Usefulness of Olanzapine as an Adjunct to Opioid Treatment and for the Treatment of Neuropathic Pain

Torigoe, Kazuhiro; Nakahara, Kae; Rahmadi, Mahardian; Yoshizawa, Kazumi; Horiuchi, Hiroshi; Hirayama, Shigeto; Imai, Shoichi; Kuzumaki, Naoko; Itoh, Toshimasa; Yamashita, Akira; Shakunaga, Kiyoshi; Yamasaki, Mitsuaki; Nagase, Hiroshi; Matoba, Motohiro; Suzuki, Tsutomu; Narita, Minoru

doi:10.1097/aln.0b013e31823c7e56

Cited by 35 publications

(23 citation statements)

References 29 publications

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“…In the study of gastrointestinal transit (Torigoe et al, 2012), mice were fasted for 12 hours before the experiments. At 30 minutes after the administration of morphine (0.3-10 mg/kg s.c.), 10 minutes after the administration of oxycodone (0.3-10 mg/kg s.c.), or 10 minutes after the administration of fentanyl (10-300 mg/kg s.c.), blue ink (0.3 ml/mouse; Pilot Co. Ltd., Tokyo, Japan) was administered orally.…”

Section: Methodsmentioning

confidence: 99%

Mechanisms That Underlie μ-Opioid Receptor Agonist–Induced Constipation: Differential Involvement of μ-Opioid Receptor Sites and Responsible Regions

Mori

Shibasaki

Matsumoto

et al. 2013

J Pharmacol Exp Ther

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Reducing the side effects of pain treatment is one of the most important strategies for improving the quality of life of cancer patients. However, little is known about the mechanisms that underlie these side effects, especially constipation induced by opioid receptor agonists; i.e., do they involve naloxonazinesensitive versus -insensitive sites or central-versus-peripheral m-opioid receptors? The present study was designed to investigate the mechanisms of m-opioid receptor agonist-induced constipation (i.e., the inhibition of gastrointestinal transit and colonic expulsion) that are antagonized by the peripherally restricted opioid receptor antagonist naloxone methiodide and naloxonazine in mice. Naloxonazine attenuated the fentanylinduced inhibition of gastrointestinal transit more potently than the inhibition induced by morphine or oxycodone. Naloxone methiodide suppressed the oxycodone-induced inhibition of gastrointestinal transit more potently than the inhibition induced by morphine, indicating that m-opioid receptor agonists induce the inhibition of gastrointestinal transit through different mechanisms. Furthermore, we found that the route of administration (intracerebroventricular, intrathecally, and/or intraperitoneally) of naloxone methiodide differentially influenced the suppressive effect on the inhibition of colorectal transit induced by morphine, oxycodone, and fentanyl. These results suggest that morphine, oxycodone, and fentanyl induce constipation through different mechanisms (naloxonazine-sensitive versus naloxonazine-insensitive sites and central versus peripheral opioid receptors), and these findings may help us to understand the characteristics of the constipation induced by each m-opioid receptor agonist and improve the quality of life by reducing constipation in patients being treated for pain.

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Section: Methodsmentioning

confidence: 99%

Mechanisms That Underlie μ-Opioid Receptor Agonist–Induced Constipation: Differential Involvement of μ-Opioid Receptor Sites and Responsible Regions

Mori

Shibasaki

Matsumoto

et al. 2013

J Pharmacol Exp Ther

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“…In a ferret model, olanzapine decreased opioid-induced nausea and vomiting in a dose-dependent manner 17 . Coadministration of prochlorperazine, which inhibits dopamine receptors, and diphenhydramine, which inhibits histamine receptors, is another candidate for a balanced therapeutic effect.…”

Section: Discussionmentioning

confidence: 99%

Incidence of Nausea and Vomiting Induced by Oxycodone Administered with Prochlorperazine in Japanese Cancer Patients

et al. 2015

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Background: Nausea and vomiting are the most frequent side effects of opioids and may cause the opioids to be discontinued. New methods for preventing opioid-induced nausea can improve cancer pain management. Oxycodone is one of the most frequently used opioid used in Japan because patients receiving oxycodone report less nausea and vomiting than do patients receiving morphine. The reported incidence of oxycodone-induced nausea varies widely, although the true incidence remains unclear. As a first step toward preventing oxycodone-induced nausea, we aimed to determine the incidence of and risk factors for oxycodone-induced nausea and vomiting. Methods:In this observational study, we analyzed a series of consecutive inpatients with cancer who received oxycodone with prochlorperazine as a preventive antiemetic agent. Oxycodone (5 mg) was administered either at 08:00 and 20:00 or at 09:00 and 21:00, and prochlorperazine (5 mg) was also given at the same times for 5 days.Results: Of the 145 enrolled patients, 138 were suitable for analysis. The incidence of nausea was 18.1%, and that of vomiting was 5.8%. The incidence of nausea was higher, but not to a significant degree, in women than in men (P=0.07). Furthermore, the incidence of vomiting in women was equal to that in men (P=0.28), whereas the incidences of both nausea (P=0.99) and vomiting (P=0.89) in elderly patients were equal to those in younger patients. In addition, the incidence of nausea (P=0.52) and vomiting (P= 0.91) in patients with digestive system cancer was equal to that of patients with non-digestive system cancer. Conclusions:The incidence of nausea induced by oxycodone with prochlorperazine was 18.1% in opioid-naïve Japanese inpatients. Female sex may be a risk factor for oxycodone-induced nausea. These results suggest that a clinical study would require 314 participants (157 in each group) to decrease the incidence from 18% to 8% (10% decrease) with a new preventive treatment (alpha error=0.05, beta error=0.2). (J Nippon Med Sch 2015; 82: 100 105)

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“…In an experimental model of neuropathic pain, nerve injury suppressed the hypnotic effect of the benzodiazepines, but not that of pentobarbital, in association with decreased GABAergic transmission in the cingulate cortex (53). Interestingly, olanzapine inhibited thermal hyperalgesia and completely alleviated the sleep disturbance induced by sciatic nerve ligation (50). Against the background of increasing concern about 'polypharmacy,' olanzapine can be used as a single adjunctive agent and can be given at doses tailored to the clinical state of the patients, which would be expected to improve the quality of life of the patients while greatly reducing the side effects of opioids.…”

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confidence: 97%

“…Based on these backgrounds, 'the basic research team in Japan' investigated the effects of olanzapine on morphine-induced emesis in animals. Olanzapine has been demonstrated to show high affinity for the muscarinic M1 receptor in animal brain tissues (50). Intriguingly, olanzapine decreased morphine-induced nausea and vomiting in a dosedependent manner (50), although at the dose at which it exerted the antiemetic effect, it did not induce catalepsy or hyperglycemia (50).…”

mentioning

confidence: 99%

“…Olanzapine has been demonstrated to show high affinity for the muscarinic M1 receptor in animal brain tissues (50). Intriguingly, olanzapine decreased morphine-induced nausea and vomiting in a dosedependent manner (50), although at the dose at which it exerted the antiemetic effect, it did not induce catalepsy or hyperglycemia (50). In addition, olanzapine, at this dose, had no effect on the morphine-induced release of dopamine or the inhibition of gastrointestinal transit (50), indicating that olanzapine may be useful for the treatment of morphine-induced emesis.…”

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confidence: 99%

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Recent Developments in the Management of Cancer Pain in Japan: Education, Clinical Guidelines and Basic Research

Yamaguchi

Narita

Morita

et al. 2012

Japanese Journal of Clinical Oncology

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Usefulness of Olanzapine as an Adjunct to Opioid Treatment and for the Treatment of Neuropathic Pain

Abstract: These findings suggest that olanzapine may be useful for the treatment of morphine-induced emesis and as an adjunct for the treatment of neuropathic pain associated with sleep disturbance.

Cited by 35 publications

References 29 publications

Mechanisms That Underlie μ-Opioid Receptor Agonist–Induced Constipation: Differential Involvement of μ-Opioid Receptor Sites and Responsible Regions

Mechanisms That Underlie μ-Opioid Receptor Agonist–Induced Constipation: Differential Involvement of μ-Opioid Receptor Sites and Responsible Regions

Incidence of Nausea and Vomiting Induced by Oxycodone Administered with Prochlorperazine in Japanese Cancer Patients

Recent Developments in the Management of Cancer Pain in Japan: Education, Clinical Guidelines and Basic Research

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