Multichannel functional near-infrared spectroscopy (fNIRS) is a tool used to capture changes in cerebral blood flow. A consistent result for depression is a decrease in blood flow in the frontal cortex leading to hypofrontality, which indicates multidomain functional impairment. Repetitive transcranial magnetic stimulation (rTMS) and elective convulsive therapy (ECT) are alternatives to antidepressant drugs for the treatment of depression but the underlying mechanism is yet to be elucidated. The aim of the current study was to evaluate cerebral blood flow using fNIRS following rTMS treatment in patients with depression. The cerebral blood flow of 15 patients with moderate depression after rTMS treatment was measured using fNIRS. While there was clear hypofrontality during pre-treatment (5 ± 2.5), a notable increase in oxygenated hemoglobin was observed after 30 sessions with rTMS (50 ± 15). This increased blood flow was observed in a wide range of channels in the frontal cortex; however, the centroid values were similar between the treatments. Increased blood flow leads to the activation of neuronal synapses, as noted with other neuromodulation treatments such as electroconvulsive therapy. This study describes the rTMS-induced modulation of blood oxygenation response over the prefrontal cortex in patients with depression, as captured by fNIRS. Future longitudinal studies are needed to assess cerebral blood flow dynamics during rTMS treatment for depression.
Objective The effectiveness of clozapine is clearly superior to other antipsychotics in the treatment of refractory schizophrenia. Clozapine leads to various side effects, and therefore many patients are forced to discontinue. In this study, we analyzed the registry database of all cases in Japan to identify risk factors for discontinuation of clozapine. Methods The Clozaril patient monitoring service ® (CPMS) database from July 31, 2009 to January 26, 2020 was acquired. We defined the following exclusion criteria: patients who had ever taken clozapine by a non-CPMS method, such as an individual import or clinical trial, patients who did not receive clozapine after being enrolled in CPMS, and patients with initial doses other than 12.5 mg (outside the current protocol). Therefore, all patients in this study are new users. Multivariate Cox regression analysis was used to investigate independent risk factors associated with time to discontinuation of clozapine. Results We identified 8,263 patients as the study population. Clozapine discontinuation was significantly associated with age 40 and older [hazard ratio (HR)=1.66, p<0.001], intolerance to olanzapine (HR=1.31, p=0.018), previous treatment with clozapine (HR=1.30, p=0.001), and leukocyte counts <6,000/mm 3 (HR=1.24, p<0.001). The Kaplan-Meier curves for clozapine discontinuation by age group revealed that older age at the time of clozapine introduction tended to have lower continuation rates. Conclusion Careful administration is important because patients with these factors have a high risk of discontinuation. In addition, the initiation of clozapine during the younger period was more effective and more tolerated.
Selective serotonin reuptake inhibitors (SSRIs) are useful for the treatment of obsessive-compulsive disorder (OCD). Although combination therapies are recommended for treatment-resistant OCD, combination therapies involving the use of two SSRIs are not recommended. Here we report the case of a Japanese female who experienced improvement from combination therapy with escitalopram (ESC) and fluvoxamine (FLV). This patient had previously stopped taking other antidepressants because of tolerability issues. Since ESC had been partially effective, she refused to stop taking ESC. We therefore augmented her ESC therapy with FLV 25 mg/day, which resulted in inhibition of the metabolism of ESC by cytochrome P450 2C19 (CYP2C19). After this augmentation, the patient experienced a remarkable improvement in social functioning. The patient had a CYP2C19*1/*1 polymorphism. The patient's serum levels of ESC in the use of ESC plus FLV combination therapy and in the use of ESC alone were 67.7 ng/mL and 36.0 ng/mL, respectively. ESC and FLV combination therapy may be effective provided patients' CYP2C19 polymorphisms are checked and their serum concentrations of ESC are monitored.
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