In a nutshell
This study evaluated the effectiveness and safety of combinations of anti-depressive medication for the treatment of diabetic peripheral neuropathic pain (DPNP) in patients with diabetes. The study showed that combination treatment improved pain in these patients and was well tolerated.
DPNP occurs in patients with diabetes because of nerve damage due to high blood glucose (sugar) levels. Heart disease may also be a risk factor that predisposes patients to DPNP. Commonly affected nerves are in the legs and feet. Pain associated with DPNP may feel like an electric shock, a piercing or stabbing pain, a deep ache, or a burning sensation.
First-line medications for pain relief from DPNP include antidepressants such as amitriptyline (Elavil), duloxetine (Cymbalta), or seizure medications such as pregabalin (Lyrica) or gabapentin (Neurontin). By themselves, these medications are limited by partial pain relief and by the highest dose allowed.
Standard combination treatment with duloxetine and pregabalin has been shown to be equally effective as the highest dose of duloxetine or pregabalin. Due to insufficient evidence on combined therapies, current DPNP guidelines do not recommend their use. It is necessary to determine the treatment option that provides the most benefits, clinically for patients with DPNP.
Methods & findings
This study included 140 patients with DPNP from 13 centers in the United Kingdom. All patients had an average daily pain numerical rating (NRS) of at least 4 out of 10 (10 being the worst). Patients were assigned to 3 treatment groups for 16 weeks. Group 1 included patients treated with amitriptyline supplemented with pregabalin (A-P). Group 2 included patients treated with pregabalin supplemented with amitriptyline (P-A). Group 3 included patients treated with duloxetine supplemented with pregabalin (D-P). Single-use therapy was given initially for 6 weeks. If pain relief was less than optimal (NRS was more than 3), combination therapy was added. The 7-day average daily pain was determined in the final week for each group.
All three treatment groups had similar and significant pain reduction after 16 weeks. NRS was reduced from an average of 6.6 at the beginning of the study to 3.3 at week 16 in all groups. Patients on combination therapy received a higher average NRS reduction compared to those on single treatments.
Treatment side effects included dizziness, nausea, and dry mouth. Most patients stopped treatment in the alone therapy due to side effects.
The bottom line
The study concluded that all three treatment combinations had similar and significant effectiveness for DPNP.
The fine print
The study had a high number of patients that were lost to follow-up. A placebo group was not used for treatment comparison.
Published By :
Lancet (London, England)
Original Title :
Comparison of amitriptyline supplemented with pregabalin, pregabalin supplemented with amitriptyline, and duloxetine supplemented with pregabalin for the treatment of diabetic peripheral neuropathic pain (OPTION-DM): a multicentre, double-blind, randomise