The Trend in Morning Levels of Salivary Cortisol in Children With ADHD During 6 Months of Methylphenidate Treatment.

OBJECTIVE: To determine the trend in cortisol levels in children with ADHD treated with methylphenidate (MPH) and nontreated healthy controls over a 6-month period. METHOD: The morning salivary cortisol levels of 50 patients with ADHD (40 boys and 10 girls, mean age = 7.6 years) and 50 age- and gender-matched healthy controls were measured at baseline and at 1, 3, and 6 months from baseline. The neuropsychological performance of the ADHD patients was measured via administration of the Continuous Performance Test. RESULTS: The cortisol levels of ADHD patients increased significantly after 1 month of MPH treatment before decreasing to an intermediate level, but were significantly positively correlated with neuropsychological performance throughout the 6-month treatment period. The cortisol levels of the controls did not change significantly over the 6-month period. CONCLUSION: MPH administration appears to positively influence the functioning of the hypothalamic-pituitary-adrenal axis in ADHD patients.

Difference in pre- and post-treatment plasma DHEA levels were significantly and positively correlated with difference in pre- and post-treatment Hamilton depression scores following successful therapy for major depression.

OBJECTIVE: Clinical studies of endogenous concentrations of dehydroepiandrosterone (DHEA) and its relation to depression are limited. This study examined whether pre- and post-treatment changes in plasma DHEA levels are correlated with pre- and post-treatment differences in Hamilton depression scores following successful antidepressant therapy for major depression with venlafaxine XR. METHOD: Thirty-four medication-free major depressive outpatients (Hamilton Rating Scale for Depression 17, HAM-D 17 score > or = 17) were treated with antidepressants. At baseline, plasma DHEA levels of all subjects were measured but only those who remitted (HAM-D 17 score < or = 7) before the end of this study had their plasma DHEA levels measured at remission-onset. Blood from subjects was drawn at 0900-1100 h. Depression severity was assessed with the HAM-D 17 scale at baseline, and on day 7, 14, 28, 56 and 84. Subjects were administered at minimum 75 mg/day venlafaxine XR until remission onset. RESULTS: Fifteen patients remitted before the end of this study. Plasma DHEA levels decreased from baseline to remission was significant (P=0.017). After controlling for age and gender, pre- and post-treatment difference in Hamilton depression scores and the pre- and post-treatment difference in DHEA concentrations were significantly correlated (P=0.044). CONCLUSION: This preliminary study provides the first clinical evidence identifying that difference in pre- and post-treatment plasma DHEA levels were significantly and positively correlated with difference in pre- and post-treatment Hamilton depression scores following successful therapy with venlafaxine XR for major depression in remitters; but non-remitters were not examined. It is not known if DHEA levels would show similar or dissimilar changes in non-remitters.

Amisulpride and symptomatic bradycardia: a case report.

OBJECTIVE: Amisulpride is a second-generation antipsychotic agent indicated for the treatment of schizophrenia and other major psychotic illnesses. Amisulpride-induced bradycardia is a rare condition of unknown etiology and mechanism. Asymptomatic bradycardia has been associated with amisulpride in only two cases. In our case, the association was rated as "probable" on the Naranjo adverse drug reaction probability scale. METHOD: Case report. RESULTS: A 45-year-old male patient developed symptomatic bradycardia during usage of amisulpride (400-800 mg/day), which dramatically improved after the complete termination of amisulpride usage. The psychiatric condition remained relatively stable without bradycardia after administration of another antipsychotic agent [risperidone (3 mg/day)]. CONCLUSION: This is the first case report of symptomatic bradycardia associated with the use of amisulpride. Although bradycardia is a rare adverse reaction to antipsychotics, this finding may alert psychiatrists and physicians to this antipsychotic drug side effect. Further study is needed to disclose the role of antipsychotics in bringing about symptomatic bradycardia.

A double-blind, randomized, group-comparative study of the tolerability and efficacy of 6 weeks' treatment with mirtazapine or fluoxetine in depressed Chinese patients.

AIM: To compare the efficacy and tolerability of mirtazapine and fluoxetine treatment in a sample population consisting of Chinese patients suffering moderate-to-severe depression. METHOD: 133 patients with a diagnosis of major depressive episode (DSM-IV) and scoring 15 or more on the 17-item Hamilton Rating Scale for Depression (HAM-D) were randomly assigned to receive 6 weeks of treatment with either mirtazapine (15-45 mg/day) or fluoxetine (20-40 mg/day). Efficacy was assessed using the HAM-D and Clinical Global Impressions scale, with analyses performed on the intent-to-treat sample using the last-observation-carried-forward method. Safety analysis was based on the all-subjects-treated group. RESULTS: Mean daily doses were 34.1 mg for mirtazapine (N = 66) and 30.7 mg for fluoxetine (N = 66). Thirty patients in the mirtazapine group and 22 in the fluoxetine group dropped out. Both drugs proved equally effective for reduction of the overall symptoms of depression throughout the treatment period. At day 42, the mean reductions in HAM-D total score (compared with baseline) were 11.8 and 10.6 for the mirtazapine and fluoxetine groups, respectively; however, the changes were not statistically significant. Both treatments were well tolerated, with more nausea and influenza-like symptoms observed for the fluoxetine group, and greater weight increase and somnolence for the mirtazapine analog. CONCLUSION: Both mirtazapine and fluoxetine were indistinguishable in effectiveness for treatment of depressive symptoms, and both were well tolerated by our population of depressed Chinese patients. In line with analogous Western reports, the safety of mirtazapine and fluoxetine was comparable for our depressed Chinese patients; however, slightly different side effect profiles were noted for the 2 drugs in our study.

Adjunctive effects of aripiprazole on metabolic profiles: comparison of patients treated with olanzapine to patients treated with other atypical antipsychotic drugs.

Metabolic abnormalities are serious adverse effects of atypical antipsychotic treatment. This study aims to determine the effects of adjunctive aripiprazole on metabolic profiles among patients receiving treatment with atypical antipsychotics, and to examine whether these effects are different from that of pre-existing atypical antipsychotics. In the 8-week open-label trial, aripiprazole was added to patients who were receiving treatment with atypical antipsychotics and had experienced weight gain or dyslipidemia. The dosage of pre-existing atypical antipsychotics was fixed, while the dosage of aripiprazole ranged from 5 to 20 mg/day during the study period. Metabolic profiles, including body weight, body mass index (BMI), plasma levels of fasting glucose, triglycerides, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and adiponectin, were measured at baseline and week 8. As a result, 43 subjects (16 males and 27 females, mean age: 37.8±10.8 years) completed the study. The pre-existing antipsychotics were olanzapine (n=12), risperidone (n=19), quetiapine (n=6) and amisulpiride (n=6). The mean dosage of adjunctive aripiprazole was 9.9±3.2 mg/day. After the aripiprazole-augmented regimen for 8 weeks, patients treated with olanzapine had significant decreases in body weight, BMI and triglyceride levels, and had significant increases in adiponectin levels. For patients treated with other atypical antipsychotics, none of the metabolic parameters significantly changed after administering aripiprazole. In conclusion, aripiprazole-augmented treatment might be beneficial for the metabolic regulation of patients being treated with a stable dose of olanzapine, but not for those treated with other atypical antipsychotics. A long-term, randomized, double-blind controlled design is suggested to confirm these findings.

Low plasma DHEA-S increases mortality risk among male hemodialysis patients.

OBJECTIVE: The incidence of chronic kidney disease (CKD) is on the rise. CKD patients are at high risk of cardiovascular (CVD) and all-cause mortality. CKD patients have several endocrine disorders, including low levels of dehydroepiandrosterone sulfate (DHEA-S). In the general population, low levels of DHEA-S are associated with high CVD and all-cause mortality. The aim of this study was to analyze the prognostic value of plasma DHEA-S on the survival of CKD patients on hemodialysis. METHOD: This was a single-center prospective cohort study on two hundred CKD patients on hemodialysis, which assessed the prognostic value of plasma DHEA-S on their survival. RESULT: We found that plasma DHEA-S levels were negatively associated with age, and positively associated with dialysis duration and plasma creatinine, albumin, and phosphate levels in hemodialysis men. Elderly patients with co-morbidities (i.e. diabetes mellitus, congestive heart failure, and chronic obstructive pulmonary disease), poorer fluid control which was evaluated by higher cardiothoracic ratio, and low plasma creatinine and albumin levels seemed to have poor prognosis in hemodialysis men. Furthermore, low plasma DHEA-S levels were significantly associated with CVD-related [hazard ratio (HR)=3.877; P=0.021], non-CVD-related (HR=3.522; P=0.016), and all-cause mortality (HR=3.667; P=0.001) in hemodialysis men. But low plasma DHEA-S levels were not significantly associated with CVD-related, non-CVD-related, and all-cause mortality in hemodialysis women. Multivariate Cox regression analysis suggested that low plasma DHEA-S levels are significantly and independently associated with all-cause mortality in hemodialysis men (HR=2.933; P=0.033). CONCLUSION: The study suggested that low plasma DHEA-S was independently and significantly associated with all-cause mortality in CKD hemodialysis men.

Amisulpride and neuroleptic malignant syndrome.

Neuroleptic malignant syndrome (NMS) is a rare but lethal complication of neuroleptics. Its incidence ranges between 0.02% and 3%. Amisulpride, a second generation neuroleptic, was associated with rhabdomyolysis in one report and NMS in 2 reports. Although the precise pathogenesis is still unclear, dopamine receptor blockade is theorized to play a central role. Conventional presentations include hyperthermia, muscle rigidity, and elevated creatine kinase concentrations. However, similar to other second generation neuroleptics, amisulpride induces an atypical form of NMS, which presents with lower degrees of hyperthermia and elevation of creatine kinase than the typical form. This phenomenon makes it difficult to identify early signs of NMS. This study describes the first case of amisulprideinduced NMS in Taiwan, together with a review of the current knowledge on NMS. In this case, the correlation between NMS and amisulpride was categorized as "probable" on the Naranjo adverse drug reaction probability scale.

Rapid initiation of quetiapine well tolerated as compared with the conventional initiation regimen in patients with schizophrenia or schizoaffective disorders.

A 2-week, randomized, parallel-group open trial was designed to evaluate the safety and tolerability of a rapid initiation regimen with a higher dose of quetiapine (up to 800 mg/d by Day 4) than that used in the conventional initiation regimen of quetiapine (up to 400mg/d by Day 5) in patients with schizophrenia or schizoaffective disorders. Forty patients were recruited and randomly (3:1) assigned to either the group with rapid initiation of quetiapine or the group with conventional initiation. At the end of the investigation, the difference between the groups in the incidence of adverse events was not significant; a significant drop in the Barnes Akathisia Rating Scale and Simpson-Angus Scale scores was observed only in the group with the rapid initiation regimen. The groups did not differ in terms of improvement on the Clinical Global Impression-Severity of Illness and Positive and Negative Syndrome Scale at the end of the study. The results of our 2-week study suggest that rapid initiation with a higher dose of quetiapine (up to 800 mg/d by Day 4) is well tolerated in patients with schizophrenia or schizoaffective disorders and does not compromise efficacy relative to the conventional initiation.

Elevated serum cholesterol levels in women with premenstrual dysphoric disorder.

OBJECTIVES: To study the association of premenstrual serum total cholesterol level (TC) with premenstrual dysphoric disorder (PMDD). METHOD: The premenstrual serum cholesterol levels of 34 patients with PMDD and 20 normal controls were measured, and the rates ofhypercholesterolemia in the 2 groups were compared. RESULTS: The mean of the premenstrual cholesterol level of the study group was 180.82 +/- 34.47 mg/dL, while that of the control group was 162.45 +/- 21.29 mg/dL (t = 2.152, df = 52, p = 0.036). The prevalence of premenstrual hypercholesterolemia (serum total cholesterol > 200 mg/dL) was 23.53% (8/34) in the PMDD group and zero in the normal control group (chi-square = 5.524, df = 1, p = 0.019). CONCLUSION: The results showed elevated premenstrual serum cholesterol in PMDD and implied a new direction of research to further explore the etiology of PMDD. It is suggested that the pathophysiology of premenstrual dysphoric disorder may be similar to that of anxiety disorders.

Association of salivary dehydroepiandrosterone levels and symptoms in patients with attention deficit hyperactivity disorder during six months of treatment with methylphenidate.

This prospective study aimed to determine whether salivary levels of dehydroepiandrosterone (DHEA) in patients with attention deficit hyperactivity disorder (ADHD) change significantly during 6 months of treatment with methylphenidate (MPH), and to investigate long-term relationship between these levels and ADHD symptoms. Fifty ADHD patients aged between 6 and 12 years, and 50 age- and gender-matched healthy subjects were recruited. ADHD patients were prescribed oral MPH with a dose range of 5-15 mg/day at the discretion of the psychiatrist. DHEA levels were determined from saliva samples collected from both ADHD patients and healthy subjects at pretreatment and 1, 3, and 6 months from pretreatment visit. ADHD symptoms were evaluated with the Swanson, Nolan, and Pelham, Version IV Scale for ADHD and the ADHD Rating Scale, and computerized Continuous Performance Test (CPT). The results showed that salivary DHEA levels significantly increased in ADHD patients during the 6-month course of methylphenidate treatment, but the DHEA levels did not significantly change in the untreated healthy group during the 6-month period of natural observation. For the longitudinal observation, among ADHD patients, the salivary DHEA levels were independently correlated with distraction and impulsivity performance in the CPT, but not correlated with inattention and hyperactivity in the clinical ADHD symptoms. Whether DHEA exerts effects on neurocognitive functions as mediators or independently of MPH warrants further investigation.

Differential add-on effects of aripiprazole in resolving hyperprolactinemia induced by risperidone in comparison to benzamide antipsychotics.

UNLABELLED: Hyperprolactinemia is associated with typical antipsychotic agents and atypical antipsychotics such as risperidone and amisulpride. This study investigates the effects of 8-week adjunctive treatment with aripiprazole in patients with hyperprolactinemia induced by risperidone in comparison to benzamide antipsychotics (amisulpride and sulpiride). Aripiprazole was administered to 24 patients with antipsychotic-induced hyperprolactinemia. The doses of pre-existing antipsychotics were fixed, while the aripiprazole dose was 5-20 mg/day during the 8-week study period. Serum prolactin levels were measured at weeks 4 and 8. Symptoms and side effects were assessed using the Positive and Negative Syndrome Scale (PANSS), Arizona Sexual Experience Scale, Abnormal Involuntary Movement Scale, Simpson-Angus Scale, Barnes Akathisia Scale, and metabolic measures at weeks 2, 4 and 8. Mean (standard error) prolactin levels decreased from 77.0±13.3 ng/mL to 18.3±2.1 ng/mL (p<0.001 vs. baseline), from 144.9±24.4 ng/mL to 127.5±21.7 ng/mL (p=0.099 vs. baseline) and 71.4±24.6 ng/mL to 43.3±14.7 ng/mL (p=0.106 vs. baseline) for those taking risperidone, amisulpride, and sulpiride, respectively. For those who took risperidone before the study started, 14 of 15 (93.3%) patients had normalized prolactin levels, while only 1 of 10 (10%) taking benzamide antipsychotics had normalized prolactin levels. The PANSS score improved significantly, and aripiprazole had no significant influence on metabolic measures or scales of movement side effects. Adjunctive aripiprazole treatment reversed effectively hyperprolactinemia induced by risperidone, but was less effective for that induced by benzamide antipsychotics. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00541554.

Lack of association between plasma dehydroepiandrosterone sulfate (DHEA-S) levels and depression in hemodialysis patients: a cross-sectional study.

OBJECTIVE: Depression is common in hemodialysis patients. Reduced DHEA-S levels have been shown to be associated with depression in general population. Abnormalities in hormone production and metabolism are found in hemodialysis patients. However, the association between DHEA-S levels and depression in hemodialysis patients has not been established. METHOD: We conducted a cross-sectional study, in which 80 patients under regular hemodialysis were studied, and their serum DHEA-S levels were analyzed. RESULTS: The prevalence of depression in our studied hemodialysis population is 37.5% (30/80). The DHEA-S level was 1138.1+/-1216.9 ng/mL in male patients and 502.1+/-389.4 ng/mL in female patients. The levels were not significantly different between patients with or without depression (910.8+/-1127.1 ng/mL vs. 769.3+/-848.3 ng/mL, P=0.533). As compared to the non-depressed patients, the depressed patients were more likely to be male, with lower body mass index, consuming more alcohol, and with more co-morbidity. The prevalence of depression was not associated with age, educational background, smoking, duration of dialysis, hemoglobin, albumin, CRP, ferritin, and urea clearance (Kt/V and URR). The serum DHEA-S levels exhibited significant and independent associations with age, gender, diabetes mellitus, and the levels of serum albumin. CONCLUSION: The study suggested a lack of association between plasma DHEA-S levels and depression in hemodialysis patients.

Analysis of association of clinical correlates and 5-HTTLPR polymorphism with suicidal behavior among Chinese methamphetamine abusers.

Substance use disorders are familial, and genetic factors explain a substantial degree of their familial aggregation. Methamphetamine (MAP) abusers are commonly noted as having psychosis, depression and suicidal behavior. The goals of the present study were (i) to investigate relations of clinical correlates, such as gender, drug use behavior, psychiatric comorbidity and psychiatry family history, with suicidal behavior among Chinese MAP abusers; and (ii) to investigate whether there is an association between a polymorphism in the promotor region of the serotonin transporter gene (5-HTTLPR) and suicidal behavior among Chinese MAP abusers. A total of 439 MAP abusers from a hospital and detention center in Taipei were interviewed with the Diagnostic Interview for Genetic Study and the Family Interview for Genetic Study. The 5-HTTLPR polymorphism was compared between 94 MAP abusers with suicide attempts and 294 MAP abusers without suicide attempts, for whom DNA data were available. The results of the present study indicate that among MAP abusers in Taiwan, suicide attempts were significantly related to female gender, history of MAP-induced psychotic disorder, history of MAP-induced depressive disorder, and family history of psychotic disorders. Among suicide attempters, the attempters with moderate to severe lethality used higher MAP doses than those with minimal to mild lethality. In the present sample the triallelic 5-HTTLPR polymorphism (S, L(G), L(A)) was not associated with MAP-induced depressive disorder, MAP-induced psychotic disorder or suicidal behavior, but studies with larger sample sizes are warranted before excluding the role of the 5-HTTLPR polymorphisms in suicidal behavior among MAP abusers.

Positive correlation between anxiety severity and plasma levels of dehydroepiandrosterone sulfate in medication-free patients experiencing a major episode of depression.

Although numerous studies have identified a correlation between dehydroepiandrosterone sulfate (DHEAS) levels and anxiety or depression, those findings remain controversial. The purpose of the present study was to determine whether a correlation exists between depression severity and anxiety severity and serum DHEAS concentrations in medication-free patients experiencing a major depressive episode. Twenty-eight medication-free major depressive outpatients (Hamilton Rating Scale for Depression 17 [HAM-D 17] score >or=17) were enrolled consecutively. Plasma DHEAS levels of all subjects were measured. Blood from subjects was drawn at 0900-1100 h Depression severity was assessed with the HAM-D 17 and the Hospital Anxiety and Depression Scale (HADS) depression subscale. Anxiety was assessed using the HADS anxiety subscale. Serum concentrations of DHEAS were measured immediately following the HAM-D 17 and HADS assessments. A significant, positive correlation was identified between HADS anxiety subscale total score and morning serum DHEAS concentration (P = 0.013) after controlling for age, gender and body mass index (BMI). No statistically significant correlations were found between depression ratings and morning serum DHEAS concentrations. This preliminary study provides pilot data indicating that morning serum DHEAS concentrations were positively correlated with HADS anxiety subscale score (anxiety severity) after controlling for age, gender and BMI in medication-free outpatients experiencing a major depressive episode. It is not known if morning serum DHEAS levels would show similar or dissimilar changes in non-depressed subjects. The present result needs subsequent replication.

No correlation of depression and anxiety to plasma estrogen and progesterone levels in patients with premenstrual dysphoric disorder.

A number of studies have demonstrated the correlation of depression and anxiety to estrogen and progesterone in premenstrual dysphoric disorder (PMDD), but the findings are still controversial. The purpose of this study was to determine the correlation of depression and anxiety to estrogen and progesterone concentrations in blood plasma in Taiwanese women with PMDD. A total of 43 women who met the 4th edition of the Diagnostic and Statistical Manual diagnostic criteria for PMDD were enrolled in this study. Blood samples were obtained for determination of estrogen and progesterone levels, and depression and anxiety ratings were summed for each subject during one menstrual cycle to obtain a premenstrual result (2-6 days before menses) and a postmenstrual result (menstrual cycle days 7-11). Anxiety was assessed using the 14-item Hamilton Anxiety Scale-A and was also assessed by the patients themselves using the Trait Anxiety Inventory. Depression was rated using the 21-item Hamilton Anxiety Scale-D. Calculations were made to determine the relationships between hormonal changes and mood changes. There were no statistically significant correlations between depression or anxiety ratings and estrogen or progesterone concentrations.

Premenstrual symptoms and premenstrual exacerbation in patients with psychiatric disorders.

The aim of the present study was to examine the frequencies of premenstrual syndrome (PMS) and premenstrual exacerbation (PME) of a number of psychiatric disorders in Chinese subjects. Premenstrual syndrome was assessed using a symptom checklist based on International Classification of Diseases (10th revision; ICD-10) criteria. Premenstrual exacerbation was defined as premenstrual worsening of pre-existing generalized anxiety disorder (GAD), major depressive disorder or dysthymic disorder (depressive disorders, DD), panic disorder (PD), or schizophrenia (SCH). Fifty outpatients were randomly sampled for each diagnostic group. Diagnosis was performed by psychiatrists using the structured Mini-International Neuropsychiatric Interview (MINI), and the frequencies of PMS and PME were compared for the different diagnostic groups. The PMS symptoms were reported by 78%, 80%, 68%, and 52% of GAD, DD, PD, and SCH patients, respectively, with 52%, 52%, 36%, and 20% fulfilling the definition of PME. No significant statistical relationships between diagnostic entities and family history of PMS, years of education, or age were demonstrated, but number of PMS symptoms was associated with severity of PME. No significant relationships were demonstrated between PME and marital status, parity, years of education, age, or family history of PMS. The results showed that high PME rates were noted for a sample of Chinese women with mental disorders, especially those with depressive and anxiety disorders.

Psychiatric comorbidity and gender differences of persons incarcerated for methamphetamine abuse in Taiwan.

Methamphetamine (MAP) abuse has been common in Taiwan for the past decade. The purpose of the present study was to investigate MAP abuse in Taiwan, with specific attention to psychiatric comorbidity and gender differences. A total of 325 MAP abuse subjects (180 male, 145 female) from a detention center in Taipei were assessed with the Diagnostic Interview for Genetic Studies. The following were studied: drug use behavior, treatment-seeking behavior, lifetime prevalence of mood disorders, MAP psychosis, alcohol use disorders, pathological gambling and antisocial personality. The MAP-abuse subjects in Taiwan had high psychiatric morbidity and low access to mental health services. There also exist certain differences in the prevalence of psychiatric illnesses and treatment-seeking behavior between male and female subjects. Compared with their male counterparts, more female subjects reported experience of mental disturbance and experience of psychiatric treatment. The female subjects more commonly reported suicidal behaviors than the male subjects.

Obesity in schizophrenic outpatients receiving antipsychotics in Taiwan.

This investigation estimates and compares, for the first time, the distribution of body mass index (BMI: kg/m(2)) and the prevalence of obesity among Chinese outpatients with schizophrenia treated with antipsychotics. The BMI of 201 outpatients with schizophrenia-spectrum disorders was studied via a cross-sectional naturalistic study. This investigation also compared the BMI of the subjects with a Taiwanese reference population. This investigation found no significant difference in the prevalence of obesity between male and female subjects. The prevalence of obesity among male and female patients in this investigation was, respectively, 2.74- and 2.51-fold greater than the Taiwanese reference population, and the prevalence of severe obesity among male and female patients was 4.66- and 3.53-fold greater than that in the Taiwanese reference population, respectively. The rate of severe obesity was especially high in patients treated with olanzapine. Atypical antipsychotics other than olanzapine did not seem to be more closely associated with obesity or severe obesity compared to typical antipsychotics.