Use of antidepressants with pharmacogenetic prescribing guidelines in a 10-year depression cohort of adult primary care patients

Abstract

Objective To describe the usage patterns of antidepressants with published CYP2D6- and CYP2C19-based prescribing guidelines among depressed primary care patients and estimate the proportion of patients taking antidepressants not recommended for them based on their CYP2C19 and CYP2D6 genotype-predicted metabolizer status. Methods Medication use and pharmacogenetic testing results were collected on 128 primary care patients enrolled in a 10-year depression cohort study. At each 12-month interval, we calculated the proportion of patients that: (1) reported use of one or more of the 13 antidepressant medications (i.e. amitriptyline, citalopram, escitalopram, clomipramine, desipramine, doxepin, fluvoxamine, imipramine, nortriptyline, paroxetine, sertraline, trimipramine, venlafaxine) with published CYP2D6- and CYP2C19-based prescribing guidelines, (2) were taking an antidepressant that was not recommended for them based on their CYP2C19 and CYP2D6 genotype-predicted metabolizer phenotype, and (3) switched medications from the previous 12-month interval. Results The annual proportion of individuals taking an antidepressant with a CYP2D6- and CYP2C19-based prescribing guidelines ranged from 45 to 84%. The proportion of participants that used an antidepressant that was not recommended for them, based on available CYP2D6 and CYP2C19 metabolizer phenotype, ranged from 18 to 29% and these individuals tended to switch medications more frequently (10%) compared to their counterparts taking medication aligned with their metabolizer phenotype (6%). Conclusion One-quarter of primary care patients used an antidepressant that was not recommended for them based on CYP2D6- and CYP2C19-based prescribing guidelines and switching medications tended to be more common in this group. Studies to determine the impact of CYP2D6 and CYP2C19 genotyping on reducing gene-antidepressant mismatches are warranted.

Clinical Impact of Functional CYP2C19 and CYP2D6 Gene Variants on Treatment with Antidepressants in Young People with Depression: A Danish Cohort Study

“…A systematic review and meta-analysis [ 5 ] showed that CYP2C19 PMs had higher sertraline plasma concentrations, while Poweleit et al [ 18 ] showed that CYP2C19 status from PM to UM was inversely associated with sertraline doses at the beginning of treatment but not with doses in association with response. Overall, Jessel et al [ 19 ] found that 10% of individuals tended to switch if they were using antidepressants that were not in line with their CYP2C19 and/or CYP2D6 status, compared with 6% of patients who were using antidepressants that were aligned with their metabolizer phenotype.…”

Role of JNK in the Regulation of Xenobiotic Metabolizing Function of Hepatocytes

“…The discovered properties of the JNK inhibitor can be used to develop a fundamentally new approach to personification and increase the effectiveness of venlafaxine antidepressant therapy [7,8]. Based on the identified phenomena, JNK inactivation in liver cells can increase the level of drug transformation in low metabolizers (persons with low CYP2D6 expression, or in patients with liver diseases [3,4,6]) to the normal level (i.e. in extensive metabolizers of venlafaxine).…”

“…High incidence of depressive disorders in the population determines the widespread use in the medical practice of antidepressants, including venlafaxine [2,3]. This psychotropic pharmaceutical (presented by a racemate of R-and S-enantiomers) is one of the most effective modern antidepressants; its therapeutic effect is realized via blockade of serotonin, norepinephrine, and dopamine reuptake [9].…”

“…This psychotropic pharmaceutical (presented by a racemate of R-and S-enantiomers) is one of the most effective modern antidepressants; its therapeutic effect is realized via blockade of serotonin, norepinephrine, and dopamine reuptake [9]. However, its low efficiency in some cases [3,5,6] requires the development of personalized approaches to venlafaxine therapy, including modification of its pharmacokinetics and pharmacodynamics [1].…”

Pharmacogenetic testing among patients with depression in a US managed care population

“…[11][12][13] The annual proportion of patients taking an antidepressant with published CYP2D6-or CYP2C19-based pharmacogenetic guidelines is high, ranging from 45% to 84%, in the adult primary care setting. 13 In some clinical studies, the use of pharmacogenetic-guided treatment in depression has been associated with increased treatment efficacy (i.e., symptom remission and treatment response) and increased medication tolerability. [14][15][16][17][18][19][20] However, other findings are inconsistent, with some trials not finding sustained responses or significant improvements in primary outcomes.…”