of co-medications mainly metabolized by CYP 1A2, 2B6, 2C8/9/19 and 3A4, through induction of their metabolism

The answer to whether carbamazepine induces or interacts with stimulants is that there is no direct information in the provided drug label about the interaction between carbamazepine and stimulants. However, it can be inferred that carbamazepine, as a potent inducer of hepatic enzymes, may decrease the plasma levels of certain medications, including potentially some stimulants, through the induction of their metabolism.

• Key points:
  • Carbamazepine is a CYP3A4 inducer.
  • It may decrease the plasma levels of co-medications mainly metabolized by CYP1A2, 2B6, 2C8/9/19, and 3A4.
  • The label does not provide direct information on the interaction between carbamazepine and stimulants. 2

From the Research

Carbamazepine and Stimulant Interaction

• Carbamazepine (CBZ) is known to induce the metabolism of various drugs, including its own, by inducing cytochrome P450 (CYP) 3A4 and CYP2B6 3.
• The induction potential of CBZ on CYP enzymes has been evaluated, showing that it can induce CYP1A2, CYP2B6, and CYP3A4 in human hepatocytes and HepaRG cells 4.
• CBZ has been shown to inactivate CYP2D enzyme in rats and CYP1A2 in humans, resulting in the formation of reactive metabolites 5.
• The effect of CBZ on the activity and protein content of hepatic CYP subfamilies in rats has been studied, showing that CBZ induces multiple CYP subfamilies, except CYP2E1 6.
• The role of human CYP enzymes in the formation of 2-hydroxyiminostilbene, a potentially reactive species, has been investigated, showing that CYP3A4 preferentially catalyzes this formation 7.

Induction of Stimulants by Carbamazepine

• While there is no direct evidence on the induction of stimulants by CBZ, its ability to induce CYP enzymes suggests that it may affect the metabolism of stimulants that are substrates of these enzymes 3, 4.
• The induction of CYP3A4 and CYP2B6 by CBZ may lead to increased metabolism of stimulants that are substrates of these enzymes, potentially affecting their efficacy and safety 3, 4.
• However, the specific effects of CBZ on stimulant metabolism and interaction would depend on the individual stimulant and its metabolic pathways, which require further investigation 3, 4, 5, 6, 7.