Indian Journal of Palliative Care
Open access journal 
  Print this page Email this page   Small font sizeDefault font sizeIncrease font size Users online: 120  
     Home | About | Feedback | Login 
  Current Issue Back Issues Editorial Board Authors and Reviewers How to Subscribe Advertise with us Contact Us Analgesic Prescription  
  Navigate Here 
 Search
 
  
 Resource Links
  »  Similar in PUBMED
 »  Search Pubmed for
 »  Search in Google Scholar for
 »Related articles
  »  Article in PDF (272 KB)
  »  Citation Manager
  »  Access Statistics
  »  Reader Comments
  »  Email Alert *
  »  Add to My List *
* Registration required (free)  

 
  In this Article
 »  Abstract
 » Introduction
 » Case Report
 » Discussion
 »  References

 Article Access Statistics
    Viewed511    
    Printed23    
    Emailed0    
    PDF Downloaded41    
    Comments [Add]    

Recommend this journal

 


 
Table of Contents 
CASE REPORT
Year : 2018  |  Volume : 24  |  Issue : 3  |  Page : 372-374

Olanzapine in the treatment of refractory nausea and vomiting in palliative care settings


Department of Onco-Anaesthesiology and Palliative Medicine, Dr. BRAIRCH, AIIMS, New Delhi, India

Date of Web Publication16-Jul-2018

Correspondence Address:
Dr. Nishkarsh Gupta
Room No 139, Department of Onco-Anaesthesiology and Palliative Medicine, Dr. Brairch, AIIMS, New Delhi
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJPC.IJPC_30_18

Rights and Permissions

 » Abstract 

The patients often present to palliative care with intractable nausea and vomiting. This may reduce the effectiveness of oral drugs and significantly affects the quality of life of these patients. Despite multiple drugs available for treatment, it is often difficult to control the symptoms. Olanzapine is an atypical antipsychotic and acts on multiple receptors and may help in treating vomiting in a patient with advanced malignancy. We report a case of gallbladder carcinoma who presented to us with intractable vomiting which was not relieved with a combination of traditional antiemetics but showed marked improvement with olanzapine.


Keywords: Gallbladder carcinoma, intractable vomiting, olanzapine


How to cite this article:
Gupta N, Puri S, Kumar V, Garg R, Bharati SJ, Mishra S, Bhatnagar S. Olanzapine in the treatment of refractory nausea and vomiting in palliative care settings. Indian J Palliat Care 2018;24:372-4

How to cite this URL:
Gupta N, Puri S, Kumar V, Garg R, Bharati SJ, Mishra S, Bhatnagar S. Olanzapine in the treatment of refractory nausea and vomiting in palliative care settings. Indian J Palliat Care [serial online] 2018 [cited 2018 Dec 10];24:372-4. Available from: http://www.jpalliativecare.com/text.asp?2018/24/3/372/236766



 » Introduction Top


Nausea and vomiting is a common occurrence in patients with advanced cancer. The prevalence of nausea in the palliative population has been estimated to range from 16% to 68%.[1] Persistent nausea and vomiting in patients with palliative conditions can lead to unplanned hospital visits. Reasons can be multifactorial comprising metabolic issues, vestibular problems, central nervous system disorders, or metastasis.[2],[3] In some cases, the cause remains unknown.

Various classes of antiemetics (phenothiazines, butyrophenones, benzamides, corticosteroids, serotonin (5HT3) receptor antagonists, anticholinergics, antihistamines, and cannabinoids) are used to control nausea and vomiting depending on the mechanism. Often, a combination therapy may be required to control vomiting.[4]

Olanzapine is an atypical antipsychotic agent of the thienobenzodiazepine class which acts as antagonist on multiple receptors including dopaminergic (D1, D2, D3, and D4), serotonergic (5-HT2A, 5-HT2C, 5-HT3, and 5-HT6), adrenergic (alpha1), histaminic (H1), and muscarinic (M1, M2, M3, and M4) receptors. Olanzapine has few extrapyramidal side effects because it has five times more affinity for 5HT2 receptors than for D2 receptors.[5]

Reports on the use of olanzapine in refractory nausea and vomiting in palliative care setting are limited.


 » Case Report Top


A 65-year-old female with gallbladder carcinoma presented to our palliative care unit (PCU) with a history of pain abdomen and vomiting. Patient had pain in the right upper quadrant of abdomen, which had increased over the past 15 days. Pain was associated with vomiting for the past 3 days. The patient was taking tablet hyoscine butyl bromide 10 mg tds and tablet metoclopramide 10 mg tds without any improvement.

A contrast-enhanced computed tomography abdomen revealed gallbladder mass with liver and periportal nodal metastasis. An ultrasound-guided fine-needle aspiration cytology from gallbladder mass was suggestive of adenocarcinoma. Since patient had an Eastern Cooperative Oncology Group 4 status, she was deemed unsuitable for chemotherapy and referred to PCU.

In the PCU, she was started on morphine-based analgesic titration. After 3 mg bolus of injection morphine, an infusion of injection morphine 0.5 mg/h was started. She was started on injection metoclopramide 10 mg thrice a day for nausea and vomiting. Her abdominal pain was reduced in intensity, but nausea and vomiting persisted and was severe in nature. Considering liver metastasis, she was started on injection dexamethasone 8 mg twice a day.

Pain was settled but vomiting still uncontrolled. Addition of ondansetron also did not relieve the symptoms. Her vomiting persisted and adversely affected her quality of life (QOL). Hence, injection haloperidol 0.5 mg twice a day was added. Even with the use of a combination of different classes of antiemetics, her nausea and vomiting was not controlled.

A diagnosis of functional small bowel obstruction was made, and patient was kept on nasogastric tube decompression along with nil per oral for 24 h as per surgical oncology opinion. After 24 h of fasting, intermittent feeds were started with Ryle's tube clamping, but patient symptoms of nausea and vomiting persisted. We decided to start tablet olanzapine 2.5 mg once daily Ryle's tube. There was a dramatic response after the first dose of olanzapine; her nausea and vomiting had reduced both in intensity and frequency. Ryle's tube was removed and she started accepting feed without symptoms. She was discharged with tablet olanzapine 2.5 mg hora somini and metoclopramide on as on required basis. In the follow-up period after 1 week, she had no complaints of nausea and vomiting.


 » Discussion Top


Nausea and vomiting is distressing symptoms that decrease the QOL of a cancer patient.

Emesis is controlled in our brain by chemoreceptor trigger zone (CTZ), the reticular formation in the medulla oblongata, and the central pattern generator (CPG). The CPG is an interconnected neural network that receives afferents from the cerebral cortex and higher brainstem, thalamus, hypothalamus, the vestibular system, and through the vagus and splanchnic nerves. The main receptors present within the CTZ are dopamine Type 2 (D2) and serotonin (5HT2 and 5HT3), whereas in CPG, the principal receptors are serotonin muscarinic cholinergic (Ach), 5-HT3, and histamine Type 1 (H1) receptors. Various antiemetics act on different receptors.[1],[6],[7] Haloperidol has its action on D2 receptors, whereas metoclopramide also acts peripherally to block D2 within the gastrointestinal tract and stimulates prokinesis through 5-HT4 receptors. Phenothiazines are mainly anticholinergic and antihistaminic as compared to antihistamines which act on H1 receptors in the CPG and on vestibular afferents. Anticholinergics drugs like hyoscine act on peripheral acetylcholine receptors located in the CPG. 5-HT3 receptor antagonists such as ondansetron act on receptors located both centrally at the CTZ and CPG and on the terminals of vagal afferents in the gut.[1],[2],[3]

Olanzapine is a broad-spectrum antiemetic with potential action of multiple receptors (D2, H1, ACh, and 5-HT3). Olanzapine has been suggested as a second-line antiemetic for patients with chemotherapy-induced nausea refractory to butyrophenones or phenothiazines or who have extrapyramidal reactions to usual antiemetics.[8],[9] In addition, a decreased cost and improved compliance have added advantage over other classes of antiemetic drugs.[10] There is not enough literature to suggest its use for intractable nausea and vomiting in advanced palliative care settings.

An open-label pilot study explored the antiemetic activity of olanzapine in patients with advanced cancer requiring opioid analgesics for pain. Olanzapine in three doses (2.5, 5, and 10 mg) was associated with significant reductions in nausea without extrapyramidal symptoms.[11]

It is also associated with weight gain and improved appetite which might also be helpful is cachectic patient.[12] It is associated with few drug–drug interactions, has a wide therapeutic index, and can be used safely in renal and liver dysfunction.[13]

In palliative care settings, the patients commonly present late with intractable nausea vomiting. The etiology is often multifactorial, and it is difficult to localize the emetogenic source. A mechanism-based treatment of vomiting has been suggested, but it may not be easy to recognize the cause of vomiting. A combination antiemetic therapy consisting of different classes of antiemetic drugs is one approach that can successfully treat refractory nausea and vomiting in some patients. However, it not only adds the cost but also the side effects. Furthermore, despite this, some patients do not have desired response. Our patient also had intractable vomiting which was refractory to multiple standard medications including metoclopramide, butyrophenones, corticosteroids, and 5HT3 antagonists. She subsequently showed improvement in symptoms after starting olanzapine. By virtue of acting on a number of key receptor sites, olanzapine as a single agent has a distinct advantage over combinations of various antiemetics by improving compliance and reducing drug interactions.

Olanzapine, in our experience, is an effective antiemetic drug in the treatment of refractory nausea and vomiting in advanced cancer patients. It should be started as a first-line drug initially in palliative care patients with intractable nausea and vomiting where it is often difficult to delineate the cause.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 » References Top

1.
Glare P, Miller J, Nikolova T, Tickoo R. Treating nausea and vomiting in palliative care: A review. Clin Interv Aging 2011;6:243-59.  Back to cited text no. 1
    
2.
Davis MP, Walsh D. Treatment of nausea and vomiting in advanced cancer. Support Care Cancer 2000;8:444-52.  Back to cited text no. 2
    
3.
Walsh D, Davis M, Ripamonti C, Bruera E, Davies A, Molassiotis A, et al. 2016 updated MASCC/ESMO consensus recommendations: Management of nausea and vomiting in advanced cancer. Support Care Cancer 2017;25:333-40.  Back to cited text no. 3
    
4.
Davis MP, Hallerberg G; Palliative Medicine Study Group of the Multinational Association of Supportive Care in Cancer. A systematic review of the treatment of nausea and/or vomiting in cancer unrelated to chemotherapy or radiation. J Pain Symptom Manage 2010;39:756-67.  Back to cited text no. 4
    
5.
MacKintosh D. Olanzapine in the management of difficult to control nausea and vomiting in a palliative care population: A Case series. J Palliat Med 2016;19:87-90.  Back to cited text no. 5
    
6.
Darmani NA, Ray AP. Evidence for a re-evaluation of the neurochemical and anatomical bases of chemotherapy-induced vomiting. Chem Rev 2009;109:3158-99.  Back to cited text no. 6
    
7.
Chu CC, Hsing CH, Shieh JP, Chien CC, Ho CM, Wang JJ, et al. The cellular mechanisms of the antiemetic action of dexamethasone and related glucocorticoids against vomiting. Eur J Pharmacol 2014;722:48-54.  Back to cited text no. 7
    
8.
Mizukami N, Yamauchi M, Koike K, Watanabe A, Ichihara K, Masumori N, et al. Olanzapine for the prevention of chemotherapy-induced nausea and vomiting in patients receiving highly or moderately emetogenic chemotherapy: A randomized, double-blind, placebo-controlled study. J Pain Symptom Manage 2014;47:542-50.  Back to cited text no. 8
    
9.
Hocking CM, Kichenadasse G. Olanzapine for chemotherapy-induced nausea and vomiting: A systematic review. Support Care Cancer 2014;22:1143-51.  Back to cited text no. 9
    
10.
Srivastava M, Brito-Dellan N, Davis MP, Leach M, Lagman R. Olanzapine as an antiemetic in refractory nausea and vomiting in advanced cancer. J Pain Symptom Manage 2003;25:578-82.  Back to cited text no. 10
    
11.
Kaneishi K, Nishimura K, Sakurai N, Imai K, Matsuo N, Takahashi N, et al. Use of olanzapine for the relief of nausea and vomiting in patients with advanced cancer: A multicenter survey in japan. Support Care Cancer 2016;24:2393-5.  Back to cited text no. 11
    
12.
Navari RM, Brenner MC. Treatment of cancer-related anorexia with olanzapine and megestrol acetate: A randomized trial. Support Care Cancer 2010;18:951-6.  Back to cited text no. 12
    
13.
Atkinson SR. Olanzapine for intractable nausea and vomiting in palliative care patients not receiving chemotherapy. J Palliat Med 2014;17:503-4.  Back to cited text no. 13
    




 

Top
Print this article  Email this article
Online since 1st October '05
Published by Wolters Kluwer - Medknow