Pharmacotherapy in Patients with Alzheimer-type Dementia Presenting with Behavioral and Psychological Symptoms of Dementia: A Retrospective Chart Review of 102 Patients Available for 12-month Follow-up after Initiation of Treatment.

Objectives: Alongside non-pharmacological intervention, pharmacotherapy particularly with atypical antipsychotics is assumed to be effective for behavioral and psychological symptoms of dementia (BPSD). Methods: This retrospective study investigated the effectiveness and safety of pharmacotherapy including antipsychotics in outpatients or inpatients with BPSD. Results: Of all Alzheimer-type dementia (AD) patients with BPSD initiating treatment between March and August 2011, a total of 102 patients available for 12-month follow-up comprised the subjects in this chart review. Of these, 68 (66.7%) continued treatment in the ambulatory or inpatient setting, with their MMSE scores improved from 17.3 ± 3.6 at baseline to 18.3 ± 3.53, 17.9 ± 3.80 and 17.0 ± 4.14 after 3, 6 and 12 months, respectively. In contrast, their NPI scores were significantly different from 11.7 ± 11.2 at baseline to 4.86 ± 5.40, 3.56 ± 4.65 and 2.27 ± 3.77 after 3, 6 and 12 months, respectively. Of the 36 inpatients available for follow-up, 27 (75%) on concurrent antipsychotics (chlorpromazine [CP] equivalent, 162.2 mg) at baseline remained on concurrent antipsychotics (CP equivalent, 212.5 mg) after 12 months, while, of the 66 outpatients available for follow-up, 13 (19.7%) on concurrent antipsychotics (CP equivalent, 93.4 mg) at baseline remained on concurrent antipsychotics (CP equivalent, 113.0 mg) after 12 months. Conclusions: Study results confirmed the effectiveness and safety of the study treatment in Japanese AD patients with BPSD for up to 12 months. How best to incorporate antipsychotics into the treatment of BPSD in clinical settings lies in the hands of us Japanese clinicians.

Real-world effectiveness of antipsychotic treatments in 1011 acutely hospitalized patients with schizophrenia: A one-year follow-up study.

PURPOSE: To compare the real-world effectiveness of antipsychotic treatments focusing on long-acting injectable antipsychotic medications (LAIs) and antipsychotic polytherapies except polytherapy involving clozapine (APEC) for patients with schizophrenia. METHODS: This prospective study was conducted over a 19-month period in 12 psychiatric emergency hospitals in Japan. Patients who were newly admitted to psychiatric emergency wards between September 2019 and March 2020 because of acute onset or exacerbation of Schizophrenia and Other Psychotic Disorders as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, were included. All patients were followed for one-year after discharge or until March 31, 2021. The primary outcome was the risk of treatment failure defined as psychiatric rehospitalization, discontinuation of medication, death, or continuation of hospitalization for one year. Cox proportional hazards multivariate regression was used for analyses. RESULTS: A total of 1011 patients were enrolled (women, 53.7%; mean [SD] age, 47.5 [14.8] years). During follow-up, 588 patients (58.2%) experienced treatment failure including rehospitalization (513 patients), discontinuation of medication (17 patients), death (11 patients), and continuation of hospitalization for one-year (47 patients). Switching to LAIs (hazard ratio [HR] 0.810, 95%CI 0.659-0.996) and APEC (HR 0.829, 95%CI 0.695-0.990) were significantly associated with a low rate of treatment failure. CONCLUSIONS: Switching to LAIs and APEC in early non-responders seems to be beneficial for the prevention of treatment failure in acutely admitted patients with schizophrenia. The risk of treatment failure was about 19% and 17% lower in patients treated with LAIs and APEC, respectively, than in patients treated without them.

Real-world effectiveness of antipsychotic monotherapy and polytherapy in 1543 patients with acute-phase schizophrenia.

PURPOSE: The effectiveness of antipsychotic treatments in the acute phase of schizophrenia in actual clinical practice remains somewhat unclear. Therefore, the purpose of the present naturalistic, multi-center study conducted from 1 year starting in September 2017 was to examine the response rate to an initial or second antipsychotic in newly admitted patients with acute-phase schizophrenia, as well as the response rate and quality of augmentation with two antipsychotics in patients who failed to respond to both the initial and second antipsychotics. RESULTS: In total, there were 660 (42.8%) and 243 (15.7%) responders to an initial and a second antipsychotic, respectively; thus, 58.5% of all patients were responders to an initial or second antipsychotic. Among 581 nonresponders (37.7%), the initial antipsychotic or a third antipsychotic was added to the second antipsychotic. Among these patients, 89.8% showed a Clinical Global Impression-Improvement score ≤3 (from 'minimally improved' to 'very much improved'). The rates of adverse events such as hyperglycemia, hyper-low-density lipoprotein cholesterolemia, hypertriglyceridemia, hyperprolactinemia, QTc prolongation, and extrapyramidal symptoms were not high in patients receiving augmentation with two antipsychotics compared with all patients, and no serious adverse events were reported. CONCLUSION: Antipsychotic augmentation may be an option in acute-phase treatment for patients who do not respond to either an initial or a second antipsychotic.

A prospective naturalistic multicenter study on choice of parenteral medication in psychiatric emergency settings in Japan.

AIM: To provide information about psychiatric emergency situations in Japan, we examined psychiatrists' preference among parenteral medication since intramuscular (IM)-olanzapine became available and clinical characteristics in patients given IM-olanzapine compared to those given other parenteral medication. METHODS: We conducted a naturalistic study proceeding over a 1-year period in 9 psychiatric emergency departments. RESULTS: Among 197 patients, the distribution of IM-injections (n = 89) was as follows: IM-olanzapine, 66 patients (74.2%), IM-levomepromazine, 17 patients (19.1%), IM-haloperidol, 5 patients (5.6%), and IM-diazepam, 1 patient (1.1%). The distribution of intravenous (IV)-injections (n = 108) was as follows: IV-haloperidol, 78 patients (72.2%), and IV-benzodiazepines (diazepam, flunitrazepam, or midazolam), 30 patients (27.8%). Advantages of IM-olanzapine over other parenteral medications in efficacy were found as follows: less frequent needs of an additional injection despite no difference in duration until a patient became cooperative for oral administration, and less frequent needs of restraint after the injection. Furthermore, advantages of IM-olanzapine over other injections in safety were found as follows: less frequent appearance of extrapyramidal symptoms, no occurrence of ECG abnormality and other serious adverse events except a fall, less frequent needs of an adjunctive anticholinergic drug, and less frequent needs of another kind of drug additionally injected. CONCLUSIONS: Olanzapine has rapidly become the first choice of intramuscular medication in psychiatric emergency situations since it became available in Japan, probably due to the advantages in both efficacy and safety. This study reflecting psychiatric emergency practice in Japan may contribute to periodic international comparison of psychiatric emergency practice.

The neural effects of positively and negatively re-experiencing mental fatigue sensation: a magnetoencephalography study.

Fatigue sensation is an essential biological alarm that urges us to take rest to avoid disrupting homeostasis and thus plays an important role in maintaining well-being. However, there are situations in which the anticipation of unpleasant fatigue sensation undesirably reduces motivation for activity. The aim of this study was to examine whether thinking positively about the fatigue sensation would increase motivation to accomplish the workload. Fourteen healthy male volunteers participated in this study and performed a two-back test for 30 min to induce mental fatigue sensation. After their subjective level of fatigue had recovered to the baseline level, they re-experienced the fatigue sensation experienced in the two-back test positively, negatively, and without any modification (i.e., re-experienced the fatigue sensation as it was). The level of motivation to perform another two-back test they felt during the re-experiencing was assessed. The neural activity related to the re-experiencing was recorded using magnetoencephalography. The level of the motivation to perform another two-back test was increased by positively re-experiencing the fatigue sensation. The increase in delta band power in Brodmann area 7 was positively associated with the increase in motivation. These results show that positive thinking about fatigue sensation can enhance motivation and suggest that this enhanced motivation may have some effects on visual attention system.

Electroconvulsive therapy improves severe pain associated with fibromyalgia.

The pathophysiology of fibromyalgia remains unknown. Several reports have recently suggested the novel concept that fibromyalgia is due to the central nervous system becoming hyper-responsive to a peripheral stimulus. The effect of electroconvulsive therapy (ECT) as pain remedication in cases of fibromyalgia without major depressive disorder was studied in a prospective trial lasting three months. All of the patients taking part in the study fulfilled the American College of Rheumatology diagnostic criteria for fibromyalgia. Technetium-99m ethyl cysteinate dimer single photon emission computed tomography was used to assess regional cerebral blood flow (rCBF) before and after a course of ECT. Pain assessment in the patients was undertaken by use of the visual analog scale (VAS) and by evaluation of tender points (TPs). Beck's depression inventory (BDI) was further used to assess depressive mood change in the patients. Our study clearly demonstrated that pain was significantly less severe after ECT, as indicated by the VAS scale for pain and the evaluation of TPs. A further notable observation was that thalamic blood flow was also improved. We conclude that a course of ECT produced notable improvements in both intractable severe pain associated with fibromyalgia and also in terms of thalamic blood flow.

Effect of IL-6 polymorphism on risk of Alzheimer disease: genotype-phenotype association study in Japanese cases.

Interleukin-6 (IL-6), an inflammatory cytokine might be involved in the pathophysiology of Alzheimer disease (AD); several studies have reported that the "C allele of IL-6 variable number of tandem repeat polymorphism" (IL-6vntr) delayed initial onset of AD and also decreased its risk per se. Another polymorphism, G/C allele of IL-6 gene promoter region (IL-6prom), is also a candidate because it has an influence on the regulation of plasma IL-6 concentration. We examined these IL-6 polymorphisms in 128 Japanese AD cases and 83 control cases using a PCR-RFLP method. The results showed the frequency of the IL-6prom G allele was significantly increased in AD, although IL-6vntr polymorphism was not. Plasma IL-6 concentration of the AD cases was also significantly higher than that of the control cases. Moreover, the IL-6prom G allele-positive AD patients showed a tendency to have higher IL-6 concentration in the AD group. These findings suggest that the IL-6prom G allele which may affect plasma IL-6 concentration might be a risk factor for sporadic AD in Japanese.

The effect of IL4 +33C/T polymorphism on risk of Japanese sporadic Alzheimer's disease.

Interleukin-4 (IL4) is an anti-inflammatory cytokine that may play a role in the inflammation pathology observed surrounding senile plaques, and may also associate with Alzheimer's disease (AD) pathogenesis. Recently, it has been reported that a single nucleotide polymorphism in the IL4 gene promoter region, IL4 +33C/T polymorphism, associates with its phenotype. It was thought that the IL4 +33C/T polymorphism causing high IL4 production may reduce the risk for AD. In the present study, therefore, we investigated this mutation in 108 healthy controls and in 178 sporadic AD cases by the polymerase chain reaction restriction fragment length polymorphism method in a Japanese AD population. Allelic frequencies with +33C/T polymorphism in the gene were 35.6 and 32.6% in the control and AD groups, respectively. Our results failed to demonstrate an association between this polymorphism and Japanese sporadic AD. We also tested whether the IL4 functional variants were regulated by this polymorphism in a portion of the subjects (16 AD cases and 13 control cases). We could not find any relationship between the IL4 +33C/T polymorphism and plasma IL4 concentration.