Opioid-gabapentinoid therapy for GI diseases increases risk of depression

Despite manageable gastrointestinal (GI) side effects, opioid-gabapentinoid combo therapy may be linked to a higher risk of central nervous system (CNS) depression and mortality says an article published in Frontiers in Pharmacology.

Combinations of opioid and gabapentin have become more popular, creating various security issues. There aren't many meta-analysis studies, nevertheless, that address this problem. In order to compare the risks of central nervous system depression, gastrointestinal side events, and mortality of combination therapy with those of opioid therapy and to examine the variations in outcomes according to research design and indications, Jongsung Hahn and team conducted the study.

By examining the EMBASE, MEDLINE, and CENTRAL databases, pertinent studies that were published before 30 January 2022 were chosen for this study. Using the Mantel-Haenszel method, the pooled odds ratios (OR) and 95% confidence intervals (CI) of the results were calculated. Analyses of subgroups and meta-regression were conducted in accordance with the characteristics of the study. The Risk of Bias 2 tool and the Cochrane Collaboration's Risk of Bias in Non-RCTs tool were used for the quality assessment of randomized controlled trials (RCTs) and non-randomized trials, respectively.

The key findings of the study were:

1. Mortality was observed in 10 non-RCTs, while adverse events were documented in 26 RCTs and 7 non-RCTs.

2. Dizziness, cognitive dysfunction, and respiratory depression in combination therapy considerably increased when compared to opioid therapy in non-RCTs, and a comparable trend for these side effects was also found in the RCT analysis, while the difference was not statistically significant.

3. In a subgroup analysis, combination medication for cancer pain was linked to the highest risk of sedation.

4. Constipation, vomiting, and other GI side effects were all greatly reduced by combination therapy.

5. Compared to opioid medication, the mortality risk linked with combo therapy was greater.

In conclusion, these findings imply that combination therapy, particularly in cancer patients, necessitates careful monitoring of CNS depression. Due to the lack of a risk difference in respiratory depression in the RCT-only analysis and the lack of RCT or prospective studies looking at mortality, caution should be used when interpreting the clinical findings.

Reference:

Hahn, J., Jo, Y., Yoo, S. H., Shin, J., Yu, Y. M., & Ah, Y.-M. (2022). Risk of major adverse events associated with gabapentinoid and opioid combination therapy: A systematic review and meta-analysis. In Frontiers in Pharmacology (Vol. 13). Frontiers Media SA. https://doi.org/10.3389/fphar.2022.1009950