The GG genotype of the serotonin 4 receptor genetic polymorphism, rs1345697, is associated with lower remission rates after antidepressant treatment: findings from the METADAP cohort

BackgroundThe gene product of the ABCB1 gene, the P-glycoprotein, functions as a custodian molecule in the blood–brain barrier and regulates the access of most antidepressants into the brain. Previous studies showed that ABCB1 polymorphisms predicted the response to antidepressants that are substrates of the P-gp, while the response to nonsubstrates was not influenced by ABCB1 polymorphisms. The aim of the present study was to evaluate the clinical application of ABCB1 genotyping in antidepressant pharmacotherapy.MethodsData came from 58 depressed inpatients participating in the Munich Antidepressant Response Signature (MARS) project, whose ABCB1 gene test results were implemented into the clinical decision making process. Hamilton Depression Rating Scale (HAM-D) scores, remission rates, and duration of hospital stay were documented with dose and kind of antidepressant treatment.ResultsPatients who received ABCB1 genotyping had higher remission rates [χ2(1) = 6.596, p = 0.005, 1-sided] and lower Hamilton sores [t(111) = 2.091, p = 0.0195, 1-sided] at the time of discharge from hospital as compared to patients without ABCB1 testing. Among major allele homozygotes for ABCB1 single nucleotide polymorphisms (SNPs) rs2032583 and rs2235015 (TT/GG genotype), an increase in dose was associated with a shorter duration of hospital stay [rho(28) = –0.441, p = 0.009, 1-sided], whereas other treatment strategies (eg, switching to a nonsubstrate) showed no significant associations with better treatment outcome.DiscussionThe implementation of ABCB1 genotyping as a diagnostic tool influenced clinical decisions and led to an improvement of treatment outcome. Patients carrying the TT/GG genotype seemed to benefit from an increase in P-gp substrate dose.ConclusionResults suggest that antidepressant treatment of depression can be optimized by the clinical application of ABCB1 genotyping.

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Enhancing Outcomes from Major Depression: Using Antidepressant Combination Therapies with Multifunctional Pharmacologic Mechanisms from the Initiation of Treatment

CNS Spectrums ◽

10.1017/s1092852900027334 ◽

2010 ◽

Vol 15 (2) ◽

pp. 79-94 ◽

Cited By ~ 22

Author(s):

Stephen M. Stahl

Keyword(s):

Major Depression ◽

Depressive Episode ◽

Major Depressive Episode ◽

Antidepressant Treatment ◽

Symptomatic Improvement ◽

Good News ◽

Sustained Remission ◽

Major Depressive ◽

Remission Rates ◽

Antidepressant Combination

Traditional guidelines call for treatment of major depression with a sequence of single antidepressants. Augmentation with a second agent generally only occurs when the first agent is well tolerated and when it also provides at least some symptomatic improvement on its own. Since this standard approach leads to low rates of attaining and sustaining remission by the first agent, with diminishing returns for each subsequent agent, there is growing dissatisfaction with this approach to the treatment of major depression. One new trend is to attempt to enhance the rates of sustained remission from a major depressive episode by combining two therapeutic agents from the very initiation of treatment of a major depressive episode.Traditional treatment of major depression begins with a single “first line” antidepressant, and if it does not work or is not tolerated, trying another and then another. Unfortunately, this strategy results in disappointing remission rates for the first antidepressant (Figure 1), and disappointing rates of maintaining any improvement that is attained by this first agent because of high relapse rates over the next year despite continuing treatment with the first antidepressant (Figure 2A). And that is the good news. The bad news is that with each subsequent antidepressant treatment administered remission rates are progressively reduced (Figure 1). For those patients who do improve, they are progressively less likely to sustain their therapeutic gains despite continuing to take the drug that led to their initial improvement (Figure 2).

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S.17.03 Gender, age and genetic polymorphism and the response to antidepressant treatment

European Neuropsychopharmacology ◽

10.1016/s0924-977x(03)91666-x ◽

2003 ◽

Vol 13 ◽

pp. S143

Author(s):

P.R. Joyce

Keyword(s):

Genetic Polymorphism ◽

Antidepressant Treatment

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SOD2 genetic polymorphism (rs4880) has no impact on 6‐month response to antidepressant treatment and inflammatory biomarkers in depressed patients

Basic & Clinical Pharmacology & Toxicology ◽

10.1111/bcpt.13385 ◽

2020 ◽

Vol 126 (3) ◽

pp. 289-295

Author(s):

Abd El Kader Ait Tayeb ◽

Laurent Becquemont ◽

Khalil El‐Asmar ◽

Kaïna Mahmoudi ◽

Romain Colle ◽

...

Keyword(s):

Genetic Polymorphism ◽

Antidepressant Treatment ◽

Inflammatory Biomarkers ◽

Depressed Patients

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Adjunctive benzodiazepines in depression: a clinical dilemma with no recent answers from research

BJPsych Advances ◽

10.1192/bja.2020.17 ◽

2020 ◽

Vol 26 (6) ◽

pp. 321-326

Author(s):

Angharad N. de Cates ◽

Riccardo De Giorgi

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Receptor Binding ◽

Combination Treatment ◽

Antidepressant Treatment ◽

Inhibitory Effect ◽

Anxiety Symptoms ◽

Major Depressive ◽

Remission Rates ◽

Clinical Dilemma

SUMMARYComorbid anxiety symptoms are common in depression, and adding benzodiazepines to antidepressant treatment may seem a rational clinical solution. Benzodiazepines also have potential to reduce the initial anxiety that may be caused by early antidepressant treatment (owing to their inhibitory effect via GABAA receptor binding). This month's Cochrane Corner review examines the evidence behind combination treatment versus antidepressants alone in major depressive disorder, in terms of both the clinical and neuroscientific context. The review provides evidence that, in the first 4 weeks of treatment, additional medication with a benzodiazepine may lead to greater improvements than antidepressant alone on ratings of severity, response rates and remission rates for depression, but not on measures of anxiety.

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