From the eccentric compulsion of its full title onwards (The Anatomy of Melancholy, What it is: With all the Kinds, Causes, Symptomes, Prognostickes, and Several Cures of it. In Three Partitions with their severall Sections, Members, and Subsections. Philosophically, Medicinally, Historically, Opened and Cut Up), Burton’s masterpiece is garrulous, repetitive and often exasperating, but strangely addictive. I imagine that some readers of Karl Ove Knausgaard will understand the fascination of this book.

Ostensibly a medical study of melancholia, a subject first captured in a celebrated engraving by Dürer in 1514, it becomes a sublime literary doorstop (some 1,400 pages in my paperback edition) that exploits every facet of its subject, to explore humanity in all its paradoxical complexity, drawing from the science of the age and mixing it with astrology, meteorology, psychology, theology and rich, old-fashioned kidology. Teasingly, Burton describes himself as “a loose, plain, rude writer… I call a spade a spade”. He may say “all poets are mad”, but he is neither plain nor rude. Parts of The Anatomy are outstandingly comic: no surprise that Laurence Sterne should send up Burton in Tristram Shandy. Indeed, Burton’s voice is never less than inimitable: “I might indeed (had I wisely done) observed that precept of the poet [blank] – nonumque prematur in annum – and have taken more care: or, as Alexander the physician would have done by lapis lazuli, fifty times washed before it be used, I should have revised, corrected and amended this tract, but I had not (as I said) that happy leisure, no amanuenses or assistants.”

According to Boswell, Dr Johnson (No 86 in this series) said that The Anatomy was “the only book that ever took him out of bed two hours sooner than he wished to rise”. Keats derived the story of his poem Lamia wholesale from Burton and claimed this to be his favourite book.

Literature and melancholy are intimately related, as Graham Greene suggests when he writes (in Ways of Escape): “Writing is a form of therapy; sometimes I wonder how all those who do not write, compose or paint can manage to escape the madness, the melancholia, the panic and fear which is inherent in the human situation.”

Also from the 20th century, Samuel Beckett was another devotee. Burton’s Anatomy lurks behind the writing of his first novel, Murphy. Other 20th-century admirers include (it is said): Jorge Luis Borges, Philip Pullman, the poet Jay Parini, William Gass, and the American artist Cy Twombly.

Before embarking on the magical mystery tour of Burton’s Anatomy, it might be as well to remind ourselves of the dictionary definition of melancholy, a word with a rich and polyvalent back story, derived from ancient Greek – melan meaning black and hole the word for bile. Thus “melancholy” literally means black bile.

The OED has three principal definitions:

1. Affected with the disease of melancholy;

2. Irascible, angry, sullen;

3. Depressed in spirits; sad, gloomy; dejected, mournful.

“Melancholy”, in contemporary terms, must be understood to border depression: encompassing unpleasant states and negative emotions, from existential malaise and bitterness to everyday despondency. For Burton, melancholy also covered madness and mania. Anyone could be afflicted by melancholy – lovers, scholars, rulers. Monomaniacs were melancholics. Poets were famously afflicted; melancholy at its best was the fount of inspiration and creativity.

Aside from the OED, Burton’s own account of the word is extensive: “Melancholy, the subject of our present discourse, is either in disposition or in habit. In disposition, is that transitory Melancholy which goes and comes upon every small occasion of sorrow, need, sickness, trouble, fear, grief, passion, or perturbation of the mind, any manner of care, discontent, or thought, which causes anguish, dulness [sic], heaviness and vexation of spirit, any ways opposite to pleasure, mirth, joy, delight, causing forwardness in us, or a dislike. In which equivocal and improper sense, we call him melancholy, that is dull, sad, sour, lumpish, ill-disposed, solitary, any way moved, or displeased. And from these melancholy dispositions no man living is free, no Stoic, none so wise, none so happy, none so patient, so generous, so godly, so divine, that can vindicate himself; so well-composed, but more or less, some time or other, he feels the smart of it. Melancholy in this sense is the character of Mortality... This Melancholy of which we are to treat, is a habit, a serious ailment, a settled humour, as Aurelianus and others call it, not errant, but fixed: and as it was long increasing, so, now being (pleasant or painful) grown to a habit, it will hardly be removed.”

Burton’s Anatomy is among the strangest books on this list, but in its day it was cult reading: wildly popular among the Jacobean reading class. Subsequently, it has influenced figures as diverse as Charles Lamb and General Custer. It continues to exert a spell over the susceptible imagination as an offbeat, encyclopedic, stream-of-consciousness meditation on the mysteries of existence.

Taken at face value, and in appearance, Burton’s comprehensive work is a medical text as allusive as the internet, but really it’s a benign satire on the fallibility of the human mind. The author finds “melancholy” ingrained in the human condition, or, in his words, “an inbred malady in every one of us”.

As advertised in its subtitle, the book falls into a long introduction and three parts (on the symptoms of melancholy; on its cure; and thirdly, on “love-melancholy” and religious melancholy). Rather in the manner of Montaigne, Burton, who was a highly educated man, stuffs his exposition with quotations from a remarkable range of writers. He also adopts a playful pseudonym (“Democritus Junior”, a pointed allusion to the classical writer known as “the laughing philosopher”).

To the contemporary reader, The Anatomy of Melancholy is less a work of humour, more a bizarre masterpiece of late Renaissance English prose, replete with wonderful nuggets of observation, sardonic utterances on the human condition: “I may not here omit those two main plagues, and common dotage of human kind, wine and women, which have infatuated and besotted myriads of people. They commonly go together.”

Aside from many asides about the battle of the sexes, Burton is ironic about his chosen profession: “From this it is clear how much the pen is worse than the sword.” He closes with some good advice to all his readers: “Be not solitary, be not idle.”

A Signature Sentence

“A good, honest painful man many times hath a shrew to his wife, a sickly, dishonest, slothful, careless woman to his mate, a proud, peevish flirt, a liquorish, prodigal quean, and by that means all goes to ruin: or if they differ in nature, he is thrifty, she spends all, he is wise, she sottish and soft; what agreement can there be? What friendship?”

Three To Compare

Laurence Sterne: The Life & Opinions of Tristram Shandy, Gentleman (1759)

Holbrook Jackson: Anatomy of Bibliomania (1930)

WG Sebald: The Rings of Saturn (1995)

• The Anatomy of Melancholy by Robert Burton is published by New York Review Books (£20). To order a copy for £17 go to guardianbookshop.com or call 0330 333 6846. Free UK p&p over £10, online orders only. Phone orders min p&p of £1.99