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.

The Effects of Fluvoxamine on the Steady-State Plasma Concentrations of Escitalopram and Desmethylescitalopram in Depressed Japanese Patients.

BACKGROUND: The aim of this study was to determine the impact of fluvoxamine, an inhibitor of Cytochrome P450 (CYP) 2C19 (CYP2C19), on the pharmacokinetics of escitalopram, a substrate of CYP2C19. METHODS: Thirteen depressed patients initially received a 20-mg/d dose of escitalopram alone. Subsequently, a 50-mg/d dose of fluvoxamine was administered because of the insufficient efficacy of escitalopram. Plasma concentrations of escitalopram and desmethylescitalopram were quantified using high-performance liquid chromatography before and after fluvoxamine coadministration. The QT and corrected QT (QTc) intervals were measured before and after fluvoxamine coadministration. RESULTS: Fluvoxamine significantly increased the plasma concentrations of escitalopram (72.3 ± 36.9 ng/mL versus 135.2 ± 79.7 ng/mL, P < 0.01) but not those of desmethylescitalopram (21.5 ± 7.0 ng/mL versus 24.9 ± 12.0 ng/mL, no significance [ns]). The ratios of desmethylescitalopram to escitalopram were significantly decreased during fluvoxamine coadministration (0.37 ± 0.21 versus 0.21 ± 0.10, P < 0.01). The CYP2C19 genotype did not fully explain the degree of the change. Fluvoxamine coadministration did not change the QT or QTc intervals. CONCLUSIONS: The results of this study suggest that adjunctive treatment with fluvoxamine increases the concentration of escitalopram. The QTc interval did not change in this condition.

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.

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.

Preanalysis storage conditions influence the measurement of brain-derived neurotrophic factor levels in peripheral blood.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a pivotal role in regulating neuronal function throughout life, and this factor is regarded as a potential biomarker of mental disorders. However, previous studies have suggested that plasma BDNF levels are more variable than serum BDNF levels. METHODS: We determined the influence of time and temperature on the measurement of peripheral blood BDNF levels. Blood samples were aliquoted into four types of tubes, including tubes containing heparin, ethylenediaminetetraacetic acid (EDTA), and citrate for plasma, and anticoagulant-free tubes for serum. The samples were stored at 4 or 25°C for 0, 1, 2, 4, 6, 24 or 48 h, and the plasma and serum BDNF levels were measured using enzyme-linked immunosorbent assay. RESULTS: There were interindividual and interanticoagulant compound variability in the plasma BDNF levels. The measured plasma BDNF levels increased over time, whereas the serum BDNF levels remained unchanged. Furthermore, the BDNF levels detected in plasma stored in heparin tubes at 4°C and those for samples stored in EDTA tubes at 25°C were much higher than those of the other samples. CONCLUSION: This study indicates that measurements of plasma BDNF levels are dependent not only on the anticoagulant compounds but also on the storage time and temperature conditions used after blood sampling.

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.

Interaction between paliperidone and carbamazepine.

BACKGROUND: This aim of this study was to determine the impact of carbamazepine on the pharmacokinetics of paliperidone. METHODS: Six schizophrenic patients initially received a 6-12 mg/d dose of paliperidone alone. Subsequently, a 200 mg/d dose of carbamazepine was administered, and the carbamazepine dose was increased to 400 mg/d and then 600 mg/d. Plasma concentrations of paliperidone before and after carbamazepine coadministration were quantified using liquid chromatography tandem mass spectrometry (LC-MS/MS). RESULTS: Carbamazepine significantly reduced the plasma concentration of paliperidone. The plasma concentration of paliperidone at baseline and with coadministration of 200, 400, and 600 mg/d were 45.8 ± 11.7, 26.9 ± 13.7, 17.1 ± 8.2, and 15.9 ± 7.6 ng/mL, respectively. The concentration of paliperidone with carbamazepine coadministration at doses of 200, 400, and 600 mg/d were 55.7% ± 20.7%, 36.1% ± 12.2%, and 33.6% ± 10.4%, respectively, of baseline. This effect occurred even at the carbamazepine dose of 200 mg/d and reached a plateau at doses higher than 400 mg/d. However, carbamazepine coadministration exacerbated the psychotic symptoms in some patients. CONCLUSIONS: The results of the present study suggest that adjunctive treatment with carbamazepine reduces the concentration of paliperidone in a dose-dependent manner, most likely because of the induction of several drug-metabolizing enzymes and several drug transporters.

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.

Attitudes toward long-acting injectable antipsychotics among patients with schizophrenia in Japan.

BACKGROUND: Long-acting injectable antipsychotics (LAIs) are regarded as an important alternative to oral medication for patients with schizophrenia. However, LAIs remain under-utilized in clinical practice. AIMS: The aims of this investigation were to 1) obtain information on patients' attitudes toward LAIs and 2) assess factors associated with patients' acceptance of LAIs, and 3) identify predictors of the discrepancy between patients and referring psychiatrists' opinions regarding the appropriateness for LAIs. METHODS: Anonymized data were collected from a questionnaire distributed to 159 patients with schizophrenia and their referring psychiatrists at three psychiatric hospitals between February 2014 and July 2014. The patients completed an original questionnaire developed to evaluate their attitudes regarding LAIs. Regarding the appropriateness of LAI prescription, patients and their referring psychiatrists were asked to rate, on a 5-point scale, how appropriate they felt the depot prescription was for the patients. The participants also answered instruments to assess symptom severity, antipsychotic-induced extrapyramidal symptoms, functions, quality of life, and self-esteem levels. RESULTS: Patients currently on LAIs have favorable attitudes toward LAIs with respect to side effects, relapse prevention, efficacy, pain, and cost. Expectation of relapse prevention was significantly associated with patients' acceptance of LAIs (answering that those drugs are appropriate for their own treatment). In addition, the discrepancy between the patients' and referring psychiatrists' opinions regarding the appropriateness of LAI treatment was significantly associated with symptom severity, expectation of relapse prevention, belief that LAIs are painful, and belief that LAIs offer a reduced range of antipsychotic choices. CONCLUSION: Attitudes toward LAIs need to be considered when deciding whether to prescribe this formulation. Access to information on LAIs, including their benefit in relapse prevention, might enhance the acceptance and use of this formulation among patients with schizophrenia.

Sex Differences In Psychoeducation For Patients With Depression: A Comparison Of Frequency And Efficacy Of Psychoeducation.

BACKGROUND: We aimed to reveal sex differences in depression comprehension by reanalyzing data from a previous study of patients who were administered antidepressants. METHODS: A total of 424 outpatients were enrolled in the study. Participants were provided an original self-administered questionnaire that comprised eight items: depressive symptoms, course of depression, cause of depression, treatment plan, duration of antidepressant use, how to discontinue antidepressants, side effects of antidepressants, and psychotherapy. Each item consisted of the following two questions: "Have you received an explanation from the doctor in charge?" and "How much do you understand about your treatment?" The level of patients' comprehension of these questions was rated on a scale of 0-10 (11 anchor points). Symptoms were evaluated using the Quick Inventory for Depressive Symptomatology, Japanese version, and other scales. Patients were divided on the basis of sex, regardless of whether they were in remission. RESULTS: Compared with male patients, female patients with depression exhibited lower levels of depression and did not receive adequate psychoeducation from their physicians. While depression comprehension of female patients might not necessarily be associated with remission, male patients in remission received more explanations about depression and understood more compared with female patients. CONCLUSION: Depression comprehension of male patients might be associated with remission, and psychoeducation should be sex-oriented to improve treatment responses.

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.

Timing of psychoeducation for patients with depression who were treated with antidepressants: when should patients receive psychoeducation.

BACKGROUND: We analyzed data on the understanding of depression among patients who were prescribed antidepressants to determine when psychoeducation should be provided. PATIENTS AND METHODS: A total of 424 outpatients were enrolled in this study. We used an original self-administered questionnaire consisting of eight categories: (A) depressive symptoms, (B) the course of depression, (C) causes of depression, (D) the treatment plan, (E) the duration of antidepressant use, (F) discontinuation of antidepressants, (G) the side effects of antidepressants, and (H) psychotherapy. Each category was assessed with the following two questions: "Have you received an explanation of this topic from the doctor in charge?" and "How much do you understand about your treatment?" The level of understanding of patients was rated on a scale from 0 to 10 (no understanding to full understanding; 11 anchor points). Symptoms were evaluated using the Quick Inventory for Depressive Symptomatology, Japanese version (QIDS-J) and other scales. Participants were divided into two groups: patients receiving psychoeducation at their first visit vs patients receiving psychoeducation after their first visit. RESULTS: Of the patients who had received an explanation of each psychoeducation item, a greater proportion were in the first visit group than in the after first visit group for nearly all items. Compared with the after first visit group, the first visit group showed a better understanding of each psychoeducation item and significantly lower QIDS scores for those receiving explanations of Items A and C. There was no significant difference between the two groups in remittance rates. CONCLUSION: Psychoeducation on depression, especially regarding the symptoms and causes of depression, should be provided at patients' first visit.

The Association Between the Severity and Level of Understanding of Depression Among Patients Treated With Antidepressants: A Survey of 424 Outpatients in Japan.

OBJECTIVES: The present study investigated the association between the severity and knowledge of depression and attempted to reveal the specific aspects of understanding associated with severity. METHODS: A total of 424 outpatients were enrolled in this study. We used an original self-administered questionnaire: (a) the symptoms of depression, (b) the course of depression, (c) the cause of depression, (d) the treatment plan, (e) the duration of antidepressant use, (f) how to discontinue antidepressant use, (g) the adverse effects of antidepressants, and (h) psychotherapy. Each category consisted of the following questions: "How much do you understand about your treatment?" The level of understanding was rated on an 11-point scale ranging from 0 to 10. The following scales were administered: the Quick Inventory of Depressive Symptomatology, Japanese version (QIDS-J); the Global Assessment of Functioning; and the Clinical Global Impression, Severity scale. Subjects were divided in 5 groups according to severity of QIDS-J. Clinical characteristics were also investigated. RESULTS: Based on an analysis of variance, significant differences were found among the 5 groups with regard to age at onset, duration of disease, and duration of antidepressant use. A multiple regression analysis revealed that item B significantly and negatively predicted the QIDS-J scores, whereas item C significantly and positively predicted these scores. Some multiple logistic regression models seeking to distinguish severity found that all but items E to H were significantly associated with severity. CONCLUSIONS: Items B and C were significantly negatively and positively associated with depression severity, respectively. Sufficient and suitable psychoeducation in and knowledge of depression might improve the treatment responses in patients with depression.

The characteristics of understanding of depression among older patients treated with antidepressants: a comparison between older and younger patients.

BACKGROUND: To reveal characteristics of understanding of depression among older patients, we reanalyzed the data from a previous study of patients who were administered antidepressants. METHODS: A total of 424 outpatients were enrolled in this study. We used an original self-administered questionnaire consisting of eight items: depressive symptoms, the course of depression, the cause of depression, the treatment plan, the duration of antidepressant use, how to discontinue antidepressants, the side effects of antidepressants, and psychotherapy. Each item consisted of the following two questions: "Have you received an explanation from the doctor in charge?" and "How much do you understand about your treatment?". The level of understanding was rated on a scale of 0-10 (11 anchor points). Subjects were divided into two groups: younger patients who were <65 years of age and older patients who were ≥65 years of age. RESULTS: Older patients with depression showed lower levels of understanding of depression and did not receive sufficient psychoeducation from their physicians, but their understanding of depression might not be associated with their remission. In the younger group, the scores of understanding of the course of depression, the treatment plan, how to discontinue antidepressants, and psychotherapy items, and the total understanding score of remitters, were significantly higher than those of non-remitters. In contrast, there were no significant differences in the items score or total score between remitters and non-remitters in the older group. CONCLUSION: Older patients showed lower levels of understanding of depression and did not appear to receive sufficient psychoeducation, but their understanding of depression might not be associated with their remission.

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.

Characteristics of Escitalopram Discontinuation Syndrome: A Preliminary Study.

BACKGROUND: Antidepressant discontinuation syndrome (ADS) frequently occurs in patients who undergo an abrupt discontinuation of their antidepressant medication. METHODS: We evaluated 25 consecutive outpatients with depression who discontinued their use of escitalopram. The presence of ADS was evaluated according to the Antidepressants Discontinuation Syndrome checklist. RESULTS: Antidepressant discontinuation syndrome was observed in 14 of 25 patients. Frequent symptoms were dizziness (44%), muscle tension (44%), chills (44%), confusion or trouble concentrating (40%), amnesia (28%), and crying (28%). The treatment doses and plasma concentrations of escitalopram were significantly higher in patients with ADS than in patients without ADS. No group differences were observed regarding age, sex, or duration of escitalopram treatment before the discontinuation. CONCLUSIONS: These findings suggest that a higher dose and lower clearance of escitalopram lead to a higher risk of ADS. Very slow tapering is recommended for all patients.

Glutathione S-transferase K1 genotype and overweight status in schizophrenia patients: A pilot study.

Elevated oxidative stress in mitochondria and mitochondrial dysfunction are associated with weight gain in schizophrenia (SCZ) patients. Glutathione S-transferase kappa 1 (GSTK1) protects cells against exogenous and endogenous oxidative stress in the mitochondria. This exploratory study investigated the possible effects of a common GSTK1 polymorphism (rs1917760, G-1308T) on the risk for overweight status among 329 SCZ patients and 305 age- and gender-matched controls and on the GSTK1 mRNA level in peripheral blood mononuclear cells among 14 SCZ patients. The GSTK1 T/T genotype was associated with having a higher BMI value among SCZ male patients, whereas this genotype tended to be associated with a lower BMI value among female patients. Conversely, these associations were not observed among the controls. The GSTK1 T/T genotype was associated with decreased GSTK1 mRNA level among SCZ patients. The GSTK1 T/T genotype may be a novel risk factor for the prediction of overweight status in SCZ male patients, although the results of this pilot study should be verified by a larger study.

Hyperprolactinemia during antipsychotics treatment increases the level of coagulation markers.

OBJECTIVE: The strong association between psychiatric patients who receive antipsychotics and the incidence of venous thromboembolism (VTE) is known. Although previous reports suggest that hyperprolactinemia often increases markers of activated coagulation, few studies have examined the direct relationship between the prolactin level elevated by antipsychotics and activated markers of activated coagulation. METHOD: The participants included 182 patients with schizophrenia (male =89, female =93) who received antipsychotic treatments for at least 3 months. Markers of VTE (D-dimer, fibrin/fibrinogen degradation products, and thrombin-antithrombin complex) and serum prolactin concentrations were measured. RESULTS: Prolactin levels were significantly correlated with the logarithmic transformation of the D-dimer (r=0.320, P=0.002) and fibrin/fibrinogen degradation product levels (r=0.236, P=0.026) but not of the thrombin-antithrombin complex level (r=0.117, ns) among men. However, no correlations were found between the VTE markers and prolactin levels among women. These results were confirmed using multiple regression analyses that included demographic factors and antipsychotic dosages. CONCLUSION: The current study indicates that hyperprolactinemia is associated with an increase in markers of activated coagulation among men receiving antipsychotics. This finding clinically implies that monitoring and modulating prolactin levels among men are important to decrease the risk of VTE.

Attitudes toward Placebo-Controlled Clinical Trials of Patients with Schizophrenia in Japan.

BACKGROUND: Although the use of placebo in clinical trials of schizophrenia patients is controversial because of medical and ethical concerns, placebo-controlled clinical trials are commonly used in the licensing of new drugs. AIMS: The objective of this study was to assess the attitudes toward placebo-controlled clinical trials among patients with schizophrenia in Japan. METHOD: Using a cross-sectional design, we recruited patients (n = 251) aged 47.7±13.2 (mean±SD) with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder who were admitted to six psychiatric hospitals from December 2013 to March 2014. We employed a 14-item questionnaire specifically developed to survey patients' attitudes toward placebo-controlled clinical trials. RESULTS: The results indicated that 33% of the patients would be willing to participate in a placebo-controlled clinical trial. Expectations for improvement of disease, a guarantee of hospital treatment continuation, and encouragement by family or friends were associated with the willingness to participate in such trials, whereas a belief of additional time required for medical examinations was associated with non-participation. CONCLUSIONS: Fewer than half of the respondents stated that they would be willing to participate in placebo-controlled clinical trials. Therefore, interpreting the results from placebo-controlled clinical trials could be negatively affected by selection bias.

The low level of understanding of depression among patients treated with antidepressants: a survey of 424 outpatients in Japan.

BACKGROUND: We used self-administered questionnaires to investigate the level of understanding of depression among outpatients who were administered antidepressants. METHODS: A total of 424 outpatients were enrolled in this study. We used an original self-administered questionnaire that consisted of eight categories: (A) depressive symptoms, (B) the course of depression, (C) the cause of depression, (D) the treatment plan, (E) the duration of taking antidepressants, (F) how to discontinue antidepressants, (G) the side effects of the antidepressants, and (H) psychotherapy. Each category consisted of the following two questions: "Have you received an explanation from the doctor in charge?" and "How much do you understand about it?" The level of understanding was rated on a scale of 0-10 (11 anchor points). The Quick Inventory of Depressive Symptomatology Japanese version, Global Assessment of Functioning, and Clinical Global Impression - Severity scale were administered, and clinical characteristics were investigated. RESULTS: The percentages of participants who received explanations were as follows: 61.8% for (A), 49.2% for (B), 50.8% for (C), 57.2% for (D), 46.3% for (E), 28.5% for (F), 50.6% for (G), and 36.1% for (H). The level of understanding in participants who received explanations from their physicians was significantly higher compared with patients who did not receive explanations for all evaluated categories. Patient age, age at disease onset, and Global Assessment of Functioning scores were significantly associated with more items compared with the other variables. CONCLUSION: Psychoeducation is not sufficiently performed. According to the study results, it is possible for patients to receive better psychoeducation and improve their clinical outcomes.