Oral scopolamine augmentation for major depression.

Han, Changsu,Pae, Chi-Un Future Drugs Ltd 2013 Expert review of neurotherapeutics Vol.13 No.1

<P>Major depressive disorder (MDD) is a chronic, recurrent and devastating mental illness affecting approximately 16% of individuals in the USA in their lifetime. Selective serotonin reuptake inhibitors are the most widely prescribed and standard antidepressants in the treatment of MDD. The reason for such antidepressants being the first-trial antidepressant treatment choice has mainly come from proven efficacy, florid experience, and improved tolerability and safety compared with older antidepressants. However, currently available evidence from placebo-controlled or large practical clinical trials have demonstrated that the efficacy of such modern antidepressants is still limited to MDD patients in full remission as well as functional recovery in clinical practice. Almost 70% of MDD patients fail to remit after initial antidepressant treatment, and the risks to relapse and recurrence dramatically increase with further treatment steps. Thus, clinicians conclude that they have to make a proper and timely decision in management of their MDD patients in clinical practice, depicting that better understanding regarding diverse treatment strategies are not optional but mandatory for difficult-to-treat patients with MDD. Among different treatment strategies, augmentation with current antidepressant is attractive since it does not need any delay in switching to a different antidepressants, prevents loss of efficacy from previous antidepressants, enhances the efficacy of initial antidepressants or produces a synergistic effect with current antidepressants. Recently, Khajavi et al. investigated the efficacy and safety of oral scopolamine (anticholinergic agent) augmentation in moderate-to-severe MDD in a randomized, double-blind, placebo-controlled clinical trial (randomized controlled trial). This article summarizes the study background, methods and important results. Clinical implications, related practical issues, major pitfalls and future research direction are also presented.</P>

Corrigendum: 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 2020 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.18 No.4

Dilemma for enhancing psychiatrists' adherence to guideline (evidence)-based practice.

Han, Changsu,Wang, Sheng-Min,Lee, Soo Jung,Patkar, Ashwin A,Masand, Prakash S,Pae, Chi-Un Future Drugs Ltd 2013 Expert review of neurotherapeutics Vol.13 No.7

<P>Bipolar disorder (BD) is a prevalent and chronic devastating disorder that is associated with considerable psychosocial and economic morbidity. However, its complexity in the clinical course and manifestation of bipolar disorder is still a significant barrier to accurate differential diagnosis from unipolar depression (UD), by which it is still underdiagnosed and undertreated in clinical practice. In community studies, first onset of BD is usually in the adolescent ages, and the occurrence of UD is usually its first clinical manifestation. In addition, reliable criteria for differentiating UD from BD along with validated treatment guidelines for BD are currently not sufficient or adequate, commonly resulting in misdiagnosis and mismanagement of both clinical conditions. Therefore, the study under evaluation results from clinician practice patterns in the real world will substantially enhance the current understanding on the actual situation and unmet needs for accurate and proper diagnosis and management of bipolar depression.</P>

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.

Intimate partner violence and incidence of depression in married women: A longitudinal study of a nationally representative sample

Han, Kyu-Man,Jee, Hee-Jung,An, Hyonggin,Shin, Cheolmin,Yoon, Ho-Kyoung,Ko, Young-Hoon,Ham, Byung-Joo,Kim, Yong-Ku,Han, Changsu Elsevier 2019 Journal of affective disorders Vol.245 No.-

<P><B>Abstract</B></P> <P><B>Background</B></P> <P>Intimate partner violence (IPV) has a serious detrimental effect on mental health outcomes. We aimed to investigate the association of verbal or physical IPV with incidence of depressive symptoms in both married women and men according to the victim-perpetrator role. The potential mediating role of verbal or physical IPV in the association between satisfaction level with family relationships or childhood adversity and the incidence of depressive symptoms in married adults was also explored.</P> <P><B>Methods</B></P> <P>The Korea Welfare Panel Study (KOWEPS) in 2006 and 2007 dataset was analyzed for 9217 married respondents aged 19 years or older. Physical and verbal IPV was assessed according to victim-perpetrator role in 2006. Depressive symptoms were evaluated by the Center for Epidemiologic Studies Depression Scale, 11-item version in 2006 and 2007. Association of IPV with incidental depressive symptoms was investigated with logistic regression analysis fully-adjusted for all potential confounding factors.</P> <P><B>Results</B></P> <P>The bidirectional role of verbal IPV and victimization by physical IPV led to incidence of depressive symptoms in married women. Verbal IPV significantly mediated the association between satisfaction level with the family relationship and incidental depressive symptoms in women.</P> <P><B>Limitations</B></P> <P>We did not investigate the influence of premorbid depressive symptoms on new-onset IPV.</P> <P><B>Conclusions</B></P> <P>This study is the first to demonstrate that gender and the victim-perpetrator role are critical moderating factors in the association between IPV and depressive symptom incidence using a nationally representative sample</P> <P><B>Highlights</B></P> <P> <UL> <LI> Influence of intimate partner violence (IPV) on incidence of depression was assessed. </LI> <LI> 9217 married adults in data of Korea Welfare Panel Study (KOWEPS) 2006 and 2007. </LI> <LI> Center for Epidemiologic Studies Depression Scale, 11-item version was used. </LI> <LI> Bidirectional role of verbal IPV led to incidence of depression in married women. </LI> <LI> Victimization by physical IPV led to incidence of depression in married women. </LI> </UL> </P>

Second-generation antipsychotics in the treatment of major depressive disorder: current evidence.

Han, Changsu,Wang, Sheng-Min,Kato, Masaki,Lee, Soo-Jung,Patkar, Ashwin A,Masand, Prakash S,Pae, Chi-Un Future Drugs Ltd 2013 Expert review of neurotherapeutics Vol.13 No.7

<P>Major depressive disorder (MDD) is a chronic and recurrent mental condition leading to huge impacts on direct and indirect personal and public medical costs. To overcome such a serious mental disorder, we currently have a number of different classes of antidepressants, such as selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, noradrenergic and specific serotonin receptor antagonists, dopamine and norepinephrine reuptake inhibitors, along with newly introduced antidepressants (e.g., vilazodone and agomelatine). However, a number of well-controlled clinical trials, meta-analyses and practical clinical studies have found that only a third of such MDD patients remit following adequate antidepressant treatment, while most MDD patients suffer from significant core depressive or residual symptoms during their clinical course. There have been some treatment approaches to overcome such a shortage of antidepressant efficacy, such as augmentation of psychotropics other than antidepressants, switching to a different antidepressant and combinations of different antidepressants. Among these different second treatment options, augmentation treatment has some favorable points compared with the combination and switching option (e.g., maintaining previous antidepressant partial response, synergistic effect between different pharmacological profile and no need to wash out previous antidepressants). Recently, second-generation antipsychotics (SGAs), olanzapine plus fluoxetine, quetiapine extended release and aripiprazole have clearly demonstrated efficacy in the treatment of MDD patients through a number of small-scale, open-label studies or randomized, placebo-controlled clinical trials. Eventually, in November 2007, aripiprazole was the first approved by the US FDA as an adjunctive treatment to antidepressants for treating MDD, followed by the approval of quetiapine and olanzapine plus fluoxetine at 2009. This comprehensive review provides an overview of the clinical trial data of SGAs for treating MDD and clinical issues raised in the use of SGA therapy in patients with MDD in clinical practice.</P>

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

Changsu Han,Sheng Min Wang,Won-Myong Bahk,Soo-Jung Lee,Ashwin A Patkar,Prakash S Masand,Chi Un Pae 대한정신약물학회 2019 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.17 No.4

Objective: The 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. Methods: Data 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. Results: In 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. Conclusion: The 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.

Adiposity parameters and cognitive function in the elderly: Application of “Jolly Fat” hypothesis to cognition

Han, Changsu,Jo, Sangmee Ahn,Seo, Ji A,Kim, Byoung Gwon,Kim, Nan Hee,Jo, Inho,Park, Moon Ho,Park, Kun Woo Elsevier 2009 ARCHIVES OF GERONTOLOGY AND GERIATRICS Vol.49 No.2

<P><B>Abstract</B></P> <P>Obesity has a strong association with cardiovascular and metabolic diseases, which have also been linked with dementia. While recent studies have reported an association between mid-life obesity and dementia, the role that later-life obesity may have is less clear. A total of 721 community-dwelling elderly (60–85 years old) were selected. Obesity parameters, like body mass index (BMI), waist-hip ratio (WHR), waist circumference (WC), and percent body fat (PBF), as well as cognitive functions were measured over a period of approximately 2 years, and then the relationships between these variables were assessed. The change in cognitive function in the elderly was associated with the baseline assessment of BMI (linearly, <I>β</I> =0.092), WC (quadratic, <I>β</I> =1.333), and PBF (linearly, <I>β</I> =0.097). Using multiple regression analyses, the differences exist in the change of cognitive function over time according to the sex. For men, increased obesity over time when obese in the baseline assessment (BMI, WHR, WC) were associated with a positive change in cognitive function. For women, a decreased obesity over time when obese in the baseline assessment (WHR) and an increased obesity over time when they had a normal adiposity in the baseline assessment (WC) were both associated with cognitive decline. The relationship between obesity and cognitive decline in the elderly is complex and some differences exist between the sexes. The application of the “Jolly Fat” hypothesis to cognitive function can only be applied to elderly men and not to elderly women.</P>

Relationship of depression, chronic disease, self-rated health, and gender with health care utilization among community-living elderly

Han, Kyu-Man,Ko, Young-Hoon,Yoon, Ho-Kyoung,Han, Changsu,Ham, Byung-Joo,Kim, Yong-Ku Elsevier 2018 Journal of affective disorders Vol.241 No.-

<P><B>Abstract</B></P> <P><B>Background</B></P> <P>We investigated the interactive effects of depressive symptoms and chronic diseases on health care utilization among elderly people and explored the potential moderating effect of gender and the mediating effect of self-rated health (SRH) on the association between depressive symptoms and health care utilization.</P> <P><B>Method</B></P> <P>We analyzed data from 5223 people aged 60 years or older living in the community from the Korea Welfare Panel Study in 2015. Depressive symptoms were measured using an 11-item version of the Center for Epidemiologic Studies Depression (CES-D-11) Scale and morbidity within 28 disease categories was assessed. Health care utilization was evaluated as the number of outpatient visits (OV), number of hospitalizations (NH), and number of days spent in the hospital (DH) during past year. Hierarchical moderated regression analyses were applied to investigate the interactive effects. We also adopted the mediation analysis method by Hayes and Preacher.</P> <P><B>Results</B></P> <P>A significant interactive effect of CES-D-11 score and chronic disease on OV was found. A positive correlation between CES-D-11 score and OV was only observed in those with chronic disease. Gender had a moderating effect on the association of depression symptoms with OV, NH, and DH among elderly people with chronic disease. SRH had mediating effects on the association of CES-D-11 with OV, NH, and DH only among those with chronic disease.</P> <P><B>Limitations</B></P> <P>The severity or multimorbidity of chronic diseases, which could affect health care utilization among elderly were not considered.</P> <P><B>Conclusions</B></P> <P>We elucidated the complex aspects of the relationship between depressive symptoms and chronic disease and their interactive effects on health care utilization among elderly people, and identified important roles of gender and SRH.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A nationally representative sample of 5223 community-living elderly (≥60 years). </LI> <LI> Significant interactive effect of depression and chronic disease on health care use. </LI> <LI> Gender moderated association of depression with health care use in chronically ill. </LI> <LI> Self-rated health mediated the association of depression with health care use. </LI> <LI> The mediation by self-rated health was moderated by gender and chronic disease. </LI> </UL> </P>

Optimizing the Use of Aripiprazole Augmentation in the Treatment of Major Depressive Disorder: From Clinical Trials to Clinical Practice

Han, Changsu,Wang, Sheng-Min,Lee, Soo-Jung,Jun, Tae-Youn,Pae, Chi-Un Chonnam National University Medical School 2015 CMJ Vol.51 No.2

<P>Major depressive disorder (MDD) is a recurrent, chronic, and devastating disorder leading to serious impairment in functional capacity as well as increasing public health care costs. In the previous decade, switching therapy and dose adjustment of ongoing antidepressants was the most frequently chosen subsequent treatment option for MDD. However, such recommendations were not based on firmly proven efficacy data from well-designed, placebo-controlled, randomized clinical trials (RCTs) but on practical grounds and clinical reasoning. Aripiprazole augmentation has been dramatically increasing in clinical practice owing to its unique action mechanisms as well as proven efficacy and safety from adequately powered and well-controlled RCTs. Despite the increased use of aripiprazole in depression, limited clinical information and knowledge interfere with proper and efficient use of aripiprazole augmentation for MDD. The objective of the present review was to enhance clinicians' current understanding of aripiprazole augmentation and how to optimize the use of this therapy in the treatment of MDD.</P>