Dysbindin associated with selective serotonin reuptake inhibitor antidepressant efficacy

Pae, Chi-Un,Serretti, Alessandro,Mandelli, Laura,De Ronchi, Diana,Patkar, Ashwin A.,Jun, Tae-Youn,Kim, Jung-Jin,Lee, Chang-Uk,Lee, Soo-Jung,Lee, Chul,Paik, In-Ho Lippincott Williams Wilkins, Inc. 2007 PHARMACOGENETICS AND GENOMICS Vol.17 No.1

OBJECTIVE: Antidepressant drug efficacy is partially under genetic control and a number of gene variants have been associated with antidepressants efficacy over the last few years. In the search for further genes influencing antidepressant response we focused on the dysbindin gene (dystrobrevin-binding-protein 1, DTNBP1). BASIC METHODS: One hundred and four Korean inpatients affected by major depressive disorder were treated with various antidepressants at standard therapeutic daily doses and rated with the 10-items Montgomery–Åsberg Depression rating scale (MADRS) at baseline and discharge. Five DTNBP1 variants (rs3213207 A/G, rs1011313 C/T, rs2005976 G/A, rs760761 C/T and rs2619522 A/C) were analysed for all patients. RESULTS: Rs2005976 was found to be significantly associated with final MADRS scores, with the rarest A allele associated with higher final scores (P=0.00055), rs760761 also showed a significant association (P=0.0058) and rs2619522 showed a positive trend (P=0.025). Markers were not significantly associated with Clinical Global Impression Scale scores. Five marker haplotypes were mildly associated with MADRS final scores but when considering the block composed of the three single nucleotide polymorphisms individually associated with response (rs2005976, rs760761 and rs2619522), results were more marked (P=0.0096), with the more frequent G–C–A haplotype associated with a positive outcome. CONCLUSIONS: Despite limitations due to the sample size and the mild antidepressant response, we observed a significant association between DTNBP1 variants and antidepressant response.

Effect of the Dysbindin Gene on Antimanic Agents in Patients with Bipolar I Disorder

Dong-Hwan Yun,Chi-Un Pae,Antonio Drago,Laura Mandelli,Diana De Ronchi,Ashwin A. Patkar,In Ho Paik,Alessandro Serretti,Jung-Jin Kim 대한신경정신의학회 2008 PSYCHIATRY INVESTIGATION Vol.5 No.2

Objective: We previously reported an association between dysbindin gene (DTNBP1) variants and bipolar I disorder (BID). This paper expands upon previous findings suggesting that DTNBP1 variants may play a role in the response to acute mood stabilizer treatment. Methods: A total of 45 BID patients were treated with antimanic agents (lithium, valproate, or carbamazepine) for an average of 36.52 (±19.87) days. After treatment, the patients were evaluated using the Clinical Global Impression (CGI) scale and the Young Mania Rating Scale (YMRS) and genotyped for their DTNBP1 variants (rs3213207 A/G, rs1011313 C/T, rs2005976 G/A, rs760761 C/T and rs2619522 A/C). Results: There was no association between the variants investigated and response to mood stabilizer treatment, even after considering possible stratification factors. Conclusion: Although the small number of subjects is an important limitation in our study, DTNBP1 does not seem to be involved in acute antimanic efficacy. Objective: We previously reported an association between dysbindin gene (DTNBP1) variants and bipolar I disorder (BID). This paper expands upon previous findings suggesting that DTNBP1 variants may play a role in the response to acute mood stabilizer treatment. Methods: A total of 45 BID patients were treated with antimanic agents (lithium, valproate, or carbamazepine) for an average of 36.52 (±19.87) days. After treatment, the patients were evaluated using the Clinical Global Impression (CGI) scale and the Young Mania Rating Scale (YMRS) and genotyped for their DTNBP1 variants (rs3213207 A/G, rs1011313 C/T, rs2005976 G/A, rs760761 C/T and rs2619522 A/C). Results: There was no association between the variants investigated and response to mood stabilizer treatment, even after considering possible stratification factors. Conclusion: Although the small number of subjects is an important limitation in our study, DTNBP1 does not seem to be involved in acute antimanic efficacy.

Abelson Helper Integration Site-1 Gene Variants on Major Depressive Disorder and Bipolar Disorder

Stefano Porcelli,배치운,한창수,이수정,Ashwin A Patkar,Prakash S. Masand,Beatrice Balzarro,Siegfried Alberti,Diana De Ronchi,Alessandro Serretti 대한신경정신의학회 2014 PSYCHIATRY INVESTIGATION Vol.11 No.4

Objective The present study aimed to explore whether 4 single nucleotide polymorphisms (SNPs) within the AHI1 gene could be associated with major depressive disorder (MD) and bipolar disorder (BD), and whether they could predict clinical outcomes in mood disorders. Methods One hundred and eighty-four (184) patients with MD, 170 patients with BD and 170 healthy controls were genotyped for 4 AHI1 SNPs (rs11154801, rs7750586, rs9647635 and rs9321501). Baseline and final clinical measures for MD patients were assessed through the Hamilton Rating Scale for Depression (HAM-D). Allelic and genotypic frequencies in MD and BD subjects were compared with those of each disorder and healthy group using the χ2 statistics. Repeated measures ANOVA was used to test possible influences of SNPs on treatment efficacy. Results The rs9647635 A/A was more represented in subjects with BD as compared with MD and healthy subjects together. The rs9647635 A/A was also more presented in patients with MD than in healthy subjects. With regard to the allelic analysis, rs9647635 A allele was more represented in subjects with BD compared with healthy subjects, while it was not observed between patients with MD and healthy subjects. Conclusion Our findings provide potential evidence of an association between some variants of AHI1 and mood disorders susceptibility but not with clinical outcomes. However, we will need to do more adequately-powered and advanced association studies to draw any conclusion due to clear limitations.

ZNF804A Gene Variants Have a Cross-diagnostic Influence on Psychosis and Treatment Improvement in Mood Disorders

Marco Calabrò,Laura Mandelli,Concetta Crisafulli,Marco Di Nicola,Roberto Colombo,Luigi Janiri,Soo-Jung Lee,Tae-Youn Jun,Sheng Min Wang,Prakash S Masand,Ashwin A Patkar,Changsu Han,Chi-Un Pae,Alessandr 대한정신약물학회 2020 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.18 No.2

Objective: Genetic variations in the gene encoding zinc finger protein 804A gene (ZNF804A) have been associated with major depression and bipolar disorder. In this work we focused on the potential influence of ZNF804A variations on the risk of developing specific sub-phenotypes as well as the individual response to available treatments. Methods: We used two samples of different ethnic origin: a Korean sample, composed by 242 patients diagnosed with major depression and 132 patients diagnosed with bipolar disorder and 326 healthy controls; an Italian sample composed 151 major depression subjects, 189 bipolar disorder subjects and 38 outpatients diagnosed for a primary anxiety disorder. Results: Our analyses reported an association of rs1344706 with psychotic phenotype in the cross-diagnostic pooled sample (geno p = 4.15 × 10−4, allelic p = 1.06 × 10−4). In the cross-diagnosis Italian sample but not in the Korean one, rs7597593 was involved with depressive symptoms improvement after treatment (geno p = 0.025, allelic p = 0.007). Conclusion: The present study evidenced the role of ZNF804A alterations in symptoms improvement after treatment. Both manic and depressive symptoms seem to be modulated by ZNF804A, though the latter was observed in the bipolar pooled sample only. The role of this factor is likely related to synaptic development and maintenance; however, further analyses will be needed to better understand the molecular mechanics involved with ZNF804A.

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

Changsu Han,Sheng Min Wang,Won-Myong Bahk,Soo-Jung Lee,Ashwin A Patkar,Prakash S Masand,Laura Mandelli,Chi-Un Pae,Alessandro Serretti 대한정신약물학회 2018 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.16 No.4

Objective: Pharmacogenomic-based antidepressant treatment (PGATx) may result in more precise pharmacotherapy of major depressive disorder (MDD) with better drug therapy guidance. Methods: An 8-week, randomized, single-blind clinical trial was conducted to evaluate the effectiveness and tolerability of PGATx in 100 patients with MDD. All recruited patients were randomly allocated either to PGATx (n=52) or treatment as usual (TAU, n=48) groups. The primary endpoint was a change of total score of the Hamilton Depression Rating Scale-17 (HAMD-17) from baseline to end of treatment. Response rate (at least 50% reduction in HAMD-17 score from baseline), remission rate (HAMD-17 score ≤7 at the end of treatment) as well as the change of total score of Frequency, Intensity, and Burden of Side Effects Ratings (FIBSER) from baseline to end of treatment were also investigated. Results: The mean change of HAMD-17 score was significantly different between two groups favoring PGATx by −4.1 point of difference (p=0.010) at the end of treatment. The mean change in the FIBSER score from baseline was significantly different between two treatment groups favoring PGATx by −2.5 point of difference (p=0.028). The response rate (71.7 % vs. 43.6%, p=0.014) were also significantly higher in PGATx than in TAU at the end of treatment, while the remission rate was numerically higher in PGATx than in TAU groups without statistical difference (45.5% vs. 25.6%, p=0.071). The reason for early drop-out associated with adverse events was also numerically higher in TAU (n=9, 50.0%) than in PGATx (n=4, 30.8%). Conclusion: The present study clearly demonstrate that PGATx may be a better treatment option in the treatment of MDD in terms of effectiveness and tolerability; however, study shortcomings may limit a generalization. Adequately-powered, well-designed, subsequent studies should be mandatory to prove its practicability and clinical utility for routine practice.

A review of current evidence for vilazodone in major depressive disorder

Wang, Sheng-Min,Han, Changsu,Lee, Soo-Jung,Patkar, Ashwin A.,Masand, Prakash S.,Pae, Chi-Un Informa Healthcare 2013 International journal of psychiatry in clinical pr Vol.17 No.3

<P><I>Objectives.</I> This review is to inform clinicians of currently available data on vilazodone for treating patients with major depressive disorder (MDD), focusing on its differential action mechanism and extended clinical utility. <I>Methods.</I> A data search was conducted in June 2012 using the PubMed/ MEDLINE/relevant clinical trial databases with the key terms “vilazodone” or “Viibryd.” <I>Results.</I> The efficacy, safety, and tolerability of vilazodone have been demonstrated in two pivotal 8-week, randomized, double-blinded, placebo-controlled studies. Certain pharmacological characteristics of vilazodone were observed, including early onset of action, fewer sexual side effects, the absence of known cardiac toxicity, and minimal effect on weight gain, that may provide potential clinical advantages compared with currently available antidepressants. However, such possibilities should be replicated and confirmed in more well-designed and adequately powered clinical trials. Vilazodone requires dose titration up to 2 weeks to reach a target dose of 40 mg/d due to high rate of gastrointestinal side effects. No direct comparative studies with other antidepressants are currently available to confirm the aforementioned potential clinical utility. <I>Conclusion.</I> Vilazodone is a newer antidepressant possessing different action mechanisms compared to currently available antidepressants but whether it has superiority to other class of antidepressants in terms of efficacy and safety should still warrant further evaluation through more well-controlled and direct comparison clinical trials.</P>

The relationship between fibromyalgia and major depressive disorder: a comprehensive review

Pae, Chi-Un,Luyten, Patrick,Marks, David M.,Han, Changsu,Park, Sung-Hwan,Patkar, Ashwin A.,Masand, Prakash S.,Van Houdenhove, Boudewijn Informa UK (Librapharm) 2008 Current medical research and opinion Vol.24 No.8

<P>OBJECTIVE: A large body of evidence suggests that the relationship between major depressive disorder (MDD) and fibromyalgia (FM) is complex. Improved understanding of this relationship promises to provide clinicians with better assessment and treatment options for both disorders. METHOD: This paper reviews research on the prevalence, etiology and pathogenesis, clinical characterization, and treatment of FM and MDD, as well as studies that examined the relationship between these disorders. Studies were identified via PubMed literature search. RESULTS: Our findings point to substantial similarities in neuroendocrine abnormalities, psychological characteristics, physical symptoms and treatments between FM and MDD. However, currently available findings do not support the assumption that MDD and FM refer to the same underlying construct or can be seen as subsidiaries of one disease concept. CONCLUSION: New methodological and theoretical approaches may lead to a better understanding of the link between FM and MDD, and to more effective psychological and psychopharmacological therapies for FM patients. In the meantime, clinicians should carefully screen for a history of MDD in patients with FM.</P>

Vortioxetine: a meta-analysis of 12 short-term, randomized, placebo-controlled clinical trials for the treatment of major depressive disorder.

Pae, Chi-Un,Wang, Sheng-Min,Han, Changsu,Lee, Soo-Jung,Patkar, Ashwin A,Masand, Praksh S,Serretti, Alessandro Journal of Psychiatry and Neuroscience] 2015 JOURNAL OF PSYCHIATRY AND NEUROSCIENCE Vol.40 No.3

<P>Vortioxetine was approved by the U.S. Food and Drug Administration (FDA) in September 2013 for treating major depressive disorder (MDD). Thus far, a number of randomized, double-blind, placebo-controlled clinical trials (RCTs) of vortioxetine have been conducted in patients with MDD. We performed a meta-analysis to increase the statistical power of these studies and enhance our current understanding of the role of vortioxetine in the treatment of MDD.</P>

Vilazodone for the Treatment of Depression: An Update

Sheng Min Wang,한창수,이수정,Ashwin A. Patkar,Prakash S. Masand,배치운 전남대학교 의과학연구소 2016 전남의대학술지 Vol.52 No.2

Vilazodone is a novel antidepressant having a selective serotonin (5-HT) reuptake inhibitorand 5-HT1A receptor partial agonist profile, so it has been regarded as a serotoninpartial agonist-reuptake inhibitor (SPARI). We aimed to provide Vilazodone’s clinicalimplications mainly by reviewing published clinical trials. Vilazodone has been speculatedto have three potential benefits including faster onset of action, greater efficacy,and better tolerability owning to its SPARI properties. However, no studies conductedso far have directly proven the above speculations. Five initial phase II trials failed todistinguish vilazodone from placebo in the treatment of MDD, but 4 randomized clinicaltrials (RCT), 3 post-hoc or pooled analysis, 1 long-term open label study, and ameta-analysis showed vilazodone’s superior efficacy over placebo. The studies alsoshowed vilazodone is generally safe and tolerable. However, diarrhea, nausea, headache,dizziness, dry mouth, and insomnia warrant close attention in clinical practicebecause they have been constantly noted throughout the clinical studies. 2 RCTs recentlydocumented the efficacy and safety of vilazodone in patients with generalizedanxiety disorder, which could be a start of broadening vilazodone’s usage or FDA approvalin diverse anxiety disorders.

Does Pregabalin Have Neuropsychotropic Effects?: A Short Perspective

David M. Marks,Ashwin A. Patkar,Prakash S. Masand,배치운 대한신경정신의학회 2009 PSYCHIATRY INVESTIGATION Vol.6 No.2

Pregabalin is a newly developed synthetic gamma-aminobutyric acid (GABA) that is approved for the treatment of fibromyalgia and several neuropathy. It has been proven to show analgesic, anxiolytic, anticonvulsant and sleep enhancement effects, which could be applicable in the treatment of a variety of psychiatric disorders. There have been consistent reports that unexplained somatic symptoms (i.e., pain) may be a part of psychiatric disorders such as major depressive disorder (MDD) and anxiety disorders. Previous researches have also suggested the possible therapeutic potential of anticonvulsants as augmentation therapy or monotherapy in the treatment of mood disorders and anxiety disorders. Hence this short perspective tries to prompt and facilitate a shifting of researchers’ attention to potential neuropsychotropic drug role of pregabalin to treat a wide range of neuropsychiatric disorders.