BackgroundAlthough the validity and safety of antipsychotic polypharmacy remains unclear, it is commonplace in the treatment of schizophrenia. This study aimed to investigate the degree that antipsychotic polypharmacy contributed to metabolic syndrome in outpatients with schizophrenia, after adjustment for the effects of lifestyle.MethodsA cross-sectional survey was carried out between April 2007 and October 2007 at Yamanashi Prefectural KITA hospital in Japan. 334 patients consented to this cross-sectional study. We measured the components consisting metabolic syndrome, and interviewed the participants about their lifestyle. We classified metabolic syndrome into four groups according to the severity of metabolic disturbance: the metabolic syndrome; the pre-metabolic syndrome; the visceral fat obesity; and the normal group. We used multinomial logistic regression models to assess the association of metabolic syndrome with antipsychotic polypharmacy, adjusting for lifestyle.ResultsSeventy-four (22.2%) patients were in the metabolic syndrome group, 61 (18.3%) patients were in the pre-metabolic syndrome group, and 41 (12.3%) patients were in visceral fat obesity group. Antipsychotic polypharmacy was present in 167 (50.0%) patients. In multinomial logistic regression analyses, antipsychotic polypharmacy was significantly associated with the pre-metabolic syndrome group (adjusted odds ratio [AOR], 2.348; 95% confidence interval [CI], 1.181-4.668), but not with the metabolic syndrome group (AOR, 1.269; 95%CI, 0.679-2.371).ConclusionsThese results suggest that antipsychotic polypharmacy, compared with monotherapy, may be independently associated with an increased risk of having pre-metabolic syndrome, even after adjusting for patients' lifestyle characteristics. As metabolic syndrome is associated with an increased risk of cardiovascular mortality, further studies are needed to clarify the validity and safety of antipsychotic polypharmacy.
BackgroundMeta-analyses of several randomized controlled trials have shown that cognitive behavioral therapy (CBT) has comparable efficacy to antidepressant medication, but therapist availability and cost-effectiveness is a problem.ObjectiveThis study aimed to evaluate the effectiveness of Web-based CBT blended with face-to-face sessions that reduce therapist time in patients with major depression who were unresponsive to antidepressant medications.MethodsA 12-week, assessor-masked, parallel-group, waiting- list controlled, randomized trial was conducted at 3 medical institutions in Tokyo. Outpatients aged 20-65 years with a primary diagnosis of major depression who were taking ≥1 antidepressant medications at an adequate dose for ≥6 weeks and had a 17-item GRID-Hamilton Depression Rating Scale (HAMD) score of ≥14 were randomly assigned (1:1) to blended CBT or waiting-list groups using a computer allocation system, stratified by the study site with the minimization method, to balance age and baseline GRID-HAMD score. The CBT intervention was given in a combined format, comprising a Web-based program and 12 45-minute face-to-face sessions. Thus, across 12 weeks, a participant could receive up to 540 minutes of contact with a therapist, which is approximately two-thirds of the therapist contact time provided in the conventional CBT protocol, which typically provides 16 50-minute sessions. The primary outcome was the alleviation of depressive symptoms, as measured by a change in the total GRID-HAMD score from baseline (at randomization) to posttreatment (at 12 weeks). Moreover, in an exploratory analysis, we investigated whether the expected positive effects of the intervention were sustained during follow-up, 3 months after the posttreatment assessment. Analyses were performed on an intention-to-treat basis, and the primary outcome was analyzed using a mixed-effects model for repeated measures.ResultsWe randomized 40 participants to either blended CBT (n=20) or waiting-list (n=20) groups. All patients completed the 12-week treatment protocol and were included in the intention-to-treat analyses. Participants in the blended CBT group had significantly alleviated depressive symptoms at week 12, as shown by greater least squares mean changes in the GRID-HAMD score, than those in the waiting list group (−8.9 points vs −3.0 points; mean between-group difference=−5.95; 95% CI −9.53 to −2.37; P<.001). The follow-up effects within the blended CBT group, as measured by the GRID-HAMD score, were sustained at the 3-month follow-up (week 24) and posttreatment (week 12): posttreatment, 9.4 (SD 5.2), versus follow-up, 7.2 (SD 5.7); P=.009.ConclusionsAlthough our findings warrant confirmation in larger and longer term studies with active controls, these suggest that a combined form of CBT is effective in reducing depressive symptoms in patients with major depression who are unresponsive to antidepressant medications.Trial RegistrationUniversity Hospital Medical Information Network Clinical Trials Registry: UMIN000009242; https://u...
Aims: A review of the published work on treatments for major depressive disorder suggests that there is an alarming gap between guideline recommendations and actual clinical practices worldwide. The purpose of this study was to compare early-career psychiatrists' selections of treatment for mild to moderate major depression in Japan and the USA. Methods:The authors surveyed 120 early-career psychiatrists from two residency programs in Japan and the USA using web-based questionnaires. In response to two case vignettes of mild to moderate major depression, the subjects selected treatment modalities and first-and second-line pharmacotherapy.Results: Eighty-one psychiatrists (68%) returned surveys, of whom 42 (52%) were Japanese and 39 (48%) American. Fewer Japanese subjects selected psychotherapy than Americans. The Japanese psychiatrists favored benzodiazepine monotherapy for the treatment of mild depression, whereas the American psychiatrists favored antidepressant monotherapy.For the initial treatment of moderate depression, approximately half of the Japanese selected antidepressant monotherapy, and a quarter selected benzodiazepine monotherapy, whereas the Americans unanimously selected selective serotonin reuptake inhibitors monotherapy. As a second-line strategy, the Japanese were more likely to augment medication and less likely to increase dosage for moderate depression than their American counterparts.Conclusions: Differences were found between the treatment selections of early-career psychiatrists in Japan and the USA, despite comparable guidelines and postgraduate training. The results suggest that the gap between guidelines and practice may also be shaped by physician workload, attitudes toward sideeffects, and the sociocultural contexts in which clinical decisions are made.
We have cloned a cDNA encoding Toxoplasma gondii pyruvate kinase and obtained the full-length recombinant enzyme with a calculated molecular mass of 57.5 kDa. The predicted amino acid sequence of T. gondii pyruvate kinase exhibited a highest identity (63%) to that of Eimeria tenella pyruvate kinase and a lower identity of less than 25% to the pyruvate kinases from other organisms. Southern blot analysis indicated that the pyruvate kinase gene existed as a single copy in the T. gondii tachyzoite. The active recombinant enzyme contained four subunits and produced a strongly sigmoid saturation curve with phosphoenolpyruvate as the variable substrate. Fructose 1,6-diphosphate, a general activating factor of pyruvate kinase in most species, did not affect the enzyme activity. However, glucose 6-phosphate radically activated the enzyme. Fructose 2,6-diphosphate suppressed the reaction velocity at a higher concentration of phosphoenolpyruvate. These properties indicate that pyruvate kinase activity in T. gondii is regulated by unusual phosphorylated sugars.
BackgroundA growing body of evidence shows that reducing the duration of untreated illness (DUI) correlates with improved clinical outcome and course of depression. However, the factors involved in delaying treatment contact after the first onset of lifetime depression are not fully understood. This cross-sectional study aims to identify the characteristics that may predict the delay in initial treatment contact after the first onset of lifetime depression by comparing the socio-demographics and clinical characteristics between those with longer and shorter DUI in a well-characterized Japanese clinical sample.MethodsNinety-five patients with depression with longer (>12 months) and shorter DUI (≤12 months) at three Japanese outpatient clinics were studied. Subjects received a comprehensive evaluation, including semi-structured clinical interviews and assessment battery, and their clinical charts were reviewed.ResultsOf the total sample, the median of DUI was 4 months (interquartile range (IQR) 25th–75th percentile, 2–13). We found that 72.6% of patients seek treatment contact within the first year of depression onset. Multivariate logistic regression analysis showed that longer DUI in patients was associated with marital status (never married). Further, the DSM-IV melancholic features approached significance.ConclusionsOur findings suggest that most Japanese patients with depression are likely to seek treatment within 1 year of onset, and that marital status and melancholia may be potential predictors of the delay in the initial treatment contact after the first onset of lifetime depression.
I read with interest Zhdanava et al's article titled: "Impact of COVID-19 pandemic on prescribing of long-acting injectable antipsychotics for schizophrenia: Results from a United States prescriber survey", 1 in which the authors stated that, of 401 long-acting injectable (LAI) prescribers in their study, 64.6% reported no change to their LAI prescriptions during the COVID-19 pandemic. Moreover, 50% of LAI prescribers reported no change in adherence rates to oral antipsychotic medications. The authors concluded that 68.1% of prescribers did not switch to less frequently administered LAI. The findings of this interesting study raise the following issues.First, in terms of the LAI prescribers' demographics, 79.8% were physicians, whereas the remainder were paramedical staff. While 50.4% of the physicians had >15 years of practice experience, the rest appeared to be less experienced. It would be worthwhile to examine LAI prescribing trends among occupations and among physicians according to years of experience.Second, 50.1% of LAI prescribers in the United States reported no change in medication adherence among patients with schizophrenia during the COVID-19 pandemic, whereas a recent meta-analysis concluded that adequate adherence was not achieved. 2 Did no change mean that medication adherence did not deteriorate further but remained at a low level? Further, it is also likely that the group of respondents in Figure 4 who reported "high medication adherence" and the group in Figure 5 who reported a "low relapse" formed only part of the total sample.Third, questions can be raised concerning the finding that 68.1% of prescribers did not switch to less frequently administered LAI. The main reason given to explain this finding was "no medical need for switching"; however, was this reasoning influenced by reports of "no change in medication adherence among patients with schizophrenia during the COVID-19 pandemic"? In our survey, 70% of Japanese psychiatrists reported that relapses increased during the COVID-19 pandemic. While there were more opportunities for online treatment, doubts remain concerning its effectiveness. 3 The present study and that of Ifteni et al also raised concerns regarding online medical care. 1,4 In terms of LAI treatment, Ifteni et al showed that extending the frequency of administration as much as possible during the COVID-19 pandemic was desirable. 4 Our study also showed higher expectations for longer formulation of atypical antipsychotics. 3 Indeed, the difference was clear, as the time from treatment interruption to relapse, which tended to occur during the COVID-19 pandemic, was approximately 6 months for the 1-month formulation versus approximately 13 months for the 3-month formulation. 5 Several questions have been raised in response to this interesting study and further research is warranted.
Postpsychotic depression (PPD) is depression that presents after the acute phase of schizophrenia. Mino and Ushijima 5 refer to PPD as a "postpsychotic collapse" and indicate that it is a state of inactivity with a loss of energy and vitality after the improvement of psychotic symptoms. In his latest review, 6 Guerrero stated, "We have always focused on hallucinatory delusions in patients with schizophrenia, but in the last two decades we have begun to reaffirm the importance of the emotional aspect as part of the recovery process in psychotic patients."The World Federation of Societies of Biological Psychiatry (WFSBP) guidelines suggest that in treating PPD, typical antipsychotics may cause a depressed or unpleasant mood depending on the degree of dopamine D2 blockade. 7 In contrast, certain atypical antipsychotics may improve depressive symptoms. 7,8 Data on antidepressant administration for treating depressive symptoms of schizophrenia are limited. 7 In recent The American Psychiatric Association practice guideline, there is evidence supporting the use of antidepressants to treat depression in people with schizophrenia; however, many trials had small sample sizes or other issues that raise the possibility of bias in the results. [8][9][10][11] Although
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