Efficacy and Safety of Escitalopram, Desvenlafaxine, and Vortioxetine in the Acute Treatment of Anxious Depression: A Randomized Rater-blinded 6-week Clinical Trial

Cheolmin Shin(Cheolmin Shin),Sang Won Jeon(Sang Won Jeon),Seung-Hoon Lee(Seung-Hoon Lee),Chi-Un Pae(Chi-Un Pae),Narei Hong(Narei Hong),Hyun Kook Lim(Hyun Kook Lim),Ashwin A. Patkar(Ashwin A. Patkar ) 대한정신약물학회 2023 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.21 No.1

Objective: Anxious depression is associated with greater chronicity, higher severity of symptoms, more severe functional impairment, and poor response to drug treatment. However, evidence for first-choice antidepressants in patients with anxious depression is limited. This study aimed to compare the efficacy and safety of escitalopram, desvenlafaxine, and vortioxetine in the acute treatment of anxious depression. Methods: Patients (n = 124) with major depressive disorder and high levels of anxiety were randomly assigned to an escitalopram treatment group (n = 42), desvenlafaxine treatment group (n = 40), or vortioxetine treatment group (n = 42) in a 6-week randomized rater-blinded head-to-head comparative trial. Changes in overall depressive and anxiety symptoms were assessed using the 17-item Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Rating Scale (HAMA), respectively. Results: Patients demonstrated similar baseline-to-endpoint improvement in scores and similar response and remission rates for HAMD and HAMA. Analysis of the individual HAMD items revealed that desvenlafaxine significantly reduced anxiety somatic scores (p = 0.013) and hypochondriasis scores (p = 0.014) compared to escitalopram. With respect to the individual HAMA items, desvenlafaxine treatment showed significantly lower scores for respiratory symptoms (p = 0.013) than escitalopram treatment and cardiovascular symptoms (p = 0.005) than vortioxetine treatment. The treatments were well tolerated, with no significant differences. Conclusion: Our results indicated no significant differences in the efficacy and tolerability of escitalopram, desvenlafaxine, and vortioxetine in this subtype of patients with anxious depression during the acute phase of treatment.

Erratum: Correction of Acknowledgements Second Generation Antipsychotics in the Treatment of Major Depressive Disorder: An Update

왕승민,한창수,이수정,전태연,Ashwin A. Patkar,Prakash S. Masand,배치운 전남대학교 의과학연구소 2019 전남의대학술지 Vol.55 No.1

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.

Simultaneous resection of synchronous colorectal liver metastasis: Feasibility and development of a prediction model

Mufaddal Kazi,Shraddha Patkar,Prerak Patel,Aditya Kunte,Ashwin Desouza,Avanish Saklani,Mahesh Goel 한국간담췌외과학회 2023 Annals of hepato-biliary-pancreatic surgery Vol.27 No.1

Backgrounds/Aims: Timing of resection for synchronous colorectal liver metastasis (CRLM) has been debated for decades. The aim of the present study was to assess the feasibility of simultaneous resection of CRLM in terms of major complications and develop a prediction model for safe resections. Methods: A retrospective single-center study of synchronous, resectable CRLM, operated between 2013 and 2021 was conducted. Upper limit of 95% confidence interval (CI) of major complications (≥ grade IIIA) was set at 40% as the safety threshold. Logistic regression was used to determine predictors of morbidity. Prediction model was internally validated by bootstrap estimates, Harrell’s C-index, and correlation of predicted and observed estimates. Results: Ninety-two patients were operated. Of them, 41.3% had rectal cancers. Major hepatectomy (≥ 4 segments) was performed for 25 patients (27.2%). Major complications occurred in 20 patients (21.7%, 95% CI: 13.8%–31.5%). Predictors of complications were the presence of comorbidities and major hepatectomy (area under the ROC curve: 0.692). Unacceptable level of morbidity (≥ 40%) was encountered in patients with comorbidities who underwent major hepatectomy. Conclusions: Simultaneous bowel and CRLM resection appear to be safe. However, caution should be exercised when combining major liver resections with bowel resection in patients with comorbid conditions.

Pain and Depression:What Links do we Know?

Aayushman Misra,박근영,Ashwin Patkar,심동석,배치운 대한우울조울병학회 2010 우울조울병 Vol.8 No.1

Pain may be caused by various medical illnesses, for example, fibromyalgia, diabetic neuropathy, herpetic neuralgia,trigeminal neuralgia, and irritable bowel syndrome. It is not uncommon to see such patients simultaneously suffering significant depressive symptoms in clinical practice. In addition, pain and depression commonly share pathophysiologies and clinical manifestations. Patients with depression present with emotional symptoms (depressed mood, sadness, and apathy, etc) and/or physical symptoms (pain, fatigue, and dizziness, etc), since the disorder is multi-faceted. In particular, a reciprocal relationship exists between painful physical symptoms and depression. Data suggest that approximately 65% of depressed patients may have accompanied painful physical symptoms and vice versa. In fact patients showing 2 or more pain symptoms may increase the risk of developing clinical depression than in those without pain symptoms. The co-occurrence of pain and depression may worsen not only clinical outcomes but also occupational, social, and global functioning of such patients. These findings clearly indicate that clinicians must be aware of the common co-occurrence of pain and depression in order to effectively treat and enhance remission for their patients with this comorbidity. Although there have been no clear etiological findings in relation with pain symptoms and depression, possible links between pain and depression may exist in the central and peripheral nervous systems. Both serotonin and norepinephrine are principal neurotransmitters in the ascending and descending pathways as well as in frontal and limbic regions involving in the pathophysiology of both pain and depression. Other biological markers also have overlapping roles in both conditions. As seen in diagnostic criteria for major depressive disorder (MDD), some depressive symptoms are also commonly seen in patients with pain symptoms such as lack of energy and insomnia. Familial aggregation studies have also suggested higher prevalence of MDD in pain symptoms than in general population. In conclusion, pain and depression may share common neuronal pathways, neurochemical findings, principal neurotransmitters and symptomatologies as well as have reciprocal impacts on each clinical course and treatment outcomes. Better understanding on the relationship between pain and depression may shed a light on the further roadmap for diagnosis and management for both conditions in clinical practice.

Addressing the side effects of contemporary antidepressant drugs: a comprehensive review

왕승민,한창수,박원명,이수정,Ashwin A. Patkar,Prakash S. Masand,배치운 전남대학교 의과학연구소 2018 전남의대학술지 Vol.54 No.2

Randomized trials have shown that selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) have better safety profiles than classical tricyclic antidepressants (TCAs). However, an increasing number of studies, including meta-analyses, naturalistic studies, and longer-term studies suggested that SSRIs and SNRIs are no less safe than TCAs. We focused on comparing the common side effects of TCAs with those of newer generation antidepressants including SSRIs, SNRIs, mirtazapine, and bupropion. The main purpose was to investigate safety profile differences among drug classes rather than the individual antidepressants, so studies containing comparison data on drug groups were prioritized. In terms of safety after overdose, the common belief on newer generation antidepressants having fewer side effects than TCAs appears to be true. TCAs were also associated with higher drop-out rates, lower tolerability, and higher cardiac side-effects. However, evidence regarding side effects including dry mouth, gastrointestinal side effects, hepatotoxicity, seizure, and weight has been inconsistent, some studies demonstrated the superiority of SSRIs and SNRIs over TCAs, while others found the opposite. Some other side effects such as sexual dysfunction, bleeding, and hyponatremia were more prominent with either SSRIs or SNRIs.

Aripiprazole augmentation for treatment of patients with inadequate antidepressants response

Pae, Chi-Un,Patkar, Ashwin A.,Jun, Tae-Youn,Lee, Chul,Masand, Prakash S.,Paik, In-Ho Wiley Subscription Services, Inc., A Wiley Company 2007 Depression and Anxiety Vol.24 No.7

<P>This study evaluated whether or not augmentation with aripiprzazole is beneficial and tolerable to patients with an inadequate response to antidepressants (ADs). Thirteen patients with nonpsychotic major depression, who had failed to respond to an adequate trial of at least one AD, were prescribed aripiprazole (dose, 5–30 mg) for 8 weeks. The dose of their preexisting ADs was not changed. The treatment response was defined as the mean changes in the scores of the Hamilton Depression Rating Scale (HAM-D) from the baseline to the end of treatment. Eleven (84.6%) patients returned for at least one follow-up visit, and 7 (53.8%) patients completed the study. The HAM-D and Clinical Global Impression—Severity (CGI-S) scores decreased significantly from the baseline to the end of treatment by 53.8% and 56.0%, respectively (Z = −2.937, P =.003; Z = −2.961, P =.003). Seven (63.6%) patients showed a ≥ 50% reduction in the HAM-D score at the end of treatment. Three (27.3%) patients met the remission criteria at the end of treatment. There were no serious side effects. Despite the high dropout rate in this open study, aripiprazole appears to be reasonably effective and tolerated as an augmentation strategy in conjunction with conventional ADs treatment in patients with an inadequate AD response. These results highlight the potential benefits of aripiprazole for these patients. However, adequately powered, randomized, controlled trials are needed to confirm these results. Depression and Anxiety 24:522–526, 2007. © 2006 Wiley-Liss, Inc.</P>

임상연구 논문의 질 평가를 위한 도구들

신철민,한창수,배치운,Ashwin A Patkar 대한정신약물학회 2011 대한정신약물학회지 Vol.22 No.2

Quality of medical research reports should be evaluated before they are applied to clinical practice. Since 1990s, several guidelines on research reports were suggested. Most recently published Consolidated Standards of Reporting Trials statement 2010 consists of 25 checklists and flow diagram for reporting an randomized controlled trial. Strengthening the reporting of observational studies in epidemiology statement is a checklist of items that should be addressed in articles reporting on the observational studies in epidemiology. TREND statement for the reporting of nonrandomized designs consists of 22 checklists. The Quality of Reporting of Meta-analyses checklist proposes to provide checklist and flow diagram for reporting of meta-analyses. The Meta-analysis of Observational Studies in Epidemiology statement proposes a checklist for compensating the study errors about observational studies in epidemiology. After development of reporting guidelines, improvements in the quality of reports are continuously reported, so using guidelines in the medical research will be expected to be more generalized. 1990년대부터 임상연구 논문의 질을 평가하기 위한 도구들이 제안되기 시작하였다. 무작위대조시험에 대한 평가 도구인 CONSORT, 관찰연구의 평가 도구인 STROBE, 비무작위 설계 연구에 대한 평가 도구인 TREND, 메타분석 보고의 질을 평가하기 위한 QUOROM, 관찰연구의 메타분석에 대한 질 평가를 위한 MOOSE 등이 있다. 이들 평가도구들이 개발되어 사용된 이후 임상연구 논문의 질이 좋아지고 있다는 보고가 이어지고 있으며, 이는 추후 임상의학 발전에 보다 긍정적으로 이바지할 것이다.

Epistatic Interactions between CREB and CREM Variants in Affective Disorder

Alberto Chiesa,배치운,Agnese Marsano,한창수,이수정,Ashwin A. Patkar,Alessandro Serretti 대한신경정신의학회 2014 PSYCHIATRY INVESTIGATION Vol.11 No.2

The aim of the present work is to investigate the existence of epistatic interactions possibly influencing psychotropic agents’ response between rs6740584 within Cyclic adenosine monophosphate Response Element Binding (CREB) and rs12775799 within cAMP response element-modulator (CREM) variants in bipolar disorder (BD) and major depressive disorder (MDD). All BD and MDD patients were administered with the Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HAMD) at baseline and at endpoint, respectively. A multiple regression model was employed to investigate the existence of possible epistatic interactions between the two variants and diverse clinical factors including drug response in affective disorders. No significant epistatic interaction was observed between rs6740584 within CREB and rs12775799 within CREM on both symptom improvement and other clinical factors in affective disorders. Our preliminary results suggest that no epistatic interaction between rs6740584 within CREB and rs12775799 within CREM should exist on clinical improvement and clinical factors in affective disorders.

Desvenlafaxine succinate: a newer antidepressant for the treatment of depression and somatic symptoms.

Seo, Ho-Jun,Sohi, Manmohandeep Singh,Patkar, Ashwin A,Masand, Prakash S,Pae, Chi-Un McGraw-Hill] 2010 Postgraduate medicine Vol.122 No.1

<P>Desvenlafaxine succinate (DVS) is one of several serotonin-norepinephrine reuptake inhibitors (SNRIs). Others are venlafaxine hydrochloride, milnacipran, and duloxetine. Desvenlafaxine has been approved by the US Food and Drug Administration (FDA) for the treatment of major depressive disorder (MDD) based on a number of randomized, placebo-controlled clinical trials. Clinical studies have investigated the efficacy of DVS in doses ranging from 50 to 400 mg/day for the treatment of MDD in adult outpatients. The effects of DVS 50 mg/day have been clearly distinguished from placebo in the reduction of MDD symptoms in such clinical trials. No additional therapeutic benefits were found at doses > 50 mg/day. The recommended dose of DVS ranges from 50 to 100 mg. Desvenlafaxine is currently the third SNRI approved by the FDA for this indication. Preliminary evidence also suggests the clinical usefulness of DVS in the treatment of vasomotor symptoms of menopause, anxiety symptoms, and painful physical symptoms. The modified pharmacokinetic and pharmacodynamic profiles of DVS differentiate this drug from the original product, venlafaxine. Significant points of difference, compared with venlafaxine, are once-daily dosing and the achievement of steady-state plasma concentrations within 4 to 5 days. To summarize, current evidence indicates that DVS has proven efficacy, acceptable safety and tolerability profiles, convenient dosing, and minimal impact on the cytochrome P450 enzyme system. A reduced risk for pharmacokinetic drug interactions is a potential advantage over other selective serotonin noradrenaline reuptake inhibitors. Desvenlafaxine succinate has demonstrated its efficacy for treating MDD but its variable efficacy, as shown in individual studies, limited long-term data, and its different risk-to-benefit ratio compared with earlier antidepressants, means that further investigation of this drug is necessary.</P>