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Many of the antiseizure I'm aware of are described as having the potential for behavior altering side-effects. I am curious about this.

  • Is there something about the chemistry of the brain that frequently makes anticonvulsants also psychoactive? Does it have to be this way?

OR

  • Maybe the anticonvulsant drug profiles are like this because much more money is invested in R&D for psychoactive drugs used in psychology than is invested in R&D for epilepsy drugs. And, during the R&D process the anticonvulsant property of a drug is discovered as being the side effect of the drugs whose main property is psychoactivity. And this might be why the anticonvulsants being sold are psychoactive?

Viagra was discovered during R&D into high blood pressure. Viagra does lower high blood pressure. Viagra also has a side effect. People take Viagra for the side effect.

So, might it be like:
During R&D into psychoactive drugs, Zonisamide was discovered to have the side effect of elevativing the seizure threshold. Zonisamide is psychoactive. Zonisamide also elevates the seizure threshold as a side effect. People take Zonisamide for the side effect?

Is it understood why anti-epileptic drugs are always mood altering? Is it chemical? a product of the R&D cycle? a simple correlation that a person with the disease might be more emotional?

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  • $\begingroup$ Welcome and nice question! It seems that many psychiatric drugs either raise or lower seizure threshold. Some are the opposite of anticonvulsants, e.g. seroquel (and other antipsychotics) and probably most stimulants, including the mild ones like bupropion. Why this happens is an interesting question. $\endgroup$ Commented Jan 21, 2018 at 10:07
  • $\begingroup$ My guess is that since most psychoactive drugs either raise or lower some neurotransmitter they also have the potential to raise or lower the seizure threshold in the brain areas that use that neurotransmitter. $\endgroup$ Commented Jan 21, 2018 at 10:18
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    $\begingroup$ @OP - could you give examples of drugs you are talking about? Secondly, and more importantly, what do you mean with 'psychoactive'? Anticonvulsants have many side effects, so a definition of psychoactive is essential. -1 $\endgroup$
    – AliceD
    Commented Jan 24, 2018 at 9:08
  • $\begingroup$ As far as I can gather, with the exception of Felbamate all Anticonvusants mentioned in this list are Psychoactive as described in this Wikipedia article $\endgroup$ Commented Jan 24, 2018 at 14:05
  • $\begingroup$ @AliceD The drugs I am referencing are the drugs, such as Lamictal, Topamax, Zonisamide, Keppra, etc. The definition of psychoactive that was described to me by my friend is the wikipedia definition of "psychoactive drug". Taking the drug alters "mood and perception". $\endgroup$
    – Khae
    Commented Jan 27, 2018 at 5:07

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Note: I have epilepsy, and have been taking anticonvulsants for the best part of 2 decades. I've stumbled across this post after researching some things related to recent changes in side-effects, dosage, and other issues that stem from my treatment plan.

Are they coincidentally psychoactive?

No. Absolutely not. By definition, every anticonvulsant drug has to be psychoactive. I noticed that Chris Rogers in a comment mentioned Felbamate as the only non-psychoactive drug. I want to address this directly and say that Felbamate most definitely fits the cited description of a psychoactive substance:

a chemical substance that changes nervous system function, and results in alterations in perception, mood, consciousness, cognition, or behavior

Just like any other anticonvulsant, felbamate relies on GABA and GABA receptors to do its job. GABA (or gamma aminobutyric acid) is the main inhibitory neurotransmitter. Its primary role is to reduce excitability of neurons. Now let's clarify what a seizure actually is:

A seizure is the hyper-excitability of neuron(s) that trigger hyper-synchronisation of surrounding neurons, resulting in something akin to a neurological Kessler syndrome where (over simplified): a single neuron gets hyper excited, and triggers an ever larger group of surrounding neurons to join in and fire at the same time. If that happens in your motor cortex, that can lead to most of the muscles in your body to contract and relax at the same time (ie a tonic-clonic seizure).

All anticonvulsants rely on GABA to reduce the excitability of neurons to prevent these cells from triggering your neurons into this mexican wave type of firing. No medication exists that specifically targets the neurons that are hyper-excitable, though, and thus there isn't an anticonvulsant out there that doesn't list any of the following side effects:

  • Drowsiness
  • Fatigue
  • Memory loss
  • Brain fog
  • Depression
  • Suicidal thoughts
  • Weight gain

Like many people with epilepsy, I often describe the effects of the medication as "feeling suppressed". It's as though I've not slept for 24 hours. Like a severe lack of sleep, it definitely impacts things like mood, cognition, consciousness, and even perception. My perception of time, for instance, is absolutely not the same as it was before I went on medication. The medication-induced feelings of depression are very real, too. The inability to perform physical tasks with the precision, speed, and energy that comes natural to any human being just isn't there anymore. Your metabolism is impacted (hence weight gain is a common complaint), and so on...

In addition to this, most of these meds have an effect on endocrine hormone production/regulation, which in turn either reinforces mood/behaviour changes, or causes a slew of new ones.

I recently tried to switch to a new treatment plan, and moved to a high dose of levetiracetam (keppra). A side effect of this is affectionately known as "kepprage". The leaflet in the box just calls it "aggression/assertiveness". While the specifics about how levetiracetam exactly works is (AFAIK) not fully understood, I found a paper a while back specifically looking into the causes of behavioural changes. The neuro-chemistry of this drug has some remarkable similarities to steroid abuse. source

All in all: when talking about anticonvulsant medication, we're talking about drugs that work because they regulate/alter the functioning of your central nervous system. That's the first half of the definition of psychoactive as cited above. Because their job is to reduce excitability of neurons, they all (AFAIK) use GABA in some capacity to do their job. This, by definition, will have an effect. The bare minimum is that you'll feel tired, but more often than not (AFAIK, always), it'll impact your ability to focus, remember things, and very commonly will make people feel more down (mood changes). Feelings of depression, fatigue, and confusion, combined with memory loss will result in behavioural changes. TL;DR all anticonvulsants are, by definition psychoactives.

Is the anticonvulsant effect a side-effect?

This is a bit more of a grey area. Sodium valproate (or valproic acid) was first synthesised in the late 19th century, and for 80 years, it was uniquely used as a "metabolically inert" organic solvent. Its anticonvulsant effects were accidentally discovered, and the drug has since seen ever more medical applications (epilepsy treatment, bipolar disorder, schizophrenia treatment, etc...). wiki:

Valproic acid was first synthesized in 1882 by Beverly S. Burton as an analogue of valeric acid, found naturally in valerian. Valproic acid is a carboxylic acid, a clear liquid at room temperature. For many decades, its only use was in laboratories as a "metabolically inert" solvent for organic compounds. In 1962, the French researcher Pierre Eymard serendipitously discovered the anticonvulsant properties of valproic acid while using it as a vehicle for a number of other compounds that were being screened for antiseizure activity. He found it prevented pentylenetetrazol-induced convulsions in laboratory rats. It was approved as an antiepileptic drug in 1967 in France and has become the most widely prescribed antiepileptic drug worldwide. Valproic acid has also been used for migraine prophylaxis and bipolar disorder.

So in a way, sodium valproate became an anticonvulsant as its use in treating epilepsy was an unintended side-effect. Then again, its initial use was not one of a psychoactive drug either.

Levetiracetam, on the other hand, was a more recently developed drug that, as far as I know, was specifically developed to be used as an anticonvulsant. It is a psychoactive, so it's not a stretch to assume that the R&D that lead up to its discovery was focused on psychoactive compounds, but the end product was clearly not a psychoactive drug that just so happened to have anticonvulsant properties. Its an anticonvulsant by design that just happens to have psychoactive properties.

From my own experience, I can also say that its psychoactive properties are pretty damn terrible. When I was on a high dose of the stuff, I had an episode where I screamed at my girlfriend, threw stuff around, and just raged for extended periods of time. When I woke up the next day to find her packing, I asked what was going on. I had no recollection of the incident. Naturally, I immediately got in touch with my neurologist and changed my treatment plan.

Serendipity and R&D

All this, of course, is not to say that there aren't psychoactive drugs that are developed, and then found to have anticonvulsant properties. However, the opposite is just as common. Again: sodium valproate started out as a solvent, was repurposed as an anticonvulsant, is now used to treat things like bipolar disorder, anxiety disorders, migraines, and I know people personally who have received it as part of their treatment for schizophrenia and narcolepsy.

The one thing these conditions have in common is that they are, at least physiologically speaking, neurological in nature. It stands to reason that any substance that effects the central nervous system represents an a potential use-case to explore. That's why things like levetiracetam are currently being evaluated as potential treatments in patients with Alzheimer's and Parkinson's disease.

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