Effects of Pharmacogenetic Screening for CYP2D6 Among Elderly Starting Therapy With Nortriptyline or Venlafaxine

Schans, Jurjen van der; Postma, Maarten J.; Breuning, Laura; Brouwers, Jacobus; Ditters, Kaspar; Jansen, Paul A. F.; Kok, Rob; Maring, Jan Gerard; Marum, Rob van; Mulder, Hans; Nanninga, Jaap; Voshaar, Richard C. Oude; Risselada, Arne; Vleugel, Liesbeth; Stek, Max L.; Schaik, Ron H.N. van; Berm, Elizabeth J J; Wilffert, Bob

doi:10.1097/jcp.0000000000001129

Cited by 17 publications

(12 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The impact of our findings on further genomic evidence for the treatment of alcohol use disorders is potentially interesting. Genotyping has been considered as a possible tool for precision medicine, with a special focus in the area of mental health [38][39][40][41]. Even if many studies supported the genotyping OPRM1 in the treatment with naltrexone [42][43][44], our data would suggest genotyping for ADH1B, ADH1C and ALDH2 before the treatment.…”

Section: Discussionmentioning

confidence: 68%

Exploring the Role of Alcohol Metabolizing Genotypes in a 12-Week Clinical Trial of Naltrexone for Alcohol Use Disorder

et al. 2021

View full text Add to dashboard Cite

Background: The efficacy of naltrexone in the treatment of alcohol use disorder (AUD) has been associated with a set of variables not directly related with the expression of opioid receptors. All the variables have been found to be highly associated with AUD itself or more severe clinical levels of AUD. Objectives: Given the high association between alcohol metabolizing enzymes (AME) and the outcome of AUD, the present study aims to investigate the role of AME genotype variants in the treatment of AUD with naltrexone. Methods: We carried out a 12-week longitudinal clinical trial based on the treatment of AUD patients with naltrexone (N = 101), stratified by different alcohol metabolization genotypes. Genotyping was performed after the inclusion of the patients in the study, based on the individual presence of single nucleotide polymorphisms (SNPs) in the ADH (alcohol dehydrogenase)1B (ADH1B*2 and ADH1B*3), ADH1C (ADHC*1) and ALDH (aldehyde dehydrogenase) 2 (ALDH2*2) genes. The outcome of alcohol use has been monitored employing the timeline follow-back during the treatment. Results: The ADH1C*1 (Ile350Val, rs698) and ALDH2*2 (Glu504Lys, rs671) polymorphisms were associated with a better response to naltrexone treatment, whereas the ADH1B*3 (Arg370Cys, rs2066702) allelic variant showed a negative outcome. Conclusions: The present study explores a genomic setting for the treatment of AUD with naltrexone. According to our findings, the association between ADH1C*1 and ALDH2*2 variants and better outcomes suggests a successful treatment, whereas the ADH1B*3 mutated allele might lead to an unsuccessful treatment. Further studies should be performed to investigate the relationship between alcohol metabolizing genotypes, the family history of alcohol use disorders and the effect of naltrexone on the outcomes. Genotyping may be a valuable tool for precision-medicine and individualized approach, especially in the context of alcohol use disorders. The small number of subjects was the main limitation of the present study.

show abstract

Section: Discussionmentioning

confidence: 68%

Exploring the Role of Alcohol Metabolizing Genotypes in a 12-Week Clinical Trial of Naltrexone for Alcohol Use Disorder

et al. 2021

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

“…To date, only 1 study has been conducted in which CYP2D6-informed dosing was compared with standard treatment using therapeutic plasma concentrations as an outcome measure. In this study, nortriptyline and venlafaxine were investigated in older adults with MDD. For both antidepressants, the study did not detect a difference in the time needed to attain a therapeutic plasma concentration .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Effectiveness of Genotype-Specific Tricyclic Antidepressant Dosing in Patients With Major Depressive Disorder

et al. 2023

View full text Add to dashboard Cite

ImportanceEvidence of the clinical benefit of pharmacogenetics-informed treatment (PIT) with antidepressants is still limited. Especially for tricyclic antidepressants (TCAs), pharmacogenetics may be of interest because therapeutic plasma concentrations are well defined, identification of optimal dosing can be time consuming, and treatment is frequently accompanied by adverse effects.ObjectiveTo determine whether PIT results in faster attainment of therapeutic TCA plasma concentrations compared with usual treatment in patients with unipolar major depressive disorder (MDD).Design, Setting, and ParticipantsThis randomized clinical trial compared PIT with usual treatment among 111 patients at 4 centers in the Netherlands. Patients were treated with the TCAs nortriptyline, clomipramine, or imipramine, with clinical follow-up of 7 weeks. Patients were enrolled from June 1, 2018, to January 1, 2022. At inclusion, patients had unipolar nonpsychotic MDD (with a score of ≥19 on the 17-item Hamilton Rating Scale for Depression [HAMD-17]), were aged 18 to 65 years, and were eligible for TCA treatment. Main exclusion criteria were a bipolar or psychotic disorder, substance use disorder, pregnancy, interacting comedications, and concurrent use of psychotropic medications.InterventionIn the PIT group, the initial TCA dosage was based on CYP2D6 and CYP2C19 genotypes. The control group received usual treatment, which comprised the standard initial TCA dosage.Main Outcomes and MeasuresThe primary outcome was days until attainment of a therapeutic TCA plasma concentration. Secondary outcomes were severity of depressive symptoms (measured by HAMD-17 scores) and frequency and severity of adverse effects (measured by Frequency, Intensity, and Burden of Side Effects Rating scores).ResultsOf 125 patients randomized, 111 (mean [SD] age, 41.7 [13.3] years; 69 [62.2%] female) were included in the analysis; of those, 56 were in the PIT group and 55 were in the control group. The PIT group reached therapeutic concentrations faster than the control group (mean [SD], 17.3 [11.2] vs 22.0 [10.2] days; Kaplan-Meier χ21 = 4.30; P = .04). No significant difference in reduction of depressive symptoms was observed. Linear mixed-model analyses showed that the interaction between group and time differed for the frequency (F6,125 = 4.03; P = .001), severity (F6,114 = 3.10; P = .008), and burden (F6,112 = 2.56; P = .02) of adverse effects, suggesting that adverse effects decreased relatively more for those receiving PIT.Conclusions and RelevanceIn this randomized clinical trial, PIT resulted in faster attainment of therapeutic TCA concentrations, with potentially fewer and less severe adverse effects. No effect on depressive symptoms was observed. These findings indicate that pharmacogenetics-informed dosing of TCAs can be safely applied and may be useful in personalizing treatment for patients with MDD.Trial RegistrationClinicalTrials.gov Identifier: NCT03548675

show abstract

“…However, there are discrepancies in the benefits of routine CYP2D6 genotyping. Some studies suggest that changes of drug metabolism that are rooted from CYP2D6 genetic variants make insufficient effects on the therapeutic levels of venlafaxine and that CYP2D6 genotyping would not forecast the treatment efficacy of venlafaxine in patients with depression [66][67][68][69].…”

Section: Venlafaxinementioning

confidence: 99%

Pharmacogenomic Biomarkers and Their Applications in Psychiatry

Kam

Jeong

2020

Genes

View full text Add to dashboard Cite

Realizing the promise of precision medicine in psychiatry is a laudable and beneficial endeavor, since it should markedly reduce morbidity and mortality and, in effect, alleviate the economic and social burden of psychiatric disorders. This review aims to summarize important issues on pharmacogenomics in psychiatry that have laid the foundation towards personalized pharmacotherapy and, in a broader sense, precision medicine. We present major pharmacogenomic biomarkers and their applications in a variety of psychiatric disorders, such as depression, attention-deficit/hyperactivity disorder (ADHD), narcolepsy, schizophrenia, and bipolar disorder. In addition, we extend the scope into epilepsy, since antiepileptic drugs are widely used to treat psychiatric disorders, although epilepsy is conventionally considered to be a neurological disorder.

show abstract

Effects of Pharmacogenetic Screening for CYP2D6 Among Elderly Starting Therapy With Nortriptyline or Venlafaxine

Abstract: Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.

Cited by 17 publications

References 30 publications

Exploring the Role of Alcohol Metabolizing Genotypes in a 12-Week Clinical Trial of Naltrexone for Alcohol Use Disorder

Exploring the Role of Alcohol Metabolizing Genotypes in a 12-Week Clinical Trial of Naltrexone for Alcohol Use Disorder

Effectiveness of Genotype-Specific Tricyclic Antidepressant Dosing in Patients With Major Depressive Disorder

Pharmacogenomic Biomarkers and Their Applications in Psychiatry

Contact Info

Product

Resources

About