From Aretaeus on the Aegean to Abilfy: A Brief History of Bipolar Disorder

Doesn’t it start to seem like the Greeks invented just about everything? Of course they invented geometry, for which some are not completely grateful, philosophy–which has provided a haven for many rudderless college students–and just imagine a wold without parchment. Oh–and who could forget the catapult?

For crying out loud, they invented the Olympics, and look what a brouhaha that still is, even in our jaded day and age.

So it should really come as no surprise at all when I tell you that the study of bipolar illness starts with these enterprising folks on the Aegean Sea. One Aretaeus of Cappadocia, a Greek doctor who practiced in Alexandria, wrote a lot about medical illnesses, describing epilepsy, pleurisy, and diphtheria, just to get himself going in the morning. This Aretaeus, in around 150 AD, is generally considered to be the first to connect a depressed mood with a kind of euphoria. He wrote, “It appears to me that melancholy is the commencement and a part of mania.” And his encapsulation of mania was pretty spot-on, especially for the time, as brought down by Dr. Hagop S. Akiskal: “There are infinite forms of mania but the disease is one…. If mania is associated with joy, the patient may laugh, play, dance night and day, and go the market crowned as if victor in some contest of skill…. The ideas the patients have are infinite…. [They] believe they are experts in astronomy, philosophy, or poetry….” He had more to say of the mood-cycler, as well: “They are prone to change their mind readily; to become base, mean-spirited, illiberal, and in a little time … extravagant, munificent, not from any virtue of the soul, but from the changeableness of the disease.” A keen observer, he noted exacerbations of the illness in the spring. Interestingly enough, within the next decade, a doctor had a large key to the management of the illness within his hands–he just didn’t know quite what he had. Soranus Of Ephesus–another Greek, of course– noted that the alkaline waters of his city were quite helpful in treating both mania and depression. It would turn out that the water had high levels of lithium. Many years pass, during which time the Greek gods continue to act petty, Rome becomes an empire (perhaps holy) and then crumbles, and Chaucer writes, with some fairly primitive humor, his tales of Canterbury, which will occupy English majors for hundreds and hundreds of years to come. file1731342724997 But little observable progress appears to have been made on the bipolar front–until an unprepossessing Swiss physician named Théophile Bonet, came along and forever linked depression and mania by coining the term ‘manico-melancolicus’ in 1686.’ This illness, according to Bonet, didn’t just exhibit signs of mania and depression. Rather, it also had periods of stability in between. Skip ahead two hundred years to 1854 and you’ve really got the ball rolling. A French physician named Jean-Pierre Falret actually publishes a journal article on the illness, describing what he calls “la folie circulaire” (circular insanity). The Bipolar Post notes that this description is the earliest documented one of what is today’s bipolar disorder. Emil Kraeplin is one of the biggest early names in psychiatric diagnosis. A German psychiatrist, many consider him the founder of modern scientific psychiatry (no more blood-letting and leeches for Dr. Kraeplin). He actually believed psychiatric diseases had biological origins (no more spirits and poltergeist, either–times they were a’changin’). Dr. Kraeplin wrote a veritable tome, his Compendium der Psychiatrie which he began in 1883. He published several revisions of the multi-volume work, and in the 6th edition, in 1899, made the first distinction between bipolar psychosis and what he called ‘dementia praecox,’ which we now call schizophrenia. He also believed that manic-depressive orders could be treated (he did not hold out the same hope for schizophrenia). His astute observation and analysis determined that:

  • Bipolar was a recurrent illness characterized by symptom-free periods.
  • “The superimposed episodes were commonly opposite to the patient’s habitual temperament; that is, mania was superimposed on a depressive temperament and depression was superimposed on a hypomanic temperament.”
  • There was such a thing as a ‘mixed state,’ during which depressive and manic symptomatology could occur during the same time.

For a detailed post on the accidental discovery on lithium–which a Dr. John Cade knew had anti-manic effects as early as 1949 (despite the fact that it wouldn’t be approved for use in the U.S. for decades)– see “Landing on Lithium: A Chance Discovery That Changed Bipolar Disorder Treatment,” which I wrote under different auspices. Cade published his work in the Medical Journal of Australia in 1949, and knew he had something. It would take the FDA over 20 years to agree with him. But note that it is not until 1951 that the term ‘bipolar’ comes into existence. A German psychiatrist, Karl Leonhard, introduced the term to fully differentiated between major depressive disorder. When the American Psychiatric Association pioneers its Diagnostic and Statistical Manual of Mental Disorders in 1952, manic-depression reaction takes its place, only to be renamed in each of the next two editions. In the DSM-II it is renamed ‘manic-depressive illness,’ and in 1980, with DSM-IV, the term ‘bipolar disorder’ has replaced manic-depression for good. In the meantime, in 1970, lithium is approved by the U.S. Food and Drug Administration (FDA) as a bipolar disorder medication. This will change the face of the illness forever. In the DSM-IV (1994) Bipolar II was introduced as a separate diagnosis from Bipolar I. Second generation antipsychotic Clozapine was approved by the FDA in 1989. Although it was never officially approved for use in bipolar (despite the number of doctors who prescribe it ‘off-label’ for the diagnosis), its appearance on the scene heralded in the era of the newer, or atypical antipsychotics, now prescribed in well over half the cases of bipolar. (Think Zyprexa, Risperdal, Seroquel, Geodon, and Abilify–all big bucks for the drug companies–and you’ve completely got the idea.) We’ve surely come a long way from the Greeks in our understanding of the illness (although they still get high marks for the Olympics, no matter what) and a long way from the waters of Soranus when it comes to treatment. For this we should all be grateful. But sometimes, on some days, it seems like we may have a whole lot farther to go.

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