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An 83-year-old man presented with visual disturbance and right hemiparalysis, one month after daratumumab, bortezomib, and dexamethasone administration for multiple myeloma (MM). Blood screens revealed a CD4+ T-lymphocyte count of 132/μl. Diffusion weighted and fluid-attenuated inversion-recovery MR imaging showed high intensity signals in the both occipital lobes and left precentral area. The patient had no history of human immunodeficiency virus infection. Cerebrospinal fluid (CSF) JC virus (JCV) was positive (83 copies/ml), as indicated by PCR. The patient was diagnosed with progressive multifocal leukoencephalopathy (PML). MM treatment was discontinued, and mefloquine and mirtazapine therapy was started. However, the CSF JCV-DNA PCR count did not improve (111 copies/ml) after 30 days from starting mefloquine and mirtazapine therapy. The patient died six months after symptom onset. Conclusively, patients with decreased CD4+ T lymphocyte counts following DBd therapy for MM, the possibility of PML should be considered.

Patient 1 was a 59-year-old woman receiving prednisolone for idiopathic hypereosinophilia. Brain MRI of patient 1 disclosed slight gadolinium enhancement at lesions, indicating inflammation. Patient 2 was a 32-year-old woman with systemic lupus erythematosus under immunosuppressive therapy. Brain biopsy of patient 2 showed balanced infiltration of CD8+ and CD4+ T lymphocytes at the sites of lesions. Both subjects were diagnosed as having progressive multifocal leukoencephalopathy (PML) shortly after the onset of neurological symptoms and were treated with a combination of mefloquine, mirtazapine, and risperidone. Both patients remain alive with improved neurological symptoms even after long-term follow-up (24 months in patient 1 and 45 months in patient 2). Although the prognosis of PML is very poor, our findings suggest that pharmacotherapy may be effective for patients with well-controlled immune reactions against the JC virus.

An 83-year-old man with chronic renal failure was referred to our hospital because of subacute progressive right hemiparesis. A brain MRI showed high-intensity lesions in bilateral middle cerebellar peduncles and white matter of the left frontal lobe on T 2 -weighted images. The lesions increased gradually, so we suspected a brain tumor because 1 H-MRS images showed elevated Cho and decreased NAA, and also pathologic findings of the brain biopsy suggested glioblastoma. However, JC virus (JCV) in cerebrospinal fluid was revealed highly positive by PCR. So we reconsidered pathologically and finally found bizarre astrocytes which were infected with JCV in immunohistochemical studies and we diagnosed progressive multifocal leukoencephalopathy at last. Then we medicated with mefloquine and mirtazapine, and the JCV in cerebrospinal fluid disappeared, without new MRI lesions. This is a rare case in respect of the background of the patient and the clinical course.

A 65 year-old woman with small lymphocytic leukemia presented with subacute cerebellar ataxia. Six months after rituximab chemotherapy, a cranial MRI revealed lesions in the bilateral middle cerebellar peduncles. Both cerebrospinal fluid (CSF) JC virus (JCV)-DNA PCR test on three occasions and brain biopsy were negative. CSF tests were repeated. The fourth test performed 6 months after the onset showed positive JCV-DNA, and a definite diagnosis of progressive multifocal leukoencephalopathy (PML) was made. Neuroimaging of cerebellar atrophy was considered to be coexistence of granule cell neuronopathy. Medication with mirtazapine and mefloquine was temporarily effective for several months. Little are known solitary bilateral MRI lesions of the middle cerebellar peduncle in PML. JCV-PCR test of CSF may be negative at an earlier stage of PML. Repeated CSF tests should be essential to confirming the diagnosis in such cases.

Objective: To report a case of warfarinization involving a patient who developed nasal bleeding and an elevated prothrombin time-international normalized ratio (PT-INR) after taking 15 mg of mirtazapine., Case Summary: A 70-year-old Japanese man with anxiety and irritation was admitted to the ER of our hospital with nasal bleeding. His medical history included atrial fibrillation, treated with warfarin at 3.0 mg a day, hypertension, and diabetus mellitus. He had also been taking mirtazapine at 15 mg. He experienced nasal bleeding 4 days after the initiation of therapy with mirtazapine. His PT-INR markedly elevated from 1.21 before therapy to 7.93 after therapy. Both mirtazapine and warfarin were immediately discontinued by his cardiologist. One week later, PT-INR had normalized (1.00) and the nasal bleeding had resolved., Discussion: The metabolism of warfarin involves several cytochrome P450 isoenzymes, including CYP1A2, CYP2C9, CYP2C19, and CYP3A4. Mirtazapine is metabolized primarily by CYP2D6 and CYP3A4, with lesser contributions by CYP1A2. A competitive enzyme inhibition may occur, with CYP3A4 metabolizing the two drugs. No drug interaction was seen with his other medications., Conclusion: The coadministration of mirtazapine and warfarin can result in an increase in the anticoagulant effect of warfarin. This case shows the need to closely monitor potential drug interactions in the elderly, especially those taking mirtazapine and warfarin.

Background: Previous research has reported that mirtazapine, a 5-HT3 antagonist, is effective for alleviation of digestive symptoms., Purpose: To elucidate the effect of low-dose mirtazapine on digestive symptoms., Patients and Methods: Mirtazapine was administered to 50 cancer patients with digestive symptoms in palliative care, and the data were retrospectively examined. The initial doses ranged from 1.875 to 7.5 mg, and were increased to a maintenance dose according to its effects and the degree of somnolence., Results: The cases were divided into 2 groups based on the cause of the digestive symptoms, including unknown causes(27 cases)and chemotherapy and/or opioid treatment(23 cases). At the initial dose, the efficacy rate was 74.4%, and the effectiveness was significantly higher in patients whose symptoms were due to chemotherapy and/ or opioid use than in those with symptoms of unknown cause(p=0.008). The rate of somnolence was 29.5%. Discontinuation of treatment within 1 week occurred in 10 cases. In 40 cases that continued administration of the maintenance dose, the efficacy rate was 82.5%, and the increased doses provided relief in the patient group with digestive symptoms of unknown cause., Conclusions: Low-dose mirtazapine showed different effects depending on the cause of digestive symptoms; therefore, the dose should be increased in patients whose symptoms are of unknown cause. Somnolence often appeared even at a low-dose, and this should be taken into consideration in the palliative care setting.

This case report describes a successful outcome of mirtazapine treatment in a patient with difficult post-thoracotomy pain. A 63-year-old man received thoracotomy for the resection of esophageal tumor. The pain continued 2 years after the operation. Allodynia was present in the region of the intercostal nerves from the surgical wound. Remedies such as clonazepam, amitriptyline, gabapentin, and acetaminophen were not effective, and epidural block effect was only temporal. The patient experienced a reduction in shooting pain after taking pregabalin; however, he still suffered from persistent pain and, mirtazapine was additionally administrated. One month after this, shooting and persistent pain was reduced, and the patient's appetite was improved, which had been present since the thoracotomy. Since then, his weight slightly increased and the administration of mirtazapine was stopped in accordance with the patient's request. The pain became worse again. Therefore, mirtazapine, commonly used as an antidepressant agent, was considered to be beneficial for neuropathic pain as an analgesic adjuvant.

This paper presents a man in his 80's with pancreatic cancer(cStage IV). He suffered from nausea duringS -1 therapy, and therefore, prochlorperazine maleate at a daily dose of 15 mgwas administered. However, refractory nausea was diagnosed because it did not improve, and mirtazapine at a daily dose of 7. 5 mgbefore bedtime was started. Nausea was improved in the next morning, and the patient ate almost all of his breakfast. After that, no nausea appeared, and his food intake was robust. Mirtazapine is a new antidepressant called noradrenergic and specific serotonergic antidepressant(NaSSA)and blocks 5-HT3 receptors to improve nausea. Mirtazapine is usually started at a daily dose of 15 mg, but this dose induces somnolence. Therefore, mirtazapine was administered at a low daily dose of 7. 5 mgin the present case. No somnolence or disturbance of daily life was seen, and administration was safely continued. We conclude that low-dose mirtazapine is one effective option for refractory nausea duringS -1 therapy.

In the medication of depression, the antidepressants such as selective 5-HT reuptake inhibitors (SSRIs) and a 5-HT and NA reuptake inhibitor (SNRI) are mainly in use in Japan. However, remission rates for SSRI or SNRI are 60% or less. This means that there are still many patients with treatment-resistant depression (TRD). Meanwhile it is considered that the DA nerve system plays an important role for recovery from troublesome feelings and a sense of aimlessness in life in patients with TRD. Recently, new generation antidepressants under development in Japan (escitalopram, duloxetine, mirtazapine, and bupropion) are expected as an option in the medical treatment of TRD. We introduce the pharmacological (focusing on the DA nerve system) and clinical data on these new antidepressants and their putative positioning of each antidepressant. Escitalopram is a stronger and safer SSRI with an earlier onset of action. The antidepressant effect of duloxetine is considered stronger than that of other SNRIs. Mirtazapine is an antagonist of alpha2, 5-HT2A, and 5-HT2C receptors and promotes releases of NA, 5-HT, and DA. Clinically, mirtazapine shows an earlier onset of action and a sedative effect. Bupropion is a DA and NA reuptake inhibitor, and is considered useful to activate DA neurons.

Mirtazapine is a noradrenergic and specific serotonergic antidepressant(NaSSA). Some studies reported that mirtazapine has a receptor-binding profile that may be suitable for use in controlling appetite loss and nausea of cancer patients. We examined its efficacy for these symptoms in 9 cases administered mirtazapine for 9 days. After administration for 4-6 days, the efficacy of nausea was shown at 15 mg of the initial dosage; it was particularly useful in a mild stage. However, its efficacy for appetite loss was not clear for these cases. This study was performed by an open trial. Because of the small number of cases and follow-up period, future study is awaited.