US Brand Name: Depakote
Other Brand Names: Epival (Canada), Valcote (Colombia, Peru)
Generic Name: divalproex sodium

Other Forms: Extended-release tablets

Class: Anticonvulsants, specifically a valproate
Read up on these sections if you haven’t done so already, because they cover a lot of information about multiple medications that I’m not going to repeat on many pages.  I’m just autistic that way about not repeating myself.

Depakote’s FDA Approved Uses: Epilepsy: Monotherapy (used by itself) and adjunctive treatment (i.e. you must use another drug along with it) for a variety of epileptic seizures. These include complex partial seizures and absence seizures. Depakote is approved for use with epilepsy for adults and children aged 10 and up. An example of a simple partial seizure is when you’re still conscious and one limb goes completely nuts on you.   Complex partial seizures can mimic various forms for bipolar and psychotic flip-outs.  They’re freaky, believe me. An absence seizure is when you just “go away” for a period of time and you may or may not experience missing time. That is also freaky if you’re ever aware of or witness the damn things.

Depakote is approved to treat bipolar mania and migraines. There’s no mention of kids for either of these ailments, so I presume it’s officially adults-only.

Depakote’s Off-Label Uses: Treatment for types of Epilepsy not listed (e.g. tonic-clonic seizures – here’s one study showing it effective in that regard, and one showing that Dilantin (phenytonin) is better.), Borderline Personality Disorder (see also this study), PTSD, OCD, Alcohol (see also this study), Cocaine & other Drug Dependencies, Anxiety (mostly anecdotal evidence and animal studies, no good human studies), PMS, Sleep Disorders (including Restless Leg & PLMD), Schizophrenia and Schizoaffective Disorder, and Alzheimer’s-related
Depakote’s pros and cons:
Pros: Proven to be effective for wide spectra of epileptic and bipolar disorders. It’s been around for so long that the long-term effects are well known and well documented. If you can get past the initial side effects and get used to a valproate medication, you don’t have to worry about anything biting your ass in the long run.

Cons: The side effects suck donkey dong! The valproates are amongst the harshest meds to take. Everyone hates them so much that they’ve given the entire class of anticonvulsants a bad name.

Depakote’s Typical Side Effects: The usual for anticonvulsants plus a special set for valproates: instant old age. You’ll get fat, bald, tired, confused, uninterested in sex, unable to hold your liquor and everything will give you heartburn and/or the runs.

For tips on how to cope with these side effects, please see our side effects page.

Depakote’s Not So Common Side Effects: Edema. Being more prone to respiratory infections. Getting a ringing in your ears.

These may or may not happen to you don’t, so don’t be surprised one way or the other.

Depakote’s Freaky Rare Side Effects: Flesh eating virus! It was all of two cases in the whole wide world and there were extenuating circumstances, so it was in no way Depakote’s fault, but the law is the law when it comes to reporting these things. No, really, Depakote (divalproex sodium) had nothing to do with it. The unfortunate people who contracted toxic epidermal necrosis (Which isn’t a virus, I just like how “Flesh eating virus!” reads. Besides, only bacteria eat flesh. Flesh eating viruses don’t exist, but flesh eating bacteria do.) were probably doomed to get it anyway, and they just happened to be taking Depakote as well. Also breast enlargement (some people will complain about anything), irreversible deafness (ouch!) and bone pain. I told you you’d get instantly old.

You aren’t going to get these. I promise.

Interesting Stuff Your Doctor Probably Won’t Tell You: Taking Depakote (divalproex sodium) with food helps reduce a lot of the gastrointestinal problems. In fact the sprinkles capsule is designed to be opened up and mixed in with stuff like “applesauce or pudding”. So if the extended release tablets don’t help with the GI issues, you might try literally mixing the sprinkles with food. Abbott states in the PI sheet that absorption may vary with formulation (i.e. Depakote (divalproex sodium) vs. Depakene (valproic acid) or Depacon (valproate sodium)) or if taken with food or not, but that it shouldn’t really matter. This is opposed to the Topamax sprinkles (topiramate), which were designed for caregivers to slip to people unable or unwilling to take pills. That’s not so blatant on the PI sheet Ortho-McNeil publishes online now, but one I have shows you how to open up the capsule and mix it into food so it’s nice and hidden and somebody doesn’t know they’re taking their medicine.

Depakote (divalproex sodium) interacts with aspirin. Aspirin prevents you from metabolizing Depakote properly, so you’re better off with ibuprofen.

Your doctor had better damn well be telling you about the regular blood work you need, to check your valproate levels and to make sure your liver is functioning normally.

Depakote’s Dosage and How to Take Depakote: Depakote, like lithium, is all about blood levels. It’s also about which FDA-approved ailment we’re discussing. As always, I’m going to mainly cover the adult dosages, as pediatrics is just way too tricky and outside of our experience.
Bipolar disorder – Abbott recommends starting at 750mg a day divided into two doses. I would think that with a 9 to 16-hour half-life three times a day dosing could be useful, and there is a study to back that up. Abbott is all about ramping the dosage up “as rapidly as possible” until you either get the desired clinical effect or you reach the sweet spot of the blood plasma level – somewhere between 50 and 125. They expect you to do that within 14 days and damn any GI trouble you might be having.

What do they think we are crazy or something?

Then, get this, the maximum recommended dosage is 60mg/kg/day. What does that mean? It means if you weigh 150 pounds your doctor could keep upping your dosage to 4,000mg a day if you’re still flipping out! After just two weeks!

That, friends, is crazy.

And we’re not the only ones who think so. Once again there’s a study that indicates Depakote is at least as effective as lithium and Zyprexa at controlling mania when started at 750mg a day. But it’s taken three times a day, the titration is slower, the blood level is between 40 and 150 and the maximum dosage is 750mg plus 20mg/kg/day. Thus the maximum dosage for someone weighing in at 150 pounds would be a much more reasonable 2,000mg a day.

In a big, long study comparing Zyprexa to Depakote, Zyprexa tested somewhat better. But, hey, guess what? That was an Eli Lilly study, so there’s no surprise there. But look at the numbers for Depakote. In my readings of the PI sheets of Lilly products and studies done by Lilly researchers I’ve noticed one thing, they are totally on the ball when it comes to pharmacokinetics and how drugs hit your liver. And here we have people taking 500mg of Depakote and it was effective! They also topped off at a rather sane maximum dosage of 2,500mg a day. Once again my hat is off to the Eli Lilly researchers.

Another study of cyclothymia, PMS and schizoaffective disorder had people taking 125 to 500mg a day and achieving a positive effect. Note, it states, “there may be a correlation between the severity of bipolar disorder and the blood level of valproate required for stabilization such that milder forms of bipolar cycling require lower doses of valproate.” We’ll give them that.

But just from the point of a starting dosage, beginning with 500mg a day, or even lower, at three times a day seems to be the way to start Depakote. From what I’ve read in the support groups the people whose doctors prescribe it that way bitch about the side effects a lot less. A least some doctors are reading the studies or these data are making it to conferences.

For epilepsy the initial dosage is based on your weight. Why the hell not? Personally I think that’s better than just throwing 750mg a day at someone and ramping up drastically like they recommend for the bipolar. While weight isn’t always a good factor at determining how burly your liver is (I could drink bigger men than I under the table), until tests of liver enzyme functions are more widely available, it’s as good a guess as any. So you start at 10 to 15mg/kg/day. So for that 150-pound person that’s between 650 and 1,000mg a day. Abbott is all about taking it two times a day. The only study I’ve found that suggests a three-times-a-day dosing schedule for epilepsy was comparing immediate release to extended release. I haven’t found anything regarding starting at a lower dosage for epilepsy in adults to deal with the side effects. I guess this is a case of what sucks less, seizures or side effects? I haven’t been reading the epilepsy support groups, so I don’t know if there’s any anecdotal evidence to support starting at a lower dosage either.

Anyway, after that you can up the dosage by 5-10mg/kg/day until the seizures abate or you max out at 60mg/kg/day or you reach the sweet spot of blood levels between 50 & 100.

For migraines you start at 250mg taken twice a day (hey, it’s the minimum 500mg a day that seems to work). After that you can move up to 750mg a day then 1,000mg a day. Clinical trials don’t support dosages higher than that and I haven’t researched migraines.

For everything else, it’s up to your doctor and whatever studies your doctor is following.

Days to Reach a Steady State: Depakote’s non-linear. So that’s why it’s good for borderline personality disorder! Anyway, that means you can’t pin down a hard number on it. I haven’t found a number for it in any study.

When you’re fully saturated with the medication and less prone to peaks and valleys of effects. You still might have peaks of effect after taking many meds, but with a lot of the meds you’ll have fewer valleys after this point. In theory anyway.

How Long Depakote Takes to Work: In theory you should start feeling results once you’re in the therapeutic range of your blood levels. So for epilepsy that’s generally in the neighborhood of 50-100, and for bipolar it’s a wider range of 40-150. Getting to that blood level is between you and your liver. Once there it’s up to your brain if it’s going to respond to a valproate or not. So unlike most anticonvulsants where you feel something in a matter of days, or there’s a definite dosage where we can write, “here is where you should notice effect or not,” it’s just not like that with the valproates. So once you’re there, here’s a study with PET scans indicating 2-6 weeks to start feeling something.

Depakote’s Half-Life & Average Time to Clear Out of Your System: 9-16 hours. It’s out of your system in 2-3 days.

How to Stop Taking Depakote: Your doctor should be recommending that you reduce your dosage by however much you increased it (keep good records about that!) a day every two to three days at the quickest, based on the 9-16 hour half-life. But it’ll probably be slowly than that, with at least one blood level thrown in for shits & grins. For more information, please see the page on how to safely stop taking these crazy meds.

Like any anticonvulsant, if you’ve been taking Depakote for more than a couple months and you’ve reached the therapeutic blood levels, you just can’t stop cold turkey if you’re not at the therapeutic dosage for another anticonvulsant that is known to work for you, otherwise you risk partial onset or absence seizures to tonic-clonic grand mals, even if you’ve never had a seizure disorder before! The risk is worse if you’re taking a lithium variant, and/or any antidepressant, especially Wellbutrin (bupropion). Anyone with a history of a seizure disorder who needs to stop taking an anticonvulsant cold turkey needs to be discussing that with two neurologists and not getting your information from some stupid web site. Get off your computer and start making appointments!

If you’ve worked your way up to a particular dosage, it’s usually best to spend this many days at the next lowest dosage before going down the next lowest dosage before that and so forth. This is the least sucky way to avoid problems when stopping any psychiatric medication. Presuming you have the option of slowly tapering off them.

Comments: Be sure to read the sections on anticonvulsants and valproate drugs if you haven’t done so already.
Known as Depabloat for its weight-gain effect, the harsh side effects of all members of the valproate family have given a bad name to all anticonvulsants. The thing is most of the side effects common to valproates aren’t as bad with Depakote (divalproex sodium), especially the weight gain. While some of these side effects may be countered by slower titration and three-times-a-day dosing, Depakote (divalproex sodium) is not always an easy medication to take. Which is too bad, because it is quite effective when it comes to things like generic Bipolar 1, mixed states, mild to severe rapid cycling and generally the broad spectrum of bipolar disorder. Although as pointed out in the previous review and other studies, Depakote (divalproex sodium) usually sucks when it comes to bipolar depression. And if you’ve got rapid cycling combined with Bipolar 2, Lamictal (lamotrigine) is the drug for you. Oh, and if you’ve got ultradian rapid cycling like I have, where you can switch moods several times a day (or an hour as I have), then Topamax (topiramate) is the drug you should evaluate. Bipolar users who’ve been through a few meds report that brand name Depakote ER typically causes less weight gain and gastrointestinal effects than lithium and certainly less weight gain than Zyprexa (olanzapine). Especially if a slow titration and three or four times a day dosing is used. The bad rap Depakote gets for weight gain most likely comes from people taking generic valproic acid and being told that it’s the generic for Depakote (divalproex sodium), when it’s not. Currently there is no generic available for Depakote (divalproex sodium) in the US; you can only get the generic in Canada.

Depakote (divalproex sodium) is even effective for truly oddball stuff, as this case study illustrates. It quelled the rare case of a man on a strict 48-hour bipolar cycle. Manic one day, depressed the next, like clockwork. He experienced complete remission after four weeks of treatment at 1,800mg a day with the help of a SPECT scan to aid in his diagnosis.

If you’re on Medicaid, getting charity treatment or even with an HMO you might be told you’re getting Depakote (divalproex sodium), but look carefully at the prescription. The odds are it’s for valproic acid. That’s generic Depakene. By the time it gets to your brain it’s the same thing, but the road for generic valproic acid is much rockier than that of brand name Depakote(divalproex sodium), and you’ll probably experience far more side effects than you would with actual Depakote ER.

As for dealing with those awful side effects:
Depakote (divalproex sodium) has been tested with every known antacid, because, you know, Depakote (divalproex sodium) messes with your stomach so much. At least you can take antacids and Depakote together. Just don’t use Alka-Seltzer, as that has aspirin, and you don’t want to mix aspirin and valproates.
I had hoped to provide all y’all with something to give you some hope on the hair-loss front. Sorry. Nutritional supplements usually don’t do squat for hair loss. There was one letter published in an obscure journal which may state just the opposite when it comes to Depakote (divalproex sodium), but it’s not online so I don’t have a clue. Here’s the cite if you want to dig it up yourself.
For the lethargy, like all anticonvulsants the only safe thing to counter it seems to be Provigil (modafinil). Everything else is just too likely to trigger either mania or seizures.
Beta blockers like Inderal (propranolol) have been used to counter the tremors associated with lithium. I haven’t seen a reference to their being used with valproates.
The weight gain is going to suck. Diet and exercise are going to do only so much, and everyone is going to give you shit about how lazy and weak-willed you are for gaining weight when it’s the pills that are causing the weight gain! Yet every pill out there that can counter that weight gain is most likely a no-no. Diet pills that work will trigger seizures and/or manias. Anticonvulsants with weight loss as a side effect such as Topamax (topiramate) or Zonegran (zonisamide) may be inappropriate for you and make you worse, not better. There are some wacky alternatives thought that may work out. They are a bit strange, and will require careful consultation with your doctor. They are also unlikely to be covered by any form of insurance.
The anti-Alzheimer’s medications Exelon (rivastigmaine tartrate) and Aricept (donepezil hydrochloride). You need take one or the other. These are a two-fer, as they help deal with the memory issues and fuzzy-headedness that come with anticonvulsants. They also frequently cause weight loss. Like Zonegran (zonisamide) this happens more often for women than men. Go figure.
Symmetrel is an antiviral and anti-Parinkson’s medication. There was one small study done on its effects reversing the weight gain caused by Zyprexa. While it may not help with any cognitive issues, at least it has a study backing it up that it doesn’t fuck up the benefits of a psychiatric med. I’ll keep all y’all posted if I find out any more about this med and the whole weight issue in general on a separate article about weight and meds.
There’s not much that I know of that you can do for your liver. Oh sure, there’s that wonderful milk thistle (silymarin) and the amino acid NAC. There are just two big problems with those:
Like any supplements you don’t know if you’re getting the real thing or not.
When you do get the real thing, they work. They work too well. Milk thistle extract has been used to save people who have eaten the wrong type of amanita mushroom. So what does that mean to someone taking a med like Depakote that is heavily processed by your liver? It means that the milk thistle and NAC flush the Depakote out of your liver before it gets metabolized! So, yeah, your liver gets cleaned out all right, and your Depakote doesn’t work! There has been one double-blind study involving silymarin and Haldol [1] indicating that, yeah, the milk thistle helped prevent liver toxicity, but at what cost to the efficacy of the psychiatric meds? The doctor who is treating me for environmental sensitivities who had me taking the milk thistle and NAC advised me to stop when I began a course of psychiatric meds, otherwise I’d just have to take more meds, and that would be counterproductive.


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