How long, for whom and in which way is maintenance therapy necessary?

統合失調症の再発予防に抗精神病薬による維持療法が有効であるが，どのような患者にどれだけ長くどのような投与量と投与法で使用するのが最適かは不明確な点が多い。抗精神病薬にはリスクもあることを考えると，理想的には本当に必要な患者に限定して，必要最小限の用量による必要最短期間の使用が望ましい。最近では，維持療法中断，間駄投与法，低用量維持療法などできるだけ累積投与量を減じる試みが研究されている。それらから導かれる結論は，低用量よりも常用量，間駄的投与よりも持続投与，安定後の中断よりは継続，経口薬より持効性製剤が，再発予防のための安全策ということになる。しかしこれまでの研究は再発（陽性症状増悪）のみが指標とされがちであった。減量または中断による一時的増悪のリスクと引き換えに薬物継続の必要性の有無と必要最小用量が判明すれば，その後の長い診療には有益となるかもしれない。再発のみでなくリカバリーをも視野に入れた維持療法の長期的検討が必要となっている

Pharmacotherapy and pathophysiology of schizophrenia

Antipsychotic drugs are indispensable in the treatment of schizophrenia. They are useful in ameliorating positive symptoms as well as preventing psychotic relapses. However, there are patients who become refractory to the drug after repeated relapses. We conducted a retrospective study in fifty outpatients with paranoid schizophrenia who have been seen at our clinic for a duration of 15 years or more since their first psychotic episodes. It was found that the maintenance dose was correlated significantly with the number of previous relapses and total duration of psychotic episodes. These results suggest that repetitive psychotic relapses lead to a lower threshold for relapse and consequently require a higher antipsychotic dose for prevention. Behavioral sensitization to amphetamine may provide a model to study neuroplastic change after repeated relapses. Another limitation of antipsychotic drugs is the lack of effects in the negative symptoms. A dopamine agonist rather than a dopamine antagonist may be useful in the treatment of negative symptoms. Atypical antipsychotics may have some advantage to improve these symptoms. In addition to the dopaminergic system, glutamatergic and serotonergic systems seem to be involved in the pathophysiology of the negative symptoms of schizophrenia

Vitamin B6 and schizophrenia

Accumulating evidence indicates that alterations in one-carbon metabolism may play an important role in the pathogenesis of schizophrenia. We focused on vitamin B6 (pyridoxal), which works as a coenzyme in one-carbon metabolism. We first conducted a case-control study and demonstrated that serum pyridoxal levels were significantly lower in the schizophrenia group than in the control group. Subsequently, we conducted a meta-analysis of case-control studies and achieved the similar result to the case-control study. Finally, we investigated the causality between serum pyridoxal levels and schizophrenia by a Mendelian randomization analysis. However, we could indicate no significant causality between serum pyridoxal levels and schizophrenia in the Japanese population. Further studies such as a longitudinal study will be needed because there are several studies on the benefits of vitamin B6 in schizophrenia

BPSD and care burden

Purpose : We investigated the cognitive function, behavioral and psychological symptoms of dementia (BPSD), and activities of daily living (ADLs) of elderly individuals admitted in care facilities. Moreover, the factors affecting the care burden experienced by facility staffs were examined. Method : 24 care facilities for elderly individuals participated in the study. The Revised Hasegawa Dementia Scale (HDS-R), Japanese version of the Neuropsychiatric Inventory (NPI), and Crichton Geriatric Behavioral Rating Scale (CGBRS) were used to evaluate cognitive function, BPSD, and ADL, respectively. The short Japanese version of the Zarit Burden Interview was used to assess the care burden. A multiple regression analysis was conducted with data obtained from 464 elderly individuals who fulfilled all the scales. Results : The care burden was correlated to the scores of HDS-R, but not with those of dysphoria/depression and disinhibition of NPI, restlessness of CGBRS, and subjective mood of CGBRS (R2 = 0.309, p < 0.005). Conclusion : Dysphoria/depression, disinhibition, restlessness, and subjective mood, but not cognitive decline, have an effect on the care burden experienced by facility staffs who manage elderly individuals. These results indicated that the appropriate diagnosis and treatment of BPSD are important in reducing the burden of facility staffs

Effectiveness of SSRIs for GAD in children

Generalized anxiety disorder (GAD) sometimes exists in the background of social withdrawal and school refusal. Although clinical evidence suggests that selective serotonin reuptake inhibitors (SSRIs) are an effective treatment for GAD, they are not officially approved for GAD in Japan. In addition, it has been established that the use of SSRIs increases the risk for suicide and activation syndrome among young individuals. As such, there is currently little domestic clinical experience in prescribing SSRIs to young patients with GAD. The authors report two cases involving 10-year-old patients with GAD who were treated successfully with escitalopram and experienced subsequent improvement in social withdrawal and school refusal. One patient had autistic spectrum disorder and exhibited self-harm associated with anxiety symptoms, requiring careful use of SSRIs under hospitalization. The other patient was treated at an outpatient clinic without any side effects. In each case, improvement of anxiety symptoms with the use of SSRIs facilitated the introduction of psychoeducation and psychotherapy. It is important to accurately diagnose GAD, which may exist in the background of patients exhibiting social withdrawal and school refusal, and to treat the disorder appropriately

Japan useful medication program for schizophrenia (JUMPs)-long-term study on discontinuation rate, resolution and remission, and improvement in social functioning rate associated with atypical antipsychotic medications in patients with schizophrenia

Background: It is desirable to establish evidence for the selection of antipsychotics from the viewpoint of recovery of social activity in individual patient with schizophrenia receiving medication. From this perspective, awareness of the importance of studies about drug effectiveness on treatment discontinuation rate, remission rate, and improvement in QOL has grown recently. In Western countries, numerous reports are available in effectiveness studies, which are related to olanzapine and risperidone primarily, whereas evidence for other second-generation antipsychotics (SGAs) is poor. In Japan, no effectiveness study has been reported: thus, it is desirable to collect data that will serve as evidence for selection of the 3 SGAs approved after olanzapine. Methods: The present study was a long-term effectiveness study under healthcare setting in Japan. It was designed as an open-label, multicenter, randomized, comparative study involving 104-week oral treatment with 1 of the 3 drugs (aripiprazole, blonanserin, and paliperidone) in patients with schizophrenia aged 20 years or over who required antipsychotic medication or switching of the current medication to others for reasons such as lack of efficacy and intolerability. The primary endpoint is treatment discontinuation rate for any causes. The secondary endpoints include remission rate, improvement of social activity, alleviation, aggravation or recurrence of psychiatric symptoms, and safety. The target number of subjects was set at 300. Discussion: Because this study is expected to yield evidence regarding the selection of antipsychotics for facilitating the recovery of social activity in patients with schizophrenia, it is considered highly valuable to perform this effectiveness study under ordinary healthcare setting in Japan

Personality profiles in patients with eating disorders

The present review focused on the personality profiles of patients with eating disorders. Studies using the Structured Clinical Interview for DSM-III-R Personality Disorder showed high rates of diagnostic co-occurrence between eating disorders and personality disorders. The most commonly observed were histrionic, obsessive-compulsive, avoidant, dependent and borderline personality disorders. Studies using the Cloninger’s personality theory suggested that high Harm Avoidance might be relevant to the pathology of anorexia nervosa and high Novelty Seeking and Harm Avoidance to bulimia nervosa. Moreover, high Self-Directedness was suggested to be associated with favorable outcome in bulimia nervosa. The assessment of personality in a cross-sectional study, however, might be influenced by the various states of the illness. Therefore, a sophisticated longitudinal study will be required to advance this area of research

Clozapine Pharmacogenetic Studies in Schizophrenia

Clozapine is an efficacious atypical antipsychotic for treatment-refractory schizophrenia. Clinical response and appearance of adverse events vary among individual patients receiving clozapine, with genetic and non-genetic factors potentially contributing to individual variabilities. Pharmacogenetic studies investigate associations between genetic variants and drug efficacy and toxicity. To date, most pharmacogenetic studies of clozapine have been conducted through candidate gene approaches. A recent advance in technology made it possible to perform comprehensive genetic mapping underlying clinical phenotypes and outcomes, which allow novel findings beyond biological hypotheses based on current knowledge. In this paper, we will summarize the studies on clozapine pharmacogenetics that have extensively examined clinical response and agranulocytosis. While there is still limited evidence on clozapine efficacy, recent genome-wide studies provide further evidence of the involvement of the human leukocyte antigen (HLA) region in clozapine-induced agranulocytosis

Traumatic reactions in train disasters

Objective : The purpose of this study was to examine the relationship between peritraumatic reactions, posttraumatic stress disorder (PTSD) symptoms, and pain in people injured in train disasters. Methods : The participants were injured in a train crash in Japan that left more than 100 dead. There were 218 participants in the analysis, with a mean age of 37.50 ± 14.67 years. Peritraumatic reactions were assessed using the Peritraumatic Distress Inventory. PTSD symptoms were evaluated using the Impact of Event Scale-Revised Japanese-language version. Pain was measured using the Visual Analog Scale. Results : Peritraumatic reactions did not directly affect PTSD symptoms but were found to be associated via latent variables. Regarding pain and PTSD symptoms, intrusive memories were more associated with pain than other symptoms were. There was an associative path from intrusion to pain, but no such path from pain to intrusion. Conclusions : Our results suggest that a therapeutic approach to intrusion may be effective in ameliorating the pain caused by injury. Future research should examine integrated treatment approaches for both PTSD and pain, rather than just for aspects of PTSD