Effectiveness of pharmacogenetic information in the treatment of major depressive disorder: results from the AB-GEN randomized clinical trial

Pérez, Ví­ctor; Espadaler, Jordi; Tuson, Miquel; Salavert, Ariana; Sáiz, Jerónimo; Bobes, Julio; Vieta, Eduard; Álvarez, Eva Carbajo; Menchón, José M.

doi:10.1016/s0924-977x(16)31367-0

Cited by 6 publications

(8 citation statements)

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“…The clinical utility of CYP2D6 and CYP2C19 genotype-guided drug treatment has previously been addressed in a controlled manner as part of a combined genetic approach in 5 industrysponsored studies focusing on the efficacy of antidepressants on major depressive disorder. [20][21][22][23][24] Figure 20,21 showed improved results on Hamilton Depression Rating Scale in the genotype-guided arm compared with the control group; however, these results were not reproduced in a masked confirmatory randomized clinical trial. 24 Another randomized clinical trial 22 showed a tendency toward a higher responder rate in participants whose treatment was genotype guided, but no differences in the primary outcome, sustained response.…”

Section: Discussionmentioning

confidence: 99%

“…[20][21][22][23][24] Figure 20,21 showed improved results on Hamilton Depression Rating Scale in the genotype-guided arm compared with the control group; however, these results were not reproduced in a masked confirmatory randomized clinical trial. 24 Another randomized clinical trial 22 showed a tendency toward a higher responder rate in participants whose treatment was genotype guided, but no differences in the primary outcome, sustained response. The fifth study, 23 using a test solely focusing on genes that affect pharmacokinetics (CYP2D6, CYP2C19, UGT1A1 [OMIM 191740], and ABC transporters), showed a remission rate of 70% in the genotype-guided group compared with 28% in the control group when studied in a 12-week, double-masked randomized clinical trial with 148 participants.…”

Section: Discussionmentioning

confidence: 99%

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Effect of Routine Cytochrome P450 2D6 and 2C19 Genotyping on Antipsychotic Drug Persistence in Patients With Schizophrenia

et al. 2020

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IMPORTANCEGenetic polymorphism of genes encoding the drug metabolizing enzymes, cytochrome P450 2D6 and 2C19 (CYP2D6 and CYP2C19), is associated with treatment failure of and adverse reactions to psychotropic drugs. The clinical utility of routine CYP2D6 and CYP2C19 genotyping (CYP testing) is unclear. OBJECTIVE To estimate whether routine CYP testing effects the persistence of antipsychotic drug treatment. DESIGN, SETTING, AND PARTICIPANTS This single-masked, 3-group randomized clinical trial included patients aged 18 years or older who had been diagnosed within the schizophrenic spectrum (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes, F20-F29) and not previously genotyped. A total of 669 of 1406 potentially eligible patients from 12 psychiatric outpatient clinics in Denmark were approached between July 2008 and December 2009. Overall, 528 patients were genotyped and randomly allocated to 1 of 3 study groups or exclusion in a sequence of 1:1:1:3 using a predictive enrichment design, aiming to double the proportion of poor or ultrarapid metabolizers for CYP2D6 or CYP2C19. Outcome measurements were recorded at baseline and 1-year follow-up. Data analysis was performed in December 2012 and updated March 2019. INTERVENTIONS The trial included 2 intervention groups, where antipsychotic drug treatment was guided by either CYP test (CYP test-guided [CTG]) or structured clinical monitoring (SCM), in which adverse effects and factors influencing compliance were systematically recorded at least once quarterly, and 1 control group. MAIN OUTCOMES AND MEASURES Primary outcome was antipsychotic drug persistence, ie, days to first modification of the initial treatment. Secondary outcomes were number of drug and dose changes, adverse effects, and psychotic symptoms, ie, hallucinations and delusions. RESULTS A total of 528 participants were genotyped, and 311 (median [interquartile range {IQR} age, 41 [30-50] years; 139 [45%] women; median [IQR] duration of illness, 6 [3-13] years) were randomly allocated to 1 of 3 study groups. Overall, 61 participants (20%) were extreme metabolizers.There was no difference in antipsychotic drug persistence between the CTG group and the control group (hazard ratio [HR], 1.02; 95% CI, 0.71-1.45) or SCM and the control group (HR, 0.88; 95% CI, 0.61-1.26). Subanalyses among extreme metabolizers showed similar results (CTG: HR, 0.99; 95% CI, 0.48-2.03; SCM: HR, 0.93; 95% CI, 0.44-1.96).

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effect of Routine Cytochrome P450 2D6 and 2C19 Genotyping on Antipsychotic Drug Persistence in Patients With Schizophrenia

et al. 2020

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“…The CNSDose group conducted a randomized, double-blind, 12-week prospective study and reported a 2.5-fold increase in remission rates in the CNSDose group (P<0.0001) (16). The Neuropharmagen group conducted a randomized, double-blind, 12-week prospective study and reported a higher proportion of responders at 12 weeks in the guided group vs. unguided group (P=0.0476) (32). The three RCTs were all industry-sponsored, hence independent replication and head-to-head trials are needed.…”

Section: Review Of Pharmacogenetic Decision Support Tools For Major Dmentioning

confidence: 99%

Pharmacogenetic Decision Support Tools: A New Paradigm for Late-Life Depression?

Abbott

Chang

Eyre

et al. 2018

The American Journal of Geriatric Psychiatry

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Clinicians still employ a "trial-and-error" approach to optimizing treatment regimens for late-life depression (LLD). With LLD affecting a significant and growing segment of the population, and with only about half of older adults responsive to antidepressant therapy, there is an urgent need for a better treatment paradigm. Pharmacogenetic decision support tools (DSTs), which are emerging technologies that aim to provide clinically actionable information based on a patient's genetic profile, offer a promising solution. Dozens of DSTs have entered the market in the past 15 years, but with varying level of empirical evidence to support their value. In this clinical review, we provide a critical analysis of the peer-reviewed literature on DSTs for major depression management. We then discuss clinical considerations for the use of these tools in treating LLD, including issues related to test interpretation, timing, and patient perspectives. In adult populations, newer generation DSTs show promise for the treatment of major depression. However, there are no primary clinical trials in LLD cohorts. Independent and comparative clinical trials are needed.

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“…Independently replicated randomized controlled trials will be needed to draw firmer conclusions about the merits of such testing. To date, only three such trials have been completed (all industry sponsored); two were positive, and the other yielded a nonsignificant trend supportive of the utility of antidepressant pharmacogenetics (11)(12)(13). Additional randomized trials are under way, and they will help shed more light on the clinical merits of antidepressant pharmacogenetics.…”

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confidence: 99%

Antidepressant Pharmacogenetics

Singh

Bousman

2017

AJP

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Effectiveness of pharmacogenetic information in the treatment of major depressive disorder: results from the AB-GEN randomized clinical trial

Cited by 6 publications

References 0 publications

Effect of Routine Cytochrome P450 2D6 and 2C19 Genotyping on Antipsychotic Drug Persistence in Patients With Schizophrenia

Effect of Routine Cytochrome P450 2D6 and 2C19 Genotyping on Antipsychotic Drug Persistence in Patients With Schizophrenia

Pharmacogenetic Decision Support Tools: A New Paradigm for Late-Life Depression?

Antidepressant Pharmacogenetics

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