by Albrecht Dürer.]] Melancholia (from Greek μελαγχολία - melancholia, also lugubriousness, from the Latin lugere, to mourn; moroseness, from the Latin morosus, self-willed, fastidious habit; wistfulness, from old English wist: intent, or saturnine, (see Saturn), in contemporary usage, is a mood disorder of non-specific depression, characterized by low levels of enthusiasm and eagerness for activity. In a modern context, "melancholy" applies only to the mental or emotional symptoms of depression or despondency; historically, "melancholia" could be physical as well as mental, and melancholic conditions were classified as such by their common cause rather than by their properties. Similarly, melancholia in ancient usage also encompassed mental disorders which might now be classed as schizophrenias or bipolar disorders.
The name "melancholia" comes from the old medical theory of the four humours: disease or ailment being caused by an imbalance in one or other of the four basic bodily fluids, or humours. Personality types were similarly determined by the dominant humour in a particular person. Melancholia was caused by an excess of black bile; hence the name, which means 'black bile' (Ancient Greek μέλας, melas, "black", + χολή, kholé, "bile"); a person whose constitution tended to have a preponderance of black bile had a melancholic disposition. See also: sanguine, phlegmatic, choleric.
Melancholia was described as a distinct disease with particular mental and physical symptoms in the fifth and fourth centuries BC. Hippocrates, in his Aphorisms, characterized all "fears and despondencies, if they last a long time" as being symptomatic of melancholia.
In the medieval Arab world, the Arab psychologist Ishaq ibn Imran (d. 908), known as "Isaac" in the West, wrote an essay entitled Maqala fi-l-Malikhuliya, in which discovered a type of melancholia: the "cerebral type" or "phrenitis". He carried out a diagnosis on this mental disorder, describing its varied symptoms. The main clinical features he identified were sudden movement, foolish acts, fear, delusions and hallucinations. In Arabic, he referred to this mood disorder as "malikhuliya", which Constantine the African translated into Latin as "melancolia", from which the English term "melancholia" is derived.
Ali ibn Abbas al-Majusi (d. 982) discussed mental illness in his medical encyclopedia, Kitab al-Malaki, which was translated into Latin as Liber pantegni, where he discovered and observed another type of melancholia: clinical lycanthropy, associated with certain personality disorders. He wrote the following on this particular type of melancholia: "Its victim behaves like a rooster and cries like a dog, the patient wanders among the tombs at night, his eyes are dark, his mouth is dry, the patient hardly ever recovers and the disease is hereditary."
In The Canon of Medicine (1020s), Avicenna dealt with neuropsychiatry and described a number of neuropsychiatric conditions, including melancholia. He described melancholia as a depressive type of mood disorder in which the person may become suspicious and develop certain types of phobias. The Canon of Medicine was also translated into Latin in the 12th century.
The most extended treatment of melancholia comes from Robert Burton, whose The Anatomy of Melancholy (1621) treats the subject from both a literary and a medical perspective. Burton wrote in the 16th century that music and dance were critical in treating mental illness, especially melancholia. In November 2006, Dr. Michael J. Crawford  and his colleagues again found that music therapy helped the outcomes of Schizophrenic patients. 
A famous allegorical engraving by Albrecht Dürer is entitled Melencolia I. This engraving portrays melancholia as the state of waiting for inspiration to strike, and not necessarily as a depressive affliction. Amongst other allegorical symbols, the picture includes a magic square, and a truncated rhombohedron . The image in turn inspired a passage in The City of Dreadful Night by James Thomson (B.V.), and, a few years later, a sonnet by Edward Dowden.
The present classification of psychiatric disorders is ill-defined, offering poor guidelines for the treatment of the ambulatory and the severe mentally ill. One form of depressive illness, described for millennia as melancholia, has defined criteria and effective treatments. In modern practice, melancholia is separated from the amorphous concepts of major depression, bipolar disorder, and other mood disorders.1 It is widely recognized in patients with severe mood disorder, especially among those with suicidal preoccupation and psychotic thoughts.
History: A syndrome of “madness” with “bodily causes” has long been clinically recognized.1 Except for two periods in Western history -- the Middle Ages in Europe when church teachings dominated Western thought and in the 20th century when psychoanalytic notions usurped psychiatric thinking -- melancholia was identified as a distinct periodic mood disorder with both manic and depressive phases, without progressive deterioration. It was associated with high fatality rates.2 Emil Kraepelin, the German psychopathologist, described an alternating mood disorder labeled manic-depressive insanity which he contrasted with a more malignant progressive dementia praecox.3 In 20th century classifications, psychoanalysts defined psychiatric illnesses as of “mental,” not of brain origin, with depressive and manic periods as “reactions” to personal experience. The classic example is the formulation by Adolf Meyer; his influence dominated the principal 20th Century psychiatric classifications, known as DSM-I and DSM-II.4
The introduction of the convulsive therapies in the 1930s and the antipsychotic and antidepressant drugs in the 1950s and 1960s found the psychiatric classification inadequate to identify which patients were best served by the available somatic, chemical, and verbal psychotherapies.1,3 Subsequent revisions of the nomenclature in 1980, based on committee concepts and not on evidence based medical criteria, listed 265 disorders increased to 295 in 1994.5,6 These classifications offered inadequate criteria to identify patients with definable disorders for which assured treatments could be recommended. Persons who feel saddened by life events or who are disgruntled and unhappy by virtue of life’s vicissitudes or by their personality traits meet criteria for major depression if their moods are associated with decreased energy or interest.1,5,6 Their inclusion within the class of major depression does not assure them adequate treatment and confounds the results of clinical treatment trials. Many respond to “placebo” interventions (biologically inactive though psychologically active).7
In the 1970s, interest in neuroendocrine gland products in psychiatric illness identified elevated serum cortisol (the hormone of the adrenal gland) as a specific marker for a melancholic, often psychotic, form of depressive illness.1,8-10 A formal test, the dexamethasone suppression test (DST) was found to be abnormal in melancholic depression, to revert to normal with adequate treatment, and to again become abnormal with relapse.1,8 By the end of the 20th century, melancholia was identified as a specific syndrome from among the subjects otherwise defined as suffering from mood disorders then labeled major depression or bipolar disorder.1,11
Melancholia defined. Severe mood disturbance (unremitting apprehension and sadness, suicide thoughts), psychomotor disturbance (agitation or bradykinesia), and vegetative signs are essential elements in defining melancholia. About one-third exhibit delusional thoughts.1,11 The onset is often acute, and associated with environmental events, such as loss of a spouse or child, pregnancy and delivery, or surgery. The course is variable, with patients remaining depressed for prolonged periods; exhibiting excited states and manic moods; alternating depression and mania. The illness has an unpredictable duration: it may be unremitting, or remit spontaneously, or fluctuate with periods of days, weeks or months.
The diagnosis of a melancholic depression is verified by abnormal neuroendocrine tests and disturbed sleep EEG measures.1,9,10 Hypercortisolemia is a prominent marker, particularly when the melancholic patient is agitated or psychotic.8-10 Similar findings, although less robust, are seen in thyroid function tests and sleep EEG measures.1 Although developed heuristically and without a central theory, these tests buttress the melancholia diagnosis. They are as useful (e.g. similar sensitivity and specificity) as are the EEG, brain imaging, and serum prolactin levels in defining a seizure disorder. (Table 1).1
Diagnostic criteria for melancholia1 (all must be present)
A. An episode of illness characterized by an unremitting mood of apprehension and gloom that compromises normal daily activities that persists for at least two weeks.
B. Psychomotor disturbance as agitation, retardation (including stupor and catatonia), or both.
C. At least one of the following:
Applying these criteria to the individual entities described in the psychiatric classification finds patients with diverse syndromes meet the criteria for melancholia (Table 2).1 Patients with mood disorders who do not meet criteria for melancholia comprise a large heterogeneous population best labeled for the present as within the “non-melancholic mood disorders.” Table 2
Proposed inclusions in melancholia 1
Psychotic depression Manic-depression Puerperal depression Abnormal bereavement Depression with stupor or catatonia
Characterological depression Reactive depressive disorders Premenstrual dysphoria
The proposed criteria for melancholia have face validity for high specificity. They make false positive diagnoses unlikely, and maximize the identification of homogeneous population samples for clinical trials and studies of pathophysiology.
ECT: The development of highly efficient antibiotics for bacterial infections and vitamin and hormone replacements for dietary and hormone deficiencies offered treatment response as validation of a clinical diagnosis.12 The astonishing efficacy of ECT in remitting melancholia supports the diagnosis. Melancholia remits with greater than 90% efficiency within three weeks with bilateral ECT.1,13-16
The multi-site collaborative ECT study of continuation ECT and continuation pharmacotherapy (known as CORE) used bilateral ECT in patients meeting rigorous criteria for unipolar major depression. They reported an overall remission rate of 87% among treatment completers, with an astonishing 95% rate for the 30% of patients identified as psychotic depressed.15,17 Although characterized as meeting criteria for major depression, the major part of the CORE sample meets the criteria for melancholia by the severity of the mood disorder, high incidence of psychosis and suicide risk, and their failure to respond to multiple medication trials.16-18 A post-hoc analysis of the rating scale items on the HAMD24, SCID, and IDS scales in these severely ill patients finds that more than 80% meet symptom criteria for melancholia.16
Lesser remission rates of 50% to 60% with ECT in hospitalized unipolar depressed patients are reported, but probably result from the use of unilateral electrode placement and inadequate energy dosing, examples of inefficient treatment methods.18 The efficacy of ECT is directly related to the clinician’s skills in diagnosis, selecting treatment frequency, technical parameters, managing concurrent medications, and continuation treatments.1,19 While patients with well defined melancholia, catatonia, and mania respond to ECT rapidly and well, those with such diagnoses as [major depression], depression secondary to substance abuse, dysthymia, and characterological forms of depression fare poorly.
Successful ECT also reverses the hormone imbalances seen in depressive illness.20 The same reversal in other hormone tests has been observed and these experiences are the basis for a neuroendocrine explanation of the mode of action of induced seizures in melancholia.13,21
Medications. Broad pharmacodynamic spectrum antidepressants are more effective in melancholic than in non-melancholic patients. Tricyclic antidepressants effectively relieve melancholic depression but do so less efficiently than ECT. The imbalance is seen in the relative inefficacy of TCA in psychotic melancholic patients where remission rates are low.1,22 The combination of classical antipsychotic agents (chlorpromazine, perphenazine) and tricyclic antidepressants were considered effective for the treatment of psychotic depression.23 The evidence for the use of SSRI and SNRI antidepressants and atypical antipsychotics is lacking.1,22,23
Lithium is effective moderating abnormal mood and reducing suicidal drive, and is the most effective augmenting agent in the treatment of acute depressive illness when the patient is melancholic. It is efficient as continuation therapy for melancholic patients, especially when combined with the tricyclic nortriptyline.1,15,22
Although the more recently induced SSRI antidepressants and similar agents are widely recommended as the first agents in treatment algorithms for major depression, their overall 30-40% remission rates differ only minimally from placebo rates.24 They are much less effective in hospitalized patients, those more likely to be suffering from melancholic depression. These experiences speak against their use in melancholia.
Psychotherapy. No form of psychotherapy has been shown to be effective in the treatment of melancholic depression.23 Yet, the fluctuations in severity of melancholia enable some clinicians to offer psychotherapy with or without supplementary medication waiting for the natural course of illness to improve the condition.
Brain stimulation. As of May 2009, none of the newly introduced brain stimulation methods, notably transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS), surgical deep brain stimulation (DBS), or magnetic seizure therapy (MST) has demonstrated efficacy in relieving melancholia.
Unipolar-bipolar distinction. Patients with mood disorder are now dichotomized by a history of manic or hypomanic episodes into recurrent depressive or bipolar disorder.5,6,22 When depressive illness is grouped by criteria of melancholia, however, the unipolar/bipolar dichotomy fails. No characteristic psychopathology separates the melancholic patient with a history of mania or hypomania from one without such a history.1,23 The illnesses are commonly recurrent and in succeeding episodes 70% of patients initially classified as bipolar disorder meet criteria for major depression; and, in the course of a major depressive illness, 10% exhibit episodes of mania and over half features of mania when depressed.1,22
The present classification of mood disorders is arbitrary, divided into a multitude of presumed disorders with imprecise criteria. The formulations are not helpful in selecting effective treatment. Melancholia is a distinct medical syndrome that is defined by symptoms, signs and course of illness, verified by laboratory tests, and validated by effective treatment. It is distinguished from other depressive mood disorders by its characteristic psychopathology. The unipolar/bipolar dichotomy is not supported when the criteria for melancholia are used to classify depressive illness. The treatment algorithm for melancholia differs from that of non-melancholic depressions, but the treatment algorithms for melancholia with or without mania are similar.1,11,22,23
Hypercortisolemia is characteristic of severely ill depressed patients, and tests of this hormone (and other hormones) should be considered in the classification and the management of patients with depressive mood disorders.1,8-10,25 Various treatments -- lithium, tricyclic antidepressants, and ECT – effectively relieve the depressive and the manic phases of the syndrome when properly applied. Psychotherapy and brain stimulation methods are best avoided. The expert treatment algorithms require substantial revision if they are to claim that they are “evidence-based”.
1. Taylor MA, Fink M. Melancholia: The Diagnosis, Pathophysiology and Treatment of Depressive Illness. Cambridge UK: Cambridge University Press, 2006.
2. Kraepelin E: Manic-Depressive Insanity and Paranoia. Translated by RM Barclay. Edited GM Robertson. Edinburgh: E&S Livingstone, 1921. Reprinted New York: Arno Press, 1976.
3. Shorter E: A History of Psychiatry. New York: John Wiley & Sons, 1997.
4. Lewis AJ: Melancholia: a historical review. J Ment Sci 1934;80:1-42.
5. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders. Revision III. Washington DC: American Psychiatric Association, 1980.
6. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders. Revision IV. Washington DC: American Psychiatric Association, 1994.
7. Rush AJ, Trivedi MH, Wisniewski SR et al. Bupropion-SR, Sertraline, or Venlafaxine- XR after failure of SSRIs for depression. N Engl J Med 2006; 354:1231-42.
8. Davies BJ, Carroll BJ, Mowbray RM: Depressive Illness: Some Research Studies. Springfield, IL: C C. Thomas, 1972.
9. Carroll BJ, Curtis GC, Mendels J: Neuroendocrine regulation in depression. II. Discrimination of depressed from nondepressed patients. Arch Gen Psychiatry 1976; 33:1051-1058.
10. Carroll BJ, Feinberg M, Greden JF et al. A specific laboratory test for the diagnosis of melancholia. Arch Gen Psychiatry 1981; 38:15-22.
11. Parker G, Hadzi-Pavlovic D: Melancholia: A Disorder of Movement and Mood. Cambridge UK: Cambridge University Press, 1996.
12. Robins E, Guze SB. Establishment of diagnostic validity in psychiatric illness: its application to schizophrenia. Am J Psychiatry. 1970; 126(7):983-7.
13. Fink M: Convulsive Therapy: Theory and Practice. New York: Raven Press, 1979.
14. Abrams R: Electroconvulsive Therapy. 4th ed. New York: Oxford University Press 2002.
15. Kellner CH, Knapp RG, Petrides G., et al. Continuation ECT versus pharmacotherapy for relapse prevention in major depression: a multi-site study from CORE. Arch Gen Psychiatry 2006; 63:1337-44..
16. Fink M, Rush AJ, Mueller M, Knapp R, et al. DSM melancholic features are unreliable predictors of ECT response: A CORE publication. JECT 2007; 23:139-146.
17. Petrides G, Fink M, Husain MM. et al. ECT remission rates in psychotic versus non-psychotic depressed patients: A report from CORE. JECT 2001; 17:244-253.
18. Sackeim HA, Prudic J, Devanand DP, et al. A prospective, randomized, double-blind comparison of bilateral and right unilateral electroconvulsive therapy at different stimulus intensities. Arch Gen Psychiatry 2000; 57:425-34.
19. Fink M. Electroconvulsive Therapy: A Guide for Practitioners & Their Patients. New York: Oxford University Press, 2009.
20. Carroll B: Control of plasma cortisol levels in depression: Studies with the dexamethasone suppression test. In Davies B, Carroll BJ, Mowbray RM. Depressive Illness: Some Research Studies. Springfield, IL: C C. Thomas, 1972; 5: 87-149.
21. Fink M: Electroshock revisited. Am Scientist 2000; 88:162-167.
22. Goodwin FK, Jamison KR: Manic-Depressive Illness. New York: Oxford University Press, 1990, pp. 227-244.
23. Bolwig T, Shorter E (Eds.):Melancholia: Beyond DSM, Beyond Neurotransmitters. Acta Psychiatr Scand 2007; 115: Suppl 115,183 pp.
24. Khan A, Kolts RL, Rapaport MH, Krishnan KR, Brodhead AE, Brown WA. Magnitude of placebo response and drug-placebo differences across psychiatric disorders. Psychol Med 2005; 35:743-749.
25. Fink M. Should the dexamethasone suppression test be resurrected? Acta psychiatrica scandinavica 2005; 112:245-9.
During the early 17th century, a curious cultural and literary cult of melancholia arose in England. It was believed that religious uncertainties caused by the English Reformation and a greater attention being paid to issues of sin, damnation, and salvation, led to this effect. In music, the post-Elizabethan cult of melancholia is associated with John Dowland, whose motto was Semper Dowland, semper dolens. ("Always Dowland, always mourning.") The melancholy man, known to contemporaries as a "malcontent," is epitomized by Shakespeare's Prince Hamlet, the "Melancholy Dane." Another literary expression of this cultural mood comes from the death-obsessed later works of John Donne. Other major melancholic authors include Sir Thomas Browne, and Jeremy Taylor, whose Hydriotaphia, Urn Burial and Holy Living and Holy Dying, respectively, contain extensive meditations on death.
A similar phenomenon, though not under the same name, occurred during Romanticism, with such works as The Sorrows of Young Werther by Goethe or Ode on Melancholy by John Keats. In the 20th century, much of the counterculture of modernism was fueled by comparable alienation and a sense of purposelessness called "anomie".
But to leave all declamatory speeches in praise of divine music, I will confine myself to my proper subject: besides that excellent power it hath to expel many other diseases, it is a sovereign remedy against  despair and melancholy, and will drive away the devil himself. Canus, a Rhodian fiddler, in Philostratus, when Apollonius was inquisitive to know what he could do with his pipe, told him, "That he would make a melancholy man merry, and him that was merry much merrier than before, a lover more enamoured, a religious man more devout." Ismenias the Theban, Chiron the centaur, is said to have cured this and many other diseases by music alone: as now they do those, saith Bodine, that are troubled with St. Vitus's Bedlam dance.