Kawasaki disease in childhood and psychiatric disorders: A population-based case-control prospective study in Taiwan.

BACKGROUND: Kawasaki disease (KD) is a common childhood acute inflammatory disease and potentially triggers a chronic inflammation. Although some researches have investigated neurodevelopmental consequences following KD, the findings have been inconsistent. This is the first population-based study targeted on KD and common psychiatric disorders. OBJECTIVES: We aimed to investigate the association between KD and psychiatric disorders and hypothesized that standard anti-inflammatory treatment by intravenous immunoglobulin (IVIG) may protect against development of psychiatric disorders. METHOD: We retrieved data from Taiwan's National Health Insurance Research database (NHIRD). Patients (n = 282,513) with psychiatric disorders (the case group) during 1997-2013 were included, and the control group was matched with age, sex, income and urbanization (1:1). We calculated the prevalence of KD in both groups and estimated odd ratios (ORs) and 95% confidence intervals (CIs) in the subgroup analyses for KD in conditions of age, severity, and common psychiatric comorbidity. RESULTS: Numbers of patients with KD were 460 in the cases and 380 in the controls (p = .006), and the crude OR of KD was 1.21 times greater (95% CI = 1.06-1.39, p = .006) in the case than the control groups. KD patients without IVIG treatment (n = 126) were higher in the cases than those in the controls (n = 54), with the OR of 2.33 (95% CI = 1.70-3.21, p < .0001). Subgroup analyses showed that KD survivors were at significant risk for autism spectrum disorders (ASD) (OR = 2.15, 95% CI = 1.27-3.65; p = .005) and attention deficit and hyperactivity disorders (ADHD) (OR = 1.19, 95% CI = 1.02-1.39; p = 0.03), and a trend of increased risk for anxiety disorders (OR = 1.36, 95%CI = 0.99-1.86; p = 0.05). CONCLUSIONS: Patients with KD were more likely to have comorbid psychiatric disorders, including ASD and ADHD. Moreover, anti-inflammatory treatment with IVIG may have potential prophylactic effects against the development of psychiatric disorders.

Psychoneuroimmunology goes East: Development of the PNIRSChina affiliate and its expansion into PNIRSAsia-Pacific.

The Psychoneuroimmunology Research Society (PNIRS) created an official Chinese regional affiliate in 2012, designated PNIRSChina. Now, just eight years later, the program has been so successful in advancing the science of psychoneuroimmunology that it has expanded to the whole of Asia-Oceania. In 2017, PNIRSChina became PNIRSAsia-Pacific. Between 2012 and 2019, this outreach affiliate of PNIRS organized seven symposia at major scientific meetings in China as well as nine others in Taiwan, Japan, South Korea, Australia and New Zealand. This paper summarizes the remarkable growth of PNIRSAsia-Pacific. Here, regional experts who have been instrumental in organizing these PNIRSAsia-Pacific symposia briefly review and share their views about the past, present and future state of psychoneuroimmunology research in China, Taiwan, Australia and Japan. The newest initiative of PNIRSAsia-Pacific is connecting Asia-Pacific laboratories with those in Western countries through a simple web-based registration system. These efforts not only contribute to the efforts of PNIRS to serve a truly global scientific society but also to answer the imperative call of increasing diversity in our science.

Depression-free after Interferon-α exposure indicates less incidence of depressive disorder: A longitudinal study in Taiwan.

BACKGROUND: IFN-α-induced depression in patients undergoing hepatitis C virus (HCV) treatment provides powerful support for the inflammation hypothesis of depression. Most studies have focused on the occurrence of depressive symptoms, but there has been no study yet in depression-free HCV patients receiving IFN-α. We hypothesized that HCV patients who did not develop depression after IFN-α exposure might have a lower incidence of depressive disorders after the IFN-α treatment. METHODS: We conducted a twelve-year population-based cohort study of chronic HCV patients who received IFN-α therapy. The data were obtained from the Taiwan National Health Insurance Research Database. The study cohort was patients without any depressive disorder nor antidepressant use before and during IFN-α therapy. They were matched randomly by age, sex income and urbanization at a ratio of 1:4 with the control cohort of HCV patients without IFN-α therapy. The follow-up started after the last administration of IFN-α, and the primary outcome was the incidence of depressive disorders after IFN-α therapy. RESULTS: A total of 20,468 depression-free subjects were identified from records of HCV patients receiving IFN-α therapy. Patients without IFN-α-induced depression were associated with a significantly lower incidence (per 10,000 person-years) of new-onset depressive disorders (126.8, 95% Confidential Interval [CI] of 118.5-135.6) as compared to the control cohort (145.2, 95% CI of 140.0-150.6) (p < 0.001). After adjusting for age, sex, income, urbanization and comorbid diseases, the crude hazard ratio for the incident depressive disorder was 0.87 (95% CI, 0.80-0.87) and the adjusted hazard ratios was 0.79 (95% CI, 0.72-0.87) for IFN-α-induced depression-free subjects as compared to the controls. DISCUSSION: Our study indicates that IFN-α treated depression-free patients have a lower risk for depressive disorders. This hypothesized mechanism might derive from an IFN-α-induced resilience factor as yet to be defined. CONCLUSIONS: Our study might suggest a new possibility for a new pharmacological strategy against depression.

Assessing the relationship between healthcare market competition and medical care quality under Taiwan's National Health Insurance programme.

Background: There is still significant uncertainty as to whether market competition raises or lowers clinical quality in publicly funded healthcare systems. We attempted to assess the effects of market competition on inpatient care quality of stroke patients in a retrospective study of the universal single-payer health insurance system in Taiwan. Methods: In this 11-year population-based study, we conducted a pooled time-series cross-sectional analysis with a fixed-effects model and the Hausman test approach by utilizing two nationwide datasets: the National Health Insurance Research Database and the National Hospital and Services Survey in Taiwan. Patients who were admitted to a hospital for ischemic or hemorrhagic stroke were enrolled. After excluding patients with a previous history of stroke and those with different types of stroke, 247 379 ischemic and 79 741 hemorrhagic stroke patients were included in our analysis. Four outcome indicators were applied: the in-hospital mortality rate, 30-day post-operative complication rate, 14-day re-admission rate and 30-day re-admission rate. Results: Market competition exerted a negative or negligible effect on the medical care quality of stroke patients. Compared to hospitals located in a highly competitive market, in-hospital mortality rates for hemorrhagic stroke patients were significantly lower in moderately (ß = -0.05, P < 0.01) and less competitive markets (ß = -0.05, P < 0.01). Conversely, the impact of market competition on the quality of care of ischemic stroke patients was insignificant. Conclusions: Simply fostering market competition might not achieve the objective of improving the quality of health care. Other health policy actions need to be contemplated.

Change of employment status in patients with depression - A longitudinal study using national claims data.

Depression increases an individual's risk of work disability, sick leave, unemployment, and early retirement. This population-based study identified 3673 depressive patients utilizing national claim data from Taiwan and aimed to investigate changes in employment status among depressive patients, compared to matched controls, with the longest observation of up to 12 years. This study found depressive patients had an adjusted hazard ratio of 1.24 for changing to non-income earners compared to controls. Moreover, younger age, lower payroll bracket, urbanity, and geographical area were associated with increased risk among patients with depression. Despite these increased risks, most depressive patients remained employed.

Association of Acute Postoperative Pain and Cigarette Smoking With Cerebrospinal Fluid Levels of Beta-Endorphin and Substance P.

Objectives: Cigarette smoking is associated with postoperative pain perception, which might be mediated by beta-endorphin and substance P. These effects on postoperative pain perception have never been investigated in human cerebrospinal fluid (CSF), which reflects biochemical alterations in the brain. Therefore, we investigated the associations among cigarette smoking, postoperative pain, and levels of beta-endorphin and substance P in human CSF. Methods: We recruited 160 Chinese men (80 active smokers and 80 nonsmokers) who underwent lumbar puncture before anterior cruciate ligament reconstruction, and 5-ml CSF samples were collected. Pain visual analog scale (VAS) scores, post-anesthetic recovery duration (PARD), and smoking variables were obtained. CSF levels of beta-endorphin and substance P were measured. Results: Compared to non-smokers, active smokers had significantly higher pain VAS (2.40 ± 0.67 vs. 1.70 ± 0.86, p < 0.001) and PARD scores (9.13 ± 2.11 vs. 7.27 ± 1.35, p = 0.001), lower CSF beta-endorphin (33.76 ± 1.77 vs. 35.66 ± 2.20, p = 0.001) and higher CSF substance P (2,124.46 ± 217.34 vs. 1,817.65 ± 302.14, p < 0.001) levels. Pain VAS scores correlated with PARD in active smokers (r = 0.443, p = 0.001). Conclusions: Cigarette smoking is associated with increased postoperative pain intensity, shown by delayed pain perception, higher pain VAS scores, and lower beta-endorphin and higher substance P levels in the CSF of active smokers. The more extended postoperative pain perception is delayed, the more pain intensity increases.

Association of Cigarette Smoking With Cerebrospinal Fluid Biomarkers of Neurodegeneration, Neuroinflammation, and Oxidation.

Importance: Cigarette smoking has been associated with risk of neurodegenerative disorders, such as Alzheimer disease. The association between smoking and biomarkers of changes in human cerebrospinal fluid (CSF) is not fully understood. Objective: To investigate the association of cigarette smoking with CSF biomarkers of neurodegeneration, neuroinflammation, oxidation, and neuroprotection. Design, Setting, and Participants: In this case-control study of 191 adult men in China, biomarkers in the CSF of participants with and without significant cigarette exposure were examined. Participants who did not smoke and had no history of substance use disorder or dependence were assigned to the nonsmoking group. The active smoking group included participants who consumed at least 10 cigarettes per day for 1 year. Five-milliliter samples of CSF were obtained from routine lumbar puncture conducted before anterior cruciate ligament reconstruction surgery. Data collection took place from September 2014 to January 2016, and analysis took place from January to February 2016. Exposures: Cigarette smoking. Main Outcomes and Measures: CSF levels of ß-amyloid 42 (Aß42), which has diagnostic specificity for Alzheimer disease, tumor necrosis factor alpha (TNFα), brain-derived neurotrophic factor (BDNF), total superoxide dismutase (SOD), and nitric oxide synthase (NOS) were measured. Sociodemographic data and history of smoking were obtained. Results: Of 191 participants, 87 (45.5%) were included in the active smoking group and 104 (54.4%) in the nonsmoking group. Compared with the active smoking group, the nonsmoking group was younger (mean [SD] age, 34.4 [10.5] years vs 29.6 [9.5] years; P = .01), had more education (mean [SD] duration of education, 11.9 [3.1] years vs 13.2 [2.6] years; P = .001), and had lower body mass index (mean [SD], 25.9 [3.6] vs 24.9 [4.0]; P = .005). Comparing the nonsmoking group with the smoking group, mean (SD) CSF levels of Aß42 (38.0 [25.9] pg/mL vs 52.8 [16.5] pg/mL; P < .001) and TNFα (23.0 [2.5] pg/mL vs 28.0 [2.0] pg/mL; P < .001) were significantly lower, while BDNF (23.1 [3.9] pg/mL vs 13.8 [2.7] pg/mL; P < .001), total SOD (15.7 [2.6] U/L vs 13.9 [2.4] U/L; P < .001), total NOS (28.3 [7.2] U/L vs 14.7 [5.6] U/L; P < .001), inducible NOS (16.0 [5.4] U/L vs 10.3 [2.7] U/L; P < .001), and constitutive NOS (12.4 [6.9] U/mL vs 4.4 [3.9] U/mL) were higher. In addition, in participants in the smoking group who were aged 40 years or older, total SOD levels were negatively correlated with Aß42 levels (r = -0.57; P = .02). In those who smoked at least 20 cigarettes per day, TNFα levels were positively correlated with Aß42 levels (r = 0.51; P = .006). The association of TNFα with Aß42 production was stronger than that of total SOD with Aß42 production (z = -4.38; P < .001). Conclusions and Relevance: This case-control study found that cigarette smoking was associated with at-risk biomarkers for Alzheimer disease, as indicated by higher Aß42 levels, excessive oxidative stress, neuroinflammation, and impaired neuroprotection found in the CSF of participants in the active smoking group.

Relapse and long-acting injectable risperidone: a 1-year mirror image study with a national claims database in Taiwan.

OBJECTIVES: The development of long-acting, injectable atypical antipsychotics has provided a new paradigm for schizophrenia treatment. The study was designed to assess whether a risperidone long-acting injection (RLAI) is associated with reduced relapses and service utilization in the real world. METHODS: The Psychiatric Inpatients Medical Claims dataset was used for the analysis. It is a longitudinal dataset that includes the National Health Insurance claims of service uses by a cohort of mentally ill patients. The inclusion criteria for this analysis were patients who: 1) had available information for at least 12 months after the first dose of RLAI; 2) had a primary diagnosis of schizophrenia; and 3) were regularly treated with RLAI for at least 1 year. Patients who accumulatively received at least 75-mg RLAI per 3-month period were considered to be undergoing regular treatment. Wilcoxon signed rank tests were performed to compare differences in numbers of acute admissions, hospital days, emergency room visits, and relapses between the pre- and post-RLAI periods in this 1-year mirror-image study. RESULTS: In total, 108 patients were eligible for analysis. Significant reductions in the total annual numbers of acute hospital admissions by 55% (80 vs. 36, P = 0.0003), hospital days by 48% (4106 vs. 2126, P = 0.0021), and relapses by 54% (115 vs. 53, P = 0.0005) were observed. A reduction of emergency room visits was also observed, but did not reach statistical significance (55 vs. 25, P = 0.1255). CONCLUSIONS: This 1-year mirror-image analysis with claims-based data demonstrated that RLAI treatment was associated with reductions in relapses and hospital service utilization.

Effects of antidepressant treatments on health service utilization and medical costs among patients with depression: a nationwide population-based retrospective cohort study in Taiwan.

This study aimed to assess the associations between the use of different types of antidepressants and health service utilization and costs among depressed patients. Data used in this study were retrieved from the Taiwan National Health Insurance Research Database. We identified 447 411 new antidepressant users during the study period (2011-2015) and they were individually followed for a 1-year period. Two-part generalized estimating equation models were conducted. Results demonstrated that there was a substantial decrease in outpatient service utilized by patients undertaking serotonin antagonists and reuptake inhibitors (ß = -0.2074), serotonin-norepinephrine reuptake inhibitors (ß = -0.0452), tricyclic antidepressants (ß = -0.1308), or other antidepressants (ß = -0.0637), compared with their counterparts in the selective serotonin reuptake inhibitors group (all P < 0.05). Compared with patients who were treated with selective serotonin reuptake inhibitors, those who were prescribed serotonin antagonists and reuptake inhibitors (ß = -0.4934, P < 0.05) or tricyclic antidepressants (ß = -0.4194, P < 0.05) had incurred lower costs pertaining to outpatient service, while considerably higher costs were borne by those patients embarked on the treatment of serotonin-norepinephrine reuptake inhibitors (ß = 0.3228, P < 0.05) or other antidepressants (ß = 0.1118, P < 0.05). We concluded that the initiation of various classes of antidepressants led to significant variations in health service utilization and costs among depressed patients.

Comparisons of the risk of medication noncompliance and suicidal behavior among patients with depressive disorders using different monotherapy antidepressants in Taiwan: A nationwide population-based retrospective cohort study.

BACKGROUND: The aim of this study was to assess the association between various classes of antidepressants and the risk of medication noncompliance as well as suicidal behavior among depressed patients. METHODS: A retrospective cohort study was conducted utilizing two nationwide population-based datasets in Taiwan from 2010 to 2016. The outcome measures included the risk of medication noncompliance, attempted suicide, and completed suicide. Cox proportional hazards models with stratification of the propensity score deciles were performed. RESULTS: A total of 447,411 new antidepressant users were identified. Compared to SSRIs, patients who received SARIs [adjusted hazard ratio (aHR) = 1.124, 95% confidence interval (CI) = 1.108-1.142], SNRIs (aHR = 1.049, 95% CI = 1.033-1.065), and other classes of antidepressants (aHR = 1.037, 95% CI = 1.024-1.051) were more likely to exhibit poor medication noncompliance. Patients who received SNRIs had a higher risk of attempted suicide (aHR = 1.294, 95% CI = 1.114-1.513), compared to SSRIs. However, patents in the TCAs group revealed the opposite result (aHR = 0.543, 95% CI = 0.387-0.762). Concerning the risk of completed suicide, this analysis detected no statistical significance across different types of antidepressants. LIMITATIONS: Although the universal coverage of Taiwan's national health insurance program tends to minimize the risk of selection and recall bias, it is difficult to rule out medical surveillance bias by using claim data. CONCLUSIONS: This study demonstrated that classes of antidepressants exert different degrees of impact on the risk of medication noncompliance and attempted suicide, but not completed suicide, among depressed patients.

Health service utilization and medical costs among patients with schizophrenia receiving long-acting injectable risperidone versus oral risperidone: a nationwide retrospective matched cohort study in Taiwan.

The aim of the nationwide retrospective matched cohort study was to evaluate health service utilization and medical costs between patients with schizophrenia who received long-acting injectable (LAI) risperidone and those who took risperidone orally. Data were sourced from the 2008 to 2013 Psychiatric Inpatient Medical Claim Dataset in Taiwan. The sample selection process was performed by propensity score matching. Finally, there were 691 patients in the exposed cohort and 1382 patients in the unexposed cohort. Each patient was individually followed for a 1-year period. Two-part models and generalized estimating equations were used to evaluate health service utilization and direct medical costs of patients. Analytical results showed that patients receiving LAI risperidone had used outpatient services significantly more, had greater hospital admissions, and had shorter lengths of stay than those who took risperidone orally. Furthermore, compared with their counterparts in the unexposed group, patients in the exposed group had incurred higher medical costs because of costs incurred from increased utilization of outpatient service and hospital admissions, under the special context of the healthcare system in Taiwan, a single-payer universal health coverage system with low copayment rates. In summary, this study suggested that patients with schizophrenia treated with LAI risperidone had shorter lengths of stay, higher medical costs largely because of increased utilization of outpatient service and hospital admissions, compared with those who took risperidone orally.

Change in employment status in bipolar disorder: a longitudinal study using national claims data.

OBJECTIVE: To assess change in employment status in patients with bipolar disorder in comparison with non-mentally ill controls from 1 year before bipolar incidence to 10 years after. Sociodemographic factors of change in employment status were also examined for patients with bipolar disorder. METHOD: A cohort of 502 patients with ICD-9-CM bipolar disorder was identified using claims data from the National Health Insurance Research Database of Taiwan between 1998 and 2001 and compared to non-mentally ill controls through December 31, 2008. The primary outcome measure was the time from bipolar incidence to the time of change in employment status, ie, from earning income to not earning income. RESULTS: The probability of changing to a non-income earner was significantly higher (P < .0001) in patients with bipolar disorder than in controls over time, even before the incidence of bipolar disorder (27% vs 14% for patients with bipolar disorder vs controls, respectively). Risks of occupational deterioration in patients with bipolar disorder were greater in the year before incidence and in the following year, with gradually decreasing risks over the subsequent 2 years, and comparable to controls from the third year onward. The adjusted hazard ratio of changing to a non-income earner was 2.06 (95% CI, 1.82-2.33) in patients with bipolar disorder. Male sex, ages 18 to 25 years, lower payroll bracket (< NT$50,001 [US $1,489]), and living in an urban area and insured area in the Northern region were associated with the risk of changing to a non-income earner in patients with bipolar disorder. CONCLUSIONS: Patients with bipolar disorder had poorer employment outcomes than the controls, with greater risks of occupational deterioration before and after the bipolar episodes. Employment status should be incorporated as a measure of functioning and of treatment and intervention effectiveness in clinical practices and research.

Hypoalbuminemia in drug-free patients with major depressive disorder compared with a dietary matched control group: a clinical meaning beyond malnutrition.

Serum albumin (sALB) is routinely determined in blood tests and is an excellent predictor of risk for many medical illnesses. Hypoalbuminemia has been sporadically reported in patients with psychiatric disorders, such as major depressive disorder and schizophrenia. We compared sALB levels between 19 drug-free patients of major depressive disorder with a control group of matching diets. We conducted this study by controlling the nutrition factor by assessing patient's diets, as well as other possible confounding factors such as sex, age, body mass index (BMI), liver function, and exercise, while focusing on hypoalbuminemia in patients with major depressive disorder. There is no difference in age, gender distribution, and dietary frequency on protein and albumin intake between the patient and control group. The sALB levels of the group with major depressive disorder were significantly reduced (p=0.049). The severity of depression is negatively correlated to the sALB level (r=-0.46, p=0.04). Hypoalbuminemia has clinical meanings on severity of depression and is independent of malnutrition. However, our results can only be seen as very preliminary and should be confirmed by larger studies.

Omega-3 fatty acids in the prevention of interferon-alpha-induced depression: results from a randomized, controlled trial.

BACKGROUND: Interferon (IFN)-α therapy for chronic hepatitis C virus infection is frequently associated with depression. The routine prophylaxis with antidepressants might expose patients to adverse effects, hence, the need for alternative preventive interventions. Omega-3 polyunsaturated fatty acids are safe and effective essential nutritional compounds used for the treatment of depression, putatively through an anti-inflammatory action. In addition, lower erythrocyte levels of omega-3 polyunsaturated fatty acids have been associated with an increased risk of IFN-induced depression. METHODS: We conducted a 2-week, double-blind, placebo-controlled trial comparing eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and placebo for the prevention of IFN-α-induced depression. A total of 162 patients consented to participate and were randomized to the study. All of the patients completed the 2-week trial; 152 participants were followed throughout the 24 weeks of IFN-α treatment and were included in the analysis. RESULTS: Compared with placebo, the incident rates of IFN-α-induced depression were significantly lower in EPA-treated but not in DHA-treated patients (10% and 28%, respectively, versus 30% for placebo, p = .037). Both EPA and DHA significantly delayed the onset of IFN-induced depression (week of onset: 12.0 and 11.7, respectively, versus 5.3 for placebo, p = .002). EPA and DHA were both well tolerated in this population. EPA treatment increased both EPA and DHA erythrocyte levels, but DHA only increased DHA erythrocyte levels. CONCLUSIONS: EPA is effective in the prevention of depression in hepatitis C virus patients received IFN-α therapy. Our study confirms the notion that anti-inflammatory strategies are effective antidepressants in the context of depression associated with inflammation.

A cost-consequence analysis of long-acting injectable risperidone in schizophrenia: a one-year mirror-image study with national claim-based database in Taiwan.

OBJECTIVE: The development of long-acting atypical antipsychotics has provided a new paradigm for schizophrenia treatment. The economic effectiveness of risperidone long-acting injection (RLAI) on service costs has, however, never been studied in the real world with national claim-based database. METHOD: To assess the change of service utilization and costs for schizophrenia before and after RLAI treatment, we conducted this 1-year mirror-image study with Taiwanese national claimed-data. Comparison was made for service sectors (the number of visits, acute admissions and relapse events) and cost components (outpatient, inpatient, emergency, medication and non-medication costs). RESULTS: Service uses reduced in the post-RLAI period, along with a reduction of 34% and 32% on total inpatient services costs and inpatient non-medication costs, respectively (p < 0.005). However, overall psychiatric service costs went up by 26%, with an increase of 190% on total outpatient service costs and 177% on overall medication costs (p < 0.0001). CONCLUSIONS: This 1-year mirror-image analysis showed that RLAI treatment was associated with reductions of service uses; however, overall psychiatric service costs were compromised by costs incurred from increased utilization of outpatient service and RLAI medication costs under the context of healthcare in Taiwan.

Omega-3 fatty acids for major depressive disorder during pregnancy: results from a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Perinatal depression is common, and treatment remains challenging. Depression has been reported to be associated with the abnormality of omega-3 polyunsaturated fatty acids (PUFAs). A profound decrease of omega-3 PUFAs in the mother during pregnancy is associated with the higher demand of fetal development and might precipitate the occurrence of depression. In this study, we examined the efficacy of omega-3 PUFA monotherapy for the treatment of depression during pregnancy. METHOD: From June 2004 to June 2006, we conducted an 8-week, double-blind, placebo-controlled trial comparing omega-3 PUFAs (3.4 g/d) with placebo in pregnant women with major depressive disorder (DSM-IV criteria). No psychotropic agent was given 1 month prior to or during the study period. The Hamilton Rating Scale for Depression (HAM-D) was scored every other week as the primary measurement of efficacy, while the Edinburgh Postnatal Depression Scale (EPDS) and Beck Depression Inventory (BDI) were secondary measures. RESULTS: Thirty-six subjects were randomly assigned to either omega-3 PUFAs or placebo, and 33 among them were evaluated in more than 2 visits. A total of 24 subjects completed the study. As compared to the placebo group, subjects in the omega-3 group had significantly lower HAM-D scores at weeks 6 (p = .001) and 8 (p = .019), a significantly higher response rate (62% vs. 27%, p = .03), and a higher remission rate, although the latter did not reach statistical significance (38% vs. 18%, p = .28). At the study end point, subjects in the omega-3 group also had significantly lower depressive symptom ratings on the EPDS and BDI. The omega-3 PUFAs were well tolerated and there were no adverse effects on the subjects and newborns. CONCLUSIONS: Omega-3 PUFAs may have therapeutic benefits in depression during pregnancy. In regard to the safety issue and psychotherapeutic effect, as well as health promotion to mothers and their newborns, it is worthy to conduct replication studies in a larger sample with a broad regimen of omega-3 PUFAs in pregnant women with depression. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00618865.