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Review
. 2021 Mar 2;7(2):e995.
doi: 10.1097/PR9.0000000000000995. eCollection 2022 Mar-Apr.

Nonopioid drug combinations for cancer pain: a systematic review

Gursharan Sohi  1 , Nicholas Lao  1 , Augusto Caraceni  2   3 , Dwight E Moulin  4 , Camilla Zimmermann  5 , Leonie Herx  6 , Ian Gilron  1   7   8   9
Affiliations
Review

Nonopioid drug combinations for cancer pain: a systematic review

Gursharan Sohi et al. Pain Rep. .

Abstract

Pain is highly prevalent in patients with cancer-nearly 40% report moderate-severe pain, which is commonly treated with opioids. Increasing cancer survivorship, opioid epidemics in some regions of the world, and limited opioid access in other regions have focused attention on nonopioid treatments. Given the limitations of monotherapy, combining nonopioids-such as antiepileptics and antidepressants-have shown promise in noncancer pain. This review seeks to evaluate efficacy of nonopioid combinations for cancer-related pain. Systematic searches of PubMed, EMBASE, and Cochrane CENTRAL were conducted for double-blind, randomized, controlled trials comparing a nonopioid combination with at least one of its components and/or placebo. This search yielded 4 randomized controlled trials, published between 1998 and 2019 involving studies of (1) imipramine + diclofenac; (2) mitoxantrone + prednisone + clodronate; (3) pentoxifylline + tocopherol + clodronate; and (4) duloxetine + pregabalin + opioid. In the first 3 of these trials, trends favouring combination efficacy failed to reach statistical significance. However, in the fourth trial, duloxetine + pregabalin + opioid was superior to pregabalin + opioid. This review illustrates recognition for the need to evaluate nonopioid drug combinations in cancer pain, although few trials have been published to date. Given the growing practice of prescribing more than 1 nonopioid for cancer pain and the need to expand the evidence base for rational combination therapy, more high-quality trials in this area are needed.

Keywords: Adjuvants; Analgesia; Cancer pain; Opioids; Pain medicine.

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Conflict of interest statement

A. Caraceni reports personal fees from Kyowa Kirin; Gruenenthal GmbH; Pfizer; Almiral; Helsin Healthcare; Molteni & C Soc Esercizio Spa; Shionogi; Italfarmaco; Sandoz International GmbH; Institute de Recherche “Pierre Fabre”, grants from Molteni & C Soc Esercizio Spa; Prokstrakan; Gruenenthal GmbH; Amgen; and Ipsen, outside the submitted work. D.E. Moulin reports personal fees from Bristol Myers Squibb, personal fees from Spectrum Therapeutics, outside the submitted work. I. Gilron reports personal fees from Adynxx, personal fees from Biogen, personal fees from Eupraxia, personal fees from Novaremed, and personal fees from Teva, outside the submitted work. The remaining authors have no conflicts of interest to declare.

Figures

Figure 1.
Figure 1.
PRISMA flow chart showing study inclusion for this systematic review.
Figure 2.
Figure 2.
Risk of bias visual summary for included studies.
See this image and copyright information in PMC

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