Abstract
The Dutch Pharmacogenetic Working Group (DPWG) aims to integrate pharmacogenetics into clinical practice by creating evidence-based guidelines to optimize pharmacotherapy based on genetic tests. The current guideline describes the gene-drug interactions between CYP2D6 and CYP2C19 and various tricyclic antidepressants (TCAs). For CYP2D6 poor metabolisers (PM), dose reductions are advised for amitriptyline (reduction to 60% of the normal dose), clomipramine (reduction to 50% of the normal dose for the indication depression or in case of side effects at the normal dose for the other indications), doxepin (reduction to 40% of normal dose), imipramine (30% of the normal dose), and nortriptyline (40%). For CYP2D6 intermediate metabolisers (IM) reduced dose is also recommended for amitriptyline (75%), clomipramine (70%), doxepin (80%), imipramine (70%), and nortriptyline (60%). Also, CYP2D6 ultra-rapid metabolisers (UM) require tailored dose adjustments: amitriptyline (1.6 times the normal dose), clomipramine (1.5 times), doxepin (2 times), imipramine (1.7 times), and nortriptyline (1.7 times). Additionally, alternative drugs may be needed for CYP2D6 UM due to potential safety concerns. For CYP2C19 PM, a 70% dose reduction is advised for imipramine. For CYP2C19 IM, no action is required for TCAs. For CYP2C19 UM, an alternative medication is recommended for clomipramine prescribed for anxiety and obsessive-compulsive disorder (OCD). The DPWG classifies CYP2D6 genotyping for all five TCAs and CYP2C19 genotyping for clomipramine in patients with anxiety disorders or OCD, and for imipramine as being "potentially beneficial". Genotyping prior to treatment can be considered on an individual patient basis.