Comparison of Duloxetine, Gabapentin, and Pregabalin in the Treatment of Diabetic Neuropathic Pain

Neuropathic Pain

Neuropathic pain is defined as pain caused by primary lesion or dysfunction of the nervous system. It can be part of various syndromes and pathological states, including diabetic peripheral neuropathy syndrome. Painful neuropathy affects up to 25% of patients with diabetes mellitus. Key symptoms include burning or stabbing and usually bilateral pain in the lower extremities, most often in the distal part. It typically worsens at night and may be accompanied by allodynia and hyperalgesia.

Therapy Options

Since there is currently no treatment strategy that fully restores the function of the damaged nerve, the main therapeutic goal remains pain control. Classic analgesics have only a short-term and insufficient effect, so other pharmaceuticals are used for therapy. These include antidepressants like duloxetine (DLX), a selective serotonin reuptake inhibitor (SSRI), and the tricyclic antidepressant (TCA) amitriptyline (AMT). Other medications approved for the treatment of diabetic neuropathic pain include anticonvulsants like gabapentin (GBP) and pregabalin (PGB). The effect has also been demonstrated in opioid analgesics, such as oxycodone.

Analyzed Studies and Evaluation Criteria

The meta-analysis cited below aimed to summarize the effectiveness and tolerance of drugs approved or recommended for the treatment of diabetic neuropathic pain, namely DLX, GBP, PGB, and AMT. In available resources, the authors did not find a study concerning AMT that met the set criteria, so they focused only on the first three mentioned drugs. The direct meta-analysis compared the effectiveness and tolerability of DLX, GBP, and PGB against placebo. In the indirect meta-analysis, the effectiveness and tolerability of DLX were assessed against GBP and PGB.

The authors selected randomized double-blind placebo-controlled studies with parallel or crossover designs that assessed the effects of DLX, GBP, and PGB in the treatment of painful diabetic neuropathy. They used the databases PubMed, EMBASE, and CENTRAL for searching. Studies where patients took approved doses of medications and evaluations were made after 5–13 weeks met the criteria. The chosen requirements were met by 2 studies assessing DLX, 6 focused on PGB, and 2 evaluating GBP.

The first criterion of drug effectiveness was the reduction of the average pain level over 24 hours (for all 3 drugs). As other effectiveness criteria, which applied only to duloxetine and pregabalin, the authors chose a pain reduction of ≥ 50% and improvement on the PGI-I/C scale (Patient Global Impression of Improvement/Change). The list of criteria for determining tolerability included premature discontinuation of treatment, diarrhea, dizziness, headaches, nausea, and somnolence. 

Results Findings

When comparing the named three drugs with a placebo, both duloxetine, gabapentin, and pregabalin exhibited significantly greater effectiveness in all chosen indicators. Higher incidence of adverse events was observed during the use of DLX, GBP, and PGB than among patients who were given a placebo. The most common were dizziness and somnolence.

Comparison of DLX vs. PGB did not show any differences in the level of average pain reduction over 24 hours. Regarding the PGI-I/C score, PGB achieved significantly better results. Comparison of DLX and GBP did not reveal any statistically significant differences in effectiveness and tolerability.

Conclusion

Neuropathic pain is a common complication of diabetes, which can significantly affect the quality of life and whose therapy is not easy. The results of the meta-analysis suggest that in the treatment of diabetic neuropathic pain, duloxetine, gabapentin, and pregabalin demonstrate comparable effectiveness and tolerability. Therefore, they are drugs of choice for this pathological condition.

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Sources:
1. Quilici S., Chancellor J., Löthgren M. et al. Meta-analysis of duloxetine vs. pregabalin and gabapentin in the treatment of diabetic peripheral neuropathic pain. BMC Neurol 2009; 9: 6, doi: 10.1186/1471-2377-9-6.
2. Yoo M., Sharma N., Pasnoor M., Kluding P. M. Painful diabetic peripheral neuropathy: presentations, mechanisms, and exercise therapy. J Diabetes Metab 2013; Suppl 10: 005, doi: 10.4172/2155-6156.S10-005.