Pregabalin effective against irritable bowel syndrome symptoms
Pregabalin demonstrates therapeutic potential in the treatment of irritable bowel syndrome (IBS)-related abdominal pain, bloating and diarrhoea but not constipation, according to the results of a trial.
“Abdominal pain is often cited as a major driver for patients with IBS to seek medical care. Treatment options for IBS‐related pain include antispasmodics, peppermint oil, probiotics and antidepressants,” the authors said.
“Nonetheless, many patients find incomplete symptom relief with conventional interventions. Because this trial shows efficacy in patients with moderate‐severe pain, we speculate that pregabalin may be useful to nonconstipated IBS patients who fail other conventional therapies,” they added.
The trial randomized 85 IBS patients (mean age 39.4 years; 86 percent female) with ≥3 moderate-to-severe pain attacks per month to receive pregabalin 225 mg (n=41) vs placebo (n=44) twice daily for 12 weeks. Of these patients, 37 had diarrhoea‐predominant IBS (IBS‐D), 29 had mixed-type IBS (IBS-M) and 18 had constipation‐predominant IBS (IBS‐C). All patients completed weekly, self‐administered questionnaires to assess IBS symptoms and quality of life.
Results revealed that over weeks 9–12, the primary endpoint of average pain Bowel Symptom Scale (BSS) scores were significantly lower in the pregabalin vs placebo arm (25 vs 42; p=0.008). Patients in the active treatment arm also reported greater improvements in overall symptoms (p=0.009), diarrhoea (p=0.049) and bloating (p=0.016), except for constipation. [Aliment Pharmacol Ther 2019;49:389-397]
More patients in the pregabalin vs placebo group achieved adequate relief of IBS symptoms (46 percent vs 36 percent) and a ≥30-point change in pain score from baseline (63 percent vs 45 percent), although the differences were not significant (p=0.35 and p=0.10, respectively). Post‐treatment IBS‐QoL scores were comparable between the two treatment arms.
In a subgroup analysis, patients with IBS-D and IBS-M but not IBS-D obtained the greatest benefit. This lack of effect, while could be explained by the small number of patients with IBS-D in the study population, might be a real finding in that constipation is a known side effect of pregabalin, according to the authors. This is consistent with a previous small study that also found no apparent positive benefit of pregabalin in IBS‐C patients. [Dig Liver Dis 2014;46:113‐118]
In terms of safety, side effects developed in 68 percent of patients in the pregabalin arm vs 55 percent in the placebo arm (p=0.19). Commonly reported side effects were gastrointestinal in nature.
Overall, the findings suggest that pregabalin has beneficial effects on overall IBS symptoms, as well as IBS‐related abdominal pain, diarrhoea and bloating, the authors pointed out.
“The onset of symptom relief was rapid within the first week of treatment and persisted throughout the 12 weeks of treatment… Another promising observation was the benefit in mixed‐IBS, [as] no FDA‐approved drugs are available for this IBS subtype,” they said.
“Pregabalin alters visceral sensation in animal models and in patients with IBS, and this may explain its mechanism of action,” they added.
Although the trial had relatively small sample size and did not apply the FDA outcomes for IBS, given that it was conceived and designed prior to the FDA guidance document, the data are said to be generalizable to community IBS patients as well as referral‐level IBS patients.
“[However], the applicability to those with mild or severe pain is not known,” the authors said. “A large multicentre trial of IBS‐D or IBS‐M patients utilizing the FDA outcome should be pursued, as pregabalin shows promise and treatment options for IBS‐related pain and mixed bowel habit IBS remain limited.”