Overload

Epilepsy drugs

Category: Medicines

Type

Involuntary and voluntary

Introduction and description

 

 

Epilepsy is not a single disorder but a syndrome with many different symptoms all of which result from abnormal electrical activity in the brain. The type of stimulation to which an epileptic is subjected is high stimulation, as such they are at grave risk from damage to the brain cells leading to – ultimately death from brain damage.

More details covering the symptoms, and causes of epilepsy itself can be found by following the link above.

Epilepsy drugs are intended to treat the symptoms [not the cause] of epilepsy and they have a record for producing spiritual experiences. The number of involuntary hallucinations associated with the drugs have been obtained from the eHealthme web site.

The observation descriptions are principally from EROWID, PubMed, eHealthme and Wikipedia.

Big Business

figures in billions

There is a lot of money to be made in this class of drug, simply because the number of people diagnosed with epilepsy is increasing enormously on a world-wide basis, as is the number of things causing epilepsy.  And since doctors currently work on symptom based medicine - find the symptoms, find a pharmaceutical to match the symptoms -  the pharmaceutical companies are making a lot of money.  The major players in the  market include Abbott Laboratories, Cephalon, GlaxoSmithKline, Johnson & Johnson, Novartis AG, Pfizer, Sanofi-Aventis SA, Shire, and UCB Pharma - predominantly USA companies. Pfizer maintains the largest market share in the market with 26% for its two products, Lyrica and Neurontin ($2.96 billion combined sales in 2008). Pfizer's  products are also growing at the fastest rate among major competitors, with a sales growth of 31% from 2007 to 2008.

The Classes of Drug

 

Channel blockers (CBs) are a class of drugs and natural substances that disrupt the flow of ions through channels in the cell membrane. There are a number of types that depend on the type of chemical allowed into and out of the channel. They have effects on many cells of the body, but these specific drugs target neurons in the brain.

Epilepsy drugs are generally specific channel blocker drugs. They aim to suppress the ‘rapid and excessive firing of neurons’ that start a seizure. Failing this, they prevent the spread of the seizure within the brain. Epileptic seizures can cause death and brain damage, so this class of drug has an important role to play in medication. The major molecular targets of marketed anticonvulsant drugs are: 

  • voltage-gated sodium channels
  • voltage-gated calcium channels
  • components of the GABA system, including GABAA receptors, the GAT-1 GABA transporter, and GABA transaminase
  • SV2A
  • α2δ.

SV2A is not a channel, but because it is rather a stand alone target, I have added it in to this category.

 

There are various products that can block the channels, each of which can be classified according to the main chemical that it blocks and then by types.

  • Phenyltriazines – is a miscellaneous grouping. The one drug in this group Lamotrigine, has a history of involuntary hallucinations
  • Hydantoins – are primarily sodium blocking drugs. Drugs in this group include Ethotoin, Fosphenytoin, Mephenytoin, and Phenytoin. Phenytoin has a record of providing involuntary spiritual experiences
  • Carboxamides - are also sodium blocking drugs. Drugs in this group include Carbamazepine, Eslicarbazepine acetate, Oxcarbazepine, Oxitriptyline, Rufinamide. A number of these have a record of providing involuntary spiritual experiences
  • Succinimides – Are primarily calcium blocking . Drugs in this group include Ethosuximide , Mesuximide, Phensuximide, Pregabalin and Lyrica. Plenty of experiences here too

How it works

 

These class of drugs seem to have an extraordinary record for producing spiritual experiences and I could not at first understand why.

Epilepsy itself is a known provider of spiritual experience. Epileptics in indigenous societies are looked upon as extremely special, and cared for with great reverence. Their visions are treated as prophecies. I have a section on epilepsy.

But these drugs are supposed to stop epileptic seizures and as such would seem to stop any spiritual experiences.
Then something struck me about the uses of these drugs. They have started to use them in the USA [where the eHealthme figures came from] for people without epilepsy – so called 'off-label' use.  Examples of the off-label uses include…….. 

  • Carbamazepine is used in the treatment of bipolar disorder.
  • Eslicarbazepine acetate is used for ‘bipolar disorder and trigeminal neuralgia’
  • Gabapentin - is used 'in the Treatment Protocol for methamphetamine, cocaine and alcohol addiction and has been used to treat neuropathic pain, migraines, bipolar disorder, multiple sclerosis, smoking, anxiety disorders, obsessive-compulsive disorder, in treatment-resistant depression, and for insomnia”.
  • Lamotrigine is used in the treatment bipolar disorder.
  • Levetiracetam has ‘been considered for Tourette’s syndrome, autism, bipolar disorder and anxiety but its benefit-risk ratio in these conditions is not well understood’.
  • Oxcarbazepine is also used to treat ‘anxiety and mood disorders, and benign motor tics’
  • Phenytoin - Dilantin was first synthesized in 1908. Jack Dreyfus, founder of the Dreyfus Fund, used Dilantin for depression and anxiety and is even believed to have supplied large amounts of the drug to Richard Nixon! Dilantin also made an appearance in the 1962 novel One Flew Over the Cuckoo's Nest by Ken Kesey, both as an anticonvulsant and as a mechanism to control inmate behavior.
  • Pregabilin – is also used to treat neuropathic pain and generalized anxiety disorder.
  • Tiagabine - is used in the treatment of panic disorder, anxiety disorders and neuropathic pain (including fibromyalgia).
  • Topamax - On May 21, 2010, for example, Ortho-McNeil pleaded guilty and was fined US$6.14 million by the FDA for promoting Topamax to treat psychiatric disorders, without applying for any approval and there was no data from any well-controlled clinical trial to demonstrate that Topamax was safe and effective to treat any psychiatric conditions.
  • Valproate - “has also found clinical use in the treatment of bipolar disorder, and, less commonly, major depression. It is also used to treat migraine headaches and schizophrenia and is under investigation for treatment of HIV and various cancers
  • Zonisamide – has been trialled for Parkinson's disease, obesity [to be sold under the name Empatic], migraine and neuropathic pain. It has also been used off-label by psychiatrists to treat bipolar depression
 

And once I investigated further I found a whole host of illnesses being ‘treated’ or being considered as treatment by these drugs – alcoholism, obesity, [especially to reduce binge eating]; posttraumatic stress disorder, 'infantile spasms' [sic], mood stabilisation, ‘essential tremor’, bulimia nervosa, obsessive-compulsive disorder, smoking cessation, idiopathic intracranial hypertension, neuropathic pain, cluster headache, and cocaine dependence.

And yet another statistic. The drug class was the US's 5th-best-selling in 2007. There are not that many epileptics proportionally in any country. There are only about 60 million people worldwide who have epilepsy, and nearly two out of every three new cases are discovered in developing countries, so these drugs are not being used to treat epilepsy, they are being used ‘off-label’.

And I think it may be the off-label use that is providing the spiritual experiences.  

'The white, asymmetrical area of the MRI
image above shows eggs laid by a parasite
in the patient's brain, and swelling in
the region'

As a class of drugs one can see that they have a valuable use as a one-off treatment for a totally unexpected epilepic seizure, but there seems no reason to prescribe them on a regular basis, as one should be searching out the cause of the seizure [and for that matter the cause of all the other illnesses listed above] and treating this. 

If one has a parasite on the brain, for example, the parasite will continue to eat the brain, epilepsy drugs or no epilepsy drugs.

Side-Effects

The best way to find out how these drugs work is to look for the published side effects, so I compared them and in general they seemed to be very similar. The following is not atypical and is based on a study of the effects of one drug on [effectively] well people.[Source: Roy Chengappa, KN; Schwarzman, LK; Hulihan, JF; Xiang, J; Rosenthal, NR; Clinical Affairs Product Support Study-168 Investigators (2006). "Adjunctive topiramate therapy in patients receiving a mood stabilizer for bipolar I disorder: a randomized, placebo-controlled trial". The Journal of clinical psychiatry 67 ]. The side-effects reported by > 10% of subjects in this clinical study were: 

  • Paresthesia (numbness & tingling) (23.7%)
  • upper respiratory tract infection (17.5%)
  • diarrhea (16.8%)
  • nausea (15.4%)
  • anorexia (loss of appetite) (13.3%)
  • memory problems (11.2%)

The side-effects most frequently leading to discontinuation of the drug were:

  • psychomotor slowing (4.1%)
  • memory problems (3.3%)
  • fatigue(3.3%)
  • confusion(3.2%)
  • somnolence (3.2%)
 

Another study expanded the concept of confusion by listing all the following signs of subjugation of the reasoning system - confusion, trouble with thinking, problems with speaking , problems with co-ordination, problems with handling things round you.

And here we have the answer to how they work, they subdue Memory and given the confusion caused in some people they may have an effect upon Reason as well. But their effect upon Memory will be enough to subdue the reasoning function anyway, and the Composer will be able to take over.

For more details as to why this works see How spiritual experience works.

Meyler states that “It is possible, according to experimental work from Japan, that some of the effects of anti-epileptics on the nervous system result from an impaired blood flow to the brain”. So here we might have evidence that the mechanism of action is not dissimilar to that of the other channel blockers – and in fact a number of the drugs – impaired oxygen flow leading to a gradual system shut down which starts with those functions which take up the most energy and contribute least to ultimate survival – the main ones being Reason and Memory.

hmariewv (2 years ago):  I have experienced the slowing down of the brain really bad on Lamictal. Severe memory loss and change in personality. I'm not as smart as I was before or quick to know what to do anymore. I can't organize or concentrate . I was ADHD and now I hardly do anything. I took it for 15 months and I've been off it for 2 yrs. I also became suicidal on it with the worst depression ever, crying every day! I had migraines while on it. Has anyone else quit taking it and became normal again?

Meyler’s side effects of drugs states that “cognitive side effects, especially impairment of memory and visual information processing, improve when patients are transferred from conventional to controlled release preparations”. If we now turn this round and imagine a single large dose being given, then it is clear the effects on Memory are going to be substantial. This was found to be true of all the true channel blockers drugs described here.

 

This is a composite list some of it obtained from Meyler’s Side effects of drugs, not all these drugs may have all these side effects. Any detailed information you need is available on the eHealthme site: 

  • Long term effects upon reason and memory - Some studies have cited that these drugs are linked to lowered IQ in children 
  • Children 3–12 years of age were observed to be susceptible to mild-to-moderate mood swings, hostility, concentration problems, and hyperactivity 
  • Congenital malformations in foetuses - This is really only important for pregnant women 
  • Blurred vision, double vision , nystagmus - The FDA has notified prescribers that some drugs can cause acute myopia and secondary angle closure glaucoma in a small subset of the population. The symptoms, which typically begin in the first month of use, include blurred vision and eye pain 
  • Loss of consciousness , fainting and coma 
  • Skin problems – one of the most serious is that of "Lyell's syndrome" - a rare, life-threatening dermatological condition that is usually induced by a reaction to medications. It is characterized by the detachment of the top layer of skin (the epidermis) from the lower layers of the skin (the dermis) all over the body.
  • Tics, parkinsonism 
  • Hepatotoxicity (from hepatic toxicity) – chemically driven liver damage. Some cases have been fatal 
  • Loss of libido, decreased sexual activity – particularly in men; occasional impotence 
  • Upset stomach , stomach pain and vomiting 
  • Significant reductions in bone density and mass, bone mineral content reduction 
  • Shortness of breath; fast, shallow breathing; Pounding or irregular heartbeat 
  • Depression - a statistically significant increase in suicidality
 

Abrupt or over rapid withdrawal produces severe withdrawal symptoms reminiscent of benzodiazepine withdrawal. This is because these drugs are often GABA based drugs like the benzodiazepines.

Side effects upon discontinuation of these drugs include insomnia, restlessness, agitation, anxiety, disorientation, confusion, light sensitivity, diaphoresis, headaches, palpitations, hypertension, chest pain, and flu-like symptoms – which normally indicate liver damage and a compromised immune system. Abrupt cessation can trigger seizures, for example,

In at least one case, abrupt cessation of a high dose of gabapentin triggered a seizure in an individual with no history of epilepsy” – [so one might ask, why was he using Gabapentin then?]

Further information

 

The following show the deaths from these drugs, the figures come from ehealthme

  • Valproic acid - On Aug, 21, 2014: 9,146 people reported to have side effects when taking Valproic acid. Among them, 188 people (2.06%) have Death.
  • Valproate sodium - On Aug, 27, 2014: 12,429 people reported to have side effects when taking Valproate sodium. Among them, 196 people (1.58%) have Death.
  • Depakote - On Sep, 15, 2014: 29,588 people reported to have side effects when taking Depakote. Among them, 428 people (1.45%) have Death.
  • Depakote er - On Aug, 29, 2014: 3,280 people reported to have side effects when taking Depakote er. Among them, 51 people (1.55%) have Death
  • Depakene - On Aug, 29, 2014: 11,215 people reported to have side effects when taking Depakene. Among them, 126 people (1.12%) have Death
  • Divalproex - On Sep, 17, 2014: 2,727 people reported to have side effects when taking Divalproex. Among them, 63 people (2.31%) have Death
  • Epival - On Sep, 17, 2014: 267 people reported to have side effects when taking Epival. Among them, 11 people (4.12%) have Death
  • Gabitril - On Sep, 8, 2014: 1,756 people reported to have side effects when taking Gabitril. Among them, 12 people (0.68%) have Death.
  • Keppra - On Sep, 16, 2014: 19,848 people reported to have side effects when taking Keppra. Among them, 464 people (2.34%) have Death
  • Gabapentin - On Sep, 11, 2014: 36,857 people reported to have side effects when taking Gabapentin. Among them, 870 people (2.36%) have Death
  • Phenytoin - On Sep, 10, 2014: 10,956 people reported to have side effects when taking Phenytoin. Among them, 155 people (1.41%) have Death
  • Dilantin - On Sep, 17, 2014: 357 people reported to have side effects when taking Dilantin. Among them, 2 people (0.56%) have Death
  • Zonisamide - On Aug, 24, 2014: 2,541 people reported to have side effects when taking Zonisamide. Among them, 33 people (1.30%) have Death
  • Zonegran - On Sep, 12, 2014: 2,747 people reported to have side effects when taking Zonegran. Among them, 28 people (1.02%) have Death
  • Tegretol - On Aug, 19, 2014: 23,949 people reported to have side effects when taking Tegretol. Among them, 315 people (1.32%) have Death
  • Carbamazepine - On Aug, 27, 2014: 15,457 people reported to have side effects when taking Carbamazepine. Among them, 222 people (1.44%) have Death
  • Carbatrol - On Sep, 8, 2014: 1,103 people reported to have side effects when taking Carbatrol. Among them, 21 people (1.90%) have Death
  • Oxcarbazepine- On Aug, 22, 2014: 2,705 people reported to have side effects when taking Oxcarbazepine. Among them, 53 people (1.96%) have Death
  • Trileptal - On Aug, 19, 2014: 11,153 people reported to have side effects when taking Trileptal. Among them, 208 people (1.86%) have Death
  • Topiramate - On Sep, 1, 2014: 7,841 people reported to have side effects when taking Topiramate. Among them, 126 people (1.61%) have Death
  • Pregabalin - On Aug, 24, 2014: 4,379 people reported to have side effects when taking Pregabalin. Among them, 146 people (3.33%) have Death
  • Lamotrigine - On Sep, 17, 2014: 14,706 people reported to have side effects when taking Lamotrigine. Among them, 237 people (1.61%) have Death.

Observations

A summary of the number of hallucinations from the eHealthme web site is shown below.  I have provided a link to the eHealthme site  which shows you the specific side-effects for each drug.

Medicine

Total number of hallucinations

Valproate

576

Valproic acid

64

Valproate sodium

53

Depakote/Divalproex sodium

278

Depakote Er

181

Depakene

55

Divalproex

458

Epival

98

Gabitril

22

Levetiracetam / Keppra

96

Gabapentin / Neurontin

392

Phenytoin sodium

6

Phenytoin

96

Dilantin

6

Zonisamide

44

Zonegran

40

Carbamazepine (CBZ)

175

Tegretol

205

Tegretol Xr

202

Carbatrol

131

Oxcarbazepine

86

Trileptal

186

Topiramate

159

Ethosuximide

3

Pregabalin / Lyrica

132

Lamotrigine / Lamictal

196

TOTAL

3940

Related observations