The "three buzzing conditions" are epilepsy, bipolar disorder and migraine.

The mainstream medical explanation for both epilepsy and migraine involve convulsions (seizures) triggered by abnormal electrical activity in the brain. In the case of bipolar disorder, the convulsive hypothesis has never been demonstrated to the (fortunately) high scientific standards of the biological psychiatry community, and there is actually a new field of exploration centering around neurotransmitters.

I'm not impartial. General hand-waving about neurotransmitters tends to irk me, as big pharma marketing has jeopardized the public image of biological psychiatry with oversimplified and sometimes flat out false theories like the "chemical imbalance" explanation for major depression. Actually, psychiatrists have known for a while that major depression results from neuron atrophy in the emotional center of the brain; while SSRIs make your brain marinate on serotonin, it's not until they have been on your system for long enough to stimulate neuron regrowth that relief is felt.

Also, I am bipolar. I feel that bipolar disorder being closely related to epilepsy would erase much of the stigma. Some forms of epilepsy can trigger mood episodes, psychotic symptoms like hallucinations, derealization and depersonalization crises and even automatisms, but those don't get all the press that more common forms of epilepsy most characterized by tonic-clonic seizures do. Actually, from my symptoms the diagnosis of temporal lobe epilepsy was briefly considered, though EEG readings didn't show anything.

I still have a buzzing (try to catch if the pun is intended) paranoia that, even though my doctor blows off the idea, I might have not shown any abnormal electric readings on my EEG because I was on godzilla amounts of lamotrigine, clonazepam and Depakote, and I might actually have temporal lobe epilepsy. But since I'm not restricted to any insurance-dictated lines in the sand, my doctor likes to say he's primarily interested in improving the well-being and global functioning of his patients, and data-fitting to the standard medical ontologies (like the DSM-IV and the ICD-10) is merely instrumental, though the most important first step towards that goal.

In any case, the current convulsive explanation for bipolar disorder involves seizures happening deep into the brain, into an area known as the anterior cingulate inside your "mammalian brain" complex. Unipolar major depressive disorder, if it's even a separate disease and not something inside a bipolar spectrum, is currently understood to be caused by neuron atrophy precisely there. Ordinary EEGs won't be able to detect electrical activity that deep inside the skull, and imaging studies are pretty much an exercise of Where's Waldo, where Waldo's picture is not quite known. Still, there has been some evidence of abnormal electrical conduction in the anterior cingulate in inpatient (that is, residing in a hospital, either voluntarily or not, for a period of time that could be predetermined or not) study settings.

On the other hand, what I hope that are honest-to-god researchers are looking for neurotransmitter causes in the line of the schizophrenia studies, and claim to have found important milestones as well. But is anyone paying for seizure research in bipolar disorder anymore? How about the high comorbidity of tonic-clonic seizure-indicing epilepsy and general atypical mood disorders -- let alone the uberspazz syndrome (epilepsy + bipolar + autism) identified by "citizen expert" Jerod poor from the Crazy Meds! reference site?

That's not to invalidate whatever connections between the neurotansmitter processes found in schizophrenia and bipolar activity. I myself can claim to have come down from my severest manic episode through a hard shock of risperidone and have been on Seroquel along with my anticonvulsants for the extra stabilizing kick -- specially since I'm on Ritalin now. But let's look back at how the seizure-bipolar connection first was hypothetized and how it became the standard theory among practitioners (though never pronounced official by mainstream science, I'm glad science is more careful than I am when drawing connections between things I don't fully comprehend).

The convulsive hypothesis was first posited in the 1980s, most famously by dr. Robert Post, who observed that mood episodes seemed to exhibit the same kindling behaviour epileptic seizures do -- each seizure/episode tends to lower the threshold for the next one. Epileptic disorders are different in what seems to correlate to a seizure -- infamously, rapid blinking lights have caused seizures even in kids without an epileptic brain make-up, but many people will have emotional stress-related seizures, specially in temporal lobe epilepsy. Do you see the connection there already?

Now, because bipolar kindling was in fact confirmed by further studies and is now considered for all practical means true by pretty much all psychiatrists -- even those who don't fully embrace the medical model of mental illness -- studies with antinconvulsant drugs for bipolar disorder had a boom period. Phenobarbital and similar drugs had been used to "curb" morbid mania in institutional settings already, and there were new, cleaner anticonvulsant drugs that could and did make good money for the pharmaceutical companies as soon as they entered into use in mood disorder settings.

Crazy Meds!, the drug reference I trust the most, has lots of detailed information on anticonvulsants, specially since the main editor is both epileptic and bipolar. But let me just list a few meds that either I or bipolar penpals (better than a support group; those tend to be filled with people who've already ruined their lives, while we're trying precisely to avoid that) have used. Off the top of my head; maybe a few factual corrections on FDA approval will be in order as soon as I manage to have a blotch of free time in a place (not a bus) with internet access. Please keep in mind that this is only anecodotal compilations, and the plural of data isn't proof.

  • Tegretol/Trileptal/carbamazepine/oxcarbamazepine: approved for epilepsy and bipolar disorder, afaik. I don't know personally cases of these being used for migraines, but everything leads to believe that small doses of any anticonvulsant would help preventing migraines, and this just isn't the first-line one because of its interesting suite of side-effects, drug interactions and all sorts of fun. By Jove, if you smoke you either double or halve (I don't remember) the effect of Tegretol. It's also strongly connected with weight gain and bizarre birth defects if you take it while pregnant. Generally considered a good maintenance agent, though not powerful enough to break out of either an acute manic or depressive episode.
  • Depakote/sodium valproate/valproic acid/sodium divalproex (these are somewhat distinct formulations and have to be dosed differently but work exactly the same in the brain). This is a standard first-line treatment for epileptics, a very effective way to stop acute mania (though probably antipsychotics would nowadays be used for quick deterrence of dangerous manic episodes) and for the longest while it was next to lithium as the gold-standard for bipolar maintenance. Recent studies (from the let's-push-antipsychotics era) have shown opposite results, but the statistics in medical studies is so bloody poor (compared with the miracles we are supposed to do with much crappier data in econometrics) that I really don't think this should be taken out of the algorithm. As for migraines, I guess Depakote is a cannonball trying to hit a fly -- not worth the depression side-effect risk. That said, Depakote gave me a month in heaven, where my mood was completely flat and nothing could affect me. Sadly, my short-term memory was sacked too, so I had to drop it because it gave me a cognitive impairment that couldn't coexist with my day job.)
  • Topamax/topiramate. This one was approved for epilepsy and migraine only, since those pesky clinical studies failed to show that improvement in either mood episodes or their prevention was statistically indifferentiable from placebo -- but may I kvetch again about the crappy methodology, with badly-designed samples and piss-poor early 20th-century tests. While it can not be objectively be said that my positive experience with Topamax wasn't a placebo effect, it seems to me that about half of my bipolar acquaintances (pretty much everyone was tried on Topamax; off-label use is rampant) had horrible experiences with it, showing almost disabilitating cognitive effects (interestingly linked mostly to language skills), and half found it very effective in maintenance usage. Now, Topamax is most often used for the temporal lobe flavour of epilepsy, which has language skils effect as well, and many patients and doctors informally entertain the idea that some bipolar people just have their (loosely-defined) "bipolar activity" more alongside the temporal lobe (while still lodged deep in the middle of your brain where the cingulate system is). So it's like we summed up 100 manic-depressives and 100 schizophrenics and gave them all lithium; lithium would show inefficacy, and that would be a result of a poorly-chosen sample.

    No, really, the effects of Topamax on the larger bipolar population could indicate that there are further medically-useful divisions to be made in the standard bipolar diagnosis besides variants I and II, but who is gonna fund that research? Patients that improve on Topamax stay on Topamax regardless of FDA approval. That said, Topamax helped with some of my more bizarre symptoms that let my doctor to suspect temporal lobe epilepsy. Unfortunately, the much-improved lifestyle Topamax gave me came along with cognitive impairment that just can't coexist with my day job requirements.

  • Lamictal/lamotrigine This would be the crown of the jewel in anticonvulsants, but comes with a 4 in 10,000 chance of a really nasty side-effect dubbed Stevens-Johnson syndrome. Still, lamotrigine has one of the cleanest side-effect profiles of all anticonvulsants, in spite of the nasty rash, is a first-line treatment when a doctor sees a depressed person and suspects bipolar disorder and has been in off-label usage for migraine as well. The great advantage of lamotrigine is that it pretty much doesn't come with cognitive impairment side-effects at all. Some people are even prescribing small doses of lamotrigine for mild-to-medium episodes of atypical depression, as it's even cleaner that the SSRIs and carries a lesser risk of triggering mania in those with an underlying bipolar disorder. That said, I had the best euphoric manias of my life after starting on lamotrigine -- I had only had a history of mixed episodes and dysphoric mania -- and the entire course of my treatment has been about balancing the antidepressant effect of lamotrigine. Just once we tried a combination of bupropion, which is supposed to have a low risk of triggering mania, and massive Topamax, but those were the worst two weeks of my entire life. Hell, thy name is Wellbutrin. Anyway, despite of all that, cognitive ability comes first when in my personal priority list and I don't understand why lamotrigine isn't the first-line treatment for all bipolar patients (did you know some people are still on lithium? the horror!), and I get to brag that I'm so frakking bipolar, I got manic on Lamictal
  • Neurontin/gabapentin. Like with Topamax, studies in clinical settings couldn't prove a significant improvement over placebo for bipolar disorder, but word goes around that some people balance out when some gabapentin is added to their already complicated cocktail.
  • Benzodiazepines, such as Klonopin/clonazepam, Lexotan/lorazepam, Valium/diazepam; widely marketed and prescribed as anti-anxiety drugs, benzos are actually mild anticonvulsants. If you see someone having tonic-clonic seizures, do not hesitate to part with your precious stolen tablet of Klonopin to stop the person from hurting herself. Benzos are also more addictive than many street drugs; the addiction potential of Lexotan might be one of the main factors that make people distrusting from biological treatments for mental unease
The truth is, the three buzzing conditions theory is a quasi-scientific set of beliefs that are at large based on facts and figures, but largely contaminated by wishful thinking and the lack of explicit training in neurology and psychiatry. On the other hand, I know for a fact that many practicing shrinks privately believe strongly that the line separating bipolar disorder from temporal lobe epilepsy is thin and fuzzy. Am I saying that bipolar disorder is a form of epilepsy? Well, I can always hope it is. Unfortunately, it's unlikely that this line of investigation will be furthered much in the short term.

For the time being, I sometimes need to lie and say that I have severe, disabilitating fits of migraine. It's the best form I've found to explain that I'm touched with electricity.

Update: Some published medical research on the "epileptology" of bipolar disorder in this link. This snippet from the abstract is a teaser:

By the opinion of the author the clinical importance of pharmacokinetic parameters are underestimated in the psychiatric practice. Therefore--as an original approach in the literature--he summarizes the detailed clinical indications of serum level measurements of antiepileptic drugs applied in psychiatry as mood stabilizers. The therapeutic experiences in epilepsy added a lot of practices for the most effective dosing, building, tapering and exchange of the mood stabilizer antiepileptics. ... Further targeted studies are needed for the identification and positioning of antiepileptic drugs in the palette of mood stabilizing pharmacotherapy and for the definition of evidence based, individually tailored and lifelong applied highly effective combinations of the mood stabilizing pharmacotherapy containing antiepileptic agents.
The sad thing is, no such research will be conducted in the US in the short term because all the money is on atypical antipsychotics. In Europe, otherwise, well-defined protocols for combining antiepileptics into precise bipolar cocktails are being researched.

Update 2

In the interest of full disclosure, I should mention this very good article (Berns and Nemeroff, 2003, PDF link) which spells out a comprehensive survey of what's known about bipolar disorder and states that

In spite of the attractive nature of the kindling hypothesis, no convincing neurobiological data have provided that this phenomenon actually occurs in patients with bipolar disorder
Though it's not stating a negative, it's the most comprehensive recent survey I've seen, and that an author that has gone through so much literature discredits the convulsive hypothesis weakens the Three Buzzing Conditions conjecture.

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