AEDs are evil

[Bernard]

http*//pharmatruth.tumblr.com/post/30341070/pharmatruth

The link above references numerous studies indicating that anti-epileptic drugs cause serious cognitive impairments.

[speber]

...I'm so glad this site is making one side softer.

[BuckeyeFan]

The anti-epileptic drug I noticed the most in that link was Depakote. Some really major issues with development noted. I would have liked to have seen more in these studies about late onset epilepsy (mine started at 20), but I guess that was not there focus.

Speber sure has it right about being caught between a rock and a hard place. What I worry about in addition to loosing my basic functionality without the anti-epileptic drugs is any brain/cognitive/memory damage due to uncontrolled seizures. Which is worse if they both cause brain damage?

Just starting to take baby steps towards alternatives since I am fairly controlled NOW. My concern lies more into the future. I can't retire for another 20 years and how well will I be able to function then. It may be my imagination, but I don't believe I am as mentally capable as I was 5, 10, or 15 years ago.

Good news is I have found out more about E in the last 2-3 years than I did in the previous 25. Thanks to the internet and more recently CWE.



I found this link that I feel is pretty informative on many areas of epilepsy.

http://www.ninds.nih.gov/disorders/e...l_epilepsy.htm

[Dutch mom]

Thanx Bernard, this one has an impressive collection of links.
I've posted it in the anti-epileptic drug files of our Dutch group.
Too many of our children are long term on several heavy combinations of polytherapy (several anti-epileptic drug's and benzo's) and do suffer from many seizures as well as the negative side effects of anti-epileptic drug, including increase of mental retardation.
Nasty stuff for kiddies

[Duvexy]

Yes I do agree that anti-epileptic drug's are evil. Makes you wonder which is worse, that is if you don't have a lot of seizures if they are worth it or not. I take the carbamazepine and it is true that I am losing my memory. Sometimes the memories come back in my dream too. Which is weird. Have any of you had that happened?

[Meetz1064]

just recently, as a matter of fact, I had that happen. And it was weird, it was a memory from over 30 years ago, which I hadn't been able to retrieve in quite some time....don't know why I was suddenly able to, but I did, but I did so in my dreams......I know it was real, though, as I went up and found my picture album, and found the same memory, taken in pictures from a trip out West with my aunt and uncle and cousins......

[Dutch mom]

Hello Bernard,

Thanx for notifying me the link has gone bad.
Like I wrote back, if possible I do copy-paste text with the links on our forum because links often don't work anymore after a while.
This one was very interessing for parents of our Dutch group, so you're lucky, I saved it!

copy:

http*//pharmatruth.tumblr.com/post/30341070/pharmatruth




Cognitive Side Effects of Antiepileptic Drugs in Children
These drugs, such as Depakote, are also commonly used to treat bipolar disorder and even migraines.

-Antiepileptic drugs decrease membrane excitability, increase postsynaptic inhibition or alter synchronization of neural networks to decrease excessive neuronal excitability associated with seizure development. Common side effects of decreasing neuronal excitability, however, are slowed motor and psychomotor speed, poorer attention and mild memory impairment (Meador, 2005).

-[…]treatment decisions made in childhood may have lifelong implications. Adults who developed epilepsy during their childhood tend to have less education, decreased rates of employment and employment at lower job levels, lower rates of marriage, poorer physical health, and increased incidence of psychiatric disorders (Jalava and Sillanpaa 1997a, 1997b; Jalava et al., 1997; Sillanpaa et al., 199. Importantly, these long-term effects are also present in adults who are no longer taking medications. The persistence of these effects after discontinuation of anti-epileptic drug treatment suggests a role of either seizure etiology, cumulative effects of repeated seizures or anti-epileptic drug treatment permanently altering the course of development

-Studies in rats have shown significant anti-epileptic drug effects in the developing brain including apoptotic neurodegeneration

-The AAP Committee on Drugs (1995) concluded, “Few studies have been comprehensive, and for most drugs, neuropsychological effects have been incompletely described.”

-In studies, children on phenobarbital displayed IQ declines (Farwell et al., 1990; Wolf et al., 1981), and although IQ improved following discontinuation of phenobarbital (Farwell et al., 1990; Sulzbacher et al., 1999), there continued to be long-term achievement effects when these children were tested three to five years later (Sulzbacher et al., 1999). The inability of children to fully catch up and compensate for “lost time” is important because it suggests a more complex interaction of anti-epileptic drug therapy and developmental maturation than simply interfering with new learning efficiency. Because IQ declines are thought to reflect slowed mental growth rather than a loss of previously acquired cognitive function or cognitive regression, concern exists that any anti-epileptic drug with cognitive side effects may result in significant impairment based upon cumulative effects if used over extended periods.

-In children, anti-epileptic drug effects are seen in decreased performance on the Continuous Performance Test (CPT) [a measure of ADHD] (Mandelbaum et al., 2003) or memory. In addition, some children are at heightened risk for developing disproportionate cognitive side effects with carbamazepine [Tegretol](Seidel and Mitchell, 1999). Treatment with carbamazepine has also been associated with electroencephalogram slowing in the alpha range (Frost et al., 1995). How these short-term effects translate into academic achievement has not been adequately established (Bailet and Turk, 2000). However, there appears to be some relationship between the magnitude of EEG slowing and subsequent decline on selected Wechsler Intelligence Scale for Children-Revised (WISC-R) subtests tested after one year of therapy (Frost et al., 1995).

-Topiramate [Topamax] has an approvable letter from the U.S. Food and Drug Administration for pediatric use, although there is evidence from many sources that at certain doses there is a risk of neuropsychological impairment (Dooley et al., 1999; Kockelmann et al., 2003; Meador et al., 2003; Salinsky et al., 2005). The possibility that some patients may be at heightened risk for cognitive impairment with topiramate remains a possibility (Meador et al., 2003). Although worse than those of most newer anti-epileptic drugs, the cognitive side effects of topiramate are generally comparable to those associated with valproate sodium (Meador et al., 2003). [Depakote]

-In addition, no comparative randomized, controlled trials have been conducted in children using newer anti-epileptic drugs available in the United States

http://ahrp.blogspot.com/2007/05/24-of-children-of-mothers-prescribed.html

-24 percent of the children of mothers who took valproate [Depakote] during pregnancy showed an IQ in the mental retardation range. That alarming finding was presented at the American Academy of Neurology’s 59th Annual Meeting in Boston, April 28 - May 5, 2007.

Blackwell Synergy - Epilepsia, Volume 43 Issue 5 Page 482-490, May 2002 (Article Abstract)

Blackwell Synergy - Epilepsia, Volume 43 Issue 5 Page 482-490, May 2002 (Full Text)

-Results: Both CBZ [Tegretol] and GBP [Neurontin] significantly decreased the peak frequency of the posterior (alpha) rhythm, with CBZ exerting a greater effect. Ten CBZ and six GBP subjects exceeded the 95% confidence interval (CI) for an individual. Cognitive tests revealed anti-epileptic drug vs. control group effects for two of seven measures (Digit Symbol, Stroop) and all subjective measures. However, few subjects exceeded the 95% CI for any objective test. Differences between CBZ and GBP were not significant. Greater EEG slowing was associated with greater subjective neurotoxicity and poorer test–retest performance on a cognitive test summary measure.
Conclusions: Prolonged CBZ and GBP therapy induced EEG slowing that correlated with cognitive complaints and often exceeded the confidence interval for individual subjects. Quantitative EEG measures may be useful in the objective determination of anti-epileptic drug-related neurotoxicity.

E-epilepsy - Foetal Valproate Syndrome and Autism: Additional Evidence of an Association

-Valproate is an anti-epileptic drug which is known to be potentially teratogenic, originally associated with an increased risk for neural tube defects. More recently, foetal valproate syndrome has been recognised as a clinical entity characterised by phenotypic abnormalities of the face, developmental delay and occasional major organ abnormalities involving respiratory, cardiovascular, gastrointestinal, genitourinary and skeletal systems. There have also been reports that offspring exposed to Sodium Valproate during pregnancy are more likely to have further educational needs, including autistic traits.
This paper describes a series of five patients with foetal valproate syndrome (FVS), who also had clear evidence of autism. All the patients showed evidence of cognitive deficit, manifestation of autism and typical phenotypic characteristics of FVS.
This paper describes a series of five patients with foetal valproate syndrome (FVS), who also had clear evidence of autism. All the patients showed evidence of cognitive deficit, manifestation of autism and typical phenotypic characteristics of FVS.

CJO - Abstract - Influence of major antiepileptic drugs on neuropsychological function: Results from a randomized, double-blind, placebo-controlled withdrawal study of seizure-free epilepsy patients on monotherapy

-[…]in subjects with therapeutic drug levels at baseline, drug withdrawal was associated with significant improvement in performance on the Controlled Oral Word Association Test and the Stroop Color–Word Interference Test.


Blackwell Synergy - Epilepsia, Volume 47 Issue 12 Page 2038-2045, December 2006 (Article Abstract)

-The major finding in this study is that discontinuation of major anti-epileptic drugs significantly improved performance on tests that require complex cognitive processing under time pressure. The difference in speed of cognitive processing between the two groups on these tasks was between 24 to 43 ms. Simple tasks of attention and reaction time revealed no significant differences between the discontinuation group and the nondiscontinuation group. Most of the subjects in the study were medicated with carbamazepine (CBZ) [Tegretol] and valproate (VPA) [Depakote]. The outcome of discontinuation of CBZ was similar to the outcome for the total study population, whereas withdrawal of VPA revealed only a nonsignificant tendency in the same direction.


Dr Justin H G Williams

-Dean JCS, Williams JHG , Rasalam AD, et al. Reversal of sex ratio in fetal anticonvulsant syndrome associated autistic disorder: possible evidence that some anticonvulsants disturb imprinted genes? American Journal of Human Genetics (2002) 71 (4): 31 Suppl.

Second part: see message above

[Dutch mom]

CiteULike: Effects of hyperammonaemia on brain function.

Depakote frequently causes hyperammonemia, which causes brain damage. Despite this fact, ammonia testing is not required for patients taking Depakote.


-Neuropsychiatric symptoms of hyperammonaemia include alterations of mood and personality, cognitive impairment, ataxia, convulsions and coma. The nature and severity of CNS dysfunction depend upon the aetiology and degree of hyperammonaemia, its acuteness of onset and the age of the patient. Neuropathological studies reveal Alzheimer type II astrocytosis in the adult hyperammonaemic patient, whereas hyperammonaemia in the infant resulting from congenital urea cycle disorders or Reye syndrome is accompanied by cerebral atrophy, neuronal loss and cerebral oedema. Several electrophysiological and biochemical mechanisms have been proposed to explain the deleterious effects of ammonia on CNS function. Such mechanisms include direct effects of the ammonium ion on excitatory and inhibitory neurotransmission and a deficit in cerebral energy metabolism due to ammonia-induced inhibition of alpha-ketoglutarate dehydrogenase. In addition, ammonia has been shown to interfere with normal processes of uptake, storage and release of various neurotransmitters. Ammonia disrupts monoamine storage, inhibits the high-affinity uptake of glutamate by both astrocytic and neuronal elements and activates ‘peripheral-type’ benzodiazepine receptors leading to the potential synthesis of neuroactive steroids in brain. On the basis of these actions, it has been proposed that ammonia disrupts neuron-astrocyte trafficking of amino acids and monoamines in brain. The increased formation of brain glutamine in hyperammonaemic syndromes could be responsible for the phenomenon of brain oedema in these disorders. Therapies aimed at either decreasing ammonia production in the gastrointestinal tract or increasing ammonia removal by liver or skeletal muscle are the mainstay in the prevention and treatment of the CNS consequences of hyperammonaemia. New therapeutic approaches aimed at correction of the neurotransmitter and cerebral energy deficits in these syndromes could hold promise for the future.

SpringerLink - Journal Article

Carbamazepine encephalopathy masquerading as Creutzfeldt-Jakob disease — Horvath et al. 65 (4): 650 — Neurology

IngentaConnect Carbamazepine: Encephalopathy: case report


Effects of antiepileptic drugs on EEG background a…[Clin

Electroencephalogr. 1995] - PubMed Result

Brain pseudoatrophy and mental regression on valpr…[Neurology. 2006] - PubMed Result


Reversible valproate hepatotoxicity due to mutations in mitochondrial DNA polymerase {gamma} (POLG1) — McFarland et al. 93 (2): 151 — Archives of Disease in Childhood

Reversible pseudoatrophy of the brain and mental d…[Epilepsia. 1998] - PubMed Result

-RESULTS: After 2 years and 6 months on VPA (Pseudoatrophy of the brain with valproic acid mono…[Can J Neurol Sci. 1987] - PubMed Result

-A patient is described who, while on valproic acid monotherapy [Depakote], developed reversible shrinkage of the brain, documented by computerized tomography with associated cognitive deficit.

Reversible cortical atrophy and cognitive decline …[Eur J Paediatr Neurol. 1998] - PubMed Result

-At the age of 14 years, sodium valproate [Depakote] was started as add-on therapy; 2 weeks later he was hospitalized in a stuporous state. The serum level of valproate was within the therapeutic range. Cognitive evaluation disclosed moderate mental retardation. No metabolic abnormalities were detected. Valproate was discontinued and during the 4 following months, a slow but significant improvement was documented in cognitive functions. Repeated assessment was within the range of mild mental retardation. Initially, magnetic resonance imaging (MRI) showed mild cortical atrophy. A subsequent MRI study performed 2 years later was normal.

Reversible dementia and apparent brain atrophy dur…[Ann Neurol. 1995] - PubMed Result

-Two children developed severe cognitive and behavioral deterioration suggestive of a degenerative disease while being treated with sodium valproate for idiopathic, localization-related epilepsy with centrotemporal spikes. Magnetic resonance imaging revealed marked central and generalized cortical and cerebellar atrophy.

Reversible altered consciousness with brain atroph…[Pediatr Neurol. 2003] - PubMed Result
-A 5-year-old female developed alteration of consciousness during 3 days of long-term treatment with valproic acid for localization-related epilepsy. Computed tomography revealed cerebral atrophy, and electroencephalography presented slow background activity.

Loss of autonomy related to valproic acid intake. [J Am Geriatr Soc. 2006] - PubMed Result

Reversible cognitive and neurological symptoms dur…[J Am Geriatr Soc. 2007] - PubMed Result

Antiepileptic drugs and apoptotic neurodegeneratio…[Proc Natl Acad Sci U S A. 2002] - PubMed Result
-The cause of unwanted effects of therapy with anti-epileptic drugs is unknown. Here we reveal that phenytoin, phenobarbital, diazepam, clonazepam, vigabatrin, and valproate cause apoptotic neurodegeneration in the developing rat brain at plasma concentrations relevant for seizure control in humans. Neuronal death is associated with reduced expression of neurotrophins and decreased concentrations of survival-promoting proteins in the brain. beta-Estradiol, which stimulates pathways that are activated by neurotrophins, ameliorates anti-epileptic drug-induced apoptotic neurodegeneration. Our findings present one possible mechanism to explain cognitive impairment and reduced brain mass associated with prenatal or postnatal exposure of humans to antiepileptic therapy.

IngentaConnect Carbamazepine induction of apoptosis in cultured cerebellar neurologist…

SpringerLink - Journal Article

Valproate-associated Hyperammonemic Encephalopathy — Wadzinski et al. 20 (5): 499 — The Journal of the American Board of Family Medicine

A case of Parkinsonian syndrome, cognitive impair…[Encephale. 2005 Jan-Feb] - PubMed Result

In utero antiepileptic drug exposure: Fetal death and malformations — Meador et al. 67 (3): 407 — Neurology

ScienceDirect - International Journal of Developmental

Neuroscience : The teratology of autism

Hyperconnectivity of Local Neocortical Microcircuitry Induced by

Prenatal Exposure to Valproic Acid — Rinaldi et al., 10.1093/cercor/bhm117 — Cerebral Cortex

Prenatal exposure of rats to valproic acid reprodu…[Neurotoxicol Teratol. 2000 May-Jun] - PubMed Result

SpringerLink - Journal Article

Major malformations with valproic acid

Epilepsy Ontario :: anti-epileptic drugs & Memory

wcbstv.com - Report: Drugs Found In Big Apple’s Drinking Water

Hyperconnectivity of Local Neocortical Microcircuitry Induced by
Prenatal Exposure to Valproic Acid — Rinaldi et al. 18 (4): 763 — Cerebral Cortex

Bernard,

The text was too long for one message, this is the second part (Maybe you can fix it too one by adding both messages together? Or I can send you the whole text by mail.)

[Bernard]

That's OK. Two parts are fine. I appreciate you reposting it seeing as how there is no longer any copyright concerns.

[speber]

[JLynn]

The medication I take is considered not the best for controllin siezures, but I refused to take the stronger meds, due to serious side effects as described.
I take diazepam. Yep, valium. Since my type of epilepsy is said to be hard to control anyway with most medications, I saw no reason to put myself in a much stronger drug induced state with outragious risks, and I am sensitive to many medications, including allergic to many too. I have taken it for 13-14 years, originally for panic attacks, then switched to it being used for epilepsy when I was finally diagnosed for sure after my mri. Just this month my dose was increased, because it wasnt working anymore, and probably hadnt been working for quite a long time, other than my neurologist said she thought it was at least keeping me from having stronger seizures then what I am having, and according to my mri I am at risk for tonic clonic. But I have never had one lucky me! I do not take a high dose of my med either, took 6-8mg a day all those years, and just got bumped up to 15mg a day, and am actually feeling somewhat better, and most of the attacks have stopped, weather they were panic or seizures, probably some of both.
I dont knock anyone thou for thier choice in treatment, as mine is probably not good for many.
JLynn

[RobinN]

JLynn, my daughter was "diagnosed" after an MRI scan, and she is living med free at this time. Her therapy is explained in the "story" linked below.

[JLynn]

I am so interested in this therapy. I am going to look for it in my area.
Only problem, for the first time in years... we do not have insurance, as my husband was laid off his job in May and is in the process of starting his own business, and not enough money right now to pay for insurance or cobra.
As soon as we do, Im going to try this. However, it sounds like insurance may not pay for it anyway? I will do what I have to do to try this treatment,
How wonderful it must be for your daughter now. So glad for her
I hope someday that will be me too