Archive for April 3rd, 2007


So I’ve just been reading something from Medscape written by Andres Kanner. It’s entitled Depression in Epilepsy: A New Look at This Disorder. I won’t link to it as unless you’re already a member you need to sign up and all of that. But it’s free if you want to go and have a look.

Now according to Ettinger et al., (Ettinger A, Reed M, Cramer J. Epilepsy Impact Group. Depression comorbidity in community-based patients with epilepsy or asthma. Neurology. 2004;63:1008-1014.) one in three in three people with epilepsy have experienced a moderate to severe depressive episode. Okay, so is this transient, is it representative of something more serious? Living with epilepsy or a seizure disorder can impact your quality of life so…let’s read some more.

From Kanner:

in a recent study of 200 PWE (sic: Persons With Epilepsy) also presented at the last AES meeting, deMarinis and colleagues[13] established a diagnosis of current MDEs with a structured psychiatric interview in 44 patients (22%). In 33 of these 44 patients (75%), the MDEs had been unrecognized.[13] Of note, 21 patients of the depressed patients (48%) had been seizure-free for the last year.

Okay, so we’re seeing some evidence of depression with or without seizure remission? What’s the relationship? Any ideas?

Kanner:

DD in PWE have long been thought to reflect a complication of the seizure disorder. In fact, data from population-based studies strongly suggest a bidirectional relationship between the two, whereby not only are PWE more likely to develop a DD, but patients with a DD are at greater risk of developing epilepsy.[20-22] In the first study carried out in Sweden, depression was found to be 7 times more common among patients with new-onset epilepsy than among age- and sex-matched controls. Of note, the DD preceded the seizure disorder.[20] The second study included all adults aged 55 years and older at the time of the onset of their epilepsy who were living in Olmstead County, Minnesota; in this study, the investigators found that a diagnosis of depression (also preceding the time of their first seizure) was 3.7 times more frequent among cases than among controls after adjusting for medical therapies for depression.[21] As in the previous study, this increased risk was greater among cases with partial-onset seizures.

Oooh. Now this is kind of interesting. A “bidirectional relationship” as he has termed it. Now for some science-y stuff. Because of course, that’s the only way to back it all up or try to make sense of it all? So with the two, the neurotransmitters that can be involved are Serotonin, Norepinephrine, Dopmanine, GABA and Glutamate (and probably lots more but they haven’t been discovered yet.) The tie between the two, within this article looks at Serotonin or 5HT as known by it’s shortened neurochemical name.

Kanner:

The pathogenic role of 5HT has been recognized for a long time in DD of humans and is the basis for the major pharmacologic agents in the treatment of DD today.[26] However, a pathogenic role of 5HT has also been identified in temporal lobe epilepsy (TLE) with functional neuroimaging studies. Thus, a study of patients with TLE positron emission tomographic (PET) studies with the 5HT1A receptor antagonist ([18F] trans-4-fluoro-N-2-[4-{2-methoxyphenyl}piperazin-1-yl]ethyl-N-[2-pyridyl] cyclohexanecarboxamide) demonstrated reduced 5HT1A binding in mesial temporal structures ipsilateral to the seizure focus in patients with and without hippocampal atrophy.[27] In addition, a 20% binding reduction was found in the raphe and a 34% lower binding in the ipsilateral thalamic region to the seizure focus, a difference that yielded a statistical trend. In a separate PET study aimed at quantifying 5HT1A receptor binding in 14 patients with TLE, decreased binding was identified in the epileptogenic hippocampus, amygdala, anterior cingulated cortex, and lateral temporal neocortex ipsilateral to the seizure focus as well as in the contralateral hippocampi, but to a lesser degree and in the raphe nuclei.[28] Other investigators, using the 5HT1A tracer, 4,2-(methoxyphenyl)-1-(2-[N-2-pyridinyl]-p-fluorobenzamido)ethylpiperazine ([18F]MPPF), found that the decrease in binding of 5HT1A was significantly greater in the areas of seizure onset and propagation identified with intracranial electrode recordings. As in the other studies, a reduction in 5HT1A binding was present even when quantitative and qualitative magnetic resonance imaging (MRI) was normal.[29] In a recent study of 46 patients with TLE, Theodore and colleagues demonstrated an inverse correlation between increased severity of symptoms of depression identified on the Beck Depression Inventory and 5HT1A receptor binding at the ipsilateral hippocampus to the seizure focus, and to a lesser degree at the contralateral hippocampus and midbrain raphe (presented at the American Academy of Neurology 58th Annual Meeting; San Diego, California; April 1-8, 2006; manuscript submitted).

Whoa! What the hell’s that all about, eh? Okay, basically, we all know that Serotonin (or suspect?) plays a role in Depression. Hence the treatment with SSRIs. But by using PET scans and a receptor antagonist–a substance that blocks the receptor–the trans-4-flour etc…thingy–what happened was, Serotonin would not “stick.” Not like it’s stupposed to and basically reabsorb back into your brain. What is also key is where they did this. It wasn’t just random, it was in specific areas of the brain where the seizure activity was occurring. And it was whether or not damage had been done to the hippocampus. This can occur. Other areas noted are also key areas affected by TLE (Temporal Lobe Epilepsy) and it is also interesting to note that these things were found with or without a normal MRI. I had a normal MRI. My neurologist also wonders whether I have something funky going on within my limbic area of my brain. Now this is where I personally kind of say…huh?

Kanner:

Data on the pathogenic role played by 5HT cited above would presuppose an anticonvulsant effect of serotonergic drugs, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). A recent study seems to give credence to such supposition: Alper and colleagues[49] reviewed data from regulatory studies of SSRIs and SNRIs in depressed patients and compared the incidence of seizures between patients with depression randomized to SSRIs or SNRIs and those randomized to placebo. These investigators demonstrated that those patients randomized to receive placebo were significantly more likely to have epileptic seizures than those randomized to receive the antidepressant medication.[49] These data also support results from studies suggesting an increased risk for epileptic seizures in depressed patients.

These data are contrary to the long-held belief that antidepressant drugs are proconvulsant drugs. In fact, a lowering of the seizure threshold by antidepressant medication occurs only at toxic doses and with 4 specific antidepressants: clomipramine, maprotiline, amoxapine, and bupropion. These antidepressants should be avoided in patients with epilepsy.[50]

Now, okay. Having lived through seizing from serotonergic drugs (and yes, I am Bipolar so not labelled as having “Depression” as this article states) I suppose for certain members of the population like within the study this may hold true. But my anecdotal evidence tells me otherwise. And the meds I was on (Effexor and Wellbutrin–two SNRIs) are not on the list and I was not taking them at toxic doses.

As far as the first paragraph? I don’t suspect that they’ll be handing out SSRIs to manage epilepsy or seizure disorders any time soon? I really hope not! I’m sorry but I still think antoconvulsants are the best route. Because really, Serotonin is not the only neurotransmitter involved when people seize!

ref: [13] De Marinis A, Bustamante F, Asmad C, et al. Prevalence and underrecognition of depression in patients with epilepsy: the experience of the Chilean League Against Epilepsy. Epilepsia. 2006;44(suppl4):3.214.

ref: [20] Forsgren L, Nystrom L. An incident case referent study of epileptic seizures in adults. Epilepsy Res. 1990;6:66-81.

ref: [21] Hesdorffer DC, Hauser WA, Annegers JF, et al. Major depression is a risk factor for seizures in older adults. Ann Neurol. 2000;47:246-249.

ref [22] Hesdorffer DC, Hauser WA, Olafsson E, Ludvigsson P, Kjartansson O. Depression and suicidal attempt as risk factor for incidental unprovoked seizures. Ann Neurol. 2006;59:35-41.

ref: [26] Nestler EJ, Barrot M, DiLeone RJ, Eisch AJ, Gold SJ, Monteggia LM. Neurobiology of depression. Neuron. 2002;34:13-25.

ref: [27] Toczek MT, Carson RE, Lang L, et al. PET imaging of 5-HT1A receptor binding in patients with temporal lobe epilepsy. Neurology. 2003;60:749-756.

ref: [28] Savic I, Lindstrom P, Gulyas B, Halldin C, Andree B, Farde L. Limbic reductions of 5-HT1A receptor binding in human temporal lobe epilepsy. Neurology. 2004;62:1343-1351.

ref: [29] Merlet I, Ostrowsky K, Costes N, et al. 5-HT1A receptor binding and intracerebral activity in temporal lobe epilepsy: an [18F]MPPF-PET study. Brain. 2004;127:900-913.

ref: [49] Alper K, Schwartz KA, Kolts RL, Khan A. Seizure incidence in psychopharmacological clinical trials: an analysis of Food and Drug Administration (FDA) summary basis of approval reports. Biol Psychiatry. In press.

ref: [50] Kanner AM. Depression in epilepsy: prevalence, clinical semiology, pathogenic mechanisms and treatment. Biol Psychiatry. 2003;54:388-398.


This post really has no point other than to demonstrate that my colleagues and I are bad. And perhaps the Lamictal, even though I haven’t taken any today, is still making me feel goofy. Or maybe life simply is.

Anyway, I don’t even know how we went from talking about something in the professional realm to “Art vs. Pornography” but sometimes that’s just how it goes around here. One girl was a little fearful of David Cronenberg’s Crash but another gent and I were really cheering it on. I love that film and I really love Cronenberg. I also really like David Lynch but I need to keep reviewing his films over and over again until I think I’ve finally understood at least half of the plot.

Anyway, my point about Crash (the movie) was that it wasn’t so sexually graphic but more that you had to wrap your head around the psychological concept of people becoming sexually aroused by vehicular accidents. I know, a little odd but let’s not get our knickers in a knot. Then my gentleman colleague offered his take on J.G. Ballard’s book (that I do have at home and still haven’t read…argh…) about dsytopian philosophy etc… etc… even though the movie didn’t take it in that direction. I need to read the book.

Then gentleman colleague asked if we’ve ever heard of the photographer Richard Kern? I thought I had but I wasn’t sure. So on he pops to do some searching and we’re viewing some of his work. Click, click, click…whoa! Up comes a woman with a lit candle placed rather strategically. Oh the bad puns begin!

“Talk about burning the candle at both ends!”

“I see a light at the end of the tunnel!”

I was almost on my knees laughing. My colleague was asking just why exactly was he searching for porn at work anyway sarcastically.

Then someone, another work mate, sent me this YouTube clip. It’s probably not even worth posting but if you need a good swearing fix, here it is. In fact, that’s all it is. It’s from The Departed. I never saw it but apparently, it used “fuck” in some variant 237 times. So this is an edited version.