PsychEducation.org (home)
valproate (Depakote)
(Updated 11/2007)
[The following is my original handout for Depakote, with a few updates. The language might sound different here as it was written before the development of this website. JP]
Depakote
was originally developed as an anti-seizure medication.
In the last 2-3 years we have found that it also affects mood.
Like other “mood stabilizers”, Depakote can prevent large or
rapid changes in mood. It does
not seem to have any effect on day to day mood changes, only “cyclic”
or unprovoked changes. It also
has powerful effects on anxiety, agitation, insomnia, panic symptoms, and
anger.
How
much do I take?
For most people it takes at least 1 gram per day to work.
Each milligram of this medication doesn’t have much “oomph”
so it takes a lot of them. This
is actually about half the dose of Depakote commonly used for seizure
control, though. As a result,
at “mood stabilizing” doses, many people have no side effects, or very
minor ones. “Low dose” is
1000mg; medium is 1500, high is 2000-3000 mg.
What
are the common side effects?
Most people get no side effects at all at
low doses. But weight gain is a big problem at higher doses.
See “preventing weight gain” below on how to keep that from
happening to you.
Some people get nausea when they first start Depakote.
This can be reduced by taking the pills with meals at first.
The “extended release” (ER) versions seem to cause nausea even
less often.
People sometimes notice
more hair at the bottom of the shower after they wash their hair,
especially if their hair is long. Actual
“hair loss” (which you might see on the pharmacist’s handout) is
sometimes a problem at higher doses, but only very rarely an issue at
“mood stabilizing” doses, and usually we will have considered
switching because of weight gain by that time.
Taking a multi-vitamin with selenium and zinc (e.g. “Centrum
Silver”) can prevent this problem for some people. Update
10/06: one mother wrote in to say that her daughter stopped losing hair
after using a prenatal vitamin daily. This might be a little cheaper if it
works for you. Thanks Ms. L.
Too high a dose causes a “spacey”, foggy feeling; a mild
but constant headache; and occasionally mild blurring of vision.
If you notice these, move your dose down one pill and continue that
dose until your next appointment.
Are
there any serious side effects?
Though there have been deaths due liver failure, the patients
were generally less than 2 years old, and were taking other
anti-seizure medications. In
adults, on Depakote only, the rate of liver problems is the same as it is
in those not taking any medications at all.
There have been reported cases of pancreatitis from Depakote also,
but this too is very rare.
If your first blood tests are ok, current practice
does not require repeat blood tests. If
you find you are bruising or bleeding easily, or if you have nausea and
vomiting after you’ve been used to Depakote for weeks, call for
instructions.
What
about pregnancy?
This medication can definitely cause abnormalities in all trimesters of
pregnancy. You must avoid a
pregnancy while taking it. Tell
your doctor how you will avoid becoming pregnant.
Weight gain is very common at medium or high doses,
but not common at 1000mg or less.
Fortunately, it does not “sneak up” on you.
You will notice a huge increase in appetite first.
You want to eat frequently, eat a lot, and even feel hungry just
after eating.
Fortunately again, the appetite increase is like a
light switch: it’s either “on”, or “off”.
If you notice your appetite go up, then move the dose down, you
will almost always find a lower dose that does not produce this effect.
As you lower the dose, the “switch” goes “off” for almost
everyone (rarely, some just have to stop).
Recently the makers of Depakote produced an extremely
slow release version of their pills they believe causes less trouble with
this unusual appetite increase, and thus does not cause weight gain.
If Depakote ER is available to you, use it.
People
can get their dose higher with this version than the older one, in most
cases, and it doesn't cost anymore.
[Update 2007, regarding the old and the new versions: switching back and forth between the old DR pill and the new ER pill is not a good idea. They do not produce the same dose, even though both might say "500 mg". On the other hand, with the DR version, someone can have a peak blood level of 80 (the units don't matter, but if you must know, they are micrograms/milliliter) after the dose, and a trough level of 40 12 hours later, and get perfect symptom control. The one-day how-much-is-in-your-bloodstream curves for the ER and the DR version are pretty similar, except for a much lower initial peak with the DR version. Although the ER thus has a lower average concentration over 24 hours, the net result is close enough that I usually switch one pill version for the other without changing the dose. However, to be more precise about maintaining a given blood level, when switching from DR to ER, one should add 500 mg Davis.
How
do I start?
A)
Depakote 500 mg ER
One per night to start; then 2 per night; then 3 per night.
You can increase daily if your symptoms are severe.
But if you can afford to go a bit slower, you can then evaluate
what each dose level does for you, and stop at the lowest possible dose.
In that case, you should increase as slowly as every 4 to even
every 7 days (there is probably not much benefit in going any slower than
that). Stop at the
lowest does that controls your symptoms; go back to a lower dose if you
have side effects that are not decreasing quickly.
B)
Depakote 250 mg regular tablets
This form requires both a morning and evening dose.
Increase by 1 pill per day from 1 in the morning and 1 in the
evening, each taken with meals at first.
As soon as it is clear that nausea is not a problem, you may take
the pills at the most convenient times (not necessarily with meals).
Add a pill to the evening dose, then the morning, then the evening
again, as you go up.
Increase every 3-7 days until you’re clearly responding (continue that
dose); or get a side effect (decrease until the side effect goes away and
contact your doctor for a new plan). The
highest you can go before seeing your doctor is 1500mg (3 pills a.m., and
3 pills p.m.).
Does
Depakote interact with other medications?
Depakote itself does not cause major interaction problems.
Other medications may bump Depakote off of its riding place in the
blood (protein molecules) and raise the amount of Depakote that actually
affects your cells. So if you
start taking another medicine after Depakote and get new side effects, it
could be Depakote side effects caused by this interaction.
Moderate doses of aspirin
can do this, so use Tylenol instead.
Most of these interactions do not pose any threat to you; most
likely would be an increase in side effects from Depakote or from the
other medication.
Is
this addictive?
There is no “addiction”: if you stop, there is no
“craving”. You might just
get your old symptoms back. Because
Depakote is an anti-seizure medication, though, it is best not to stop it
suddenly. In theory, a sudden
stop can cause a seizure. In
practice, we have not seen this happen, but just to be safe, do not let
yourself run out of this medication. If
you are going to stop, do so by gradually lowering the dose, one pill at a
time, over a week.
Update 2005: How rare are the liver and pancreas problems with valproate? Here is a stab at "quantifying" -- putting in numbers -- these risks, although the numbers are small enough that most people will have difficulty, I think, getting a realistic feel for how much risk they represent.
1. About liver
In a review of 35 years of experience using valproate (Depakote is one
version), it was noted that severe liver problems with Depakote occur
"with an overall incidence of 1 in 20,000, but a frequency as high as
1 in 600 or 1 in 800 in high-risk groups such as infants below 2 years of
age receiving anticonvulsant polytherapy."Perucca
Although Depakote has its problems, a
high risk of causing severe liver problems (unless taking an additional
antiseizure medication, which risperidone and clonidine are not) is not
among them. A rate of 1/20,000 is pretty close to the rate for the
general population not taking any medications.
However, it can cause an increase in liver enzyme levels that indicate some liver dissatisfaction with Depakote but are not necessarily a marker for the severe version. Nevertheless, when we see that increase in liver enzyme levels in a blood test, indicating that some liver cells are being injured, we often watch to see that this is really going to turn out to be a problem, if the increase is small -- say, up to twice normal levels of those enzymes, and some doctors say up to three times normal levels is okay. That might sound like a lot, but where the average upper limit of normal for these tests is around 35 in most labs (and thus "three times normal" would be about 100), alcohol can cause these numbers to go up to 300-400, and some forms of viral hepatitis can cause it to go much higher. I saw a patient with enzymes around 1,000 once. So up to "three times normal" is not much and not a cause of any lasting liver damage unless we leave it that way. Just "watching", for few weeks or a month, then repeating the test, is a routine thing to do. Sounds like that's what your son's doc' was doing.
2. . About pancreas
I've had difficulty nailing down a similar number for the rate of pancreas
problems with Depakote (is it higher than the 1/20,000 figure above, for
example?) An article in 2001 noted that there were 40 reported cases in
the world (reported in English).Taira
I'm not sure how many patients in the world have taken valproate. But I'll
bet that comes to a risk figure quite a bit lower than the liver risk
rate.
Update 2006: an international team of investigators searched specifically for a connection between using valproate and having pancreas problems.Norgaard They found a small increase in risk compared to never-users, but this was not higher than for other anti-seizure medications, nor was it higher than for people who had used but were no longer using valproate. They concluded that these results were not consistent with valproate as a risk factor for pancreatitis.
Update 2007: a German team found 16 cases in 10 years, in Germany alone.Gerstner This suggests that the rate of pancreatitis associated with valproate is higher than previous studies might have suggested, but still extremely uncommon.