US Brand Name: Keppra

Generic Name: levetiracetam

Other Forms: grape flavored suspension. (Yummy?  Icky?  We honestly don’t know.)Class: Anticonvulsant.
Read the section on this link for common effects and side effects for the entire class.

Keppra’s FDA Approved Uses: Adjunctive therapy for partial epilepsy in adults and children over 4 years.  Approved November, 1999.

Keppra’s Off-Label Uses:  Boy do we have off label uses! Partial epilepsy monotherapy.
Generalized epilepsies, including:
post hypoxic and post encephalic myoclonus;
negative myoclonus;
idiopathic (i.e. you were born with it) myoclonic, tonic-clonic and/or absence seizures;
absence seizures;
and the dreaded Lennox-Gastaut syndrome.  With a 50% to 100% reduction of certain seizure types along with an increase in the kids’ alertness.  Talk about win-win!
Keppra has been successfully used for Landau-Kleffner syndrome.
It’s also used for seizures and other damage caused by traumatic brain injury.

For bipolar disorder Keppra’s best used to deal with the most extreme, out-of-control manias you have around.  Either as an add-on medication, or all by itself.  One of Keppra’s best features is that if you stop taking it, either because you were crazy and thought you were cured, or because your manias are seasonal and you don’t need a potent anti-manic certain times of the year, it tends to work just as well if you stop it and restart it.

Migraines, both in adults and kids.

Neuropathic pain.

Used as an adjunctive analgesic, along with traditional opiods, in neoplastic plexopathies-not like I have any idea what that is, other than it hurts a lot and it’s involved with cancer.

Autism. Good by itself for mood stability and the ADD/ADHD related symptoms of inattention, hyperkinesis, and impulsivity. Better as an add-on for aggression.

Social anxiety.

Other anxiety disorders, and cognitive disorders, especially in old folks.

Tardive Dyskinesia.

Essential tremor – unfortunately the studies find it to be ineffective. No better than placebo. Didn’t do much. Didn’t last long and few details in the abstract.

And like all anticonvulsants, it’s being tested as a means to get clean when hooked on other drugs. It showed promise in benzodiazepine withdrawal anxiety in mice, although mice aren’t people.
Follow the links for the studies supporting or refuting the off-label claims.

Keppra’s pros and cons:
Pros: LOW side effect profile. Much less chance of your flipping out on it when compared to other anticonvulsants (E.g. Keppra: 10% of epileptics with previous histories of psychiatric or serious epileptic flippage had issues. Topamax: 24% of similar people had issues.) Tends to make people smarter, not dumber like most anticonvulsants. Even people starting with learning disabilities can get a bit of a boost. Also, unlike many anticonvulsants it’s so easy on your liver you can take it after a freaking liver transplant! It starts working right away, and many people can start at or near the therapeutic dose if required-it was designed that way. One researcher describes it as having, “close to ideal pharmacokinetic properties.”

Cons: A lot of the side effects it DOES have are psychiatric. Reports from the field (a.k.a. anecdotal evidence) suggest the most common are the deep, sometimes suicidal depression. Another favorite is the Keppra rage. Far less frequent, but still reported, are hallucinations – one woman I know with epilepsy had deep philosophical conversations with a ghost every night. And there’s this case report of a kid getting a bit psychotic on Keppra. Those kind of suck-especially when no one bothers to warn you that they might happen.

Keppra’s (levetiracetam) Side Effects

These aren’t all of the potential side effects, folks!  These are just the typical and the notable ones.  For all side effects you have to read the PI sheets and the drug class’. So you can stop sending me all the e-mails about how I missed one.  Really.  The odds are I didn’t miss anything.

You should check out the side effects page for tips on dealing with side effects that are common to all meds.  Also note that, except in very rare cases, side effects will go away when you stop taking the medication in question.  Eventually.  Usually after a medication clears out of your system.  But sometimes it takes longer.

Keppra’s Common Side Effects: Sleepiness-which could be feature-not-bug and tends to wear off. Headache. Various kinds of infections-rhinitis, pharyngitis, sinusitis, and NOS nose stuff. Dizziness/vertigo. Muscle weakness. Any or all of these can be permanent or go away with time.

Keppra’s Not-so-common Side Effects: The mood problems-depression, psychosis, hostility, anxiety in various forms (I know, it’s supposed to be good for anxiety. But yet…drugs are weird…). Appetite changes one way or another. Paresthesia, aka that fun tingling in your extremities.

Keppra’s Freaky Rare Side Effects: Peace-Love-and-Fluffy-Bunnies-Not-Manic-Just-Happy! Ok, so Kassiane is the only one who got that for very long. Fungal infection. Gingivitis. The personal hygiene supply companies have a BIG market with people takinganticonvulsants.

Keppra’s Suicide Risk: All meds have a suicide risk. And Keppra can make people damn depressed. 0.5% in trials attempted vs 0% on placebo. One succeeded. They had been on Keppra between 4 weeks and 6 months at the time of their suicide attempts.

Keppra and Weight Gain: In clinical trials, placebo made more people fat than Keppra did. Loss of appetite, it may as well be noted, occurred more with Keppra than with placebo.  A further study also concludes that Keppra is weight neutral.

Sexual Side Effects and Keppra: Not particularly. As we said-the side effect profile for Keppra is exquisitely LAME.

Keppra’s Pregnancy Risk: Still to be determined, and therefore class C. There is currently a Keppra pregnancy registry, as the company is collecting data.  In animal studies, Keppra caused minor skeletal abnormalities and small offspring—bear in mind, the doses they use tend to be, um, huge, but they do need to start somewhere. Four times the human maximum recommended dose didn’t have an effect on baby rats, for what that’s worth.   While concentrated heavily in the breast milk, it’s short half-life means the kids eliminate it quickly.  No abnormality in a nursing baby has been reported.
There is no interaction between Keppra and birth control pills.

Keppra’s Seizure Risk: Only if it’s the wrong med, or you take the dose too high. Keppra has a broad spectrum of antiepileptic efficacy-AKA it won’t fuck with you if you take it for the wrong kind of seizure, like Tegretol and Trileptal will if you take it for absences and atonics. It’s more likely to just not work at all than make things really BAD.

Interesting Stuff Your Doctor Probably Won’t Tell You: Keppra doesn’t mess with, like, ANYTHING.  In that it has practically no drug-drug interactions, a rare interaction with Tegretol is of most concern to the readers here. That in and of itself is pretty interesting. All the other super interesting stuff is really geeky and belongs on other pages.

Keppra’s (levetiracetam) Dosage, Discontinuation & Half-Life

What is Keppra’s Dosage: The normal dosage of Keppra is 1000-3000 mg a day. That is considered the therapeutic range for epilepsy. The drug company says you can start right in at 1000mgs, taken as 500mg twice daily, which is, as you can see, the bottom of the therapeutic range. One moderately-sized double-blind study even concludes you can start at 2000-4000mg a day if required. Even Dr. Faught in the edition of PeerView in Review on traditional and new antiepileptic drugs thinks thinks that Keppra can be titrated as stated, unlike any of the others (including Ortho-McNeil’s Topamax, the sponsor of the program).

Guess what? I disagree.

There is a REASON they make 250mg tablets, and there is a REASON they are so easy to cut in half! I don’t think most people need to start quite that low, but 500mg, taken as 250 twice a day, is reasonable to start if you’re not completely flipping out. That’s where the off-label bipolar studies show them starting, by the way. Then a 250mg step-up weekly, 125mg if it hits really hard. Not every 5 days, A WEEK. SEVEN DAYS. Those extra 2 days can make a big difference in getting used to a med. If less than traditional doses work for someone, then fine and wonderful. I am a big believer in the correct dose isn’t necessarily what the PI sheet says, it is the one that works.

Also with a half-life of only 6-8 hours, you may want to try taking it three times a day instead of two if you find yourself experiencing the Keppra irritability. Taking Keppra with food will delay Keppra’s peak availability by an average of an hour and a half, and can sometimes cut down on how much Keppra you absorb by up to 20%.

Overdosing on can suck, but it probably won’t kill you.

How Long Keppra Takes to Work: Not very. Like, as in two days not very. Even for refractory epilepsy Keppra can start working in one day.

How to STOP taking Keppra: Slowly, unless being on Keppra is sucking serious ass. And this is why I don’t like starting a med at a therapeutic dose. OK. End soapbox. Generally, the way you went up—was it in 250mg increments, 500mg increments? Please say it wasn’t in 1000mg increments. How you went up on Keppra is how you should go down from Keppra —500 to 250 every 5 to 7 days.

What is Keppra’s Half-life: 6-8 hours for average metabolizers.

Average Time to Keppra to Clear Out of Your System: 1-2 days. It goes in fast, it goes out fast.

Days to Reach a Steady State: Two days. Fast acting, this is.

Keppra’s Peak Time: One and one-half hours after you take it, expect it to REALLY hit, provided you have normal absorption and all. The drug itself is soaked up right away when you take it.

Keppra’s (levetiracetam) Effectiveness, Comparison with other Meds & Ratings

Odds of Keppra Working for Partial Epilepsy – Pretty damn good. 20-30% of patients with refractory epilepsy had 50% or greater reduction of weekly seizures in the approval trials. Seeing that we are looking at people who’ve failed multiple meds, and who have multiple seizures WEEKLY, those are decent odds. According to one support type site’s med listing, in the UK it’s what they try for partial epilepsy after you’ve failed a few meds.  Here’s a small, year-long study where two thirds of the people taking Keppra as monotherapy had as good or better seizure control than previous meds.  Here’s a big study showing it reducing seizures in the first day of treatment.  Keppra may be the drug of choice for late-onset partial seizures.  Geez, even if freaking epilepsy surgery fails,Keppra is the go-to drug.  “..and may have implications for its use before surgical intervention.”  Oh, thanks, doc!  Glad you thought about that beforehand!

Odds of Keppra working for Generalized Epilepsy – Looks good so far. We couldn’t find much in the way of trials or studies using Keppra as monotherapy in adults for generalized seizures.  Most of the time it’s using Keppra as on add-on, such as this one study of over 150 people where 40 people in it became seizure-free, with 25 of them on 1000mg a day or less.  We did find one for idiopathic (i.e. you were born with it) myoclonic, tonic-clonic and/or absence seizures where 42 out of 55 people had either a 50% more reduction in seizures, or became flat-out seizure-free.  As for case studies, they’re along the lines of  three people with refractory epilepsy becoming seizure free on Keppra monotherapy.  I found a single study for Lennox-Gastaut syndrome where out of 6 patients, 4 had 100% reduction in myoclonic seizures, 2 had 50% reduction in their atonic seizures, and 4 had 100% reduction in tonic-clonic seizures. That reads as fan-fucking-tastic to me.   Finally a woman with negative myoclonus has become seizure-free on Keppra. Go figure. It’s worked better for these people than for some of the people with partial epilepsy in the trials!

Odds of Keppra Working for Migraines – Chances are it’ll at least help. Oddly, it was easier to find studies on pediatric migraines. Large percentages (like, 2/3 large) are reporting reductions in number and/or severity. And of course they like the (lack of) side effect profile.

Odds of Keppra working for Neuropathic Pain – Looks promising. One study showed it working as an adjunct to help cancer patients reduce pain and opiates. Other small case studies show it as effective, too, but larger scale studies are elusive.

Odds of Keppra Working for Bipolar-Keppra will stop any and all manias dead in their tracks, either as an add-on medication (added to unspecified meds of 7 out of 16 manic or cycling people), or all by itself (one of several case reports, but this person had tried everything).  This is THE drug for happy-happy-joy-joy manias. Not as harsh as Zyprexa, not a whole lot slower, and it’ll bring you back to earth-just so long as you don’t crash into the pit of despair, all is well.   It has been reported to help people with rapid cycling as well.

My data on this stuff came from good old PubMed studies, stuff I looked up on scholar.google.com, anecdotal information on various support forums, and also taking into account the ratings below. Also, of course, taking into account report bias-that is, people are way more likely to bitch about things they don’t like or that didn’t work than they are to sing the praises of something that worked or partially worked.

Keep in mind who sponsors the study, as it will tends to make the results more favorable for the med in question (on average 3.6 times more likely, according to a Yale study).   Please see the page on how to read this page for an explanation of the various scales and ratings used by the studies.

One of the main problems we’ve found with studies that compare Keppra to others meds is there is a great scarcity of them.  At least ones where Keppra is actually compared with another med head to head.  The majority we could find are meta-analyses – where someone got a grant to study other studies and draw conclusions from that.  Sort of what we do here.  For free.  We find this surprising, because in the individual studies and case reports referenced above, as well as the various metaanalyses, Keppra scores better than all other anticonvulsants.  So why aren’t there more head-to-head studies against other meds?

Studies Comparing Keppra with Other Meds for Epilepsy

Vagus Nerve Stimulation vs. Anticonvulsant Cage Match!  In a large study of almost 900 people, about a quarter of them were able to reduce their meds.  This is the only study we’ve found so far where Keppra hasn’t had a significant impact in reducing seizures as an add-on.  However Keppra wasn’t one of the popular meds that people were able to discontinue with VNS therapy.

Keppra vs. Lamictal vs. Topamax  In the field at a UK district hospital in York. Thirteen percent of an unknown number of people became seizure free and approximately one-third had a reduction of greater than 50% in their seizures.  “All three AEDs were most successful at treating primary generalized epilepsy and least successful with symptomatic generalized epilepsy.”  While Keppra and Topamax were the most effective, Topamax sucked the most.

Anticonvulsant Cage Match! Assessing quality of life issues, cost effectiveness and, oh, I don’t know, how well they work.  This meta-analysis conducted by the University of York in the UK plowed through 1,098 studies published up through September 2002.  Of those only 212 met their criteria of being relevant enough for consideration – the studies lasted long enough, were randomized, reports of side effects weren’t vague, the usual stuff that we complain about in these studies.  But they also wanted old people and pregnant women included.  They were also looking for one more thing important to them: how much everything cost.  The aim was, “To examine the clinical effectiveness, tolerability and cost-effectiveness of Neurontin (gabapentin), Lamictal (lamotrigine), Keppra (levetiracetam), Trileptal (oxcarbazepine), Gabitril (tiagabine), Topamax (topiramate) andSabril (vigabatrin) for epilepsy in adults.”  Especially when stacked up against the older meds.  When taking into consideration cost, inclusion of the elderly and pregnant women, and the number of really good long-term studies published these days, it’s little wonder that the older meds come out on top.

Keppra vs. Topamax – which sucks more?  No, really, that’s all they wanted to know.  The loser – Topamax (topiramate).  Captain Obvious to the Netherlands: “Duh!”

Anticonvulsant Cage Match! This time for Landau-Kleffner syndrome in Spain.  Lamictal(lamotrigine) vs. Depakine (valproate sodium) vs. Trileptal (oxcarbazepine) vs. Keppra (levetiracetam) vs. Topamax (topiramate) vs. Zarotin (ethosuximide) vs. Frisium (clobazam) vs. Ospolot (sulthiame) vs. corticoids vs. ACTH.  The winner in Madrid:  Lamictal (lamotrigine).

Keppra vs. Trileptal vs. Zonegran vs. remacemide.  A meta-analysis of placebo-controlled trials where these drugs were used as add-ons for treatment-resistant, localized seizure-disorders.  Keppra was the most successful and sucked the least.  Followed by Zonegran (zonisamide) and Trileptal (oxcarbazepine).  Remacemida is an NMDA channel blocker, the sort of thing that is typically used to treat Huntington’s, Parkinson’s and/or Alzheimer’s.  As it also deals with glutamate, and NMDA is bleeding-edge stuff for epilepsy these days, I guess that’s why it’s being evaluated for refractory seizures.  Alas, it was the least effective and sucked the most in this study.

Studies Comparing Keppra with Other Meds for Bipolar Disorder 

Anticonvulsant Cage Match!  National Institute of Mental Health’s Bipolar Research Center at Case Western Reserve University School of Medicine decided to do a meta-analysis of compare the popular anticonvulsants available in the US for their efficacy in dealing with bipolar disorder.  The results:  Depakote (divalproex sodium) and Tegretol (carbamazepine) are your top anti-manics, while Lamictal (lamotrigine) is the only true mood stabilizer of the bunch, with a particularly robust antidepressant effect.  All the rest do bupkiss.  Because there haven’t been enough studies published on them is why.

Lithium vs. Anticonvulsants in Suicide Cage Match! – Lithium has conflicting studies if it does or doesn’t have a positive affect on suicide rates among the bipolar community. There’s the well-known, larger meta-analysis indicating that lithium can help prevent suicide.  But there’s also a smaller, but longer-lasting study in which lithium therapy actually increased the suicide rate.  That’s the world of research for you.  Anyway, this study tracked the suicidal ideations of bipolar people anywhere from one to twenty-five (!) years treated with any one of lithium,  Convulex (valproate sodium), Tegretol (carbamazepine), Trileptal (oxcarbazepine), Keppra (levetiracetam), Topamax (topiramate) or Lamictal (lamotrigine).  Nobody offed them self.  Only people taking Lamictal (lamotrigine) had statistically significant lower rates of suicidal ideation.  Everyone else tended to think about an early exit more than those people taking lithium.

Studies Comparing Keppra with Other Meds for Neuropathic Pain

Keppra vs. Trileptal vs. Topamax vs. Zonegran – Basically if you can’t use Tegretol (carbamazepine) or Neurontin (gabapentin), Topamax (topiramate) works the best but Keppra is by far the safest and sucks the least.

How Keppra (levetiracetam) Works in Your Brain

According to the PI sheet, Keppra acts on kainic acid and pilocarpine, which are two chemicals that cause seizures. So it makes them NOT cause seizures. Keppra also inhibits kindling, including kindling in full state, and even reverses it, which is why Keppra is so good for those of us with head injuries. Last thing it says Keppra DOES do in the PI sheet is “selectively prevent hypersynchronization of epileptiform burst firing and propagation of seizure activity.” In English? If you have a partial seizure on Keppra, the drug does its damnedest to keep the abnormal activity from generalizing and keep YOU from flopping like a fish and cracking ribs and all that.

The PI sheet says Keppra DOESN’T bind to any of these receptors: GABA, benzodiazepine (yup, they have their own receptor), gyceine, NMDA, or the second messenger systems. As far as their premarketing trials could tell Keppra didn’t touch sodium or T-gated calcium channels either, nor did it “facilitate GABAergic neurotransmission,” but-they do know that it a Petri dish it decreased negative modulators of GABA and glyceine gated currents. Do I know what most of that means? Honestly? About half.

Postmarketing studies have shown that in addition to knocking out the crap that makes GABA and glyceine less available (if I’m wrong about what that means, someone, correct me so I look less like a fool, please)-they’re thinkin’ it hits sodium channels after all , and that is why Keppra is effective against absence seizures.  And another study suggested Keppra hits calcium channels selectively too, at least in rats.  Not only that, but Keppra does the calcium thing in humans, too.  And I even found one study saying “Maybe it’s potassium.” ( This time in rats & guinea pigs). The voltage channels and Keppra are being heftily researched right now.

Keppra’s (levetiracetam) Special Effects & Issues

Issues: First and foremost, if you are taking Keppra for epilepsy you need to read the page on SUDEP and status epilepticus. I know, it is scary and nothing you want to think about, but you need to know. SUDEP and status aren’t in the PI sheet, but that doesn’t mean they cannot happen while you are on the med. OK. End soapbox. I’ve had too many scares myself to let that one pass.

Psychiatric Effects: Keppra can do weird things to your mood. It can make you depressed. It can make you DAMN depressed. If this happens, IT ISN’T YOU. IT’S THE MEDS.

Another thing Keppra is known for is making people angry. Really angry. My friend Lyssie and I have a totally-talking-out-our-asses theory on this one. Keppra actually makes me happy, and it made her happy at first. It’s when it is time for another dose that she got angry. However as the world’s slowest metabolizer, I had a steady level until I had to come off suddenly, when I became bitch queen of the universe. So our totally uneducated theory is that it isn’t Keppra, but the lack of Keppra, making people mean. It’s only got a 6-8 hour half life, after all, for average folk (a.k.a. non-smoking white males Of A Certain Age). If you are not in this group for any reason, you might be clearing Keppra faster than average even though it has few to no known drug interactions, and three times a day dosing might solve the anger problem. Hey, it’s worth a shot as long as you aren’t going on multicide sprees. And if it works, let me know, I’m full of scientific curiosity.

The rarest, and scariest, psychiatric effect that Keppra can have is hallucinations. Usually if you make it through the first week, you’re safe, but the woman on the first page with the ghostly friend had been taking Keppra over a year when she started getting visits.

Dekindling: Keppra is a dekindler. What does this mean? They think it fixes damaged areas in the brain, or at least sets up a damn good detour. So if you had a whack on the head, and now have seizures, and are now on Keppra, that’s why. Plus, unlike other anticonvulsants, it won’t make you stupid, and from my experience with head injuries, THOSE make you feel dumb enough.

Comments: This is a multiple reuptake inhibitor, acting sort of as both an SSRI and NRI, so be sure to read up on all three classes of meds, as those pages will cover a lot of stuff common to all meds similar to Effexor (venlafaxine hydrochloride).

Everybody hates their meds because of the costs and the side effects, but people just loathe Effexor (venlafaxine hydrochloride) because the discontinuation can be so harsh; it’s the med everyone wishes they never took. Yes, people will change doctors because some doctor had the nerve to punish them with Effexor (venlafaxine hydrochloride). Yet for many people it is a godsend, because the combination of serotonin, norepinephrine and dopamine reuptake is literally just what the doctor ordered for the darkest of depressions. Of course Effexor (venlafaxine hydrochloride) has to be complicated about it, it can’t just work on everything all at once from the beginning. Oh, no. First it starts to work on your serotonin. Then somewhere around 200 mg a day it starts to work on norepinephrine. Then around 300 mg a day it starts to work on your dopamine. Mileage will vary for each individual, and there’s no guarantee on getting all that much dopamine action. Of course as you up your dosage to get to the next neurotransmitter, you keep pushing the previous neurotransmitter, whether you need more action on them or not. And that’s what leads to problems, and why people have to stop taking Effexor (venlafaxine hydrochloride). So they stop taking it from a higher dosage, and they stop taking it quickly, and they learn about things like brain shivers.

For people in the bipolar spectrum Effexor (venlafaxine hydrochloride) should really be the last of the modern antidepressants that is tried. I feel that the risk/reward benefit runs too high on the risk side of things. More than most SSRIs Effexor (venlafaxine hydrochloride) is likely to trigger not just mania, but rapid cycling. Combine that with the very rare, but still real chance that you could be stuck taking Effexor (venlafaxine hydrochloride) for the rest of your life, even if it doesn’t work. That complicates things greatly in Bipolarland.

Try everything else first, and if you just react badly to SSRIs, forget about Effexor (venlafaxine hydrochloride) entirely.

As for unipolar depression, if you’re in the blackest pit of despair and your doctor recommends Effexor (venlafaxine hydrochloride), go for it. What? You don’t think I care about you people? I do. For people with unipolar depression a lifelong addiction to Effexor (again, this is a very rare side effect) is just a pain in the ass. Of course Effexor (venlafaxine hydrochloride) works with popular liver enzymes, so there would be dosage adjustments required for some meds, and you’d have extra side effects for having to take 37.5-75mg of Effexor every day, but it wouldn’t be making you manic or triggering rapid cycling. As long as the reason why you had to stop taking Effexor (venlafaxine hydrochloride) wasn’t too bad, and that reason isn’t too harsh at the low dosage, the exceedingly small risk of permanent Effexor (venlafaxine hydrochloride) maintenance is well worth running when weighed against the benefits you’d potentially receive with Effexor (venlafaxine hydrochloride).

Effexor (venlafaxine hydrochloride) is also approved for GAD. Yet it frequently makes the anxiety that is part of bipolar much worse. I can’t honestly give a good risk/reward analysis for Effexor (venlafaxine hydrochloride) and anxiety. Given the experiences I’ve read of everyone who has taken it for bipolar and depression, I’m surprised it was even approved for anxiety.

 

 

 

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