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CYP2C19 / CYP2D6 and TCAs

The enzymes CYP2C19 and CYP2D6 play an important role in the metabolisation of tricyclic antidepressants (TCAs). These drugs are prescribed to patients suffering from depression and anxiety disorders. Due to the relatively low concentration of the enzyme CYP2D6 in the liver, reduced activity of this enzyme can quickly lead to abnormalities in the metabolisation of TCAs. The response is less sensitive in the case of the enzyme CYP2C19. The doses of some TCAs are therefore determined on the basis of the activity of the enzyme CYP2D6. When it comes to dosing imipramine, clomipramine, amitriptyline and doxepin, however, the activity of the enzyme CYP2C19 also plays a role.

Clomipramine and the enzymes CYP2C19 and CYP2D6

Clomipramine is processed to a large extent by the enzymes CYP2C19 and CYP2D6.

Initially, clomipramine is metabolised (demethylated) by the enzyme CYP2C19 into another active substance. The enzymes CYP1A2 and CYP3A4 are also involved in this step to a lesser extent. After this activation step this substance is metabolised further (hydroxylated) by the enzyme CYP2D6 into less active components.

The activity of the enzymes concerned can vary considerably depending on your genetic predisposition, which means the efficacy of clomipramine can also differ from person to person. Information about your genetic predisposition may therefore provide grounds for extra vigilance in relation to a treatment with clomipramine.

Read more about Clomipramine »

Imipramine and the enzymes CYP2C19 and CYP2D6

Imipramine is processed to a large extent by the enzymes CYP2C19 and CYP2D6.

Initially, imipramine is metabolised (demethylated) by the enzyme CYP2C19 into another active substance. The enzymes CYP1A2 and CYP3A4 are also involved in this step to a lesser extent. After this activation step this substance is metabolised further (hydroxylated) by the enzyme CYP2D6 into less active components.

The activity of the enzymes concerned can vary considerably depending on your genetic predisposition, which means the efficacy of imipramine can also differ from person to person. Information about your genetic predisposition may therefore provide grounds for extra vigilance in relation to a treatment with imipramine.

Read more about Imipramine »

Genetic predisposition Your individual likelihood of a successful treatment with the tricyclic antidepressants imipramine, clomipramine, amitriptyline and doxepin may be partly explained by genetic variations. For example, it is known that mutations in the CYP2C19 gene and CYP2D6 gene can result in abnormal enzyme activity. As antidepressants need to be dosed precisely, it may be important to know what genotype you have. When a genotype is determined variations are indicated by two so-called alleles. Each allele has a name consisting of an asterisk (*) and a number. An example of a possible CYP2C19 genotype is CYP2C19*1/*3.