Improvements in Quality-Adjusted Life Years and Cost-Utility After Pharmacotherapy for Premenstrual Dysphoric Disorder: A Retrospective Study.

BACKGROUND AND OBJECTIVE: To investigate the cost-effectiveness of pharmacotherapy for premenstrual dysphoric disorder (PMDD), a relatively new classification of depressive disorder that is characterized by recurrent depression during the premenstrual phase of the menstrual cycle. METHODS: We performed a retrospective analysis of data from 49 previously untreated PMDD patients who visited our psychiatric department between October 2013 and February 2016 and received pharmacotherapy for 3 or 6 subsequent menstrual cycles. Quality-adjusted life years (QALYs) were estimated across individual menstrual cycles using mean EuroQoL-5D values. Direct costs per patient were estimated in order to conduct a preliminary cost-effectiveness analysis. RESULTS: Pharmacotherapy produced a 0.190-point increase in mean EuroQoL-5D score per menstrual cycle after 6 menstrual cycles and an improvement of approximately 0.2 QALYs. Based on direct costs of 156,000 yen per patient, the cost-effectiveness of pharmacotherapy was calculated to be 823,000 yen per QALY. A cost-effectiveness acceptability curve analysis indicated that escitalopram tended to be superior to sertraline when willingness to pay per QALY was over 4,000,000 yen, whereas sertraline was superior when willingness to pay was below 2,000,000 yen. CONCLUSIONS: Pharmacotherapy is cost effective for the treatment of PMDD. Moreover, escitalopram is a more cost-effective option than sertraline when willingness to pay is sufficiently high.

Reduction of quality-adjusted life years (QALYs) in patients with premenstrual dysphoric disorder (PMDD).

PURPOSE: Premenstrual dysphoric disorder (PMDD) refers to the depression that occurs during the premenstrual phase and remits soon after the onset of menses. It affects the quality of life (QOL) of patients with PMDD. Therefore, this preliminary survey from chart recordings aimed to understand the symptom appearance and QOL reduction patterns in patients with PMDD, and to examine the extent of the loss of their quality-adjusted life years (QALYs). METHODS: Participants were 66 untreated female patients with PMDD. Data on symptom appearance and QOL reduction during the menstrual cycle, and the EuroQoL-5D (EQ-5D) scores during the premenstrual phase and immediately after the completion of a menstrual period were collected. RESULTS: The mean EQ-5D score of the 66 patients with PMDD was 0.795 ± 0.120 (range 0.362-0.949), indicating that their expected mean loss of QALYs was about 0.14 years. CONCLUSIONS: If untreated, PMDD is expected to cause a mean loss of QALYs of about 0.14 years. However, on accounting for the period from disease development to menopause, and subtracting the menstruation-free periods such as pregnancy and breastfeeding, patients with untreated PMDD are expected to experience a QALY loss of about 3 years during their lifetime.

Association study of the G72 gene with schizophrenia in a Japanese population: a multicenter study.

G72 is one of the most widely tested genes for association with schizophrenia. As G72 activates the D-amino acid oxidase (DAO), G72 is termed D-amino acid oxidase activator (DAOA). The aim of this study is to investigate the association between G72 and schizophrenia in a Japanese population, using the largest sample size to date (1774 patients with schizophrenia and 2092 healthy controls). We examined eight single nucleotide polymorphisms (SNPs), which had been associated with schizophrenia in previous studies. We found nominal evidence for association of alleles, M22/rs778293, M23/rs3918342 and M24/rs1421292, and the genotype of M22/rs778293 with schizophrenia, although there was no association of allele or genotype in the other five SNPs. We also found nominal haplotypic association, including M15/rs2391191 and M19/rs778294 with schizophrenia. However, these associations were no longer positive after correction for multiple testing. We conclude that G72 might not play a major role in the risk for schizophrenia in the Japanese population.

Decrease of dynamin 2 levels in late-onset Alzheimer's disease alters Abeta metabolism.

Late-onset Alzheimer's disease (LOAD) is significantly associated with a single nucleotide polymorphism located in the dynamin (DNM) 2 gene, especially in non-carriers of the apolipoprotein E-epsilon4 allele. In this study we used real-time PCR to show that DNM2 mRNA is significantly reduced in the cortex of AD brains and in the peripheral blood of dementia patients. Neuroblastoma cells transfected with a dominant negative DNM2 had increased amyloid beta protein (Abeta) secretion and most of the amyloid precursor protein (APP) in these cells was localized to the plasma membrane. In addition, these cells were rich in flotillin, which is a component of lipid rafts. These data suggest that DNM2 expression is reduced in LOAD, which results in the accumulation of APP in lipid raft-rich plasma membranes. Consequently, Abeta secretion may increase in LOAD neurons.

Altered localization of amyloid precursor protein under endoplasmic reticulum stress.

Recent reports have shown that the endoplasmic reticulum (ER) stress is relevant to the pathogenesis of Alzheimer disease. Following the amyloid cascade hypothesis, we therefore attempted to investigate the effects of ER stress on amyloid-beta peptide (Abeta) generation. In this study, we found that ER stress altered the localization of amyloid precursor protein (APP) from late compartments to early compartments of the secretory pathway, and decreased the level of Abeta 40 and Abeta 42 release by beta- and gamma-cutting. Transient transfection with BiP/GRP78 also caused a shift of APP and a reduction in Abeta secretion. It was revealed that the ER stress response facilitated binding of BiP/GRP78 to APP, thereby causing it to be retained in the early compartments apart from a location suitable for the cleavages of Abeta. These findings suggest that induction of BiP/GRP78 during ER stress may be one of the regulatory mechanisms of Abeta generation.