Application of Piezoelectric PLLA Braided Cord as Wearable Sensor to Realize Monitoring System for Indoor Dogs with Less Physical or Mental Stress.

We attempted to realize a prototype system that monitors the living condition of indoor dogs without physical or mental burden by using a piezoelectric poly-l-lactic acid (PLLA) braided cord as a wearable sensor. First, to achieve flexibility and durability of the piezoelectric PLLA braided cord used as a sensor for indoor dogs, the process of manufacturing the piezoelectric PLLA fiber for the piezoelectric braided cord was studied in detail and improved to achieve the required performance. Piezoelectric PLLA braided cords were fabricated from the developed PLLA fibers, and the finite element method was used to realize an e-textile that can effectively function as a monitoring sensor. As a result, we realized an e-textile that feels similar to a high-grade textile and senses the complex movements of indoor dogs without the use of a complex computer system. Finally, a prototype system was constructed and applied to an actual indoor dog to demonstrate the usefulness of the e-textile as a sensor for indoor dog monitoring.

Augmentation of atypical antipsychotics with valproic acid. An open-label study for most difficult patients with schizophrenia.

OBJECTIVE: Most difficult inpatients with schizophrenia are in serious needs but obviously underrepresented in clinical trials. METHODS: Very challenging patients received open-label treatment with atypical antipsychotics concurrently augmented with valproic acid. The primary outcome was the newly developed Functional Assessment for Comprehensive Treatment of Schizophrenia (FACT-Sz). Patients improving more than 20 points were classified as responders. RESULTS: Mean age and illness duration of 28 participants (22 male) were 42 y.o. and 20 years, respectively. They had spent a half of their life admitted after the onset. The average Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression-Severity (CGI-S) were very severe at 79 and 6.1, respectively, with the baseline Global Assessment of Functioning (GAF) of as low as 21. As a result of augmentation, there were nine responders, 12 partial responders, and seven non-responders including only two patients who got worse. The main antipsychotics were mostly either risperidone or olanzapine. Mean maximum oral dose and blood level of valproic acid were 1907 mg and 91.7 microg/ml, respectively. Overall significant improvements whilst to an inadequate degree were noted in clinical parameters. Valproate augmentation was generally well tolerated but serious adverse effects included thrombocytopenia, anaemia and sedation/falls. CONCLUSIONS: While these preliminary results need to be tested against tenacious monotherapy or polypharmacy involving clozapine, augmenting atypical antipsychotics with valproic acid can be useful for very severe schizophrenia.

Novel rating scales for schizophrenia - Targeted Inventory on Problems in Schizophrenia (TIP-Sz) and Functional Assessment for Comprehensive Treatment of Schizophrenia (FACT-Sz).

OBJECTIVE: Many rating scales have been in use to evaluate various symptomatic domains, and eventually there are too many scales to be selected and widely utilized in busy real-world settings. Relevant, quick, and user-friendly assessment scales are needed to facilitate measurement-based treatment of schizophrenia. METHODS: The authors created unique convenient assessment scales: Targeted Inventory on Problems in Schizophrenia (TIP-Sz), and Functional Assessment for Comprehensive Treatment of Schizophrenia (FACT-Sz). The TIP-Sz consists of 10 items (behavioral dyscontrol/disorganization, hostility/agitation/violence, indifference/affective withdrawal/motor retardation, symptoms on mood/anxiety/obsession/compulsion, insight/reality testing, social competence/independence, adherence to treatment, therapeutic alliance/comfort of therapists on the situation, overall prognostic impression, and subjective well-being/satisfaction with therapy). They are all common and frequently problematic, and each item is rated from 0-10. The FACT-Sz evaluates psychosocial functioning of patients with a score of 0-100, and is judged entirely on an objective basis. Their correlations with the frequently utilized Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning (GAF), and Clinical Global Impression-Severity subscale were determined. RESULTS: Data on 36 patients, assessed separately by four experienced psychiatrists, were analyzed. Under an excellent interrater reliability among raters (Intraclass correlation coefficients: 0.822-0.966), correlations among the scales were very high (Spearman's rho: 0.825-0.909), and other indicators of the scale were generally good. Specifically, the TIP-Sz and FACT-Sz could be rated at 1/3-1/4 of time to complete the PANSS and GAF. CONCLUSION: The TIP-Sz and FACT-Sz proved to be reliable and valid, which would be of value in daily clinical practice as a minimum standardized assessment set.

Effects of age and age of onset on prescribed antipsychotic dose in schizophrenia spectrum disorders: a survey of 1,418 patients in Japan.

OBJECTIVES: The relationship between age and prescribed antipsychotic dose in patients with schizophrenia has been examined by assuming only a linear correlation in two age subgroups at most. The age of illness onset has also not been under adequate consideration in past prescription surveys. The objective of this study was to better evaluate these age effects on antipsychotic dose prescribed in these patients across a broad age range. METHODS: Review of prescriptions for antipsychotic medications in patients with schizophrenia spectrum disorders was conducted across 30 sites in Tokyo. A total of 1,418 patients (655 inpatients, 763 males, age range: 16.6-90.2 years) were studied. RESULTS: Age had significant effects on prescribed antipsychotic dose; the dose increased with age through the third decade, subsequently plateaued, and decreased after the fifth decade. The age of illness onset also had significant effects on the dose; late-onset schizophrenia (LOS) and very-late-onset schizophrenia-like psychoses (VLOS) patients received lower doses than early onset schizophrenia (EOS) patients. LOS and VLOS patients who did not experience any hospitalization for the previous year were treated with (1/2) and (1/3), respectively, of the dose for EOS of comparable current age. CONCLUSION: Our results suggested biphasic effects of age on antipsychotic dose prescribed in patients with schizophrenia spectrum disorders. The natural history of schizophrenia and physiological aging may contribute to this inverted U-shaped relationship. In addition, our results may add another evidence of distinction among EOS, LOS, and VLOS from a clinical psychopharmacological perspective.

Effectiveness of antipsychotic polypharmacy for patients with treatment refractory schizophrenia: an open-label trial of olanzapine plus risperidone for those who failed to respond to a sequential treatment with olanzapine, quetiapine and risperidone.

OBJECTIVE: To evaluate the effectiveness of antipsychotic polypharmacy in a methodologically sound manner. METHODS: In this open-label study, 17 patients with treatment-refractory schizophrenia, who failed to respond to a sequential monotherapy with olanzapine, quetiapine and risperidone, were subsequently treated with a combination therapy with olanzapine plus risperidone for at least 8 weeks. RESULTS: Seven responded according to the primary endpoint defined as the post-treatment Brief Psychiatric Rating Scale being less than 70% of the pretreatment values, and they were classified as such an average of 10 weeks after the initiation of polypharmacy. Two of them were successful in a later conversion to monotherapy. None dropped out prematurely. Four (out of 13 inpatients) got better enough to be discharged from the hospital, while six patients did not show any response. The Global Assessment of Functioning score improved from 37.1 to 53.0 in responders (mean maximum dose: olanzapine 12.9 mg; risperidone 3.14 mg), while it showed non-significant changes among others (mean maximum dose: olanzapine 14.5 mg; risperidone 5.50 mg). Body weight, prolactin, and total cholesterol increased significantly. CONCLUSIONS: Antipsychotic polypharmacy might be sometimes helpful for difficult populations but at the cost of adverse effects. More studies of antipsychotic combination therapy versus clozapine, augmentation strategies or tenacious longer- term monotherapy are warranted for refractory schizophrenia.

[Pathophysiology of depression].

Neurobiological findings of depression are reviewed in this paper. Modern neurobiological methods have revealed pathophysiological mechanism associated with depression. Monoamine hypothesis, which was advocated in the 1950's, emphasizes that the deficiency of monoamine neurotransmitters bring about depressive symptoms. This theory played an important role in promoting the development of new antidepressants, but some inconsistent findings were pointed out concerning this theory. Neuroendocrine studies have revealed the hypothalamic-pituitary-adrenal (HPA) axis dysfunctions in depressive patients, and increased activity of HPA axis are considered as state marker of depression. Morphological changes of hippocampus, polymorphism of serotonin transporter gene, and down regulation of neurotrophin are also discussed in this review.

How effective is it to sequentially switch among Olanzapine, Quetiapine and Risperidone?--A randomized, open-label study of algorithm-based antipsychotic treatment to patients with symptomatic schizophrenia in the real-world clinical setting.

RATIONALE: Evidence on sequential trial with atypical antipsychotics has been scarce. OBJECTIVES: We conducted an algorithm-based antipsychotic pharmacotherapy. MATERIALS AND METHODS: In this open-label study, patients with schizophrenia (DSM-IV) were treated with antipsychotic monotherapy, step-by-step, with each trial lasting up to 8 weeks. At baseline, they were highly symptomatic to score more than 54 in the total Brief Psychiatric Rating Scale (BPRS(1-7)) score. When the posttreatment BPRS score was above 70% of the baseline, they were subsequently treated with another and up to three atypicals. Basically, anticholinergics were prohibited, and only adjunctive allowed was lorazepam. The secondary endpoint was a clinical status good enough to be discharged for 66 inpatients and a successful continuation therapy with the same antipsychotic agent for more than 6 months for 12 outpatients. RESULTS: Three groups of 26 patients each were randomized to Olanzapine, Quetiapine, or Risperidone. Thirty-nine (50%) responded to the first agent (Olanzapine16, Quetiapine9, Risperidone14), and 14 responded to the second. Only two showed response to the third, and 16 failed to respond to all three antipsychotics, with only 7 dropouts. Overall, there were 22 Olanzapine, 14 Quetiapine, and 19 Risperidone responders. Based on the secondary outcome, 20 Olanzapine-treated (average maximum dose, 15.4 mg), 10 Quetiapine-treated (418 mg), and 20 Risperidone-treated (4.10 mg) patients responded. The difference in response as the first choice was significant (p < 0.05). Relative doses of those failing to respond were comparable (Olanzapine 18.3 mg, Quetiapine 564 mg, Risperidone5.47 mg). Extrapyramidal symptoms did not change significantly. CONCLUSIONS: When the first atypical antipsychotic is inadequate, switching to the second is worth trying, although some remain treatment-refractory. Quetiapine may be inferior to Olanzapine and Risperidone in symptomatic patients.

Simplifying psychotropic medication regimen into a single night dosage and reducing the dose for patients with chronic schizophrenia.

RATIONALE: Taking psychotropic medications is frequently problematic from both consumers' and caregivers' perspective. Occasionally missed doses may lead to pervasive non-adherence with relapse a likely outcome. OBJECTIVE: To evaluate the simple medication regimen, all psychotropics were given at night for patients with chronic schizophrenia, who had been taking them at least twice a day for more than 12 weeks before the entry. METHODS: Switching of agents took place in two ways: converting only antipsychotic medications followed by other psychotropics, and changing all psychotropics simultaneously. Any psychotropics of little clinical significance were then cautiously minimized. Final evaluation was made 12 weeks after the competed dose consolidation. Patients finally rated their subjective impression on this intervention. RESULTS: Twenty-five patients were recruited in each treatment arm (50 in total). After switching, 11 got better, 29 remained stable whereas seven got worse, according to the Global Improvement. Three were not assessable. Overall, there were no relevant changes in clinical ratings including adverse effects. However, the chlorpromazine equivalent dose of antipsychotics and the number of total psychotropics were significantly reduced from 957 to 722 mg/day (p<0.0001) and from 4.0 to 3.2 (p<0.0001), respectively. Dose deflation of psychotropics was feasible in 35 subjects (74.5%). Twenty-six (of 40 successful) patients indicated that they favored the night-time regimen mainly because it was less complicated. Sedation in the morning was identified as an important adverse event, which should be addressed by reducing the dose. CONCLUSIONS: The procedure may be of value to counteract a recent trend of psychotropic polypharmacy in schizophrenia.

Revising polypharmacy to a single antipsychotic regimen for patients with chronic schizophrenia.

Antipsychotic polypharmacy has been empirically used and a recent trend in favour of that mode of therapy has been suggested for the treatment of schizophrenia. The clinical efficacy, however, still remains to be clarified. In order to critically evaluate the usefulness of such kind of psychopharmacotherapy, antipsychotic combination regimen (polypharmacy) was switched to a treatment with the single main antipsychotic (monotherapy) in cross-tapered fashion, while approximately maintaining the total amount, for patients with chronic schizophrenia. Patients had been treated with an average of three antipsychotics and maintained with the same antipsychotic polypharmacy regimen for more than 6 months before the entry. They were followed up with an antipsychotic monopharmacy and evaluated at 24 wk after completion of switching. Forty-seven patients were recruited for this study. Of 44 patients for whom evaluation was possible, 24 (54.5%) remained stable, while 10 (22.7%) showed improvement and the same number of patients ended in a deleterious status. Twenty-two patients were converted to antipsychotic monotherapy, while another 12 needed minimal dosing of low-potency agents. Overall, social functioning, evaluated by the Global Assessment of Functioning and the Clinical Global Impression, remained unchanged. Eighteen of 34 successful patients showed adverse effects of the main antipsychotic medication, which necessitated a significant dose reduction. Nine out of 10 deteriorating patients had been treated with a combination of low- and high-potency antipsychotics. It is suggested that many instances of antipsychotic polypharmacy is avoidable. The result is compatible with the current treatment recommendations, which dictate the use of a single antipsychotic agent.

Cincinnati criteria for mixed mania and suicidality in patients with acute mania.

The association between suicidality and diagnoses of mixed mania, as defined using both DSM-IV and Cincinnati criteria, was studied in 576 consecutive manic inpatients. Of the whole sample, 51 (8.9%) had suicidal ideation and 13 (2.3%) attempted suicide during the index episode. Suicidality was significantly more frequent in patients with a diagnosis of mixed mania, whether the diagnosis was made by DSM-IV or Cincinnati criteria. A multiple logistic regression analysis revealed that an additive combination of a diagnosis of mixed mania, the depression severity, and the Global Assessment of Functioning (GAF) score was significant in predicting suicidal ideation, when using the DSM-IV criteria. A diagnosis of mixed mania alone was significant in a similar analysis, when using the Cincinnati criteria. The adjusted odds ratio for a diagnosis of mixed mania to having suicidality was much higher when using the latter criteria (4.0 v 14.0). A subsequent logistic regression analysis indicated that the Cincinnati mixed mania alone, rather than an additive combination of the DSM-IV mixed mania and the depression severity, achieved the most appropriate prediction of suicidal ideation in the sample. These findings did not differ, even when suicidality was defined as having a suicide attempt during the index episode. Our finding that suicidality was more strongly associated with Cincinnati mixed mania than with DSM-IV mixed mania is probably due to that suicidal patients who do not meet DSM-IV criteria for mixed mania are classified into mixed mania, or/and that the depressive syndrome, related to suicidality, is more appropriately assessed among manic patients, when using the Cincinnati criteria. There was no evidence that marital status, employment, a lifetime history of alcohol or substance abuse, or a history of suicide attempts before the index episode was significantly associated with suicidality in the sample. Manic patients with suicidality may have a greater severity of residual depressive symptoms at discharge.

Reducing the dose of antipsychotic medications for those who had been treated with high-dose antipsychotic polypharmacy: an open study of dose reduction for chronic schizophrenia.

Antipsychotic medications are often used at higher than the recommended dose and sometimes in a combination regimen to treat schizophrenia. However, in general, high-dose therapies have been abandoned in recent clinical studies. In this study, dose reduction of antipsychotic medication was implemented for patients with chronic schizophrenia, most of whom (81%) had been treated with an antipsychotic high-dose polypharmacy regimen consisting of more than 1000 mg/day in total amount. The results show that merely reducing the amount of antipsychotic led to favourable outcome in 23 out of 41 cases (56%), with another 13 cases (32%) showing no change. Dose reduction ended in failure in only five subjects (12%). Overall, the amount as well as the number of antipsychotic medications was significantly reduced from 1984 mg to 812 mg per day (reductions of 59% and from 3.6 to 2.2, respectively; both P<0.0001). The Global Assessment of Functioning scale improved from 30.6 to 37.2, which reached significance (P<0.001). Accordingly, the Severity of Illness improved from 4.7 to 4.2, and was also significant (P<0.01). Dose reduction is an encouraging strategy to consider for those patients with schizophrenia who have chronically been treated with high-dose antipsychotic polypharmacy, even if judged unavoidable in the past.