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Oral Methadone versus Morphine IR for Patients with Cervical Cancer and Neuropathic Pain : A Prospective Randomised Controlled Trial

Adumala, Aruna ; Palat, Gayatri ; Vajjala, Archana ; Brun, Eva LU and Segerlantz, Mikael LU (2023) In Indian Journal of Palliative Care 29(2). p.200-206
Abstract

Objectives: In India, cervical cancer is the most common cancer among women and makes up for up to 29% of all registered cancer in females. Cancer-related pain is one of the major distressing symptoms for all cancer patients. Pain is characterised as somatic or neuropathic, and the total pain experience is often mixed. Conventional opioids are the backbone of analgesic treatment but are most often not sufficient in alleviating neuropathic pain, common in cervical cancer. Accumulating evidence of the advantage of methadone compared to conventional opioids, due to agonist action at both μ and δ opioid receptors, N-methyl-D-aspartate (NMDA) antagonist activity and the ability to inhibit the reuptake of monoamines has been demonstrated. We... (More)

Objectives: In India, cervical cancer is the most common cancer among women and makes up for up to 29% of all registered cancer in females. Cancer-related pain is one of the major distressing symptoms for all cancer patients. Pain is characterised as somatic or neuropathic, and the total pain experience is often mixed. Conventional opioids are the backbone of analgesic treatment but are most often not sufficient in alleviating neuropathic pain, common in cervical cancer. Accumulating evidence of the advantage of methadone compared to conventional opioids, due to agonist action at both μ and δ opioid receptors, N-methyl-D-aspartate (NMDA) antagonist activity and the ability to inhibit the reuptake of monoamines has been demonstrated. We hypothesised that, with these properties’, methadone might be a good option for the treatment of neuropathic pain in patients with cervical cancer. Material and Methods: Patients with cervical cancer stages ll-lll were enrolled in this randomized controlled trial. A comparison was made between methadone versus immediate release morphine (IR morphine), with increasing doses until pain was controlled. Inclusion-period was from October 3rd to December 31st 2020, and the total patient-study period was 12 weeks. Pain intensity was assessed according to the Numeric Rating Scale (NRS) and Douleur Neuropathique (DN4). The primary objective was to determine whether methadone was clinically superior versus noninferior to morphine as an analgesic for the treatment of cancer related neuropathic pain in women with cervical cancer. Results: A total of 85 women were included; five withdrew and six died during the study period, leaving 74 patients completing the study. All participants showed a reduction in mean values of NRS and DN4 from the time of inclusion and to the end of the study period, for IR morphine and methadone 8.4–2.7 and 8.6–1.5, respectively (P < 0.001). The DN4 score mean reduction for Morphine and Methadone were 6.12–1.37 and 6.05–0, respectively (P < 0.001). Side effects were more common in the group of patients receiving IR morphine compared to the patients treated with methadone. Conclusion: We found that Methadone had a superior analgesic effect with good overall tolerability compared with morphine as a first-line strong opioid for the management of cancer-related neuropathic pain.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cancer, Efficacy, Methadone, Neuropathic pain, Opioid
in
Indian Journal of Palliative Care
volume
29
issue
2
pages
7 pages
publisher
Wolters Kluwer
external identifiers
  • scopus:85166335891
ISSN
0973-1075
DOI
10.25259/IJPC_58_2022
language
English
LU publication?
yes
id
2f04db53-b293-4aab-85b5-0724638235a4
date added to LUP
2023-11-06 12:24:23
date last changed
2023-11-06 12:24:23
@article{2f04db53-b293-4aab-85b5-0724638235a4,
  abstract     = {{<p>Objectives: In India, cervical cancer is the most common cancer among women and makes up for up to 29% of all registered cancer in females. Cancer-related pain is one of the major distressing symptoms for all cancer patients. Pain is characterised as somatic or neuropathic, and the total pain experience is often mixed. Conventional opioids are the backbone of analgesic treatment but are most often not sufficient in alleviating neuropathic pain, common in cervical cancer. Accumulating evidence of the advantage of methadone compared to conventional opioids, due to agonist action at both μ and δ opioid receptors, N-methyl-D-aspartate (NMDA) antagonist activity and the ability to inhibit the reuptake of monoamines has been demonstrated. We hypothesised that, with these properties’, methadone might be a good option for the treatment of neuropathic pain in patients with cervical cancer. Material and Methods: Patients with cervical cancer stages ll-lll were enrolled in this randomized controlled trial. A comparison was made between methadone versus immediate release morphine (IR morphine), with increasing doses until pain was controlled. Inclusion-period was from October 3<sup>rd</sup> to December 31<sup>st</sup> 2020, and the total patient-study period was 12 weeks. Pain intensity was assessed according to the Numeric Rating Scale (NRS) and Douleur Neuropathique (DN4). The primary objective was to determine whether methadone was clinically superior versus noninferior to morphine as an analgesic for the treatment of cancer related neuropathic pain in women with cervical cancer. Results: A total of 85 women were included; five withdrew and six died during the study period, leaving 74 patients completing the study. All participants showed a reduction in mean values of NRS and DN4 from the time of inclusion and to the end of the study period, for IR morphine and methadone 8.4–2.7 and 8.6–1.5, respectively (P &lt; 0.001). The DN4 score mean reduction for Morphine and Methadone were 6.12–1.37 and 6.05–0, respectively (P &lt; 0.001). Side effects were more common in the group of patients receiving IR morphine compared to the patients treated with methadone. Conclusion: We found that Methadone had a superior analgesic effect with good overall tolerability compared with morphine as a first-line strong opioid for the management of cancer-related neuropathic pain.</p>}},
  author       = {{Adumala, Aruna and Palat, Gayatri and Vajjala, Archana and Brun, Eva and Segerlantz, Mikael}},
  issn         = {{0973-1075}},
  keywords     = {{Cancer; Efficacy; Methadone; Neuropathic pain; Opioid}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{200--206}},
  publisher    = {{Wolters Kluwer}},
  series       = {{Indian Journal of Palliative Care}},
  title        = {{Oral Methadone versus Morphine IR for Patients with Cervical Cancer and Neuropathic Pain : A Prospective Randomised Controlled Trial}},
  url          = {{http://dx.doi.org/10.25259/IJPC_58_2022}},
  doi          = {{10.25259/IJPC_58_2022}},
  volume       = {{29}},
  year         = {{2023}},
}