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Abstract

As pointed out in the above summary, the technique of multichannel intraluminal impedance and pH offers several advantages over conventional pHmetry. It detects all forms of reflux (acid, non-acid, and re-reflux) providing refined characterization of the reflux event through its ability to typify composition (liquid, gas, or mixed), chemical nature (acid or non-acid), and clearance of both volume and acid. This makes intraluminal impedance pH a very useful tool for the study of reflux in physiologic studies and in patients with persistent symptoms despite acid suppression, and, as shown by our own study, evaluation of new therapeutic approaches to GERD. As recognized by the authors, side effects were quite frequent in our study. It is important to note that the 40-mg dose of baclofen used in our study is quite high. A reduction in side effects may be accomplished by using the more gentle and gradual loading regimen that is conventionally used in spastic motor disorder, i.e., starting at 5 mg, 3 times a day, with 5-mg increments every fourth day until a dose of 20 mg, 3 times a day, is achieved, with subsequent dose changes to be dictated by persistence of reflux symptoms or the appearance of side effects. Whether such a regimen or even lower doses might be effective over a prolonged period of time will require appropriate clinical trials. Ciccaglione and Marcio (Gut 2003;52:464–470) recently reported on 12 patients with GERD who underwent 24-hour pHmetry before and after a 4-week course of baclofen at a dose of 10 mg, 3 times a day. Two patients withdrew because of side effects (low blood pressure, dizziness, and nocturnal anxiety with sleepiness); in the remaining 10 patients, baclofen significantly reduced the number of reflux episodes and percent time pH <4. This study not only shows a therapeutic effect at a lower dose, but also speaks against development of tolerance over a 4-week period, with acid reflux being in fact greater on day one of treatment when compared with 4 weeks. GABA B agonists have been shown to reduce the rate of swallowing (Gastroenterology 2000;118:7–13, Am J Physiol 1991;261:R693–R646). Therefore, as remarked in the summary, a deleterious effect on reflux clearance via reduction of saliva-mediated neutralization might be expected. In our study, however, baclofen had no significant effect on mean seconds to acid clearance (150 vs. 84, P > 0.05) and volume clearance (17 vs. 22, P > 0.05) when compared with placebo. This observation is supported by a study reported only in abstract form, in which the mean duration of acid reflux episodes was unchanged by baclofen in 6 adult dogs undergoing 24-hour pHmetry on medication and placebo (Gastroenterology 2001;120:A431). Our study is limited to the postprandial period, carefully controlled refluxogenic conditions, and a single dose of baclofen. Further studies are needed to clarify the role of baclofen or other GABA B agonists in the treatment of GERD over prolonged periods of time, whether alone or as an adjunct to acid suppression.