Effectiveness of antiepileptic or antidepressant drugs when added to opioids for cancer pain: systematic review

Neuropathic pain mechanisms are present in up to 40% of patients with cancer pain. In these situations, additional or adjuvant analgesic drugs (such as antidepressants or antiepileptics) are often required to optimize pain control alongside standard opioid therapy. This systematic review aimed to determine the effectiveness of antidepressants and antiepileptics when added to opioids, compared to opioids alone, for the management of pain caused directly by cancer. Prospective clinical studies, published in English that used a before-after design or randomized or non-randomized group comparisons were identified. Data were extracted on pain intensity, pain relief and adverse events. Eight studies were eligible (five randomized controlled trials) that recruited 465 patients in total, of whom 370 (79.5%) completed the study period. A narrative analysis was performed because clinical and methodological heterogeneity prevented meta-analysis. Included studies suggested that adjuvants improve pain control within 4-8 days when added to opioids for cancer pain; the strongest evidence supports gabapentin. However, a reduction in pain intensity of greater than 1 point on a 0-10 numerical rating scale is unlikely, but an increase in adverse events is likely. For all adjuvants, the effect size was much less than that seen in patients with non-cancer neuropathic pain. Dosing strategies that can be examined in future clinical trials are suggested.