How many different symptom combinations fulfil the diagnostic criteria for major depressive disorder? Results from the CRESCEND study.

BACKGROUND: The polythetic nature of major depressive disorder (MDD) in DSM- IV and DSM-5 inevitably leads to diagnostic heterogeneity. AIMS: This study aimed to identify the number of depressive symptom combinations actually fulfilling the DSM-IV diagnostic criteria that can be found in Korean MDD patients and the relative frequencies of each combination. METHODS: Using the data from the Clinical Research Center for Depression (CRESCEND) study in South Korea, we enrolled 853 MDD patients diagnosed using DSM-IV and scored as 8 or more on the Hamilton Depression Rating Scale (HAMD). Descriptive statistical analyses were performed to reveal the degree of diagnostic heterogeneity of the MDD. RESULTS: This study identified 119 different depressive symptom combinations. The most common combination consisted of all nine depressive symptom profiles, and nine different combinations were each present in more than 3% of the patients. CONCLUSION: The findings support the criticism that the diagnosis of MDD is not based on a single mental process, but on a set of 'family resemblances'.

Clinical Significance of the Number of Depressive Symptoms in Major Depressive Disorder: Results from the CRESCEND Study.

Our study aimed to establish the relationship between the number of depressive symptoms and the clinical characteristics of major depressive disorder (MDD). This would enable us to predict the clinical significance of the number of depressive symptoms in MDD patients. Using data from the Clinical Research Center for Depression (CRESCEND) study in Korea, 853 patients with DSM-IV MDD were recruited. The baseline and clinical characteristics of groups with different numbers of depressive symptoms were compared using the χ(2) test for discrete variables and covariance (ANCOVA) for continuous variables. In addition, the scores of these groups on the measurement tools were compared by ANCOVA after adjusting the potential effects of confounding variables. After adjusting the effects of monthly income and history of depression, a larger number of depressive symptoms indicated higher overall severity of depression (F [4, 756] = 21.458, P < 0.001) and higher levels of depressive symptoms (F [4, 767] = 19.145, P < 0.001), anxiety symptoms (F [4, 765] = 12.890, P < 0.001) and suicidal ideation (F [4, 653] = 6.970, P < 0.001). It also indicated lower levels of social function (F [4, 760] = 13.343, P < 0.001), and quality of life (F [4, 656] = 11.975, P < 0.001). However, there were no significant differences in alcohol consumption (F [4, 656] = 11.975, P < 0.001). The number of depressive symptoms can be used as an index of greater illness burden in clinical psychiatry.

Enhanced light extraction efficiency in organic light-emitting diode with randomly dispersed nanopattern.

An optical scattering layer composed of randomly dispersed nanopatterns (RDNPs) was introduced in an organic light-emitting diode (OLED) to increase the out-coupling efficiency. An RDNP was fabricated by direct printing on a glass substrate. Owing to its low haze and high transmittance, the RDNP acted as a light extraction layer in the OLED. The RDNP OLEDs showed higher current density and luminance than the reference devices at the same voltage. The current and power efficiencies of the RDNP OLED increased by 25% and 34%, respectively, without electrical degradation. Furthermore, the RDNP devices achieved an external quantum efficiency of 27.5% at 1 mA/cm².

Age-related differences in suicidality between young people and older adults with depression: data from a nationwide depression cohort study in Korea (the CRESCEND study).

This study compared young people and older adults with depression to identify differences in suicidality between these groups. A total of 1003 patients with moderate to severe depression (Hamilton Depression Rating Scale [HDRS] score ≥14) were recruited from a national sample of 18 hospitals. Of the patients included in this study, 103 (10.3%) were placed in the younger group (age <25years) and 900 (89.7%) were placed in the older group (age ≥25years). Suicide-related variables and predictive factors associated with significant suicidal ideation were compared between the two groups. Regardless of the severity of depression, subjects in the younger group were more likely than were those in the older group to report significant suicidal ideation (scores ≥6 on the Beck Scale for Suicide Ideation [SSI-B], 79.6 vs. 53.7%, respectively; p<0.001), have had a suicide attempt at the current episode (4.9 vs. 1.6%, respectively; p=0.037), and have a history of suicide attempts (43.7 vs. 19.4%, respectively; p<0.001). Logistic regression models revealed that, in contrast to the predictive factors in the older group, subjects in the younger group were more affected by their history of suicide attempts (OR [95% CI]: 12.4, [1.5-99.1]; p=0.018) and depressive episodes (OR [95% CI]: 13.0, [1.6-104.0]; p=0.016). Also in contrast to the older group, an increase in HDRS score was not identified as a possible precipitating factor of significant suicidal ideation in younger subjects. The present findings demonstrate that suicidality in depressed young people was more severe than in older adults, but that suicidality was not correlated with the severity of depression. These data suggest that close attention should be paid to young people even in mild or moderate depression.

Hazardous drinking-related characteristics of depressive disorders in Korea: the CRESCEND study.

This study aimed to identify clinical correlates of hazardous drinking in a large cohort of Korean patients with depression. We recruited a total of 402 depressed patients aged > 18 yr from the Clinical Research Center for Depression (CRESCEND) study in Korea. Patients' drinking habits were assessed using the Korean Alcohol Use Disorder Identification Test (AUDIT-K). Psychometric scales, including the HAMD, HAMA, BPRS, CGI-S, SSI-Beck, SOFAS, and WHOQOL-BREF, were used to assess depression, anxiety, overall psychiatric symptoms, global severity, suicidal ideation, social functioning, and quality of life, respectively. We compared demographic and clinical features and psychometric scores between patients with and without hazardous drinking behavior after adjusting for the effects of age and sex. We then performed binary logistic regression analysis to identify independent correlates of hazardous drinking in the study population. Our results revealed that hazardous drinking was associated with current smoking status, history of attempted suicide, greater psychomotor retardation, suicidal ideation, weight loss, and lower hypochondriasis than non-hazardous drinking. The regression model also demonstrated that more frequent smoking, higher levels of suicidal ideation, and lower levels of hypochondriasis were independently correlates for hazardous drinking in depressed patients. In conclusion, depressed patients who are hazardous drinkers experience severer symptoms and a greater burden of illness than non-hazardous drinkers. In Korea, screening depressed patients for signs of hazardous drinking could help identify subjects who may benefit from comprehensive therapeutic approaches.

Enhanced light extraction efficiency in organic light emitting diodes using a tetragonal photonic crystal with hydrogen silsesquioxane.

We report an organic light emitting diode (OLED) with a hydrogen silsesquioxane as a scattering material, for enhancing light extraction efficiency. A tetragonal photonic crystal was used as pattern type, and fabricated using a direct printing technique. Planarization was accomplished using TiO2 solgel solution, having a refractive index identical to that of the indium zinc oxide transparent electrode. The current efficiency and power efficiency of the OLED increased by 17.3% and 43.4% at 10 mA/cm², respectively, without electric degradation.

Personality traits associated with suicidal behaviors in patients with depression: the CRESCEND study.

The aim of the current study was to identify personality traits associated with suicidal behavior in patients with depression. Of the 1183 patients screened for an observational cohort study of depression, 334 (28.2%) who completed the Temperament and Character Inventory (TCI) were included in these analyses. To minimize the effect of current mood state, the TCI was performed 12 weeks after initiation of treatment, and we adjusted for the severity of depression. Of the 344 participants, 59 had a lifetime history of at least one suicide attempt, 37 had a lifetime history of multiple suicide attempts, and 5 attempted suicide during the 12-week study period. At baseline, patients with a lifetime history of at least one suicide attempt, a lifetime history of multiple suicide attempts, and a suicide attempt during the study period expressed more serious current suicidal ideation than did those without such a history, despite the absence of differences among the groups in the severity of depressive and anxiety symptoms. Of the seven personality scales of the TCI, lower scores on the self-directedness scale of the character dimension were associated with a history of at least one suicide attempt (OR [95% CI], 0.91 [0.87-0.96]; p<0.001), a history of multiple suicide attempts (0.91 [0.86-0.97]; p=0.003), and suicide attempts during study period (0.80 [0.69-0.94]; p=0.006). These findings suggest that depressed patients with a history of suicidal behavior differ from non-attempters with regard to personality traits, especially the character dimension of self-directedness. It is noteworthy that this result emerged after controlling for the effect of current mood state.

The Change of Suicidal Ideation Over a 12-Week Naturalistic Treatment of Depression: Comparison Between Young People and Older Adults.

OBJECTIVE: We investigated the differences in suicidality between young people and older adults with depression over the course of 12-week naturalistic treatment with antidepressants. METHODS: A total of 565 patients who had moderate to severe depression (Hamilton Depression Rating Scale [HAM-D] score ≥14) and significant suicidal ideation (Beck Scale for Suicide Ideation [SSI-B] score ≥6) were recruited from 18 hospitals. Participants were classified into two groups: the younger group (13-24 years of age, n=82) and the older group (≥25 years of age, n=483). Total scores over time on the SSI-B, HAM-D, and Hamilton Anxiety Rating Scale (HAM-A) were assessed and compared between the two groups. RESULTS: At baseline, the younger group had lower HAM-D scores (21.0 vs. 22.2; p=0.028) but higher SSI-B scores (19.4 vs. 15.6; p<0.001) compared with the older group. The overall 12-week proportion of patients with resolved suicidality was 44.1% in the younger group and 69.2% in the older group. Although the improvement in the HAM-D and HAM-A scores did not differ between the groups, suicidal ideation in the younger group remained more severe than in the older group throughout the treatment. The ratio of the subjects who achieved HAM-D remission or response but did not achieve SSI-B remission was significantly higher in the younger group than in the older group. CONCLUSION: These data suggest that in depressed youths, suicide risk is a serious concern throughout the course of depression even when favorable treatment outcomes are obtained.

Distinctive clinical characteristics and suicidal tendencies of patients with anxious depression.

This study evaluated clinical characteristics and suicidality of patients with anxious depression in a large cohort of samples. Data were collected from 1003 patients who were depressed. A total of 461 patients were diagnosed with anxious depression and 542 were diagnosed with nonanxious depression. After adjusting for the severity of depression, those in the anxious depression group had significantly younger onset age, had been suffering from depression for a longer period, were more likely to experience a recurrence, and obtained lower scores on a scale assessing quality of life. The anxious depression group was characterized by a significantly higher proportion of individuals reporting significant suicidal ideation and previous suicide attempts, and those in this group tended to obtain higher scores on the Scale for Suicide Ideation. The present findings that were drawn from detailed evaluation of suicidality strongly support previous results assessed only with the help of clinical reports. More attention should be paid to assess suicide risk in these patients.

Network Analysis of the Symptoms of Depressive Disorders Over the Course of Therapy: Changes in Centrality Measures.

OBJECTIVE: Network analysis can be used in terms of a novel psychopathological approach for depressive syndrome. We aimed to estimate the successive network structures of depressive symptoms in patients with depressive disorder using data from the Clinical Research Center for Depression study. METHODS: We enrolled 1,152 South Korean adult patients with depressive disorders who were beginning treatment for first-onset or recurrent depressive episodes. We examined the network structure of the severities of the items on the Hamilton Depression Rating Scale (HAMD) at baseline and at weeks 2, 12, 25, and 52. The node strength centrality of all the HAMD items at baseline and at week 2, 12, 25, and 52 in terms of network analysis. RESULTS: In the severity networks, the anxiety (psychic) item was the most centrally situated in the initial period (baseline and week 2), while loss of weight was the most centrally situated item in the later period (weeks 25 and 52). In addition, the number of strong edges (i.e., edges representing strong correlations) increased in the late period compared to the initial period. CONCLUSION: Our findings support a period-specific and symptom-focused therapeutic approach that can provide complementary information to the unidimensional total HAMD score.

Prospective study on cytokine levels in medication-naïve adolescents with first-episode major depressive disorder.

BACKGROUND: Evidence suggests that depression is correlated with immune-inflammatory responses, and efforts have been made to identify the relationships between depression and inflammatory markers. This study investigated the level of cytokines before and after treatment for major depressive disorder (MDD) in medication-naïve adolescents with first-episode MDD and compared them with the levels in healthy adolescents. The relationship between cytokine levels and the severity of depressive symptoms was also examined. METHODS: Twenty-five adolescents with MDD and 25 healthy controls aged 13 to 18 years were included in the study. Blood samples were obtained, and depression severity was assessed twice in the MDD group before and after treatment and once in the healthy group. RESULTS: When compared with healthy controls, adolescents with MDD had lower levels of interleukin 2 (IL-2), interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α) and IL-10 before treatment and higher levels of IL-2, IFN-γ, and IL-10 after treatment. In addition, the IFN-γ levels correlated with depressive severity scores in both the Children's Depression Inventory (CDI) and Hamilton Depression Rating Scale (HDRS). The IL-10 level correlated with depressive severity only on the HDRS. LIMITATIONS: The sample size was small, and the 12-week follow-up time after treatment was relatively short. CONCLUSION: IL-2, IFN-γ, TNF-α, and IL-10 levels in medication-naïve adolescents with first-episode MDD differed from those in healthy controls. The levels of IL-2, IFN-γ, and IL-10 were altered after antidepressant treatment. Further, the IFN-γ and IL-10 levels correlated with the severity of depressive symptoms.

Psychometric validation of the Korean version of Structured Interview for Post-traumatic Stress Disorder (K-SIP).

For diagnosis and management of post-traumatic stress disorder (PTSD), the easily administered assessment tool is essential. Structured Interview for PTSD (SIP) is a validated, 17-item, simple measurement being used widely. We aimed to develop the Korean version of SIP (K-SIP) and investigated its psychometric properties. Ninety-three subjects with PTSD, 73 subjects with mood disorder or anxiety disorder as a psychiatric control group, and 88 subjects as a healthy control group were enrolled in this study. All subjects completed psychometric assessments that included the K-SIP, the Korean versions of the Clinician-Administered PTSD Scale (CAPS) and other assessment tools. The K-SIP presented good internal consistency (Cronbach's alpha=0.92) and test-retest reliability (r=0.87). K-SIP showed strong correlations with CAPS (r=0.72). Among three groups including PTSD patients, psychiatric controls, and normal controls, there were significant differences in the K-SIP total score. The potential cut-off total score of K-SIP was 20 with highest diagnostic efficiency (91.9%). At this point, the sensitivity and specificity were 95.5% and 88.4%, respectively. Our result showed that K-SIP had good reliability and validity. We expect that K-SIP will be used as a simple but structured instrument for assessment of PTSD.

Cytokine imbalance in the pathophysiology of major depressive disorder.

OBJECTIVE: A substantial body of evidence indicates that dysregulation of the immune system is associated with Major Depressive Disorder (MDD). Because most cytokines have pleiotropic effects, we measured various subsets of cytokines to examine the association between immune response and MDD. METHODS: Forty-eight hospitalized MDD patients and 63 normal controls were recruited. We measured in vitro monocytic (IL-6 and tumor necrosis factor (TNF)-alpha), Th1 (interferon (IFN)-gamma and interleukin (IL)-2), Th2 (IL-4), and Treg (transforming growth factor (TGF)-beta1) cytokine production as well as IL-2/IL-4 and IFN-gamma/IL-4 ratios for both groups. Depressive symptoms were assessed by Hamilton Depression Rating Scale. Patients were evaluated before and after 6 weeks of antidepressant treatment. RESULTS: At admission, IL-6, TNF-alpha, TGF-beta1 production, and IFN-gamma/IL-4 ratio were significantly higher, whereas IFN-gamma, IL-2, and IL-4 were significantly lower in MDD patients. After treatment, IL-6 and TGF-beta1 production were significantly lower than before treatment. CONCLUSION: We suggest that activation of monocytic proinflammatory cytokines, and inhibition of both Th1 and Th2 cytokines may be associated with immunological dysregulation in MDD. TGF-beta1 may be associated with the regulation of monocytic cytokines as well as Th1 and Th2 cytokines in MDD.

Paroxetine versus Venlafaxine and Escitalopram in Korean Patients with Major Depressive Disorder: A Randomized, Rater-blinded, Six-week Study.

OBJECTIVE: The purpose of this study was to compare the efficacy and safety of escitalopram, paroxetine and venlafaxine in Korean patients with major depressive disorder (MDD). METHODS: A total of 449 Korean MDD patients were recruited in a six-week, randomized, rater-blinded, active-controlled trial and were evenly randomized to paroxetine, venlafaxine, or escitalopram treatment. RESULTS: When comparing the mean difference for the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating Scale (HDRS) total scores during six weeks, paroxetine (-6.4±0.4, and -5.4±0.4, respectively) was found to be significantly superior to escitalopram (-3.7±0.5 and -3.1±0.4, respectively). Venlafaxine had a significantly lower MADRS total score (-5.4±0.4) than escitalopram. When adjusting baseline variables, the response, according to the MADRS and HDRS scores, in the paroxetine group was greater than that for the escitalopram group (odds ratio [OR]=2.43, 95% confidence interval [CI]=1.42-4.16 for MADRS; and OR=2.32, 95% CI=1.35-3.97 for HDRS) and the venlafaxine group (OR=1.94, 95% CI=1.17-3.21 for MADRS; and OR=1.71, 95% CI=1.03-2.83 for HDRS). Despite that the overall tolerability was high and similar among the three groups, a total of 268 subjects (59.7%) prematurely discontinued treatment, representing the main limitation of the present study. CONCLUSION: Although a low study completion rate limits generalizability, our findings suggest that paroxetine might be superior to escitalopram in Korean MDD patients. Further studies should be conducted to draw a definite conclusion.

Clinical Validation of the Psychotic Depression Assessment Scale, Hamilton Depression Rating Scale-6, and Brief Psychiatric Rating Scale-5: Results from the Clinical Research Center for Depression Study.

OBJECTIVE: The aim of this study was to validate the psychotic depression assessment scale (PDAS), which includes the six-item melancholia subscale from the Hamilton depression rating scale (HAMD-6) and the five-item psychosis subscale from the brief psychiatric rating scale (BPRS-5). Data from the Clinical Research Center for Depression (CRESCEND) study, which is a 52-week naturalistic trial, were analyzed. METHODS: Fifty-two patients with psychotic depression from the CRESCEND study met our inclusion criteria. The patients underwent the following psychometric assessments: the PDAS, including HAMD-6 and BPRS-5, the clinical global impression scales, the HAMD, the positive symptom subscale, and the negative symptom subscale. Assessments were performed at the baseline and then at weeks 1, 2, 4, 8, 12, 24, and 52. Spearman correlation analyses were used to assess the clinical validity and responsiveness of the PDAS. RESULTS: The clinical validity and responsiveness of the PDAS, including HAMD-6 and BPRS-5, were acceptable, with the exception of the clinical responsiveness of the PDAS for positive symptoms and the clinical responsiveness of BPRS-5 for negative symptoms. CONCLUSION: The clinical relevance of the PDAS has been confirmed and this clinical validation will enhance its clinical utility and availability.

Korean atomic bomb survivors' report on the present status and health of their children: a mail questionnaire survey.

A mail questionnaire survey on the present status and health of children of Korean survivors of the 1945 atomic bombing of Japan was conducted in 2004. In total, 1,115 Korean A-bomb survivors' reports on demographic factors and the health of their children (n = 4,079) were analysed. In 2004, 293 of their children were reported to have died and 3,786 children still living. Among the deceased children, the cause of death was unidentified in 64 per cent of cases. The most frequently reported cause of death was infectious disease (9.6%). Most of the deaths (51%) were reported to have occurred in children less than ten years old. The most frequently reported congenital disorders among living children were mental retardation (0.18%) and congenital bone disorders (0.18%). Further study and administrative support are needed to more accurately determine the status of Korean A-bomb survivors and their children.

Association of treatment response with obesity and other metabolic risk factors in adults with depressive disorders: Results from a National Depression Cohort study in Korea (the CRESCEND study).

BACKGROUND: Available studies indicate that obesity may exert a moderational effect on antidepressant treatment response. The aim of this study was to investigate the relationship between treatment response and metabolic abnormalities amongst patients with depressive disorders in a large naturalistic clinical setting. METHODS: A nationwide prospective study was conducted in 18 hospitals in South Korea; 541 depressive patients meeting DSM-IV criteria were recruited. After baseline evaluation, subjects received naturalistic clinician-determined antidepressant interventions. Assessment was performed at baseline and weeks 1, 2, 4, 8, 12, 24 and 52. Treatment response was defined as a ≥50% reduction from baseline on at least one evaluation point. RESULTS: In univariate comparison, the patients who showed insufficient response to antidepressant therapy were more likely to be male, unmarried, unemployed, and obese. After adjusting for baseline variables, male sex (OR=1.82) and obesity (OR=1.55) remained as were significant variables. Stratification of the subjects into one of three groups, i.e. male, pre-menopausal female and post-menopausal female, revealed that males with concurrent metabolic problems, (i.e. the presence of one or more of hypertension, hyperglycemia, or hypercholesterolemia) had significantly higher risk for insufficient response (OR=2.32) and, after adjusting for baseline variables, obesity predicted insufficient response in post-menopausal female (OR=2.41). CONCLUSIONS: The presence of metabolic abnormalities in patients with depressive disorders was associated with decreased treatment response to antidepressants. These results underscore the neurobiological relationship between obesity and the central nervous system, and provide empiric evidence supporting stratification of treatment response in depression.

Potential Relationship between Season of Birth and Clinical Characteristics in Major Depressive Disorder in Koreans: Results from the CRESCEND Study.

We aimed to examine the potential relationship between season of birth (SOB) and clinical characteristics in Korean patients with unipolar non-psychotic major depressive disorder (MDD). Using data from the Clinical Research Center for Depression (CRESCEND) study in South Korea, 891 MDD patients were divided into two groups, those born in spring/summer (n=457) and those born in autumn/winter (n=434). Measurement tools comprising the Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Brief Psychiatric Rating Scale, Scale for Suicidal Ideation, Clinical Global Impression of severity, Social and Occupation Functional Assessment Scale, WHO Quality of Life assessment instrument-abbreviated version, Alcohol Use Disorder Identification Test, and Temperament and Character Inventory were used to evaluate depression, anxiety, overall symptoms, suicidal ideation, global severity, social function, quality of life, drinking, and temperament and character, respectively. Using independent t-tests for continuous variables and χ² tests for discrete variables, the clinical characteristics of the two groups were compared. MDD patients born in spring/summer were on average younger at onset of first depressive episode (t=2.084, p=0.038), had greater loss of concentration (χ²=4.589, p=0.032), and were more self-directed (t=2.256, p=0.025) than those born in autumn/winter. Clinically, there was a trend for the MDD patients born in spring/summer to display the contradictory characteristics of more severe clinical course and less illness burden; this may have been partly due to a paradoxical effect of the 5-HT system.

The Efficacy and Safety of Clonazepam in Patients with Anxiety Disorder Taking Newer Antidepressants: A Multicenter Naturalistic Study.

OBJECTIVE: This study compared the efficacy and tolerability of clonazepam with other benzodiazepines in patients with anxiety disorders. METHODS: Inclusion criteria were as follows: age >20 years, diagnosis of anxiety disorder according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition, text revision (DSM-IV-TR) criteria, taking only one type of antidepressant, and prescribed one of three oral benzodiazepines (alprazolam, clonazepam, or lorazepam). At baseline and week 6, clinical benefit was evaluated using the Clinical Global Impression-Severity Scale (CGI-S), Clinical Global Impression-Anxiety Scale (CGI-anxiety), and Clinical Global Impression-Sleep Scale (CGI-sleep). RESULTS: Among 180 patients, no differences in demographic characteristics among the three benzodiazepine groups were noted. After six weeks of treatment, all benzodiazepine groups showed significant improvements in CGI-S, CGI-anxiety, and CGI-sleep scores (p<0.001). There were no differences in mean changes in CGI-S, CGI-anxiety and CGI-sleep among the three benzodiazepine groups. The incidence of side effects was significantly lower in the clonazepam group than with the other benzodiazepines. The incidences of adverse events for the clonazepam, alprazolam, and lorazepam groups were 26.7% (n=20), 48.4% (n=31), and 43.9% (n=18), respectively. CONCLUSION: The present study suggests that clonazepam is as efficacious as other benzodiazepines for the treatment of various anxiety disorders. Furthermore, the safety profile of clonazepam was superior to the other benzodiazepines in this study.

Comparison of efficacy and safety of milnacipran and fluoxetine in Korean patients with major depression.

OBJECT: To compare efficacy and safety of milnacipran and fluoxetine in a population of Korean patients with major depression. RESEARCH DESIGN AND METHODS: The design was a multi-centre, randomised, comparative clinical study. Patients with major depression (DSM-IV diagnostic criteria) scoring over 17 points on the 17-item Hamilton Depression Scale (HAM-D) and over 21 points on the Montgomery-Asberg Depression Rating Scale (MADRS) were recruited and randomised to receive milnacipran (50 mg/day increasing after 1 week to 100 mg/day) or fluoxetine (20 mg/day) for 6 weeks. All previous medication was stopped at least 7 days before entry into the study. Patients were evaluated (HAM-D, MADRS and clinical global impression scale, CGI) at baseline and after 1, 2, 4 and 6 weeks of treatment. All adverse events which developed during the study period were recorded. RESULTS: 70 patients (milnacipran 39; fluoxetine 31) were included in the study. Total score on both HAM-D, MADRS and CGI decreased significantly in both groups after 1 week and continued to decrease throughout the study. There was no significant difference between the two groups for any measurement at any time point. Both antidepressants were well tolerated. In the milnacipran group, 13 patients reported 28 adverse reactions, and in the fluoxetine group 11 patients reported 18 adverse reactions. Two patients discontinued due to adverse events in the milnacipran group and three in the fluoxetine group. There were no clinically significant modifications in vital signs, routine blood laboratory tests, biochemistry or ECG throughout the study. Nausea and headache were the most frequently reported adverse events with milnacipran while digestive disturbances, diarrhoea and insomnia were more common with fluoxetine. CONCLUSION: Milnacipran, like fluoxetine, was found to be effective and well tolerated for the treatment of major depression in this population of depressed Korean patients. Principal limitations of the study were its open design, its small sample size and its relatively short duration.