A Pharmacogenomic-based Antidepressant Treatment for Patients with Major Depressive Disorder: Results from an 8-week, Randomized, Single-blinded Clinical Trial

Han, Changsu; Wang, Sheng Min; Bahk, Won Myong; Lee, Soo Jung; Patkar, Ashwin A.; Masand, Prakash S.; Mandelli, Laura; Pae, Chi Un; Serretti, Alessandro

doi:10.9758/cpn.2018.16.4.469

Cited by 49 publications

(61 citation statements)

References 51 publications

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“…The ideal goal of antidepressant treatment for patients with major depressive disorder (MDD) is to achieve full recovery of individual, occupational, and psychosocial functions. However, lower remission/response rates and higher relapse rates have been consistently reported in real world treatment setting [1–3]. In addition, some sub-populations of MDD including mixed or anxious features are known to present poor clinical outcomes than those without such subsymptoms [4].…”

Section: Introductionmentioning

confidence: 99%

The Potential Utility of Aripiprazole Augmentation for Major Depressive Disorder with Mixed Features Specifier: A Retrospective Study

Han

Wang

Bahk

et al. 2019

Clin Psychopharmacol Neurosci

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ObjectiveThe present study aimed to observe potential benefit of aripiprazole augmentation in the treatment of major depressive disorder with mixed specifier (MDDM) in naturalistic treatment setting.MethodsData were collected from MDDM patients using a retrospective chart review for 8 weeks (week –8 and week 0) in routine practice. All patients were on current antidepressants upon starting of aripiprazole. Patients were treated without restriction of doses of aripiprazole. The primary endpoint was the mean change of Montgomery–Åsberg Depression Rating Scale (MADRS) total scores along with various secondary endpoint measures.ResultsIn total 38 patients were analyzed. The changes of MADRS, Clinical Global Impression (CGI)-severity, Young Mania Rating Scale, Sheehan Disability Scale, and CGI-clinical benefit total scores from baseline to the endpoint were −7.1, −0.8, −4.9, −4.1, and −3.6, respectively (all p < 0.0001). At the endpoint, the responder and remitter rates by MADRS score criteria were approximately 32% and 21%, respectively.ConclusionThe present findings have clearly shown the effectiveness and tolerability of aripiprazole augmentation for MDDM patients in routine practice. The present study warrants subsequent, adequately-powered, well-controlled studies for generalizability near future.

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Section: Introductionmentioning

confidence: 99%

The Potential Utility of Aripiprazole Augmentation for Major Depressive Disorder with Mixed Features Specifier: A Retrospective Study

Han

Wang

Bahk

et al. 2019

Clin Psychopharmacol Neurosci

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“…A larger sample size would allow to draw more conclusive remark for detecting smaller differences between PwAD and PwoAD; for instance, to detect significant difference for good outcomes based on MRS and BBS scores, we should have included at least 220 and 450 samples, respectively [ 21 , 22 ]. Other covert multiple factors influencing ADL and motor functions should be also considered in interpretation of our study findings since we performed merely a naturalistic observation but not the well- controlled study design [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

The Usefulness and Clinical Characteristics of Antidepressant Use for Stroke Patients with Rehabilitation Program: An Exploratory Analysis

Lee

Park

Bahk

et al. 2020

Clin Psychopharmacol Neurosci

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Objective: There has been a lack of data regarding the usefulness and clinical characteristic between patients-treated with and without antidepressants (Pw/Pwo ADs). Methods: One hundred and eighty inpatients were recruited and observed for a 6-month. The depressive, cognitive, daily activity, and motor symptoms were evaluated at baseline and tracked at month 6, with the use of rating scales including Beck Depression Inventory (BDI), Mini Mental State Examination (MMSE), Global Deterioration Scale (GDS), modified Rankin Scale (MRS), modified Barthel Index (MBI), and Berg Balance Scale (BBS). Results: Among 178 patients, 84 (47.2%) were treated with ADs. PwAD had numerically or significantly higher depressive cognitive, and motor symptoms along with daily activity impairment (8.3 point higher in BDI score, p ＜ 0.001; 3.6 point lower in MMSE, p = 0.003; 0.8 point higher in GDS score, p = nonsignificant; 8.2 point lower in BBS score, p = 0.053, and 0.4 point higher in MBI score, p = nonsignificant) than PwoAD. Psychiatric consultation was also significantly higher in PwAD than in PwoAD (p ＜ 0.001). The numbers need to treat for good clinical outcomes between PwAD and PwoAD were 5.8, 6.0, and 7.5, respectively, by MRS, MBI, and BBS scores. Conclusion: Our findings suggest the potential utility of AD treatment and different clinical parameters between patients-treated with and without ADs. Adequately-powered and well-controlled further studies are mandatory to confirm and fully elaborate such association.

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“…Restful sleep is an important factor in treating patients in psychiatry. A recent pharmacogenomic randomized single-blind clinical trial evaluating the clinical utility of pharmacogenomic-based prescribing vs. the treatment-as-usual of antidepressants in patients diagnosed with major depressive disorder, reported that sleep disturbance as the most commonly reported adverse event among both treatment groups (Han et al, 2018). In this study, patients treated with fluoxetine, fluvoxamine, and paroxetine—all CYP2D6 substrates—had a 337% increase in odds of nightmares and a 119% increased odds of sleep disorder and thus rejects the null hypothesis and affirms the association of the CYP2D6 SSRI substrates with of de-realization of thought processes.…”

Section: Discussionmentioning

confidence: 99%

Optimizing drug selection in psychopharmacology based on 40 significant CYP2C19- and CYP2D6-biased adverse drug reactions of selective serotonin reuptake inhibitors

Eugene¹

2019

PeerJ

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Background Selective serotonin reuptake inhibitors (SSRIs) are among the most widely prescribed class of drugs in the practice of psychiatry. Cytochrome P450 (CYP) 2C19 and CYP2D6 are established as clinically relevant drug metabolizing enzymes (DMEs) that influence the pharmacokinetics of SSRIs and may either be grouped as being primarily metabolized by CYP2C19 or CYP2D6. The aim of this study is to test the hypothesis that the primary drug metabolizing pathway for SSRI antidepressants are associated with adverse drug reactions (ADRs) related to physiological modulation of organs with the highest gene tissue expression. Methods Post-marketing ADR cases were obtained from the United States Food and Drug Administration’s Adverse Events Reporting System from each of the four quarters for the years 2016 and 2017. Cases were grouped based on one of two primary pharmacokinetic pharmacogenomic pathway biomarkers CYP2C19 and CYP2D6. Citalopram, escitalopram, and sertraline were grouped as CYP2C19 substrates and fluvoxamine, fluoxetine, and paroxetine as CYP2D6 substrates. Logistic regression was computed for the reported SSRI ADRs associated with one of two aforementioned DMEs. All data homogenization and computations were performed in R for statistical programming. Results The most commonly reported ADR among the SSRIs was anxiety (n = 3,332). The top two ADRs associated with SSRIs metabolized by CYP2D6 are: nightmare (n = 983) reporting odds-ratio (OR) = 4.37 (95% confidence interval (CI) [3.67–5.20]) and panic attack (n = 1,243) OR = 2.43 (95% CI [2.11–2.79]). Contrastingly, the top two ADRs for CYP2C19 metabolized SSRIs are: electrocardiogram QT prolonged (n = 351) OR = 0.18 (95% CI [0.13–0.24]) and small for dates baby (n = 306) OR = 0.19 (95% CI [0.14–0.26]). The study tested and produced 40 statistically significant CYP2C19- and CYP2D6-biased ADRs. In overall context, the results suggest that CYPC19 SSRI substrates are associated with ADRs related to modulation of the autonomic nervous system, seizure, pain, erectile-dysfunction, and absorption. Contrastingly, CYP2D6 SSRI substrates are associated with ADRs related to nightmares, withdrawal syndrome, and de-realization of cognitive processes. The results of this study may aid as guidance to optimize drug selection in psychopharmacology.

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A Pharmacogenomic-based Antidepressant Treatment for Patients with Major Depressive Disorder: Results from an 8-week, Randomized, Single-blinded Clinical Trial

Cited by 49 publications

References 51 publications

The Potential Utility of Aripiprazole Augmentation for Major Depressive Disorder with Mixed Features Specifier: A Retrospective Study

The Potential Utility of Aripiprazole Augmentation for Major Depressive Disorder with Mixed Features Specifier: A Retrospective Study

The Usefulness and Clinical Characteristics of Antidepressant Use for Stroke Patients with Rehabilitation Program: An Exploratory Analysis

Optimizing drug selection in psychopharmacology based on 40 significant CYP2C19- and CYP2D6-biased adverse drug reactions of selective serotonin reuptake inhibitors

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