Efficacy of Asenapine in Drug-resistant Psychotic Patients with Dopamine Supersensitivity Psychosis: Two Cases

Dopamine supersensitivity psychosis (DSP) is an unstable clinical condition observed in individuals with schizophrenia who have been treated with an antipsychotic medication at a high dosage and/or for a long period. An up-regulation of dopamine D2 receptors (DRD2) is thought to be involved in the essential pathology of DSP. An antipsychotic agent with both tight binding to DRD2 and a long half-life is generally effective for treating DSP, but a patient who meets the criteria of treatment-resistant schizophrenia sometimes needs treatment with clozapine. We report the case details of two patients whose DSP was not controlled with several antipsychotics but was successfully controlled with asenapine.Asenapine binds to a broad range of dopamine receptors and serotonin receptors, and it is thus distinct from other atypical antipsychotics. The unique profile of asenapine may contribute to the control of severe DSP symptoms in individuals with schizophrenia.

Perception of and anxiety about COVID-19 infection and risk behaviors for spreading infection: An international comparison

To control the spread of the newly developed corona viral infection diseases (COVID-19), peoples appropriate precautionary behaviors should be promoted. We conducted a series of online questionnaire survey, to gather a total of 8,000 citizens responses on March 27-28, 2020 in Japan and April 17-21 in the UK and Spain. Compared to Japan, the knowledge and anxiety level and the frequency of precautionary behaviors were higher in the UK and Spain. Participants with infected acquaintances were more concerned about COVID-19. However, participants in the UK rarely wore a medical mask. Participants in the UK and Spain were eager to get information about COVID-19 compared to those in Japan. The participants in Spain tended not to trust official information and to believe specialists' comments instead. The urgency of the spread of COVID-19, cultural backgrounds, and recent political situations appear to contribute to the differences among countries revealed herein.

Reduction of Severity of Recurrent Psychotic Episode by Sustained Treatment with Aripiprazole in a Schizophrenic Patient with Dopamine Supersensitivity: A Case Report

Dopamine supersensitivity psychosis (DSP) is a type of acute exacerbation of recurrent psychosis caused by long-term treatment with antipsychotics in schizophrenic patients. Although DSP is exceedingly troublesome for clinicians, effective treatment has not yet been established. Based on clinical research and our animal study, we hypothesize that aripiprazole, an atypical anti-psychotic, may reduce the exacerbation of recurrent psychotic episodes. We report the case of a 46-year-old female who suffered from schizophrenia with DSP. In this case, sustained treatment with a high dose of aripiprazole gradually reduced the severity of her recurrent psychotic episodes. In conclusion, sustained treatment with aripiprazole may reduce the exacerbation of recurrent psychotic episodes in schizophrenic patients with DSP, and may be an effective treatment of DSP.

An Open Study of Sulforaphane-rich Broccoli Sprout Extract in Patients with Schizophrenia

OBJECTIVE: Schizophrenia is a mental disorder characterized by severe cognitive impairment. Accumulating evidence suggests a role for oxidative stress in the pathophysiology of schizophrenia. Sulforaphane (SFN) extracted from broccoli sprout is an agent with potent anti-oxidant and anti-inflammatory activity. In this study, we attempted to evaluate the effect of SFN on cognitive impairment in medicated patients with schizophrenia. METHODS: We recruited a total of 10 outpatients with schizophrenia, all of whom gave informed consent. Participants took 3 tablets of SFN, consisting of 30 mg of SFN-glucosinolate per day, for 8 weeks. Clinical symptoms using the Positive and Negative Syndrome Scale (PANSS) and cognitive function using the Japanese version of CogState battery were evaluated at the beginning of the study and at week 8. RESULTS: A total of 7 patients completed the trial. The mean score in the Accuracy component of the One Card Learning Task increased significantly after the trial. However, we detected no other significant changes in participants. CONCLUSION: This result suggests that SFN has the potential to improve cognitive function in patients with schizophrenia.

Fluvoxamine may prevent onset of psychosis: a case report of a patient at ultra-high risk of psychotic disorder.

BACKGROUND: There is emerging evidence that antidepressants may be effective in preventing patients with non-specific and psychotic-like prodromal symptoms, defined as patients at ultra-high risk (UHR) of psychotic disorder, from transitioning to psychosis. However, the mechanism of such an effect is still unknown. METHODS: We report the case of a 19-year-old Japanese man determined to be at UHR of psychotic disorder in whom fluvoxamine (one of the antidepressants with sigma-1 receptor agonism) showed preventive effects on psychotic-like prodromal symptoms. RESULTS: Our patient's depressive symptoms were reduced and maintained below remission as a result of treatment with 100 mg/day of fluvoxamine. In addition, it is likely that an additional dose of fluvoxamine (50 mg/day) improved his psychotic-like prodromal symptoms directly, independent of its antidepressive effects. CONCLUSION: Fluvoxamine, a sigma-1 receptor agonist, may be effective in preventing patients at UHR of psychotic disorder from onset of psychosis via its neuroprotective/neurotropic actions, independent of its antidepressive effects.

Occupancy of alpha7 Nicotinic Acetylcholine Receptors in the Brain by Tropisetron: A Positron Emission Tomography Study Using 11CCHIBA-1001 in Healthy Human Subjects

OBJECTIVE: Agonists of alpha7-nicotinic acetylcholine receptors (nAChRs) have been developed as potential therapeutic drugs for neuropsychiatric diseases such as schizophrenia and Alzheimer's disease. Positron emission tomography (PET) is a noninvasive brain imaging technique to measure receptor occupancy in the living human brain. Although much effort has been expended to create specific PET radioligands for alpha7-nAChRs in the brain, only 4-[11C]methylphenyl-1,4-diazabicyclo[3.2.2.]nonane-4-carboxylate ([11C]CHIBA-1001) is currently available for clinical studies. In contrast, two 5-hydroxytryptamine-3 (5-HT3) receptor antagonists, tropisetron and ondansetron, have been used to treat patients with chemotherapy-induced or postoperative nausea and vomiting. Furthermore, tropisetron, but not ondansetron, possesses high affinity for alpha7-nAChRs. In the present study, we evaluated the receptor occupancy in the human brain after a single oral administration of tropisetron and ondansetron using [11C]CHIBA-1001 and PET. METHODS: Two serial dynamic PET scans using [11C]CHIBA-1001 in healthy non-smoking male subjects were performed before and after receiving an oral administration of these medications. RESULTS: A single oral administration of tropisetron, but not ondansetron, decreased the total distribution volume of [11C]CHIBA-1001 in the human brain. CONCLUSION: This study shows that tropisetron, but not ondansetron, could bind to alpha7-nAChRs in the human brain after a single oral administration. Therefore, [11C]CHIBA-1001 may be a useful PET radioligand to measure the occupancy of alpha7-nAChRs in the human brain.