Low-dose Gabapentin Significantly Improves Symptoms of Functional Dyspepsia
Key findings
- This retrospective, open-label study evaluated the efficacy of low-dose gabapentin in 62 adults with functional dyspepsia and normal gastric emptying
- Gabapentin resulted in significant improvements in dyspeptic symptoms as measured by change in total score and most subscale scores on the Patient Assessment of Gastrointestinal Disorders–Symptom Severity Index (PAGI-SYM)
- The greatest improvement in symptom subscores was seen with upper and lower abdominal pain
- 52% of patients treated with gabapentin met the criterion for response based on total PAGI-SYM score, and 61% responded based on postprandial fullness subscore
- Gabapentin was well tolerated overall with a low discontinuation rate and a low rate of adverse events
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The varied presentation of functional dyspepsia—epigastric discomfort, early satiation or postprandial fullness—suggests it is likely a heterogeneous disease. Gastroenterologists at Massachusetts General Hospital have begun prescribing low-dose gabapentin for patients with functional dyspepsia because it is thought to be capable of relieving visceral pain.
In a retrospective, open-label study reported in the Journal of Clinical Gastroenterology, Kyle Staller, MD, MPH, director of the Gastrointestinal Motility Laboratory in the Division of Gastroenterology at Massachusetts General Hospital, Gastroenterologist Braden Kuo, MD, MSc, director of the Center for Neurointestinal Health, and colleagues confirmed the efficacy of this approach.
Study Methods
The researchers analyzed data on 62 adults who presented between January 2012 and May 2016, met Rome III criteria for functional dyspepsia and had normal gastric emptying by scintigraphy. Patients completed the Patient Assessment of Gastrointestinal Disorders–Symptom Severity Index (PAGI-SYM) before evaluation and at least once more within the three years after gabapentin was started (dosing is discussed below). They received no other dyspepsia treatments.
Primary Outcome: Change in PAGI-SYM Score
The average baseline total PAGI-SYM score was 2.32 points. Over a median follow-up of 400 days, there were significant improvements in:
- Total score (−0.44 point)
- Upper abdominal pain (−0.68)
- Lower abdominal pain (−0.63)
- Postprandial fullness (−0.46)
- Heartburn (−0.40)
- Nausea/vomiting (−0.33)
There was no significant improvement in bloating.
The changes in abdominal pain suggest that much of gabapentin's benefit occurred because of improvement in patients' perceptions of pain.
52% of patients concurrently used an antidepressant for depression and/or anxiety. When they were excluded from the analysis, improvements were even greater in the total score (−0.69 point) and most subscales, and there was a significant improvement in bloating.
Secondary Outcome: Proportion of Responders
Response to gabapentin was defined as ≥0.3-point change in PAGI-SYM score or subscore. 52% of patients responded based on total score. 61% responded based on the change in postprandial fullness, 60% based on upper abdominal pain and 52% based on nausea/vomiting.
The change in postprandial fullness implies that gabapentin may affect gastric accommodation and motility, just as it improves rectal compliance in patients with inflammatory bowel syndrome.
Patients on an antidepressant were less likely to respond to gabapentin than other patients (37% vs. 66%; P=.04).
Tolerability
Seven patients (11%) discontinued gabapentin while enrolled in the study. Five of them (71%) discontinued due to side effects, most commonly dizziness and fatigue.
Slow Titration May Boost Success
Many patients with functional GI disorders are sensitive to medication side effects, which can lead to nonadherence. At Mass General, many patients are started on 25, 50 or 100 mg of liquid gabapentin at bedtime to promote drug tolerance. Doses are increased very slowly at two-week intervals such that a patient taking 25 mg at bedtime may increase to 50 mg and a patient taking 100 mg at bedtime may increase to 200 mg.
Gabapentin capsules are available only in denominations of 100 mg. Patients deemed to be well tolerant of medications may be started on capsules three times per day, especially if they report substantial pain. However, they are rarely started at 300 mg three times/day, the manufacturer-recommended dosage for neuropathic pain, because that dosage tends to lead to side-effect-related discontinuations in patients with functional dyspepsia.
The maximum final prescribed dose is generally 300 mg three times/day. This could be exceeded in cases where gabapentin is well tolerated but there has not been complete improvement.
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