The effect of education regarding treatment guidelines for schizophrenia and major depressive disorders on psychiatrists' hypnotic medication prescribing behavior: a multicenter study.

BACKGROUND: To examine whether the "Effectiveness of Guideline for Dissemination and Education in psychiatric treatment (EGIUDE)" project affects the rate of prescriptions of hypnotic medication and the type of hypnotic medications prescribed among psychiatrists, for schizophrenia and major depressive disorder in Japan. METHODS: The EGUIDE project is a nationwide prospective study of evidence-based clinical guidelines for schizophrenia and major depressive disorder in Japan. From 2016 to 2021, clinical and prescribing data from patients discharged from hospitals participating in the EGUIDE project were used to examine hypnotic medication prescriptions The prescribing rate of hypnotics and the prescribing rate of each type of hypnotic (benzodiazepine receptor agonist, nonbenzodiazepine receptor agonist, melatonin receptor agonist, and orexin receptor antagonist) were compared among patients who had been prescribed medication by psychiatrists participating in the EGUIDE project and patients who had been prescribed medication by nonparticipating psychiatrists. Multivariate logistic regression analysis was performed to examine the effect of the EGUIDE project on the prescription of hypnotic medications. RESULTS: A total of 12,161 patients with schizophrenia and 6,167 patients with major depressive disorder were included. Psychiatrists participating in the EGUIDE project significantly reduced the rate of prescribing hypnotic medication and benzodiazepine receptor agonists for both schizophrenia (P < 0.001) and major depressive disorder (P < 0.001) patients. CONCLUSION: This is the first study to investigate the educational effects of guidelines for the treatment of psychiatric disorders on psychiatrists in terms of prescribing hypnotic medications to patients. The EGUIDE project may play an important role in reducing hypnotic medication prescription rates, particularly with respect to benzodiazepine receptor agonists. The results suggest that the EGUIDE project may result in improved therapeutic behavior.

Human-Comparable Sensitivity of Large Language Models in Identifying Eligible Studies Through Title and Abstract Screening: 3-Layer Strategy Using GPT-3.5 and GPT-4 for Systematic Reviews.

BACKGROUND: The screening process for systematic reviews is resource-intensive. Although previous machine learning solutions have reported reductions in workload, they risked excluding relevant papers. OBJECTIVE: We evaluated the performance of a 3-layer screening method using GPT-3.5 and GPT-4 to streamline the title and abstract-screening process for systematic reviews. Our goal is to develop a screening method that maximizes sensitivity for identifying relevant records. METHODS: We conducted screenings on 2 of our previous systematic reviews related to the treatment of bipolar disorder, with 1381 records from the first review and 3146 from the second. Screenings were conducted using GPT-3.5 (gpt-3.5-turbo-0125) and GPT-4 (gpt-4-0125-preview) across three layers: (1) research design, (2) target patients, and (3) interventions and controls. The 3-layer screening was conducted using prompts tailored to each study. During this process, information extraction according to each study's inclusion criteria and optimization for screening were carried out using a GPT-4-based flow without manual adjustments. Records were evaluated at each layer, and those meeting the inclusion criteria at all layers were subsequently judged as included. RESULTS: On each layer, both GPT-3.5 and GPT-4 were able to process about 110 records per minute, and the total time required for screening the first and second studies was approximately 1 hour and 2 hours, respectively. In the first study, the sensitivities/specificities of the GPT-3.5 and GPT-4 were 0.900/0.709 and 0.806/0.996, respectively. Both screenings by GPT-3.5 and GPT-4 judged all 6 records used for the meta-analysis as included. In the second study, the sensitivities/specificities of the GPT-3.5 and GPT-4 were 0.958/0.116 and 0.875/0.855, respectively. The sensitivities for the relevant records align with those of human evaluators: 0.867-1.000 for the first study and 0.776-0.979 for the second study. Both screenings by GPT-3.5 and GPT-4 judged all 9 records used for the meta-analysis as included. After accounting for justifiably excluded records by GPT-4, the sensitivities/specificities of the GPT-4 screening were 0.962/0.996 in the first study and 0.943/0.855 in the second study. Further investigation indicated that the cases incorrectly excluded by GPT-3.5 were due to a lack of domain knowledge, while the cases incorrectly excluded by GPT-4 were due to misinterpretations of the inclusion criteria. CONCLUSIONS: Our 3-layer screening method with GPT-4 demonstrated acceptable level of sensitivity and specificity that supports its practical application in systematic review screenings. Future research should aim to generalize this approach and explore its effectiveness in diverse settings, both medical and nonmedical, to fully establish its use and operational feasibility.

Combination Psychotropic Use for Schizophrenia With Long-Acting Injectable Antipsychotics and Oral Antipsychotics: A Nationwide Real-World Study in Japan.

BACKGROUND: Although several guidelines recommend monotherapy with antipsychotics for the treatment of schizophrenia, patients who receive long-acting injectable antipsychotics (LAIs) are frequently treated with oral antipsychotics (OAPs). In the present study, we investigated the detailed use of psychotropic medications among patients throughout Japan with schizophrenia who received LAIs or OAPs. METHODS: The present study used data from the project for the Effectiveness of Guidelines for Dissemination and Education in psychiatric treatment from 94 facilities in Japan. The LAI group included patients who received any LAI, and the non-LAI group included patients who took only OAP medications at discharge. The participants of this study were 2518 schizophrenia patients (263 in the LAI group and 2255 in the non-LAI group) who received inpatient treatment and had prescription information at discharge between 2016 and 2020. RESULTS: This study revealed significantly higher rates of polypharmacy antipsychotics, number of antipsychotics, and chlorpromazine equivalents in the LAI group than in the non-LAI group. In contrast, the LAI group showed lower rate of concomitant use of hypnotic and/or antianxiety medication than the non-LAI group. CONCLUSIONS: Presenting these real-world clinical results, we want to encourage clinicians to keep monotherapy in mind for the treatment of schizophrenia, especially by reducing concomitant use of antipsychotics in the LAI group and reducing hypnotic and/or antianxiety medication in the non-LAI group.

Change of prescription for patients with schizophrenia or major depressive disorder during admission: real-world prescribing surveys from the effectiveness of guidelines for dissemination and education psychiatric treatment project.

BACKGROUND: Polypharmacy of additional psychotropics alongside the main treatment drug (antipsychotics in schizophrenia and antidepressants in major depressive disorder) is common in Japan. Our goal is to align psychotropic prescription in Japan with international standards, while reducing the differences between facilities. To achieve this goal, we aimed to compare prescriptions at the time of hospital admission and discharge. METHODS: Data on prescriptions at admission and discharge from 2016 to 2020 were collected. We divided the patients into four groups: (1) mono_mono group, monotherapy of the main drug at admission and discharge; (2) mono_poly group, monotherapy at admission and polypharmacy at discharge; (3) poly_poly group, polypharmacy at admission and discharge; and (4) poly_mono group, polypharmacy at admission and monotherapy at discharge. We compared the changes in dosage and number of psychotropics among the four groups. RESULTS: For both schizophrenia and major depressive disorder, the patients who received monotherapy with the main drug at admission were likely to receive main drug monotherapy at discharge and vice versa. For schizophrenia, the polypharmacy was prescribed more often in the mono_poly group than that in the mono_mono group. The prescription was not changed at all for more than 10% of the patients. CONCLUSIONS: It is critical to avoid a polypharmacy regimen to ensure that guideline-compliant treatment is provided. We expect higher rates of monotherapy with the main drug after the EGUIDE lectures. TRIAL REGISTRATION: The study protocol was registered in the University Hospital Medical Information Network Registry (UMIN000022645).

Effects of Japanese policies and novel hypnotics on long-term prescriptions of hypnotics.

AIM: The current study aimed to examine the effect of Japanese policies for appropriate hypnotics use and novel hypnotics (e.g. melatonin receptor agonist and orexin receptor antagonist [ORA]) on long-term prescriptions of hypnotics. METHODS: This retrospective study was conducted using a large-scale health insurance claims database. Among subscribers prescribed hypnotics at least once between April 2005 and March 2021, those prescribed hypnotics for the first time after being included in the database in three periods (period 1: April 2012-March 2013; period 2: April 2016-March 2017; and period 3: April 2018-March 2019) were eligible. These were set considering the timing of the 2014 and 2018 medical fee revisions (2014 for polypharmacy of three or more hypnotics, 2018 for long-term prescription of benzodiazepine receptor agonists for >12 months). The duration of consecutive prescriptions of hypnotics over 12 months was evaluated. Factors associated with short-term prescriptions of hypnotics were also investigated. RESULTS: In total, 186 535 participants were newly prescribed hypnotics. The mean duration of prescriptions was 2.9 months, and 9.3% of participants were prescribed hypnotics for 12 months. Prescription periods were not associated with short-term prescriptions of hypnotics. ORA use was associated with short-term prescriptions of hypnotics (adjusted hazard ratio, 1.077 [95% confidence interval, 1.035-1.120]; P < 0.001), but melatonin receptor agonist use was not. CONCLUSION: Japanese policies had no statistically significant effect on long-term prescriptions of hypnotics. Although this study suggests initiating ORA for insomniacs as a candidate strategy to prevent long-term prescriptions of hypnotics, further research is necessary to draw conclusions.

Effect of education regarding treatment guidelines for schizophrenia and depression on the treatment behavior of psychiatrists: A multicenter study.

AIM: This study aims to examine the real-world effectiveness of education regarding clinical guidelines for psychiatric disorders using 'the Effectiveness of guidelines for dissemination and education in psychiatric treatment (EGUIDE)' project. METHODS: The EGUIDE project is a nationwide prospective implementation study of two clinical practice guidelines, i.e., the Guideline for Pharmacological Therapy of Schizophrenia and the Treatment Guidelines for Major Depressive Disorders, in Japan. Between 2016 and 2019, 782 psychiatrists belonging to 176 hospitals with psychiatric wards participated in the project and attended lectures on clinical practice guidelines. The proportions of guideline-recommended treatments in 7405 patients with schizophrenia and 3794 patients with major depressive disorder at participating hospitals were compared between patients under the care of psychiatrists participating in the project and those not participating in the project. Clinical and prescribing data on the patients discharged from April to September each year from participating hospitals of the project were also analyzed. RESULTS: The proportions of three quality indicators (antipsychotic monotherapy regardless of whether other psychotropics medication, antipsychotic monotherapy without other psychotropics and no prescription of anxiolytics or hypnotics) for schizophrenia were higher among participating psychiatrists than among nonparticipating psychiatrists. As similar results were obtained in major depressive disorder, the effectiveness of the project for the dissemination of guideline-recommended treatment has been replicated. CONCLUSION: This strategy of providing education regarding the clinical guidelines for psychiatric disorders was effective in improving the treatment-related behavior of psychiatrists. The use of this education-based strategy might contribute to resolving the mental health treatment gap.

Effects of electroconvulsive therapy on the use of anxiolytics and sleep medications: a propensity score-matched analysis.

AIM: We investigated the association of electroconvulsive therapy (ECT) with anxiolytic and sleep medication use in patients with major depressive disorder (MDD) and schizophrenia (SZ). METHODS: This nationwide observational study analyzed data from 3483 MDD inpatients and 6663 SZ inpatients. Patients with MDD and SZ were classified into those who underwent ECT during hospitalization and those who did not. A propensity score-matching method was performed to adjust for preadmission characteristics and clinical information, which were expected bias between the two groups. Rates of anxiolytic and sleep medication use at discharge were compared in the matched sample. RESULTS: 500 MDD patients were assigned to both groups. In the matched MDD sample, the rate of anxiolytic and sleep medication use at discharge was significantly lower in the ECT group than in the non-ECT group (64.9% vs. 75.8%, P = 1.7 × 10-4 ). In the ECT group, the rate of anxiolytic and sleep medication use at discharge was significantly lower than that prior to admission (64.9% vs. 73.2%, P = 1.2 × 10-14 ). 390 SZ patients were allocated. In the matched SZ sample, the ECT group was not significantly different from the non-ECT group in the rate of anxiolytics and sleep medications use at discharge (61.3% vs. 68.2%, P = 4.3 × 10-2 ). In the ECT group, the rate of anxiolytics and sleep medications use at discharge was significantly lower than that before admission (61.3% vs. 70.5%, P = 4.4 × 10-4 ), although this was not the primary outcome. CONCLUSION: Reduction of anxiolytic and sleep medication use may be considered positively when ECT is indicated for treatment of MDD.

Clozapine Treatment Is Associated With Higher Prescription Rate of Antipsychotic Monotherapy and Lower Prescription Rate of Other Concomitant Psychotropics: A Real-World Nationwide Study.

BACKGROUND: Although clozapine is effective for treatment-resistant schizophrenia (TRS), the rate of clozapine prescription is still low. Whereas antipsychotic monotherapy is recommended in clinical practice guidelines, the rate of antipsychotic polypharmacy is still high. There is little evidence on whether a clozapine prescription influences changes in the rate of monotherapy and polypharmacy, including antipsychotics and other psychotropics. We therefore hypothesized that the rate of antipsychotic monotherapy in patients with TRS who were prescribed clozapine would be higher than that in patients with schizophrenia who were not prescribed clozapine. METHODS: We assessed 8306 patients with schizophrenia nationwide from 178 institutions in Japan from 2016 to 2019. We analyzed the psychotropic prescription data at discharge in patients diagnosed with TRS and with no description of TRS (ND-TRS) based on the diagnosis listed in the discharge summary. RESULTS: The rate of antipsychotic monotherapy in the TRS with clozapine group (91.3%) was significantly higher than that in the TRS without clozapine group (45.9%; P < 2.0 × 10-16) and the ND-TRS without clozapine group (54.7%; P < 2.0 × 10-16). The rate of antipsychotic monotherapy without any other concomitant psychotropics in the TRS with clozapine group (26.5%) was significantly higher than that in the TRS without clozapine group (12.6%; P = 1.1 × 10-6) and the ND-TRS without clozapine group (17.0%; P = 5.9 × 10-6). CONCLUSIONS: Clozapine prescription could be associated with a high rate of antipsychotic monotherapy. Patients will benefit from the correct diagnosis of TRS and thus from proper clozapine prescription.

Relationship between clozapine exposure and the onset of appendicitis in schizophrenia patients: a retrospective cohort study.

OBJECTIVE: Clozapine may cause serious side effects despite benefits in patients with schizophrenia. Thus, an accurate understanding of the side-effect profile of clozapine is extremely important in the management of its administration to patients with schizophrenia. Our aim was to validate the relationship between clozapine exposure and appendicitis onset in patients with schizophrenia. METHODS: In this study, we retrospectively compared the incidence and cumulative incidence of appendicitis in patients with schizophrenia with and without a history of clozapine exposure. Among the patients with schizophrenia who visited our hospital between June 2009 and August 2021, we extracted those with a history of clozapine treatment. Patients with a history of taking clozapine were defined as the clozapine exposure group, while the others were defined as the clozapine non-exposure group. Patients with a history of appendectomy before their initial visit to our hospital or with a history of clozapine use at other hospitals were excluded. RESULTS: There were 65 patients in the clozapine exposure group and 400 patients in the clozapine non-exposure group who met the inclusion criteria. The exposure group exhibited a remarkably higher incidence of appendicitis during the observation period than the non-exposure group (863 cases vs. 124 cases per 100,000 person-years). In particular, if limited to the period of clozapine exposure, the incidence of appendicitis is extremely high, at 2,086 cases per 100,000 person-years. Moreover, multivariable analysis showed that clozapine exposure was an independent factor contributing to the onset of appendicitis. CONCLUSIONS: Clozapine exposure is associated with appendicitis onset in patients with schizophrenia.

Development and validation of the Japanese version of the Hyperarousal Scale.

BACKGROUND: The objectives of this study were to develop a Japanese version of the Hyperarousal Scale (HAS-J) and investigate its factor structure, reliability, and validity, as well as to calculate a cutoff score for the HAS-J and assess different levels of hyperarousal in insomnia patients and community dwellers. METHODS: We recruited 224 outpatients receiving insomnia treatment (56.3% women; mean age 51.7 ± 15.6 years) and 303 community dwellers aged 20 years or older (57.8% women; mean age 43.9 ± 15.2 years). Exploratory and confirmatory factor analysis was performed to examine the factor structure of the HAS-J. Cronbach's α and McDonald's ω were then used to test internal consistency. To examine the scale's validity, we determined correlations between the HAS-J and other indexes and compared HAS-J scores between insomnia patients and community dwellers. We also compared HAS-J scores between two community-dweller groups (normal and poor sleepers) and two insomnia patient groups (with and without alleviation after treatment). RESULTS: Following exploratory and confirmatory factor analysis, a 20-item measure emerged comprising three factors: "Introspectiveness and Reactivity," "Neuroticism," and "Insomnia." Confirmatory factor analysis showed a generally good fit for the model of the three-factor structure suggested by the exploratory factor analysis loadings (χ2 (163) = 327.423, (p <  0.001), CFI = 0.914, GFI = 0.872, AGFI = 0.835, RMSEA = 0.067). In insomnia patients, internal consistency indicated sufficient reliability of the HAS-J. Correlation analysis showed weak to moderate positive correlations of the HAS-J score with other indexes, indicating concurrent validity of the HAS-J. All HAS-J subscale scores were significantly higher in insomnia patients than in community dwellers. Additionally, the total score in patients with alleviation of insomnia was comparable to that in poor sleepers and significantly higher than that in normal sleepers. CONCLUSIONS: This study demonstrated the reliability and validity of the HAS-J, indicating that it is useful as a clinical scale of hyperarousal. The high level of hyperarousal in insomnia patients who were assessed to be in remission by the Insomnia Severity Index suggests a risk of insomnia recurrence in these patients.

The characteristics of discharge prescriptions including pro re nata psychotropic medications for patients with schizophrenia and major depressive disorder from the survey of the "Effectiveness of guidelines for dissemination and education in psychiatric treatment (EGUIDE)" project.

BACKGROUND: Several guidelines recommend monotherapy in pharmacotherapy for schizophrenia and major depressive disorder. The content of regular prescriptions has been reported in several studies, but not enough research has been conducted on the content of pharmacotherapy, including pro re nata (PRN) medications. The purpose of this study was to evaluate the content of pharmacotherapy, including PRN medications, and to clarify the relationship with regular prescriptions. METHODS: We used data from the "Effectiveness of Guidelines for Dissemination And Education in psychiatric treatment" (EGUIDE) project to investigate the presence or absence of PRN psychotropic medications at discharge for each drug category. We compared the PRN psychotropic prescription ratio at discharge by diagnosis for each drug category. The antipsychotic monotherapy ratio and no prescription ratio of other psychotropics for schizophrenia at discharge and the antidepressant monotherapy ratio and no prescription ratio of other psychotropics for major depressive disorder at discharge were calculated for each regular prescription, including PRN psychotropic medications, as quality indicators (QIs). Spearman's rank correlation test was performed for QI values of regular prescriptions and the QI ratio between regular prescriptions and prescriptions including PRN medications for each diagnosis. RESULTS: The PRN psychotropic prescription ratio at discharge was 28.7% for schizophrenia and 30.4% for major depressive disorder, with no significant differences by diagnosis. The prescription ratios of PRN antipsychotic medications and PRN antiparkinsonian medications were significantly higher for schizophrenia. The prescription ratios of PRN anxiolytic and hypnotic and PRN antidepressant medications were significantly higher for patients with major depressive disorder. For both schizophrenia and major depressive disorder, the QI was lower for discharge prescriptions, including PRN medications, than for regular prescriptions. QI values for regular prescriptions and the QI ratio were positively correlated. CONCLUSIONS: Considering PRN psychotropic medications, the monotherapy ratio and no prescription ratio of other psychotropics at discharge decreased in pharmacotherapy for schizophrenia and major depressive disorder. A higher ratio of monotherapy and no prescription of other psychotropics on regular prescriptions may result in less concomitant use of PRN psychotropic medications. Further studies are needed to optimize PRN psychotropic prescriptions.

Patterns of hypnotic prescribing for residual insomnia and recurrence of major depressive disorder: a retrospective cohort study using a Japanese health insurance claims database.

BACKGROUND: Major depressive disorder (MDD) is highly prevalent in Japan and frequently accompanied by insomnia that may persist even with MDD remission. Hypnotics are used for the pharmacological treatment of insomnia, but their influence on MDD recurrence or residual insomnia following MDD remission is unclear. This retrospective, longitudinal, cohort study utilized a large Japanese health insurance claims database to investigate patterns of hypnotic prescriptions among patients with MDD, and the influence of hypnotic prescription pattern on MDD recurrence. METHODS: Eligible patients (20-56 years) were those registered in the Japan Medical Data Center database between 1 January 2005 and 31 December 2018, and prescribed antidepressant and hypnotic therapy after being diagnosed with MDD. Patients who had ceased antidepressant therapy for > 180 days were followed for 1 year to evaluate depression recurrence, as assessed using Kaplan-Meier estimates. Logistic regression modelling was used to analyze the effect of hypnotic prescription pattern on MDD recurrence. RESULTS: Of the 179,174 patients diagnosed with MDD who initiated antidepressant treatment between 1 January 2006 and 30 June 2017, complete prescription information was available for 2946 eligible patients who had been prescribed hypnotics. More patients were prescribed hypnotic monotherapy (70.8%) than combination therapy (29.2%). The most prescribed therapies were benzodiazepine monotherapy (26.2%), non-benzodiazepine monotherapy (28.9%), and combination therapy with two drugs (21.1%). Among patients prescribed multiple hypnotics, concomitant prescriptions for anxiolytics, antipsychotics, mood stabilizers and sedative antidepressants were more common. The 1-year recurrence rate for MDD was approximately 20%, irrespective of hypnotic mono- versus combination therapy or class of hypnotic therapy. Being a spouse (odds ratio [OR], 1.44; 95% confidence interval [CI], 1.03-2.02) or other family member (OR, 1.46, 95% CI, 0.99-2.16) of the insured individual, or being prescribed a sedative antidepressant (OR, 1.50, 95% CI, 1.24-1.82) conferred higher odds of MDD recurrence within 1 year of completing antidepressant therapy. CONCLUSIONS: Benzodiazepines are the most prescribed hypnotic among Japanese patients with MDD, though combination hypnotic therapy is routinely prescribed. Hypnotic prescription pattern does not appear to influence real-world MDD recurrence, though hypnotics should be appropriately prescribed given class differences in efficacy and safety.

Does cognitive behavioral therapy for anxiety disorders assist the discontinuation of benzodiazepines among patients with anxiety disorders? A systematic review and meta-analysis.

Long-term use of benzodiazepines (BZD) is not recommended for the treatment of anxiety disorders. Cognitive behavioral therapy (CBT) is an effective treatment option for discontinuation of BZD in patients with anxiety disorders. This systematic review and meta-analysis sought to clarify whether CBT is effective for discontinuing BZD anxiolytics in patients with anxiety disorders. This study was preregistered with PROSPERO (registration number: CRD42019125263). A literature search of major electronic databases was conducted in December 2018. Three randomized controlled trials were included in this review, and meta-analyses were performed. The proportion of discontinuing BZD anxiolytics was significantly higher in the CBT plus gradual tapering group than in the gradual tapering alone group, both in the short term (3 months after allocation; number needed to treat: 3.2, 95% confidence interval [CI]: 2.1 to 7.1; risk ratio: 1.96, 95%CI: 1.29 to 2.98, P = 0.002, three studies) and long term (6 to 12 months after allocation; number needed to treat: 2.8, 95%CI: 1.9 to 5.3; risk ratio: 2.16, 95%CI: 1.41 to 3.32, P = 0.0004, three studies). CBT may be effective for discontinuing BZD anxiolytics, both in the short term and in the long term after the allocation. Further studies with larger sample sizes are necessary to draw definitive conclusions regarding the efficacy and safety of CBT for discontinuing BZD anxiolytics in patients with anxiety disorders.

Efficacy and safety of bright light therapy for manic and depressive symptoms in patients with bipolar disorder: A systematic review and meta-analysis.

AIM: This systematic review and meta-analysis evaluated whether bright light therapy (BLT) is an effective and safe treatment for manic/depressive symptoms and a preventive measure for recurrent mood episodes in patients with bipolar disorder. METHODS: A literature search of major electronic databases was conducted in June 2019, including all published articles up to that date. Two researchers independently selected relevant publications, extracted data, and evaluated methodological quality according to the Cochrane criteria. RESULTS: Six randomized controlled trials (RCT) evaluated the efficacy of BLT for bipolar depression. A meta-analysis found no significant differences between BLT and placebo for the following outcomes: (i) rates of remission from depressive episodes (risk ratio [RR]: 1.81, 95% confidence interval [CI]: 0.43 to 7.64, P = 0.42); (ii) depressive symptom scores (standardized mean difference: -0.25, 95%CI: -0.74 to 0.23, P = 0.30); and (iii) rates of manic switching (RR: 1.00, 95%CI: 0.28 to 3.59, P = 0.26). The sensitivity analysis for studies with low overall indirectness did show a significant antidepressant effect for BLT (RR: 3.09, 95%CI: 1.62 to 5.90, P = 0.006). No RCT investigated the effect of BLT in preventing the recurrence of mood episodes in the euthymic state or in improving manic symptoms in the manic state. No severe adverse events were reported. CONCLUSION: While a meta-analysis was unable to demonstrate the efficacy of BLT for bipolar depression, a sensitivity analysis did show a significant effect. Further well-designed studies are needed to clarify the effectiveness of BLT, not only for the depressive state but also for other states, in the treatment of bipolar disorder.

Anorexia nervosa-associated pancytopenia mimicking idiopathic aplastic anemia: a case report.

BACKGROUND: Patients with anorexia nervosa (AN) often present with pancytopenia. In most cases described in the literature, AN with pancytopenia demonstrates gelatinous marrow transformation (GMT), which is a typical bone marrow feature of malnutrition. Differentiation of AN-associated pancytopenia from other types of pancytopenia, especially idiopathic aplastic anemia (IAA), has not been studied. We encountered a case of pancytopenia in a patient with AN and relatively poor nutritional status, whose hematological findings mimicked those of IAA, specifically fatty bone marrow and absence of GMT. CASE PRESENTATION: The patient was a 32-year-old woman with poorly controlled AN. At 31 years of age, her body mass index (BMI) had fallen from 17.0 kg/m2 to below 13.8 kg/m2. The patient presented with ongoing fatigue and thus was examined by a hematologist. Hematological findings were consistent with IAA: peripheral blood tests revealed pancytopenia, whereas the bone marrow displayed fatty replacement without GMT. Despite the absence of bone marrow features typically seen in malnutrition, the patient's hematological abnormalities had manifested after a decrease in body weight. Thus, although the bone marrow findings indicated IAA, we considered that the nutritional etiology of pancytopenia could not be thoroughly ruled out. Using nutritional therapy alone, the hematological abnormalities improved as BMI increased to 16.5 kg/m2. The final diagnosis was pancytopenia secondary to malnutrition because pancytopenia and fatty bone marrow improved after implementation of nutritional therapy alone. CONCLUSIONS: The present case is the first documented case of AN with pancytopenia for which bone marrow examination confirmed fatty marrow without any evidence of GMT. IAA and pancytopenia secondary to malnutrition can present the same clinical findings. This case is significant because it suggests a need to differentiate between malnutrition and IAA.

Treatment Failure and Long-Term Prescription Risk for Guideline-Recommended Hypnotics in Japan.

Importance: Although insomnia guidelines recommend the use of several individual hypnotics, the most useful hypnotic for treating insomnia in a clinical setting remains unclear. Objective: To determine which guideline-recommended hypnotics have lower risks of monotherapy failure and which hypnotics have a higher risk of long-term prescription for insomnia treatment. Design, Setting, and Participants: This retrospective observational cohort study used data from the Japan Medical Data Center Claims Database from April 1, 2005, to March 31, 2021. Participants included adults whose first prescribed pharmaceutical treatment for insomnia was guideline-recommended hypnotic monotherapy. Data were analyzed from December 24, 2022, to September 26, 2023. Exposures: Suvorexant, ramelteon, eszopiclone, zolpidem, and triazolam monotherapy. Main Outcomes and Measures: The primary outcome was monotherapy failure, defined as a change in hypnotic or having an additional hypnotic prescribed for insomnia within 6 months of the first prescription of a guideline-recommended hypnotic monotherapy. The secondary outcome was monotherapy discontinuation, defined as no prescription of any hypnotic for 2 consecutive months within 6 months after prescribing a guideline-recommended hypnotic in patients for whom monotherapy did not fail. Monotherapy failure and discontinuation were compared using Cox proportional hazards and logistic regression models, respectively. Results: The study included 239 568 adults (median age, 45 [IQR, 34-55] years; 50.2% women) whose first prescription for insomnia was guideline-recommended hypnotic monotherapy. During the 6-month follow-up period, 24 778 patients (10.3%) experienced failure of monotherapy with a guideline-recommended hypnotic. In comparison with eszopiclone, there were more cases of monotherapy failure for ramelteon (adjusted hazard ratio [AHR], 1.23 [95% CI], 1.17-1.30; P < .001), fewer cases for zolpidem (AHR, 0.84 [95% CI, 0.81-0.87]; P < .001) and triazolam (AHR, 0.82 [95% CI, 0.78-0.87]; P < .001), and no significant difference between suvorexant and eszopiclone. Among those without monotherapy failure, monotherapy was discontinued in 84.6% of patients, with more discontinuations for ramelteon (adjusted odds ratio [AOR], 1.31 [95% CI, 1.24-1.40]; P < .001) and suvorexant (AOR, 1.20 [95% CI, 1.15-1.26]; P < .001) than for eszopiclone and no significant difference between zolpidem or triazolam and eszopiclone. Conclusions and Relevance: Due to uncontrolled confounding factors in this cohort study, no conclusions regarding the pharmacologic properties of guideline-recommended hypnotics can be drawn based on these results. Further studies accounting for confounding factors, including diagnoses of chronic vs acute insomnia disorder, insomnia and psychiatric symptom severity, and physician attitudes toward hypnotic prescription, are needed.