Friday, April 1, 2016

Levetiracetam and Mr. Hyde

I wrote:  Who is using pyridoxine to try to address behavioral aberrations induced by levetiracetam therapy (i.e. my child has become a monster)? What is the success rate?

Reply 1:  I try pyridoxine occasionally but rarely see response. Inexpensive placebo.

Reply 2: Have used it (b6) with the expectation of success= flip of a coin.

If the parents are willing to go along and cope with the "flipping " of the child I try for 2-4 weeks, but more often than not - I switch to something more benign. -clobazam - oxc/cbz - based on the evidence base -assuming what the child has a focal epilepsy. If Gen Epilepsy- well VPA or LTG.-
Interestingly when I moved to Canada, I encounter here that Clobazam (which has been used here for many years) and is cheap did not have the -striking' rate of LVT-like side effects.

Reply 3:  About 30 % get much or some considerablely better. The rest, no diff.

My reply to 3:  My experience would be similar. I suggest it knowing the odds are that it won't help.

Reply 4:  Have tried - not spectacular.   I asked reply 1 a while ago and she was also unimpressed.

Reply 5: I try it regularly but have not kept score. My impression is that sometimes it works and ... So easy to try.

Reply 6: We use pyridoxine 100 mg/d from time to time, success-rate is 50% I would guess. Its worth a try 

I replied:  Although it may seem from my earlier submission that I am naive to using pyridoxine for this purpose, I am not. I suggest it knowing the odds are that it won't help.

Reply 3:  Heh, heh.  I suggest it knowing it has the amazing chance to make 1/3 better.

My comment:  It all depends on whether the glass is 1/3 full or 2/3 empty.

Reply 7:  Despite the literature (and I agree with reply 1 in general), I have found rare patients (<10%) having a dramatic beneficial response to B6. Maybe it is placebo (both my placebo as well as the patient's family). Anticonvulsant personality change (Mr Hyde) is not limited to Keppra. We have a kid with a channelopathy we are treating with CBZ and then PHT, and turned into Mr. Hyde.

Another wrote:  It has been my practice for few years to use pyridoxine as a supplement in behavioral problems encountered in kids who are on anti epileptic medications irrespective of the formulary used and quite surprisingly parents and teachers have started reporting benefits of this additive effect in them. Should I say this could an acceptable recommendation to every AED with behavioral issues?
Reply 8:  Clobazam is usually quite well tolerated but several of us have noticed that patients with autism sometimes have behavioral challenges on this drug...

So what to do? I have a patient at the school with autism and refractory seizures who failed trials of most of the other good drugs, so I prescribed clobazam. It is working extremely well, she has had no seizures for the past four months (she was having them several times a week before). But her rates of noncompliance and refusals were escalating and the staff complained to me. I suggested a trial of pyridoxine (100 mg BID), which we all know helps counteract the behavioral side effects of levetiracetam. And it is working. I just saw her last Thursday and her compliance is much better and the staff are happy.

Has anyone else tried using pyridoxine to counteract the behavioral side effects of clobazam in patients with autism? Does this sound reasonable?

Reply 2: We have a great deal of using Clobazam here in Canada where it has been approved for many years. At least over the past 6-yrs since I moved to Calgary from the US, I do not know of any benefits of adding B6.

On the other hand would the patient may have a subtle or mild form of pyridoxal kinase deficiency or PLP that improves with supplementation of B6? B6-related epileptic encephalopathies with autistic behavior may be the underlying culprit.

Reply 4:  The rationale for using pyridoxine to treat behavioral side effects of levetiracetam is that pyridoxine enhances GABA synthesis and that levetiracetam reduces GABA release. If behavioral side effects of clobazam are reduced by pyridoxine, this explanation must be incorrect, since clobazam enhances GABA affinity for its receptor. As aside, my patients who have shown behavioral side effects of levetiracetam (infrequent) were not helped by pyridoxine.

My response:  Au contraire, I and my colleagues here have a significant minority of patients on levetiracetam who experience vexing problems with adverse behavior.  Such patients may be treated with pyridoxine, which is occasionally helpful. Numerous such patients have had levetiracetam discontinued for this reason. Of the currently commonly used antiseizure medications, levetiracetam is the one most likely to result in behavioral adversity.

Reply 9 to reply 4 above:  this amazes me. My experience is about 50fi of children < 10 have personality changes on keppra. For a while I thought it was just that some physicians did not ask; but I think it must be quite variable.

I have had almost no luck with pyridoxine.

1 comment:

  1. I wrote: The US Food and Drug Administration (FDA) has added 8 drugs to its list of products to monitor because of possible signs of serious risks or new safety information. The agency spotted yellow flags for the 8 drugs in the FDA Adverse Event Reporting System (FAERS) database during April, May, and June 2012. Levetiracetam is one of those drugs. Concerns are: Potential for drug abuse, misuse, or dependence. Does this resonate with anyone?

    Reply 1: Hi, yes! Yesterday one 21 y.o. Epileptic patient was admited in hospital in focal status and receive LVT impregnation. He said to me; "hey, give more of this, I feel so cool", like peace and love.


    Reply 3: No. They are either screaming or sleeping.