Association Between the Serum Carnitine Level and Ammonia and Valproic Acid Levels in Patients with Bipolar Disorder.

PURPOSE: Valproic acid (VPA) is not only an antiepileptic drug but also a mood stabilizer for patients with bipolar disorder. Long-term VPA therapy can cause carnitine deficiency, which may result in an increase in the blood ammonia level, in patients with epilepsy. However, information about this effect in patients with bipolar disorder is limited. The aim of this study was to investigate the associations between the serum VPA level and the carnitine and ammonia levels in psychiatric adult patients with epilepsy. METHODS: The subjects were 182 consecutive Japanese adult patients (mean age 54.3 ± 19.5 years) diagnosed with bipolar disorder and treated with VPA. The serum VPA level, carnitine fraction, and plasma ammonia level were measured. Furthermore, the free carnitine and acylcarnitine fractions were measured using an enzyme cycling method. RESULTS: Sixty-nine patients (38%) had a low free carnitine level. There were significant differences in sex, height, VPA dose, serum VPA level, total carnitine level, acylcarnitine level, and acylcarnitine/free carnitine ratio between patients with a low free carnitine level and those with a normal range of free carnitine. The simple and multiple regression analyses revealed that the VPA dose and the serum VPA level were inversely and significantly correlated with the free carnitine level. The plasma ammonia level was correlated with the VPA dose, serum VPA level, and acylcarnitine level but not with the free carnitine level. CONCLUSIONS: These findings suggest that carnitine deficiency is associated with the VPA dose and the serum VPA level in patients with bipolar disorder. However, it is unlikely that carnitine deficiency is associated with hyperammonemia in patients with bipolar disorder.

An attempt to construct a 7-item short version of the temperament and character inventory to predict the treatment response of patients with depression; a validation study.

BACKGROUND: The Temperament and Character Inventory (TCI) is a psychological test that is frequently used to assess personality traits. Many studies have shown the potential of the inventory to predict the treatment response of patients with major depressive disorder (MDD). Previously, we showed the association between 10 items of the TCI and the treatment response. In the present study, we reanalyzed the 10 items and aimed to provide cut-off values. METHODS: This work is a secondary analysis of previously published work. Seventy-three patients were enrolled in the previously done study. Participants were treated with 10-40 mg/day of paroxetine for six weeks, and then the participants completed the TCI. The Montgomery-Asberg Depression Rating Scale (MADRS) was used to evaluate depression. The participants were divided into two groups (responders and non-responders). Using chi-squared tests, we reanalyzed the 10 items that had the strongest association with the treatment response in the previous study. We rated the answers to each item associated with the treatment response as a "1", and the answers associated with a non-response were rated as a "0". We calculated predictive scores using 10 models. Each model consisted of 1-10 scores of the best 1-10 items. We defined cut-off values for predicting treatment responses using a receiver operating characteristic (ROC) curve analysis. RESULTS: Ranked by the strength of the association with the treatment response, items 174, 137, 70, 237, 106, 191, 34, 232, 161, and 215 of the TCI significantly predicted treatment responses. All predictive scores from models 1 to 10 significantly predicted treatment responses. The predictive score threshold of model 7 was 3/4, with an area under the curve of 0.825, and this model showed the highest odds and likelihood ratios (19.3 and 8.86, respectively). CONCLUSIONS: We might predict the treatment response of patients with MDD using TCI predictive scoring, including items 174, 137, 70, 237, 106, 191, and 34 and a cut-off value of 3/4.

Changes in the Temperament and Character Inventory dimensions after paroxetine treatment in patients with major depressive disorder.

Previous studies have reported changes in the dimensions of the Temperament and Character Inventory (TCI) after patients with major depressive disorder are treated. We aimed to investigate the changes in the TCI dimensions after paroxetine treatment in patients with major depressive disorder. Forty-eight patients were enrolled in this study and were treated with 10-40 mg/day of paroxetine for 6 weeks. The TCI was completed twice, at weeks 0 and 6. We used the Montgomery-Asberg Depression Rating Scale (MADRS) to evaluate patients. The participants were divided into three groups (responders, non-responders, and early responders) based on treatment response. The scores of each dimension of the TCI were compared before and after treatment using repeated-measures two-way analyses of variance. In the responders group (n = 24), no TCI dimension scores changed significantly during treatment, but the interaction between sex and MADRS score change was significantly associated with the results. In the non-responders group (n = 15), the self-directedness score increased significantly during the treatment period (p = 0.000), and the change in MADRS score significantly affected the results. In the early responders group (n = 9), no TCI dimension scores changed significantly during treatment. The results of the present study may reveal a possible correlation between paroxetine treatment and changes in personality traits.

Therapeutic reference range for plasma concentrations of paroxetine in patients with major depressive disorders.

BACKGROUND: We investigated the relationship between plasma concentrations of paroxetine and the therapeutic effect of the drug, and we evaluated the therapeutic reference range for plasma concentration of paroxetine in patients with major depressive disorders (MDD). METHODS: In this study, 120 patients with MDD were treated with 10-40 mg/d of paroxetine for 6 weeks, and 89 patients completed the protocol. The Montgomery-Asberg Depression Rating Scale (MADRS) was used to evaluate the patients at 0, 1, 2, 4, and 6 weeks. At the 6-week treatment time point, the patients were divided into 7 groups according to their paroxetine plasma concentrations in increments of 20 ng/mL. We used an analysis of variance and a χ test to define the therapeutic reference range for plasma paroxetine concentrations. RESULTS: We used 50% as the cutoff values for the percentage of MADRS improvement to determine the responder rates, and we defined remitters as patients with MADRS scores <10 at the 6-week treatment time point. We analyzed the responder and remitter rates of the patients according to their plasma paroxetine concentrations: 20 ng/mL, 40 ng/mL, and 60 ng/mL using the χ test. According to the results of the χ test in the responder rates, the 20-60 ng/mL plasma paroxetine group showed the highest effect size. CONCLUSIONS: The results of this study suggested that a range of 20-60 ng/mL is the therapeutic reference range for concentrations of paroxetine in plasma in patients with MDD.

Dietary patterns are associated with obesity in Japanese patients with schizophrenia.

BACKGROUND: Obesity among patients with schizophrenia is a growing concern because being overweight is widely regarded as a major risk factor for cardiovascular disease and premature death. Dietary patterns have been suggested as one modifiable factor that may play a role in development of obesity. The objective of this study was to examine the association between dietary patterns and obesity among patients with schizophrenia in Japan. METHODS: We recruited patients (n = 338) aged 44.0 ± 13.2 (mean ± SD) years with a DSM-IV diagnosis of schizophrenia who were admitted to four psychiatric hospitals using a cross-sectional design. Diet was assessed with a validated brief-type self-administered diet history questionnaire (BDHQ). Dietary patterns from 52 predefined food groups were extracted by principal component analysis. RESULTS: A total of 61 subjects (18.0%) were classified as obese. Three dietary patterns were identified: the healthy dietary pattern, the processed food dietary pattern, and the alcohol and accompanying dietary patterns. After adjusting for age and gender, patients within the high tertile of each healthy dietary pattern (OR = 0.29, 95% CI = 0.13 to 0.62) and processed food dietary pattern (OR = 0.44, 95% CI = 0.22 to 0.89) had a significantly lower risk for obesity compared with low tertile of dietary pattern. CONCLUSIONS: Our findings suggest that dietary patterns, including higher intake of protein, fat, n-3 polyunsaturated fatty acids, n-6 polyunsaturated fatty acids, and vitamins, may be related to a decreased prevalence of obesity within patients with schizophrenia. Future longitudinal research exploring dietary patterns and obesity among patients with schizophrenia is warranted.

Body mass index and quality of life among outpatients with schizophrenia in Japan.

BACKGROUND: Obesity is becoming more prevalent and thus growing as a public health concern in patients with schizophrenia. This investigation evaluated the relationship between body weight and the self-reported quality of life (QOL) of Japanese patients with schizophrenia. METHODS: We recruited outpatients (n=225) aged 42.5 ± 12.8 (mean ± SD) years with a DSM-IV diagnosis of schizophrenia who were admitted to psychiatric hospitals. This study used a cross-sectional design. The assessments included an interview to obtain sociodemographic data, the second version of the Short Form Health Survey (SF-36v2), the 10-item version of the Drug Attitude Inventory (DAI-10), the Clinical Global Impression-Severity (CGI-S) and height and weight measurements. SF-36v2 subscores were examined for differences based on the following body mass index (BMI) categories: healthy weight (BMI < 24.9), overweight (BMI 25-29.9) and obese (BMI > 30). A multiple regression analysis was employed to assess the relationship between these BMI categories and QOL outcomes. RESULTS: The overall prevalence of obesity in our sample was 16.4%. A multiple regression model revealed that age, gender, DAI-10 scores, CGI-S scores, social functioning, role emotional functioning, mental health, and Mental Composite Summary (MCS) score were significantly and positively associated with overweight status. Physical functioning, general health, role emotional functioning, mental health, and a physical composite summary (PCS) score were significantly and negatively associated with obesity. CONCLUSIONS: The burden of obesity is both a physical and a mental problem. An obesity intervention program for patients with schizophrenia may improve health-related QOL in patients with schizophrenia.

Comparing the influence of dopamine D2 polymorphisms and plasma drug concentrations on the clinical response to risperidone.

Although several studies have reported that dopamine D2 receptor (DRD2) polymorphisms affect the therapeutic efficacy of antipsychotics, other studies have suggested that the plasma drug concentration is related to the clinical response. Currently, there are no definitive data regarding which factor has greater clinical significance. Sixty patients with acute exacerbations of schizophrenia received 6 mg/d of risperidone for 4 weeks. Clinical evaluations using the Brief Psychiatric Rating Scale and the Udvalg for Klinicke Undersøgelser Side Effect Rating Scale were performed before and after administration of risperidone. TaqI A and -141C Ins/Del polymorphisms were determined, and the plasma concentrations of risperidone and 9-hydroxyrisperidone were measured. The TaqI A polymorphism had no effect on therapeutic efficacy, but the -141C Ins/Del polymorphism was associated with an improvement in positive symptoms. In addition, the plasma concentration of the active moiety (risperidone plus 9-hydroxyrisperidone) correlated with the improvement in the total Brief Psychiatric Rating Scale score as well as with positive symptoms. Although there were no associations between DRD2 polymorphisms and psychic adverse effects, the plasma drug concentration was associated with psychic adverse effects. These findings suggest that DRD2 polymorphisms are associated with the therapeutic effects of risperidone as they relate to positive symptoms and that plasma drug concentrations are associated with overall symptoms as well as excitement and cognitive symptoms. Both the genotyping of DRD2 and the monitoring of plasma drug concentrations may be useful for improving clinically dominant symptoms. Further work involving replication in a larger sample is required to support our findings.

Inverse correlation between clinical response to paroxetine and plasma drug concentration in patients with major depressive disorders.

OBJECTIVE: There are few data concerning a clear relationship between the clinical effect of paroxetine and plasma drug concentrations, although therapeutic ranges have been established for some tricyclic antidepressants. METHODS: In this study, 120 patients with major depressive disorders were treated with 10-40 mg/day of paroxetine for 6 weeks, and a total of 89 patients completed the protocol. A clinical evaluation using the Montgomery-Asberg Depression Rating Scale (MADRS) was performed at 0, 1, 2, 4 and 6 weeks. RESULTS: Significant correlations were found between the plasma concentrations of paroxetine and the percentage improvement in the total MADRS scores (r = -0.282, p < 0.01) and the final MADRS scores at 6 weeks (r = 0.268, p < 0.05). The conventional receiver-operating-characteristic curve showed the fraction of true positive results and false negative results for various cut-off levels of paroxetine concentration for response and remission. The thresholds for both response and remission that gave the maximal sensitivity and specificity for paroxetine concentrations were 64.2 ng/ml. CONCLUSIONS: These results suggest that plasma paroxetine concentrations are negatively associated with improvement and that response occurs at the upper threshold of 64.2 ng/ml of paroxetine. These findings should be replicated with a larger patient sample.

Association between plasma paroxetine concentration and changes in plasma brain­derived neurotrophic factor levels in patients with major depressive disorder.

Recent studies have implicated brain­derived neurotrophic factor (BDNF) in the pathophysiology of depression and in the activities of antidepressant drugs. Serum BDNF levels are lower in depressed patients and increase in response to antidepressant medications; however, no studies have examined the association between plasma concentrations of antidepressant drugs and plasma BDNF levels. We assessed plasma BDNF levels and paroxetine concentrations in 45 patients with major depression who were being treated with paroxetine. Plasma samples were collected between 10:00 h and 12:00 h at baseline and after 1, 2 and 6 weeks of treatment. The BDNF level and paroxetine concentration of each sample were measured via enzyme immunoassay and high­performance liquid chromatography, respectively. Plasma BDNF levels increased after 2 and 6 weeks of paroxetine treatment. Plasma BDNF levels were significantly lower in men than in women. Changes in plasma BDNF level were correlated with plasma drug concentration after 2 (r = 0.309, p < 0.05) and 6 weeks (r = 0.329, p < 0.05) but not correlated with plasma drug concentration after 1 week (r = 0.284, ns). Multiple regression analysis confirmed that this change was only significantly correlated with plasma paroxetine concentration after 2 (standardised beta = 0.343, p < 0.05) and 6 weeks (standardised beta = 0.375, p < 0.05). These results suggest that paroxetine treatment increases plasma BDNF levels and that plasma paroxetine levels play an important role in changes in plasma BDNF levels.

No association between bone mass and prolactin levels among patients with schizophrenia.

OBJECTIVE: Decreased bone mineral density has been implicated in schizophrenic patients for long years. The purpose of this study was to assess the relationship between bone mass and prolactin levels in schizophrenic patients. METHODS: In this study, bone mass was measured using quantitative ultrasound densitometry of the calcaneus in 114 patients (49 males and 65 females). The osteosono-assessment index (OSI) was calculated as a function of the speed of sound and transmission index. Estradiol, testosterone, and prolactin levels were also measured. Factors that influenced prolactin levels and bone mass were determined via multiple linear regression analysis. RESULTS: Among the female patients, body mass index and estradiol levels were independently and significantly associated with the OSI. Neither prolactin levels nor duration of antipsychotic treatment was associated with bone mass for either gender. CONCLUSIONS: These findings suggest that prolactin levels do not contribute to poor bone mass, as assessed using the OSI among schizophrenic patients. However, the interpretation of our results was hampered by lack of data including differences in lifestyle and type of antipsychotic medications used in schizophrenic patients. Association between prolactin levels and low bone mineral density was not completely ruled out. Future research exploring prolactin levels and bone mineral density is warranted.

Comparison of prevalence of metabolic syndrome in hospital and community-based Japanese patients with schizophrenia.

BACKGROUND: Lifestyle factors, such as an unbalanced diet and lack of physical activity, may affect the prevalence of metabolic syndrome (MetS) in schizophrenic patients. The aim of this study was to compare the MetS prevalence between inpatients and outpatients among schizophrenic population in Japan. METHODS: We recruited inpatients (n = 759) and outpatients (n = 427) with a Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) diagnosis of schizophrenia or schizoaffective disorder from 7 psychiatric hospitals using a cross-sectional design. MetS prevalence was assessed using three different definitions, including the adapted National Cholesterol Education Program Adult Treatment Panel (ATP III-A). RESULTS: The overall MetS prevalences based on the ATP III-A definition were 15.8% in inpatients and 48.1% in outpatients. In a logistic regression model with age and body mass index as covariates, being a schizophrenic outpatient, compared to being a schizophrenic inpatient, was a significant independent factor (odds ratio = 3.66 for males, 2.48 for females) in the development of MetS under the ATP III-A definition. The difference in MetS prevalence between inpatients and outpatients was observed for all age groups in males and for females over 40 years of age. CONCLUSIONS: Outpatients with schizophrenia or schizoaffective disorder in Japan had a high prevalence of MetS compared to inpatients. MetS in schizophrenic outpatients should be carefully monitored to minimize the risks. A change of lifestyle might improve MetS in schizophrenic patients.

Different Attitudes of Patients and Psychiatrists Toward Benzodiazepine Treatment.

BACKGROUND: Concern regarding the benefit/risk ratio of the long-term use of benzodiazepines (BDZs) and Z-drugs is increasing. To prevent the risk of dependence in BDZ long-term use, it is essential to understand the attitudes of patients and psychiatrists toward BDZ treatment. The aims of this investigation were to 1) obtain information on patients' attitudes with long-term BDZ use and their referring psychiatrists' attitudes toward BDZ treatment, including their perception of the difficulty of reducing the dose of BDZs, and 2) identify discrepancies between patients' and psychiatrists' perceptions. METHODS: A brief questionnaire was constructed to investigate the attitudes of patients receiving BDZ treatment and their referring psychiatrists. Our sample comprised 155 patients who received BDZ treatment for more than one year and their referring eight psychiatrists. Both the patients and their psychiatrists completed our questionnaire between August 2017 and December 2017. RESULTS: Of the patients, 13% felt that it was more difficult to reduce the dose of BDZs than their referring psychiatrists (type A discrepancy), while 25% felt that it was less difficult (type B discrepancy). In the multivariate logistic regression analysis, the female sex and both the patients' ("psychotherapy plus BDZs was necessary" and "it was necessary to increase the dose of BDZs") and psychiatrists' beliefs ("short-term prescription was justified") were associated with type A discrepancies. Type B discrepancies were associated with psychiatrists' beliefs that the patient's wishes justified the use of BDZs and that the cessation of treatment with BDZs would lead to the deterioration of their rapport with their patients. CONCLUSION: To overcome the discrepancies in the attitudes of patients and psychiatrists toward the cessation of BDZ treatment, it is necessary to promote patient-centered care involving patient psychoeducation and practice guidelines for the decision-making process. Further studies investigating the promotion of patient-centered care to reduce BDZ use are needed.

No association between polymorphism in tyrosine hydroxylase and personality traits in healthy Japanese subjects.

The aim of the present study was to investigate whether there is an association between the (TCAT)(n) repeat polymorphism in the tyrosine hydroxylase (TH) gene and personality. The (TCAT)(n) repeat polymorphism in the TH gene was genotyped in 898 healthy Japanese subjects. Personality traits were evaluated using the Temperament and Character Inventory (TCI). There was no significant difference in the TCI scores of subjects with and without the T9 allele. Furthermore, no significant association was found between each genotype and the TCI scores, even when the TCI scores were compared with the homozygous genotype. These findings suggest that the (TCAT)(n) repeat polymorphism in the TH gene does not contribute to the personality traits evaluated on the TCI in healthy Japanese subjects.

Characteristics of the tree-drawing test in chronic schizophrenia.

AIMS: A tree-drawing test acts as both a projective psychological examination as well as a supplementary psychodiagnostic tool. There is little information relating the characteristics of schizophrenia and the tree-drawing test. The present study compared the structural and morphological differences in the results of the tree-drawing test between schizophrenic patients and healthy individuals, as well as between schizophrenic patients who responded well to treatment and those who responded poorly. METHODS: The subjects included 202 chronic schizophrenic patients and 113 healthy individuals. The schizophrenic patients were categorized as 'good responders' or 'poor responders' based on their response to medical treatments. The tree-drawing test was performed on all subjects. The tree drawn by each subject was analyzed structurally and morphologically. RESULTS: There were significant differences between the trunk and branches drawn by schizophrenic patients and those drawn by healthy controls. There were no significant differences between the good responders and the poor responders in any aspect of the tree drawings. Multiple regression models showed that the ratio of the tree area to the total area of the drawing paper, the width of the trunk, the trunk base opening, and the size of the branch ends were significantly associated with schizophrenia. CONCLUSION: The present study suggests that the trees drawn by schizophrenic patients are significantly different from those drawn by healthy individuals, but among schizophrenic patients, it is difficult to distinguish between good responders and poor responders using the tree-drawing test.

Augmentation of antidepressants with perospirone for treatment-resistant major depressive disorder.

We examined the efficacy and tolerability of perospirone, a dopamine D2 and 5-HT2A receptor antagonist and a partial 5-HT1A receptor agonist, in the augmentation of antidepressant treatment of partially responding and nonresponding patients with major depressive disorder. Twelve patients with major depressive disorder and an incomplete or no response to different kinds of antidepressants (selective serotonin reuptake inhibitor, milnacipran, or sulpride) monotherapy or polytherapy for 8 weeks or more were treated with perospirone augmentation in an eight-week, open-label study. Data were gathered from July 2006 to March 2008. The mean duration of antidepressant pharmacotherapy at baseline was 28 weeks. At baseline, the mean (+/-SD) of the MADRS scores was 35.8+/-10.1. The mean (+/-SD) initial dose of perospirone was 7.0+/-2.9 mg/day and the final dose was 11.7+/-6.6 mg/day. Significant reductions in MADRS scores were observed at weeks 2, 4, 6 and 8. Although two of the twelve subjects who completed the protocol achieved remission by the study endpoint, five of the twelve patients were responders (i.e., >50% improvement in the MADRS score). Sleepiness and tremor were observed in six patients and one patient, respectively, resulting in a reduction of perospirone dose due to these side effects. The discontinuation rate after 8 weeks of treatment was zero. These findings suggest that perospirone may be an effective augmentation strategy for improving therapeutic response in patients with treatment-resistant major depressive disorder when administered in combination with standard antidepressant therapy. Based on this clinical evidence, a double-blind, placebo-controlled trial is warranted.

Association between monoamine oxidase A (MAOA) and personality traits in Japanese individuals.

It has been reported that personality traits are related to several neurotransmitters. However, the association between personality traits and the central nervous system remains unclear. In the present study, we investigated the relationships between a polymorphism involving a variable number of tandem repeats in the promoter of the monoamine oxidase A (MAOA-VNTR) gene and personality traits, as assessed by the Temperament and Character Inventory (TCI). Promoter VNTRs in the MAOA were genotyped in 558 healthy Japanese individuals. Females homozygous for high-activity allele (4/4) had significantly higher persistence scores than those homozygous for the low-activity allele (3/3) (p=0.012, ANOVA). Meanwhile no difference in persistence was found between 3 and 4 allele in males. There were no differences between other scores of TCI subscales and MAOA-VNTR polymorphism. Our results suggest a gender-specific contribution of MAOA-VNTR polymorphism to persistence scores.

Association between dopamine-related polymorphisms and plasma concentrations of prolactin during risperidone treatment in schizophrenic patients.

Hyperprolactinemia is an inevitable consequence of treatment with antipsychotic agents to some extent because prolactin response to antipsychotics is related to dopamine blockade. Recent studies have suggested that polymorphisms of the dopamine receptors are associated with therapeutic response to antipsychotics. Thus, we studied the effects of major polymorphisms of dopamine-related genes on plasma concentration of prolactin. Subjects were 174 schizophrenic patients (68 males, 106 females) receiving 3 mg twice daily of risperidone for at least 4 weeks. Sample collections were conducted 12 h after the bedtime dosing. Five dopamine-related polymorphisms (Taq1A, -141C ins/del for DRD2, Ser9Gly for DRD3, 48 bp VNTR for DRD4, Val158Met for COMT) were identified. The mean (+/-SD) plasma concentration of prolactin in females was significantly higher than males (54.3+/-27.2 ng/ml versus 126.8+/-70.2 ng/ml, p<0.001). No dopamine-related polymorphisms differed the plasma concentration of prolactin in males or females. Multiple regression analyses including plasma drug concentration and age revealed that plasma concentration of prolactin correlated with gender (standardized partial correlation coefficients (beta)=0.551, p<0.001) and negatively with age (standardized beta=-0.202, p<0.01). No correlations were found between prolactin concentration and dopamine-related polymorphisms. These findings suggest that plasma prolactin concentrations in females are much higher than in males but the dopamine-related variants are not predominantly associated with plasma concentration of prolactin.

Effects of personality on the association between paroxetine plasma concentration and response.

BACKGROUND: We studied the differences between groups that were divided according to personality characteristics with respect to the relationship between drug concentration and symptom improvement. METHODS: A total of 120 patients with major depressive disorder were treated with paroxetine for 6 weeks, and 89 patients completed the protocol. The Montgomery-Åsberg Depression Rating Scale (MADRS) was used to evaluate the patients. Patients' paroxetine plasma concentrations at week 6 were measured. Their personalities were evaluated by the Temperament and Character Inventory (TCI) at the first visit. We divided the patients into two groups according to the median of each TCI dimension. We compared the responder rate between "high" and "low" groups in each TCI dimension and analyzed Pearson's correlation coefficients of paroxetine plasma concentration and MADRS-improvement rate. RESULTS: A total of 62 patients completed the TCI. Low-novelty-seeking, high-harm-avoidance, low-reward-dependence, and low-self-directedness groups exhibited significant negative correlations between paroxetine plasma concentration and MADRS improvement. Among the groups with combined personality traits, the high-harm-avoidance and low-self-directedness groups showed a markedly significant negative correlation. CONCLUSION: Patients with depression exhibiting specific personality traits, especially those with high harm-avoidance and low self-directedness scores, exhibited a significant negative association between paroxetine plasma concentration and MADRS-improvement rate. Therefore, a lower dose might be suitable for patients with specific personality traits.

Attitudes toward placebo-controlled clinical trials among depressed patients in Japan.

BACKGROUND: Placebo-controlled clinical trials are the standard in the design of clinical studies for the licensing of new drugs. Medical and ethical concerns regarding placebo use still exist in clinical trials of depressed patients. The aim of this study was to investigate the attitudes toward placebo-controlled clinical trials and to assess factors related to the willingness to participate in such trials among depressed patients in Japan. METHODS: A total of 206 depressed patients aged 49.5 ± 15.7 years (mean ± SD) who were admitted to three psychiatric hospitals were recruited for a cross-sectional study from June 2015 to March 2016. After a thorough explanation of the placebo, the study participants completed a brief 14-item questionnaire developed to evaluate patients' attitudes regarding possible participation in placebo-controlled clinical trials. The Quick Inventory of Depressive Symptomatology was also administered to assess depressive symptoms. RESULTS: The results indicated that 47% of the patients would be willing to participate in a placebo-controlled clinical trial. Expectations for the improvement of disease, desire to receive more medical care, encouragement by family or friends, and desire to support the development of new drugs were associated with the willingness to participate in such trials, whereas a belief that additional time would be required for medical examinations and fear of exacerbation of symptoms due to placebo use were associated with non-participation. LIMITATIONS: Patients were asked about possible participation in placebo-controlled clinical trials. CONCLUSIONS: Less than half of the respondents were willing to participate in placebo-controlled clinical trials. Attitudes toward participation in a placebo-controlled clinical trial need to be considered when deciding whether to conduct such a trial.