Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Palliative Care
Published in: BMC Palliative Care 1/2013

Open Access 01-12-2013 | Research article

Evidence for the use of Levomepromazine for symptom control in the palliative care setting: a systematic review

Authors: Isabel Dietz, Andrea Schmitz, Ingrid Lampey, Christian Schulz

Published in: BMC Palliative Care | Issue 1/2013

Login to get access

Abstract

Background

Levomepromazine is an antipsychotic drug that is used clinically for a variety of distressing symptoms in palliative and end-of-life care. We undertook a systematic review based on the question “What is the published evidence for the use of levomepromazine in palliative symptom control?”.

Methods

To determine the level of evidence for the use of levomepromazine in palliative symptom control, and to discover gaps in evidence, relevant studies were identified using a detailed, multi-step search strategy. Emerging data was then scrutinized using appropriate assessment tools, and the strength of evidence systematically graded in accordance with the Oxford Centre for Evidence-Based Medicine’s ‘levels of evidence’ tool. The electronic databases Medline, Embase, Cochrane, PsychInfo and Ovid Nursing, together with hand-searching and cross-referencing provided the full research platform on which the review is based.

Results

33 articles including 9 systematic reviews met the inclusion criteria: 15 on palliative sedation, 8 regarding nausea and three on delirium and restlessness, one on pain and six with other foci. The studies varied greatly in both design and sample size. Levels of evidence ranged from level 2b to level 5, with the majority being level 3 (non-randomized, non-consecutive or cohort studies n = 22), with the quality of reporting for the included studies being only low to medium.

Conclusion

Levomepromazine is widely used in palliative care as antipsychotic, anxiolytic, antiemetic and sedative drug. However, the supporting evidence is limited to open series and case reports. Thus prospective randomized trials are needed to support evidence-based guidelines.
Appendix
Available only for authorised users
Literature
1.
Klinkenberg M, Willems DL, van der Wal G, Deeg DJ: Symptom burden in the last week of life. J Pain Symptom Manage. 2004, 27 (1): 5-13. 10.1016/j.jpainsymman.2003.05.008.CrossRefPubMed
2.
Laugsand EA, Kaasa S, de Conno F, Hanks G, Klepstad P: Intensity and treatment of symptoms in 3,030 palliative care patients: a cross-sectional survey of the EAPC Research Network. J Opioid Manag. 2009, 5 (1): 11-21.PubMed
3.
Ventafridda V, Ripamonti C, De Conno F, Tamburini M, Cassileth BR: Symptom prevalence and control during cancer patients’ last days of life. J Palliat Care. 1990, 6 (3): 7-11.PubMed
4.
5.
Ellershaw J: Clinical pathways for care of the dying: an innovation to disseminate clinical excellence. J Palliat Med. 2002, 5 (4): 617-621. 10.1089/109662102760269904.CrossRefPubMed
6.
Fainsinger R, Miller MJ, Bruera E, Hanson J, Maceachern T: Symptom control during the last week of life on a palliative care unit. J Palliat Care. 1991, 7 (1): 5-11.
7.
Cherny NI, Radbruch L: European Association for Palliative Care (EAPC) recommended framework for the use of sedation in palliative care. Palliat Med. 2009, 23 (7): 581-593. 10.1177/0269216309107024.CrossRefPubMed
8.
Sivaraman P, Rattehalli RD, Jayaram MB: Levomepromazine for schizophrenia. Cochrane Database Syst Rev. 2010, 10: CD007779.PubMed
9.
Hals PA, Hall H, Dahl SG: Muscarinic cholinergic and histamine H1 receptor binding of phenothiazine drug metabolites. Life Sci. 1988, 43 (5): 405-412. 10.1016/0024-3205(88)90519-X.CrossRefPubMed
10.
Lal S, Nair NP, Cecyre D, Quirion R: Levomepromazine receptor binding profile in human brain–implications for treatment-resistant schizophrenia. Acta Psychiatr Scand. 1993, 87 (6): 380-383. 10.1111/j.1600-0447.1993.tb03391.x.CrossRefPubMed
11.
12.
Harris DG: Nausea and vomiting in advanced cancer. Br Med Bull. 2010, 96 (1): 175-185. 10.1093/bmb/ldq031.CrossRefPubMed
13.
Eisenchlas JH, Garrigue N, Junin M, De Simone GG: Low-dose levomepromazine in refractory emesis in advanced cancer patients: an open-label study. Palliat Med. 2005, 19 (1): 71-75. 10.1191/0269216305pm972oa.CrossRefPubMed
14.
Cherny NI: Sedation for the care of patients with advanced cancer. Nat Clin Pract Oncol. 2006, 3 (9): 492-500.CrossRefPubMed
15.
16.
Mannix K: Palliation of nausea and vomiting in malignancy. Clin Med. 2006, 6 (2): 144-147.CrossRef
17.
Klein C, Lang U, Bukki J, Sittl R, Ostgathe C: Pain management and symptom-oriented drug therapy in palliative care. Breast Care. 2011, 6 (1): 27-34. 10.1159/000324702.CrossRefPubMedPubMedCentral
18.
Foley KM: Controlling cancer pain. Hosp Pract. 2000, 35 (4): 101-112. 10.3810/hp.2000.04.193.CrossRef
19.
Seidel S, Aigner M, Ossege M, Pernicka E, Wildner B, Sycha T: Antipsychotics for acute and chronic pain in adults. Cochrane Database Syst Rev. 2008, 4: CD004844.PubMed
20.
Fonzo-Christe C, Vukasovic C, Wasilewski-Rasca AF, Bonnabry P: Subcutaneous administration of drugs in the elderly: survey of practice and systematic literature review. Palliat Med. 2005, 19 (3): 208-219. 10.1191/0269216304pm1006oa.CrossRefPubMed
21.
22.
Twycross R, Wilcock A: Palliative Care Formulary. 2011, 4: palliativedrugs.com
23.
Davis MP, Hallerberg G: A systematic review of the treatment of nausea and/or vomiting in cancer unrelated to chemotherapy or radiation. J Pain Symptom Manage. 2010, 39 (4): 756-767. 10.1016/j.jpainsymman.2009.08.010.CrossRefPubMed
24.
Booth S, Moosavi SH, Higginson IJ: The etiology and management of intractable breathlessness in patients with advanced cancer: a systematic review of pharmacological therapy. Nature Clinical Practice Oncology. 2008, 5 (2): 90-100. 10.1038/ncponc1034.CrossRefPubMed
25.
Morita T, Bito S, Kurihara Y, Uchitomi Y: Development of a clinical guideline for palliative sedation therapy using the Delphi method. Journal of Palliative Medicine. 2005, 8 (4): 716-729. 10.1089/jpm.2005.8.716.CrossRefPubMed
26.
Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D: The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS medicine. 2009, 6 (7): e1000100-10.1371/journal.pmed.1000100.CrossRefPubMedPubMedCentral
27.
Sladek R, Tieman J, Fazekas BS, Abernethy AP, Currow DC: Development of a subject search filter to find information relevant to palliative care in the general medical literature. Journal of the Medical Library Association: JMLA. 2006, 94 (4): 394-401.PubMedPubMedCentral
28.
29.
Simera I: EQUATOR Network collates resources for good research. BMJ. 2008, 337: a2471-10.1136/bmj.a2471.CrossRefPubMed
30.
Lebon B, Fisher S: Case report: Maintaining and withdrawing long-term invasive ventilation in a patient with MND/ALS in a home setting. Palliative Medicine. 2011, 25 (3): 262-265. 10.1177/0269216310389224.CrossRefPubMed
31.
Alonso-Babarro A, Varela-Cerdeira M, Torres-Vigil I, Rodriguez-Barrientos R, Bruera E: At-home palliative sedation for end-of-life cancer patients. Palliative Medicine. 2010, 24 (5): 486-492. 10.1177/0269216309359996.CrossRefPubMed
32.
D’Cruz RS, Agar M: Seizing the opportunity to consider uncontrollable seizures in the palliative setting. Asia-Pacific Journal of Clinical Oncology. 2009, 5: A243.
33.
Stephenson J: The use of sedative drugs at the end of life in a UK hospice. Palliative Medicine. 2008, 22 (8): 969-970. 10.1177/0269216308098801.CrossRefPubMed
34.
Reuzel RP, Hasselaar GJ, Vissers KC, van der Wilt GJ, Groenewoud JM, Crul BJ: Inappropriateness of using opioids for end-stage palliative sedation: a Dutch study. Palliat Med. 2008, 22 (5): 641-646. 10.1177/0269216308091867.CrossRefPubMed
35.
Sykes N, Thorns A: Sedative use in the last week of life and the implications for end-of-life decision making. Archives of Internal Medicine. 2003, 163 (3): 341-344. 10.1001/archinte.163.3.341.CrossRefPubMed
36.
Gambles M, McGlinchey T, Dickman A, Ellershaw JE, Murphy D: Agitation and restlessness in the last 24 hours of life on the Liverpool care pathway for the dying patient (LCP). Palliative Medicine. 2010, 1: S70.
37.
Morita T, Tsunoda J, Inoue S, Chihara S: Effects of high dose opioids and sedatives on survival in terminally ill cancer patients. Journal of Pain and Symptom Management. 2001, 21 (4): 282-289. 10.1016/S0885-3924(01)00258-5.CrossRefPubMed
38.
Fainsinger RL, Waller A, Bercovici M, Bengston K, Landman W, Hosking M, Nunez-Olarte JM, de Moissac D: A multicentre international study of sedation for uncontrolled symptoms in terminally ill patients. Palliative Medicine. 2000, 14 (4): 257-265. 10.1191/026921600666097479.CrossRefPubMed
39.
Chater S, Viola R, Paterson J, Jarvis V: Sedation for intractable distress in the dying - A survey of experts. Palliative Medicine. 1998, 12 (4): 255-269. 10.1191/026921698671831786.CrossRefPubMed
40.
Stone P, Phillips C, Spruyt O, Waight C: A comparison of the use of sedatives in a hospital support team and in a hospice. Palliat Med. 1997, 11 (2): 140-144. 10.1177/026921639701100208.CrossRefPubMed
41.
Oliver DJ: The use of methotrimeprazine in terminal care. The British journal of clinical practice. 1985, 39 (9): 339-340.PubMed
42.
Mercadante S, Porzio G, Valle A, Fusco F, Aielli F, Costanzo V: Palliative sedation in patients with advanced cancer followed at home: a systematic review. Journal of Pain and Symptom Management. 2011, 41 (4): 754-760. 10.1016/j.jpainsymman.2010.07.013.CrossRefPubMed
43.
De Graeff A, Dean M: Palliative sedation therapy in the last weeks of life: a literature review and recommendations for standards. Journal of Palliative Medicine. 2007, 10 (1): 67-85. 10.1089/jpm.2006.0139.CrossRefPubMed
44.
Morita T, Chinone Y, Ikenaga M, Miyoshi M, Nakaho T, Nishitateno K, Sakonji M, Shima Y, Suenaga K, Takigawa C: Ethical validity of palliative sedation therapy: a multicenter, prospective, observational study conducted on specialized palliative care units in Japan. Journal of Pain and Symptom Management. 2005, 30 (4): 308-319. 10.1016/j.jpainsymman.2005.03.016.CrossRefPubMed
45.
Cowan JD, Walsh D: Terminal sedation in palliative medicine definition and review of the literature. Supportive Care in Cancer. 2001, 9 (6): 403-407. 10.1007/s005200100235.CrossRefPubMed
46.
Sykes N, Thorns A: The use of opioids and sedatives at the end of life. Lancet Oncology. 2003, 4 (5): 312-318. 10.1016/S1470-2045(03)01079-9.CrossRefPubMed
47.
Molassiotis A, Brearley SG, Stamataki Z: Use of antiemetics in the management of chemotherapy-related nausea and vomiting in current UK practice. Supportive care in cancer: official journal of the Multinational Association of Supportive Care in Cancer. 2011, 19 (7): 949-956. 10.1007/s00520-010-0909-7.CrossRef
48.
Stephenson J, Davies A: An assessment of aetiology-based guidelines for the management of nausea and vomiting in patients with advanced cancer. Supportive Care in Cancer. 2006, 14 (4): 348-353. 10.1007/s00520-005-0897-1.CrossRefPubMed
49.
Amesbury B, Alloway L, Hickmore E, Dewhurst G: High-dose levomepromazine (methotrimeprazine) to control nausea in carcinoid syndrome. Journal of Palliative Care. 2004, 20 (2): 117-118.PubMed
50.
Kennett A, Hardy J, Shah S, A’Hern R: An open study of methotrimeprazine in the management of nausea and vomiting in patients with advanced cancer. Supportive Care in Cancer. 2005, 13 (9): 715-721. 10.1007/s00520-004-0768-1.CrossRefPubMed
51.
Higi M, Niederle N, Bierbaum W, Schmidt CG, Seeber S: Pronounced antiemetic activity of the antipsychotic drug levomepromacine (L) in patients receiving cancer chemotherapy. Journal of cancer research and clinical oncology. 1980, 97 (1): 81-86. 10.1007/BF00411281.CrossRefPubMed
52.
Glare P, Pereira G, Kristjanson LJ, Stockler M, Tattersall M: Systematic review of the efficacy of antiemetics in the treatment of nausea in patients with far-advanced cancer. Supportive Care in Cancer. 2004, 12 (6): 432-440. 10.1007/s00520-004-0629-y.CrossRefPubMed
53.
Atkinson CV, Kirkham SR: Unlicensed uses for medication in a palliative care unit. Palliative Medicine. 1999, 13 (2): 145-152. 10.1191/026921699676057177.CrossRefPubMed
54.
Douglas C, Murtagh FE, Chambers EJ, Howse M, Ellershaw J: Symptom management for the adult patient dying with advanced chronic kidney disease: a review of the literature and development of evidence-based guidelines by a United Kingdom Expert Consensus Group. Palliat Med. 2009, 23 (2): 103-110. 10.1177/0269216308100247.CrossRefPubMed
55.
Twycross R, Bankby G, Hallowood J: The use of low-dose methotrimeprazine (levomepromazine) in the management of nausea and vomiting. Prog Palliat Care. 1997, 5: 49-53.
56.
Stiefel F, Stagno D: Management of insomnia in patients with chronic pain conditions. CNS Drugs. 2004, 18 (5): 285-296. 10.2165/00023210-200418050-00002.CrossRefPubMed
57.
Kehl KA: Treatment of terminal restlessness: A review of the evidence. Journal of Pain and Palliative Care Pharmacotherapy. 2004, 18 (1): 5-30.PubMed
58.
Fainsinger R, Bruera E: Treatment of delirium in a terminally ill patient. Journal of Pain and Symptom Management. 1992, 7 (1): 54-56. 10.1016/0885-3924(92)90108-T.CrossRefPubMed
59.
Rogers AG: The use of methotrimeprazine (Levoprome) in a patient sensitive to opioids and possible bowel shutdown. J Pain Symptom Manage. 1989, 4 (1): 44-45. 10.1016/0885-3924(89)90065-1.CrossRefPubMed
60.
Fletcher AJ: Levomepromazine-induced lupus?. J Pain Symptom Manage. 2009, 37 (6).
61.
Harris DG: Current Practice in the Management of Terminal Haemorrhage by Palliative Care Teams in the UK. Palliat Med (Abstracts of EAPC (European Association for Palliative Care). 2010, 24 (4 Suppl): S5-229.
62.
Vandenbroucke JP, von Elm E, Altman DG, Gotzsche PC, Mulrow CD, Pocock SJ, Poole C, Schlesselman JJ, Egger M: Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration. PLoS medicine. 2007, 4 (10): e297-10.1371/journal.pmed.0040297.CrossRefPubMedPubMedCentral
63.
Sorinola O, Olufowobi O, Coomarasamy A, Khan KS: Instructions to authors for case reporting are limited: a review of a core journal list. BMC medical education. 2004, 4: 4-10.1186/1472-6920-4-4.CrossRefPubMedPubMedCentral
64.
Kelley K, Clark B, Brown V, Sitzia J: Good practice in the conduct and reporting of survey research. International journal for quality in health carez: journal of the International Society for Quality in Health Care / ISQua. 2003, 15 (3): 261-266. 10.1093/intqhc/mzg031.CrossRef
65.
Glare PA, Dunwoodie D, Clark K, Ward A, Yates P, Ryan S, Hardy JR: Treatment of nausea and vomiting in terminally ill cancer patients. Drugs. 2008, 68 (18): 2575-2590. 10.2165/0003495-200868180-00004.CrossRefPubMed
66.
67.
Darvill E, Dorman S, Perkins P: Levomepromazine for nausea and vomiting in palliative care. 2012, In: Cochrane Protocol. Cochrane Database
68.
69.
Vissers KCP, Hasselaar J, Verhagen SAHHVM: Sedation in palliative care. Current Opinion in Anaesthesiology. 2007, 20 (2): 137-142. 10.1097/ACO.0b013e328049557b.CrossRefPubMed
70.
Caraceni A, Simonetti F: Palliating delirium in patients with cancer. The Lancet Oncology. 2009, 10 (2): 164-172. 10.1016/S1470-2045(09)70018-X.CrossRefPubMed
71.
Merskey H: Pharmacological approaches other than opioids in chronic non-cancer pain management. Acta anaesthesiologica Scandinavica. 1997, 41 (1 Pt 2): 187-190.CrossRefPubMed
72.
Lasagna L, Dekornfeld TJ: Methotrimeprazine: a new phenothiazine derivative with analgesic properties. JAMA: the journal of the American Medical Association. 1961, 178: 887-890. 10.1001/jama.1961.03040480017004.CrossRefPubMed
73.
Beaver WT, Wallenstein SL, Houde RW, Rogers A: A comparison of the analgesic effects of methotrimeprazine and morphine in patients with cancer. Clinical pharmacology and therapeutics. 1966, 7 (4): 436-446.CrossRefPubMed
74.
Davidsen O, Lindeneg O, Walsh M: Analgesic treatment with levomepromazine in acute myocardial infarction. A randomized clinical trial. Acta medica Scandinavica. 1979, 205 (3): 191-194.PubMed
75.
Bloomfield S, Simard-Savoie S, Bernier J, Tetreault L: Comparative Analgesic Activity of Levomepromazine and Morphine in Patients with Chronic Pain. Canadian Medical Association journal. 1964, 90: 1156-1159.PubMedPubMedCentral
76.
Stone P, Rees E, Hardy JR: End of life care in patients with malignant disease. Eur J Cancer. 2001, 37 (9): 1070-1075. 10.1016/S0959-8049(01)00087-9.CrossRefPubMed
77.
Grande GE, Todd CJ: Why are trials in palliative care so difficult?. Palliat Med. 2000, 14 (1): 69-74. 10.1191/026921600677940614.CrossRefPubMed
78.
Hudson P, Aranda S, McMurray N: Randomized controlled trials in palliative care: overcoming the obstacles. International journal of palliative nursing. 2001, 7 (9): 427-434.CrossRefPubMed
Metadata
Title
Evidence for the use of Levomepromazine for symptom control in the palliative care setting: a systematic review
Authors
Isabel Dietz
Andrea Schmitz
Ingrid Lampey
Christian Schulz
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Palliative Care / Issue 1/2013
Electronic ISSN: 1472-684X
DOI
https://doi.org/10.1186/1472-684X-12-2

Other articles of this Issue 1/2013

BMC Palliative Care 1/2013 Go to the issue

Research article

Paediatric palliative care: development and pilot study of a ‘Directory’ of life-limiting conditions

Study protocol

Do pilocarpine drops help dry mouth in palliative care patients: a protocol for an aggregated series of n-of-1 trials

Research article

Planning ahead with children with life-limiting conditions and their families: development, implementation and evaluation of ‘My Choices’

Research article

'My dreams are shuttered down and it hurts lots’–a qualitative study of palliative care needs and their management by HIV outpatient services in Kenya and Uganda

Research article

Interventions to encourage discussion of end-of-life preferences between members of the general population and the people closest to them - a systematic literature review

Research article

Dysphagia as a predictor of outcome and transition to palliative care among middle cerebral artery ischemic stroke patients