Pregabalin for decreasing abdominal pain in people with chronic pancreatitis

Review question

Is pregabalin useful in decreasing abdominal pain in people with chronic pancreatitis?

Background

The pancreas is an abdominal organ that secretes several digestive enzymes into the pancreatic ductal system, which empties into the small bowel. It also comprises the Islets of Langerhans, which secrete several hormones, including insulin. Chronic pancreatitis is long-standing and progressive inflammation of the pancreas resulting in destruction and replacement of pancreatic tissue with fibrous tissue. This may lead to a shortage of digestive enzymes and insulin (helps regulate blood sugar), leading to diabetes (a lifelong condition in which a person's blood sugar level becomes too high). Alcohol is considered the main cause but others include: smoking, some drugs, and a variety of other disorders. Chronic abdominal pain is the major symptom of chronic pancreatitis. The pain is usually in the upper abdomen and is usually described as deep, penetrating, and radiating to the back. Various theories exist about the reason for pain in chronic pancreatitis. One theory is that the disease process affects the nerves supplying the pancreas. Pregabalin inhibits the transmission of pain through the nerves. Pregabalin may decrease pain in people with chronic pancreatitis, but may also produce a number of side-effects. Some common side-effects include: excessive sleepiness, blurred vision, double vision, dry mouth, constipation, vomiting, excessive wind, feeling excited, confusion, reduced sexual desire, irritability, feeling dizzy, feeling unsteady, tremors, speech difficulty, tingling or pricking ('pins and needles') sensation, and disturbances of attention and memory. Less frequent, but serious adverse events include: fainting episodes, heart failure, and reversible kidney failure. This review included all studies 22 June 2015, on the benefits and harms of using pregabalin to treat chronic pain in people with chronic pancreatitis.

Study characteristics

We only found one study funded by Pfizer that met our inclusion criteria. A total of 64 participants with chronic pain due to chronic pancreatitis received either increasing doses of pregabalin (150 mg per day to 600 mg per day; 34 participants) or matching placebo (sham treatment; 30 participants) on an outpatient basis. The decision about whether a participant received pregabalin or placebo was made using methods similar to toss of a coin, to ensure that the participants in the two groups were similar. Participants received pregabalin or placebo for three weeks, then the outcomes were measured. Potential participants taking other pain-killers were allowed to take part in the study. Thus, this trial evaluates the role of pregabalin in addition to other analgesics for decreasing chronic abdominal pain due to chronic pancreatitis.

Key results

Only the short-term outcomes were available in this trial. This trial found that the changes in opiate use (drugs similar to morphine), and pain scores from baseline were better in participants taking pregabalin compared to those taking placebo. It was not clear whether these changes had a significant impact on the life of the participants.This trial also found that there were more side-effects in participants taking pregabalin compared to those taking placebo. The differences between pregabalin and placebo were imprecise for short-term health-related quality of life, percentage of people with serious side-effects, and percentage of people requiring hospital admissions.

Medium- and long-term outcomes, number of work days lost, and length of hospital stay were not available in this trial.

Quality of the evidence

The quality of evidence was low or moderate. As a result, further studies are required on this topic.

Authors' conclusions: 

Based on low- to moderate-quality evidence, short-term use of pregabalin decreases short-term opiate use, and short-term pain scores, but increases the adverse events compared to placebo, in people with chronic pain due to chronic pancreatitis. The clinical implication of the decreases in short-term opiate use and short-term pain scores is not known.

Future trials assessing the role of pregabalin in decreasing chronic pain in chronic pancreatitis should assess the medium- or long-term effects of pregabalin and should include outcomes such as, quality of life, treatment-related adverse events, number of work days lost, number of hospital admissions, and the length of hospital stay, in addition to pain scores, to assess the clinical and socioeconomic impact.

Read the full abstract...
Background: 

Chronic abdominal pain is one of the major symptoms in people with chronic pancreatitis. The role of pregabalin in people with chronic pancreatic pain due to chronic pancreatitis is uncertain.

Objectives: 

To assess the benefits and harms of pregabalin in people with chronic abdominal pain due to chronic pancreatitis.

Search strategy: 

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library 2015, issue 6, and MEDLINE, EMBASE, Science Citation Index Expanded, trials registers until June 2015. We also searched the references of included trials to identify further trials.

Selection criteria: 

We considered only randomised controlled trials (RCT) performed in people with chronic pancreatic pain due to chronic pancreatitis, irrespective of language, blinding, or publication status for inclusion in the review.

Data collection and analysis: 

Two review authors independently identified trials and independently extracted data. We calculated the risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI) with RevMan 5, based on intention-to-treat analysis.

Main results: 

Only one study, funded by Pfizer, met the inclusion criteria for the review. A total of 64 participants (with chronic pain due to chronic pancreatitis) were randomly assigned to receive escalating doses of pregabalin (150 mg per day to 600 mg per day; 34 participants) or matching placebo (30 participants). Participants received pregabalin or placebo for three weeks on an outpatient basis; the outcomes were measured at the end of the treatment (i.e. three weeks from commencement of treatment). Potential participants taking concomitant analgesic medication and expected to stay on a stable regime during the trial were allowed to enter the study. This trial was at low risk of bias. The overall quality of evidence was low or moderate.

Only the short-term outcomes were available in this trial. The medium and long-term outcomes, number of work days lost, and length of hospital stay due to admissions for pain control were not available. This trial found that the changes in opiate use (MD -26.00 mg; 95% CI -47.36 to -4.64; participants = 64; moderate-quality evidence), and pain score percentage changes from baseline (MD -12.00; 95% CI -21.82 to -2.18; participants = 64; moderate-quality evidence) were better in participants taking pregabalin compared to those taking placebo. This trial also found that there were more adverse events in participants taking pregabalin compared to those taking placebo (RR 1.71; 95% CI 1.20 to 2.43; participants = 64). The differences between pregabalin and placebo were imprecise for short-term health-related quality of life measured with the EORTC CLQ-30 questionnaire (MD 11.40; 95% CI -3.28 to 26.08; participants = 64; moderate-quality evidence), proportion of people with serious adverse events (RR 1.76; 95% CI 0.35 to 8.96; participants = 64; low-quality evidence), and proportion of people requiring hospital admissions (RR 0.44; 95% CI 0.04 to 4.62; participants = 64; low quality evidence).

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