Adding gabapentinoids to opioids does not improve cancer pain relief
Combining gabapentin or pregabalin with opioid analgesics does not significantly improve cancer pain relief compared with opioid monotherapy, according to results of a recent systematic review and meta-analysis.
Although the results were negative, the researchers said the benefit of adding adjuvant analgesia in patients with definite neuropathic cancer pain cannot be excluded due to the heterogeneity of patient samples included in their study. [Palliat Med 2018;32:276-286]
In the systematic review, researchers from the University of Leeds identified seven randomized controlled trials (RCTs) published in 1992–2015 that evaluated opioid analgesics combined with antidepressants or antiepileptic drugs vs opioid analgesics alone in patients with tumour-related cancer pain. The RCTs included two trials on gabapentin (n=196 in total), two trials on pregabalin (n=222 in total), one trial on amitriptyline (n=16), one trial on phenytoin (n=50), and one trial on fluvoxamine (n=120). Results showed no significant benefit in pain relief with any of the antiepileptic drug or antidepressant, when added to opioids, as compared with opioid analgesics alone.
The meta-analysis included four RCTs, with two trials on gabapentin (n=196 in total) and two trials on pregabalin (n=222 in total). No significant difference in pain relief was found between combination therapy and opioid monotherapy when all four gabapentinoid trials were pooled. The pooled standardized mean difference between combination therapy and opioid monotherapy was 0.16, with moderate heterogeneity across trials.
Across the RCTs, the most commonly reported treatment-related adverse events were somnolence, dizziness and nausea. “In general, the frequency of adverse events in the combination arms was higher than that in the monotherapy arms, with two studies showing these differences to be significant,” the researchers reported.
However, they also noted that overall, the quality of the evidence was low due to the risk of bias within each study.
“Low-quality evidence suggests that adding gabapentinoids to stable opioid analgesia did not improve pain relief in patients with tumour-related cancer pain, while the case for amitriptyline, fluvoxamine and phenytoin remains inconclusive,” they concluded. “The benefit-harm trade-offs remain uncertain when combining opioids and adjuvant therapies for treatment-related cancer pain.”
“Adjuvant analgesia may be used with caution provided more rigorous identification of neuropathic pain is undertaken with early reassessment of benefit and adverse outcomes, and the medication stopped if there is no overall benefit,” they suggested.
Previous studies have compared triple combination therapy (antiepileptic, antidepressant and opioid) with dual combination therapy (antiepileptic or antidepressant with opioid) in the relief of cancer pain. While results showed significantly improved pain scores with triple vs dual combination therapy, these studies were not included in the present systematic review and meta-analysis because none included an opioid monotherapy arm. [Pain Physician 2013;16:E547-E552; J Anesth 2010;24:407-410]