[Effectiveness of mirtazapine for digestive symptoms in palliative care - retrospective study of 50 cases].

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.

[Low-dose mirtazapine improved nausea and appetite loss during S-1 therapy].

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.

[Oxycodone and pregabalin using transdermal fentanyl patch provided relief of symptoms for postherpetic neuropathic pain in a patient with non-small cell lung cancer].

This paper presents a man in his 70's with non-small cell lung cancer (cT3N2M0, Stage III A) after chemoradiation therapy during follow-up visits. He was referred to the department of palliative care 1 month after the occurrence of herpes zoster, because of pain. Opioids (transdermal fentanyl patch and rapid-release oxycodone) were administered for his cancer pain previously. Additionally, gabapentin was given for neuropathic pain uncontrolled by opioids. However, this was replaced by pregabalin because he experienced somnolence. Although numbing improved remarkably with pregabalin, the pain was only slightly improved. The dose of rapid-release oxycodone was increased and controlled-release oxycodone was added. This provided for marked pain relief. We conclude that administration of pregabalin as an analgesic adjuvant, and oxycodone, which is an opioid, should be considered in the treatment of cancer patients without improvement of neuropathic pain from herpes zoster through use of the transdermal fentanyl patch.

Gonadotropin releasing hormone (GnRH) enhances annexin A5 mRNA expression through mitogen activated protein kinase (MAPK) in LbetaT2 pituitary gonadotrope cells.

The mechanism by which GnRH stimulates annexin A5 expression was examined with LbetaT2 gonadotrope cells. Continuous stimulation with GnRH analog (GnRHa, Des-Gly10 [Pro9]-GnRH ethylamide) transiently elevated LHbeta mRNA expression while maintaining annexin A5 mRNA at high levels for 24 h. GnRH antagonist blocked the effect of GnRHa on annexin A5. While 12-O-tetradecanoyl-phorbol-13 acetate, a protein kinase C activator, increased the expression of annexin A5 mRNA, bisindolylmaleimide, an inhibitor of protein kinase C, suppressed GnRHa-stimulated expression of annexin A5 and LHbeta mRNA. GnRHa stimulation of LHbeta mRNA was inhibited to a greater extent than annexin A5 by a calcium chelator BAPTA/AM. Although a calcium ionophore ionomycin stimulated the expression of both genes, only LHbeta was down-regulated. The MAPK kinase inhibitor PD98059 inhibited GnRHa induction of annexin A5 but not LHbeta mRNA. EGF stimulated the expression of annexin A5 mRNA but caused only a transient effect on LHbeta mRNA expression. These results indicate that GnRH stimulation of signaling pathway for annexin A5 mRNA expression is distinct from that of LHbeta mRNA and dependent more on MAPK.