Reference: Parkman,
H.P., et al., Clinical response and side
effects of metoclopramide: associations with clinical, demographic, and
pharmacogenetic parameters. J Clin Gastroenterol, 2012. 46(6): p. 494-503
A study out from Temple
on the side effects of metoclopramide.
Brief Summary: Gastroperesis is a disorder indicative of slow
stomach emptying during digestion and is often associated with diabates. A common drug prescribed for this condition
is metoclopramide – an antiemetic drug effective against nausea and vommitting. The main aim of this study was to determine
the factors which are associated with response vs. no-response and side effects
vs. no side effects with the use of metoclopramide. 100 patients from a hospital near Philadephia
were accrued into the study, and clinical features were recorded including age,
dosage, etiology (diabetes or no-diabetes) and genotype testing for a number of
various genes though to implicate in the main find.
Results: The patients who responsed were older and had a
heavier body mass index. Genetic
polymorphisms in KCNH2 and DRA1D genes were associated with clinical response. The patients who hads side effects to
metoclopramide tended to be nondiabetic with normal gastric emptying. Genetic polymorphsisms occurred in CYP2D6,
KCNH2, and 5-HT4 receptor HTR4 genes.
Some of the side affects were very severe.
Implications for
Practice: Since some of the side
effects were severe, gastroenterologists should be very wary of prescribing metoclopramide
to nondiabetic patients. For these
non-diabetic patients, if genetic testing can be under-done, it may be very
helpful in determing the effectiveness of metoclopramide.
Discussion: Really good paper here, and I had a really fun time
reading it. These types of studies are
important in order to determine the effectiveness of various metabolic drugs. I am glad to see that the authors included
the genotype variables. Furthermore, I
really liked how the authors went in depth in the discussion section on the
various genes which were under investigation and the potential biological
mechanism at play.
Also, at the beginning
of the discussion section, it was good to see that the authors included a brief
section on the implications for practice in Gastroenterology. This is always
important and something that many authors do not do.
Overall, just a very
well investigated and written paper with
very interesting finds which every Gastroenterologist who prescribes metoclopramide
should know really.
Commentary on Statistics
and Study Design: My
biggest suggestion has to with the absense of any multi-variate analysis, which
should always be done in any type of risk factor study. The authors only included a uni-variate
(un-corrected) analysis, but it would also would have been helpful to conduct a
multi-variate (corrected) analysis with logistic regression using either a
forward or backward stepwise regression approach. Doing this, the authors could have presented
a set of clinical factors which were most associated with the outcome variable:
having a positive response. For
instance, it may be that one of the clinical factors (body mass index) is not
associated with the outcome variable (response vs. no-response) while
controlling for one of the genes. Due to
the very large number of genes, it probably would not have been possible to
include all of the genetic factors at once, but you could test just a
sub-sample at a time. You always want to
conduct this type of multi-variate analysis, and report both the uni-variate
and multi-variate results.
Also, in the statistical
analysis section, it seems as if three separate statistical techniques were
used (Fisher’s Exact Test, ANOVA, and uni-varite logistic regression); however,
it seems as if the entire paper could have been performed with just the logistic
regression. I don’t even see any of the
results for the ANOVA analysis. I’m not
too sure here. It would have been helpful if the name of the statistical test
used was under the tables. This could be
very helpful.
Overall, a good
investigation. Thanks to our buddies at Temple for doing this!
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