Pregabalin combined with antioxidants provides significant improvement in pain over placebo for patients with pancreatitis experiencing pain recurrence after endotherapy and/or surgery for ductal clearance, according to results of a prospective study presented at United European Gastroenterology (UEG) Week 2015.
Patients with chronic pancreatitis undergo recurrent intractable abdominal pain and exocrine and endocrine dysfunction. This can indicate pancreatic ductal calculi, with the current recommended first-line treatment being endotherapy.
“In the long term, more and more of these patients come back with pain recurrence, in spite of ductal clearance,” stated Rupjyoti Talukdar, MD, Asian Institute of Gastroenterology, Hyderabad, India, speaking here on October 26.
Indications for treatment of this recurrent and complex pain associated with chronic pancreatitis have included a cocktail of methionine-containing antioxidants and use of the central nervous system depressant pregabalin. Dr. Talukdar combined these 2 treatments for patients with recurrence of abdominal pain following ductal clearance by endoscopy and/or surgery.
Dr. Talukdar randomised subjects to either placebo (n = 45) or an antioxidant cocktail plus pregabalin 75 mg twice daily for 1 week, followed by 150 mg twice daily (n = 42), for a total of 8 weeks. The patients then moved to an open-label phase of the trial, and all received the antioxidant cocktail for a further 16 weeks. The antioxidant cocktail comprised one daily dose of methionine 2 g, selenium 600 microg, tocopherol 270 IU, beta-carotene 9,000 IU and ascorbic acid 540 mg.
The primary endpoint was reduction in visual analog scale (VAS) pain score at 8 weeks.
In the intention-to-treat analysis, compared with placebo, the antioxidants plus pregabalin promoted significantly reduced VAS pain score (62.1 vs 29.7; P < .0001).
Dr. Talukdar also observed significant benefit at 8 weeks for active treatment according to the Izbicki pain score (30.5 vs 14.8; P < .001), percentage reduction in VAS pain score (28.3% vs 60.5%; P = .01), and number of painful days during treatment (21.8 days vs 14.7 days; P = .03). Indeed, complete resolution of pain was achieved by 26.7% of subjects receiving placebo versus 46.5% of patients receiving active treatment (P = .04).
Significant benefits in VAS pain score (P < .0001) and number of painful episodes (P = .007) remained when all patients were maintained on antioxidants alone for the further 16 weeks.
Dr. Talukdar reported on the full range of quality-of-life measures and for Beck’s depression inventory, although these were unchanged in the comparison of placebo and active treatment.
In the safety analysis, compared with placebo, a greater proportion of patients under active treatment experienced adverse events (51.1% vs 78.6%; P = .01), a difference that was primarily driven by dizziness (4.8% vs 21.4%; P = .02), drowsiness (11.9% vs 38.1%; P = .01), nausea/vomiting (7.1% vs 23.8%; P = .03), and bad taste (4.8% vs 21.4%; P = .04).
Subjects in this study had a mean age of 30.3 years, 74.7% were male, and disease duration was a mean of 5.6 years. The mean VAS score for pain at baseline was 75.9, with all further measures similar across treatments.
Dr. Talukdar noted that significant pain reduction occurred earlier than observed with previous use of antioxidants alone. “Compared with the dose of pregabalin used in our earlier study, we could achieve similar response at a lower dose of pregabalin,” he added.
[Presentation title: Combination of Antioxidants and Pregabalin in the Management of Pain in Chronic Pancreatitis after Ductal Clearance: a Randomized, Double-Blind, Controlled Trial. Abstract OP020]