Hello P Bernstein,
One of the best places to start looking for information is in the drug
information section of Medline Plus at the National Library of
Medicine web site (www.nlm.nih.gov, click on Medline Plus). If you go
through the alphabetical listings and select Depakote, you are given
links to two information pages about valproic acid, which is formed
in the body by Depakote (divalproex) and which is the active substance
of the medication. Thus, for further research, you may find it useful
to use “valproic acid” and divalproex as well as Depakote in your
search terms.
The page on valproic acid at
http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682412.html
states that “Valproic acid can also cause life-threatening
inflammation of the pancreas. If you experience any of the following
symptoms, call your doctor immediately: recurring seizures after they
have been controlled by medication, stomach pain, upset stomach,
recurring seizures, loss of appetite, vomiting, dark urine, weakness,
tiredness, lack of energy, facial swelling, and yellowing of the skin
or eyes” This information has been synthesized from studies and also
from postmarket surveillance reports on the drug.
However, if you do want specific studies, the best resource is once
again at the NLM site, namely the Medline database. Searching on
divalproex AND pancreatitis gave me 63 references (“valproic acid” AND
pancreatitis gave 75 references). Limiting these to human studies
only, in English and available with a summary, gave 31 references
(this is a useful way to cut down on an excessive number of hits in
Medline). Due to the setup of the Medline site, it is not possible to
give you a URL for the search results themselves. If you wish to view
the complete search, you will need to repeat the procedure yourself.
However, the most pertinent studies, in terms of the information they
provide, include the following three studies for which I have
summarized the main findings.
1. Surgery Today 2001;31(11): pp1027-31
Pancreatitis induced by valproic acid: report of a case.
Taira N, Nishi H, Mano M, Waki N, Tsugita Y, Takashima S, Fukuda K,
Komatsubara S.
Department of Surgery, Okayama Rousai Hospital, Japan.
A case of chronic pancreatitis in a 22-yr-old woman who had been
prescribed valproic acid for 19 years. The authors comment that only
40 cases have been reported in the "English literature" of
pancreatitis developing in association with the use of valproic acid.
Most of the patients described in previous studies showed initial
stages of acute pancreatitis. The say that "However, the clinical
course of our patient, with acute exacerbation following a relatively
chronic course, was different from those previously described,
suggesting the presence of chronic pancreatitis related to valproic
acid.”
2. Pharmacotherapy 2001 Dec;21(12): pp,1549-60
Pancreatitis associated with valproic acid: a review of the
literature.
Chapman SA, Wacksman GP, Patterson BD.
College of Pharmacy, North Dakota State University, Fargo 58105, USA.
The authors report “Since 1979, case reports of pancreatitis induced
by valproic acid have been published in the medical literature. As a
result, pancreatitis was added to the black box warnings for valproic
acid. We performed searches of MEDLINE and International
Pharmaceutical Abstracts and found valproic acid-induced pancreatitis
in 45 patients from 31 published articles.” The article includes
descriptions of patients, accounts of the outcomes and recommendations
for how to monitor in patients the potential to develop pancreatitis.
Unfortunately, these are not summarized in the abstract, so if you are
interested, you would need to ask a library to obtain a copy of the
paper for you, or alternatively use one of the paid-for services such
as Infotrieve http://www.infotrieve.com/ to obtain a copy (you can
also do free Medline searches on Infotrieve’s site).
3. Epilepsia 1993 Jan-Feb;34(1): pp. 177-83
Valproate-associated pancreatitis.
Asconape JJ, Penry JK, Dreifuss FE, Riela A, Mirza W.
Department of Neurology, Bowman Gray School of Medicine, Wake Forest
University, Winston Salem, North Carolina 27157-1078.
This paper has some interesting results from a survey of physicians,
the clinical experience of the authors, and a literature survey. “Of
366 physicians answering the survey, 53 (14.5%) reported a case of
pancreatitis [in patients treated with valproate, ie salts of valproic
acid]… …Pancreatitis appeared to be more frequent in young persons
(mean age 16.4 years) but may occur at any age. The highest risk
appears to exist during the first months of treatment: 43.8% of the
cases developed during the first 3 months, and 68.8% developed during
the first year… …In most patients, the reaction was rapidly reversible
when valproate was discontinued…. Rechallenge with valproate was
attempted in 9 patients, with a high incidence of relapses.
Asymptomatic elevation of serum amylase in patients receiving
valproate was reported by 40 (10.9%) of the physicians surveyed.”
I think that these three papers summarize very well the current
knowledge on this topic. The other articles I retrieved tend to focus
on specific categories of patient, eg children, dialysis patients, or
they are quite old and therefore summarized in my references (2) and
(3). However, if you do want a fuller listing of the articles
retrieved on Medline, please use the clarification facility to request
this.
Thank you to politicalguru for comments on my expertise. I would like
to stress, however, that I am NOT a medical practitioner and cannot
give medical advice as such. I am a biomedical scientist (PhD) and a
qualified library and information specialist, and therefore have some
knowledge of how to search the medical literature and the Internet,
and also how to analyse the results obtained through such searches. |
