Hi from Scotland

[Highlander]

I was diagnosed with epilepsy age 3. I have tried a variety of narrow and broad spectrum antiepileptics for primary generalised epilepsy with focal elements. With the exception of phenobarbital, which worked well in my childhood, everything else has had some sort of side effect which varies from irritating to life changing. Levetiracetam was the worst. It basically ended my business of 10 years due to the behavioral side effects that can happen. I almost lost the house and my marriage very nearly ended too. The neuro who put me on the drug had beggared off to New Zealand after increasing the individual dosage by 100% from 500mg to 1000mg. Life was happy at 500mg with Topamax. From the first couple of days of the increase, it all started to do down hill with the side effects.

Managed to eventually get off it. Ended up going back to Uni too as my CV from the year dot was basically coaching/teaching Aquatic sports for councils or running my own business doing the same. And the business started after I was discriminated against about my E by one council. Gits gave me a better version of my old job back when I was self-employed. On contract, just teaching kids, double pay, no cleaning toilets.

Currently studying Pharmacology. My Mum thinks I'll be working in a Pharmacy after, I have tried to explain.

Currently going through Lamotrigine/Valproate titration again after the last neuro said it was far too complex to do and 2008 neuro ballsed it up 3 times and left me puking and dizzy in A&E.

Recently enrolled in a pre-clinical revision course, supposed to be for doctors but it had all my Physiology for this year and some case studies that were handy for disease and cancer next year. Pharmacology content? Well, body systems lectures recorded at around 25KB, Pharmacology 6KB and no way did I miss anything. Really hoping that that is only because it is PRE-clinical

 

[Porkette]

Hi Highlander,

Welcome to CWE! I've had epilepsy for 45 yrs. and had 2 surgeries to reduce my seizures because I found out I was drug resistant after having a DNA test done. Now my Dr. has me on the medical marijuana and I'm amazed at how that has decreased my absence and complex partial seizures.

It's great to see you are from Scotland that's where some of my family is from. You are playing it smart getting into pharmacology and I wish you the best of luck. I have been working in public school in special education for 32 yrs. so I understand how you feel I've been put down on the job but I didn't let the staff get away with it.
Everyone here has been a great help to me and they are wonderful friends. I wish you the best of luck and May God Bless You!

Sue

 

[Topcat]

Hi and welcome.
I am currently on Lamotrigine but had never heard of

Lamotrigine/Valproate titration

Please tell me more. Thank you.

 

[Highlander]

Vpa & ltg

Basically, there are various ways of doing it but the first one I found after a brainless neuro messed it up the first time was in:
Sale, M., Natarajan, S., Biton, V., Vuong, A., Hammer, A., Messenheimer, J. and Blum, D. (2005). A dosing algorithm for converting from valproate monotherapy to lamotrigine monotherapy in patients with epilepsy. Epilepsy & Behavior, 6(1), pp.63-70.
This explains why the algorithm is necessary
Oh seemingly I can't put in links.
OK
Here is the long hand version. All from Kanner, A. (2004). When Thinking of Lamotrigine and Valproic Acid, Think "Pharmacokinetically"!. Epilepsy Currents, 4(5), pp.206-207.
I'd put it in my own words but they do a pretty good job and tbh I'm rushing the dog calls. Sale I already had stored in a reference list. Super big quote but it is fascinating stuff if you are thinking of going from VPA & LTG to LTG or VPA to LTG
'... valproic acid (VPA) inhibits the clearance of lamotrigine (LTG) by a mean of approximately 30% at a dose of 125 mg/day and by a mean of 50% at doses of 250 mg and higher. These data complement findings from a previous study that demonstrated a maximal inhibition of LTG clearance by VPA at doses of 500 mg/day, but in which lower doses were not tested.

The first practical implication of these data applies to the conversion from a VPA plus LTG therapy to LTG monotherapy: the dose of LTG may be kept unchanged until the dose of VPA is lowered to 125 mg/day, at which point, the dose of LTG must be increased by 30% and, finally, doubled on the day VPA is discontinued.

Yet these data have practical implications beyond the conversion from VPA plus LTG to LTG monotherapy. First, low-dose (250 mg/day) VPA potentially can be considered for use exclusively as an inhibitor of LTG clearance—particularly in patients for whom cost of medication is a concern, as it can cut LTG cost by 50%. Furthermore, at such a low dose, the risk of adverse events related to VPA (e.g., weight gain, dysmenorrhea in women of child-bearing age) or to the combination of LTG and VPA (i.e., tremor) is lower than when VPA is used at doses high enough to yield an antiepileptic effect.

Second, the use of low-dose VPA as an inhibitor of LTG clearance may help achieve a successful conversion from a polytherapy regimen of LTG with an enzyme-inducing AED (such as phenytoin, carbamazepine, phenobarbital, or primidone) to LTG monotherapy. Indeed, in the presence of an enzyme-inducing AED, LTG clearance remains high and its serum concentration low, until 1 to 6 weeks from the time the enzyme-inducing AED is discontinued. The low LTG serum concentrations may fail to yield the anticonvulsant protection necessary to avert seizure occurrence during the tapering of the enzyme-inducing AED dose. The inhibitory effect of VPA on LTG clearance results in an increase of LTG serum concentration. At the time of discontinuation of the enzyme-inducing AED, the dose of VPA can be lowered to 125 mg/day and stopped 1 week later.

Third, the data from this study also can be applied to the conversion of an LTG monotherapy to a polytherapy regimen with VPA. Indeed, these data confirm the fact that the inhibition of LTG clearance by VPA is immediate; accordingly, the dose of LTG can be cut by 50% on the day that VPA is started at doses of 250 mg/day or higher and still ensure that the maintenance of LTG serum concentrations are stable, as shown in a previous study. Although the addition of LTG to VPA may increase the risk of rash, unless LTG is introduced at a low dose and tapered up slowly, the addition of VPA, per se, to an LTG regimen does not increase such risk, as the patient has already taken LTG for a long enough period to become desensitized to this effect of the drug. Unfortunately, this misunderstood risk has often limited the use of an LTG plus VPA combination, which potentially can yield a significant improvement in seizure frequency in patients with refractory epilepsy because the AED combination appears to have synergistic therapeutic effects
I was on VPA & LTG for almost 15 years until I said to a neuro ' Do you have anything which means I don't have to watch my weight all the time?' (working in aquatics tuition/fitness in a wetsuit/swimsuit or fitness gear and she put me on Topamax - lost 2 stone and ended up like a rake!)
Hope that helps.
The reaction when someone gets it wrong presents with severe dizziness, vomiting, and blurred vision. Leastways that's what I've had every time! Been there four times myself - the first time I did it accidentally when moving in with my husband to be which was how I recognised the symptoms when Mrs wouldn't open a British National Formulary Neuro screwed up.
My new neurologist is doing the titration slightly differently from Sale. I'm interested to see how it pans out.
Oh dear a bit TL;DR

 

[Nakamova]

Hey Highlander, welcome to CWE!

You mention having some success on phenobarb as a kid. Did you stop using because you later developed issues w. seizure control and/or side effects, or was it because it's potentially habit-forming? I ask because I know someone who's used it all her life for her seizures -- despite her docs suggesting that she try something else. Her seizures are controlled and any side effects are manageable.

 

[Loopy Lou]

Hi there!

Keppra is the only one i've had pretty much no side effects from lol. I was only diagnosed in 2009 at age 21ish.

I'm doing the uni thing too after getting pushed out of my job due to the E, but biomolecular science. Got a couple of modules on drugs this year though, so i'm reading up on my pharmacokinetics, it's really interesting!

Perhaps i have a vested interest though

Wonder how many other people have stories similar to ours! What do you plan to do with your degree when you're done?

 

[Highlander]

Hey Highlander, welcome to CWE!

You mention having some success on phenobarb as a kid. Did you stop using because you later developed issues w. seizure control and/or side effects, or was it because it's potentially habit-forming? I ask because I know someone who's used it all her life for her seizures -- despite her docs suggesting that she try something else. Her seizures are controlled and any side effects are manageable.

To be honest I was a kid. I had good control.
Doctors don't tend to sit down and explain the development of tolerance and
dependence with regard to phenobarbital in continuous use to a kid.
Possibly, or was he was just an insightful GP who was ahead of his time(see below)? Or had the Sanofi Aventis rep walked in with a good spiel, some very nice food, and free samples...
Personally, given what I knew of some of his other administrations, I have my own cynical opinion.
Danielsson, B., Lansdell, K., Patmore, L. and Tomson, T. (2003). Phenytoin and phenobarbital inhibit human HERG potassium channels. Epilepsy Research, 55(1-2), pp.147-157.

 

[Highlander]

Hi there!

Keppra is the only one i've had pretty much no side effects from lol. I was only diagnosed in 2009 at age 21ish.

I'm doing the uni thing too after getting pushed out of my job due to the E, but biomolecular science. Got a couple of modules on drugs this year though, so i'm reading up on my pharmacokinetics, it's really interesting!

Perhaps i have a vested interest though

Wonder how many other people have stories similar to ours! What do you plan to do with your degree when you're done?

Hi Loopy Lou

My Dad's side of the family are all in Southern Ireland. I was supposed to head over there a fortnight ago to have a bit of a clan gathering, but uni sucked up all the money - again.

I originally studied psychology but the most important lesson it taught me is that I would have been an awful psychologist. On a mental health placement, I became interested in the medication, especially the crossover mood stabilizer/anticonvulsants.

Without going into the 'too long don't read' story, I ended up 'doing drugs at university'.

I think anyone with E, especially studying subjects like ours, has a vested interest in anything remotely related to what the drugs we use are and how they work and affect us. Antiepileptics are covered in CNS suppressants next year in term 2 - the head of our course has probably already warned the lecturer about me. It's when you don't have to learn the side effects because you have practical experience of them...

What do I want to do after? Wow, If I could drive I would just go and sacrifice my soul on the altar that is pharmaceutical sales. I once saw a job with Merial working on the phone advising vets about products but it was on site and way down past London - sucks.

Probably end up doing post grad, what I do may depend on the state of my degree! Have a couple of ideas just now. Physician's Associate pays the most and at the moment they are guaranteeing posts but do you always want to be known as a cheap doctor? I've also considered an MSc in Dietetics to qualify as a Dietician. There is a chunk of pharmacology in that course. Up where we are neurology can't get anyone to support an adult on the ketogenic diet. Or stay in Pharmacology... do clinical...or...?

What do you want to do when you graduate?

 

[seagull]

Hello Scotland my dad was scot I wished he bugged off back but he never did.You had rough trot I take lamorgin and cloberzam he also put me on small dose keppra with it I will not take hear bad things like keppra rage this clever man says we no give you keppra then so promptly gave me something different I thought,I got the generic keppra.My nurolgist flys over heard from Poland every other month takes clinic then goes back to his hospital in Poland let's not comment on that one I mean I could but using that amount of sware words not cool

 

[Loopy Lou]

I'd also looked into the physicians associate!

It's seriously difficult to get into here though (I'm living in Blackpool now), and the competition is very tough. They recommend you need at least a 2:1, but the competition is so tough, i think it would need to be a first to be a contender. Missed out on my first by 0.1 of a grade last year, not even kidding. Needed 17.5 aggregate score, got 17.4. Just going into my BSC year so i can pull it back if i get at least A- for everything all year.

I love the idea of helping towards diagnostics and drug therapies, so physicians associate would probably be a good fit, and would help me save for a phd.

I see you're kind of like me and seeing where you end up depending on grades and such. With all the med changes i'm about to go through, i'm really not sure what's going to happen this year but i'm trying to give myself a head start by studying now. We're doing a lot of genetics, genetic engineering and transgenics this year too. I'm 31 now so kind of late to the party, but so glad i'm doing it despite the crushing debt!

Have you had any issues in labs and stuff with your epilepsy? My class is pretty small, there was only 12 of us at the end of last year and i think we've lost a few more, so probably only 7-10 of us by the time we go back.

 

[Highlander]

I'd also looked into the physicians associate!

It's seriously difficult to get into here though (I'm living in Blackpool now), and the competition is very tough. They recommend you need at least a 2:1, but the competition is so tough, i think it would need to be a first to be a contender. Missed out on my first by 0.1 of a grade last year, not even kidding. Needed 17.5 aggregate score, got 17.4. Just going into my BSC year so i can pull it back if i get at least A- for everything all year.

I love the idea of helping towards diagnostics and drug therapies, so physicians associate would probably be a good fit, and would help me save for a phd.

I see you're kind of like me and seeing where you end up depending on grades and such. With all the med changes i'm about to go through, i'm really not sure what's going to happen this year but i'm trying to give myself a head start by studying now. We're doing a lot of genetics, genetic engineering and transgenics this year too. I'm 31 now so kind of late to the party, but so glad i'm doing it despite the crushing debt!

Have you had any issues in labs and stuff with your epilepsy? My class is pretty small, there was only 12 of us at the end of last year and i think we've lost a few more, so probably only 7-10 of us by the time we go back.

Never had any problems in labs. Really.

The lady who deals with Chemistry always used to give me a clean beaker to get water for my drugs.

Only once messed up slightly - I was on a brivaracetam titration and was getting so ridiculously dizzy that I decided to adjust the titration myself. just made matters worse.
I had to go and fess up to the lecturer running the lab who sent me back to the halls.
I knew that his office was just down from my head of course...

I didn't calculate my aggregate score last year. I went through 2 drug changes and I couldn't get in touch with my neuro when one was going badly, so I titrated myself back onto valproate from an old prescription I had collected before the switch. All my GP said was 'where did you get the drugs'. I'm just so glad I got through it all. Don't mention the debt... god don't.

I love genetics, our coolest lecturers are geneticists. Pharmacogenetics is fascinating with respect to future research regards predicting individual responses to drugs, both in terms of therapeutic and adverse effects.

We are also going into the same years. I'm looking to claw back something too. I studied all through the summer since we weren't going to Ireland and I had exams to sit thanks to being off with side effect the first time round.

Last year I did a research piece on the pharmacology of antiepileptics - boldly titled: 'Epilepsy - the drugs don't work' ( meaning that we have nothing to halt epileptogenesis, although research has shown that anti-inflammatory drugs have been beneficial in cases where symptomatic epilepsy is a risk factor)

Anyway, after the presentation, we had a Q&A session. Most of them were quite easy. Then this really quietly spoken guy started asking about phenobarbital.
All I could make out was that two in the family were on phenobarbital for epilepsy and he was worried as he had heard it was being withdrawn.
I asked him to repeat the question, but he was still really quiet.
So I went into the blurb about the WHO using phenobarbital to combat issues with access to medication, as it is a relatively cheap and effective drug for epilepsy, ignoring issues of tolerance and dependence it is better than nothing. Yes, it does seem to be chosen less frequently as an antiepileptic as other new drugs with better side effect profiles are developed but no as far as I knew it was still in use. I asked after his family members with epilepsy, was it genetic?

Oh, it was two Persian cats... not people.

He'd asked because I had stuff about canine epilepsy on the powerpoint.

 

[Loopy Lou]

I'm surprised that you were put on brivaracetam when that and keppra are so similar in structure, side effects and mechanism of action, especially if you had such a rough time on keppra onder:

Brivaracetam is apparently going to be my next new drug. Woo.

 

[Highlander]

I'm surprised that you were put on brivaracetam when that and keppra are so similar in structure, side effects and mechanism of action, especially if you had such a rough time on keppra onder:

Brivaracetam is apparently going to be my next new drug. Woo.

Actually, my neuro gave me a choice. His plan was for Lacosamide but I had asked for a drug with a good cognitive profile as I have got pretty lucky with regards to what some people say about Topamax/topiramate. It doesn't have a very good outlook with regards to memory, attention and linguistic side effects, but I have never really had any bother from the drug. Lacosamide isn't brilliant so I thought no-one can take two crummy drugs and get really lucky.

His other choices were lamotrigine and brivaracetam. At first, I went for Lamotrigine, as I had been on it before but the neuro told me the switch was too complex. (I had been through the switch before when another neuro botched it, thrice - I had a paper with the algorithm. I did work out that if I had brought it in for him I could have charged him £1 in consultancy fees...) So Brivaracetam it was, I was a bit concerned like mention you and there wasn't a whole lot of research on the drug, however, this was reassuring, if UCB funded, like a lot of it, and having a small sample size.
Yates, S., Fakhoury, T., Liang, W., Eckhardt, K., Borghs, S. and D'Souza, J. (2015). An open-label, prospective, exploratory study of patients with epilepsy switching from levetiracetam to brivaracetam. Epilepsy & Behavior, 52, pp.165-168.

Make sure you get a slow titration, it kicks up a lot of dose-dependent side effects; or that was what I found. Since I have come off it I have heard of it working for some others who had slower titrations which really allowed them to adapt to the drug. One big tip, swear off the alcohol.

UCB Pharma have another drug from the family of racetams containing the pyrrolidone moiety in the pipeline.
This is interesting if you want to look up how that family works on a molecular level, again from UCB:
Lee, J., Daniels, V., Sands, Z., Lebon, F., Shi, J. and Biggin, P. (2015). Exploring the Interaction of SV2A with Racetams Using Homology Modelling, Molecular Dynamics and Site-Directed Mutagenesis. PLOS ONE, 10(2), p.e0116589.

Enjoy... in what time in the holidays we have left.

 

[Loopy Lou]

I had bad experiences on both Vimpat and Lamictal (Lacosamide and Lamotrigene). In someone who isn't prone to mental health problems, i became suicidal on one to the point where i took an overdose, and intensely paranoid on the other. As soon as the medications were out of my system, those feelings went, but it was seriously scary that i thought that those thoughts and feelings were coming from myself and not the chemicals. Of course everyone has different experiences.

Might give those articles a read, thanks for the info!

 

[Highlander]

I had bad experiences on both Vimpat and Lamictal (Lacosamide and Lamotrigene). In someone who isn't prone to mental health problems, i became suicidal on one to the point where i took an overdose, and intensely paranoid on the other. As soon as the medications were out of my system, those feelings went, but it was seriously scary that i thought that those thoughts and feelings were coming from myself and not the chemicals. Of course everyone has different experiences.

Might give those articles a read, thanks for the info!

I became paranoid and started to get suicidal ideations on levetiracetam but that was at it's worst.
There is no history of mental health problems anywhere in our family. Unless you want to count a very distant aunt years back who, when she heard her fiance's plane had been shot down and he was dead, went out and drowned herself in a notorious Loch in the town I was brought up in. She may actually be the ghost rumoured to haunt it.

The Irish side is all doctors, nurses and vets and my mother's side - police. Dad left home after a fall out and joined the police.

It is just as you say. I finally managed to convince a neurologist to switch levetiracetam back to valproate and as soon as levetiracetam was out of my system I was fine.

Why are they switching you to Brivaracetam? Are you having issues with levetiracetam?

 

[Loopy Lou]

When i was first told i was going onto Keppra i was pretty worried considering i'd heard from other people on here about how affected mood especially, but i had barely any side effects from it at all, and tolerated it really well. It worked well for a good few years too, but after about 8 or 9 years at the maximum dose they'll allow, they just won't increase it anymore and neuro believes i'm overly tolerant to it because seizures have been increasing again.

At least brivaracetam doesn't seem like it's going to be quite as harsh as switching to a completely different kind of medication, but i suppose that remains to be experienced for me.

 

[Highlander]

And if you ever become tolerant to brivaracetam, well go to:

ubc.com
our-clinical-studies
seletracetam
put / between them all.

I still can't put in links and I can't be bothered to reference a URL this morning.

All the info on the phase 2 trials is there so you have plenty time