What is Atypical Depression?

Introduction

Atypical depression as it has been known in the DSM IV, is depression that shares many of the typical symptoms of the psychiatric syndromes of major depression or dysthymia but is characterised by improved mood in response to positive events.

In contrast to atypical depression, people with melancholic depression generally do not experience an improved mood in response to normally pleasurable events. Atypical depression also features significant weight gain or an increased appetite, hypersomnia, a heavy sensation in the limbs, and interpersonal rejection sensitivity that results in significant social or occupational impairment.

Despite its name, “atypical” depression does not mean it is uncommon or unusual. The reason for its name is twofold: it was identified with its “unique” symptoms subsequent to the identification of melancholic depression and its responses to the two different classes of antidepressants that were available at the time were different from melancholic depression (i.e. monoamine oxidase inhibitors (MAOIs) had clinically significant benefits for atypical depression, while tricyclics did not).

Atypical depression is four times more common in females than in males. Individuals with atypical features tend to report an earlier age of onset (e.g. while in high school) of their depressive episodes, which also tend to be more chronic and only have partial remission between episodes. Younger individuals may be more likely to have atypical features, whereas older individuals may more often have episodes with melancholic features. Atypical depression has high comorbidity of anxiety disorders, carries more risk of suicidal behaviour, and has distinct personality psychopathology and biological traits.

Atypical depression is more common in individuals with bipolar I, bipolar II, cyclothymia and seasonal affective disorder. Depressive episodes in bipolar disorder tend to have atypical features, as does depression with seasonal patterns.

Refer to Masked Depression and Treatment-Resistant Depression.

Pathophysiology

Significant overlap between atypical and other forms of depression have been observed, though studies suggest there are differentiating factors within the various pathophysiological models of depression. In the endocrine model, evidence suggests the HPA axis is hyperactive in melancholic depression, and hypoactive in atypical depression. Atypical depression can be differentiated from melancholic depression via verbal fluency tests and psychomotor speed tests. Although both show impairment in several areas such as visuospatial memory and verbal fluency, melancholic patients tend to show more impairment than atypical depressed patients.

Furthermore, regarding the inflammatory theory of depression, inflammatory blood markers (cytokines) appear to be more elevated in atypical depression when compared to non-atypical depression.

Diagnosis

The diagnosis of atypical depression is based on the criteria stated in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). The DSM-5 defines atypical depression as a subtype of major depressive disorder that presents with “atypical features”, characterised by:

  • Mood reactivity (i.e., mood brightens in response to actual or potential positive events)
  • At least two of the following:
    • Significant weight gain or increase in appetite (hyperphagia);
    • Hypersomnia (sleeping too much, as opposed to the insomnia present in melancholic depression);
    • Leaden paralysis (i.e., heavy feeling resulting in difficulty moving the arms or legs);
    • Long-standing pattern of interpersonal rejection sensitivity (not limited to episodes of mood disturbance) that results in significant social or occupational impairment.

Criteria are not met for With Melancholic Features or With Catatonic Features during the same episode.

Treatment

Due to the differences in clinical presentation between atypical depression and melancholic depression, studies were conducted in the 1980s and 1990s to assess the therapeutic responsiveness of the available antidepressant pharmacotherapy in this subset of patients. Currently, antidepressants such as SSRIs, SNRIs, NRIs, and mirtazapine are considered the best medications to treat atypical depression due to efficacy and fewer side effects than previous treatments. Bupropion, a norepinephrine reuptake inhibitor, may be uniquely suited to treat the atypical depression symptoms of lethargy and increased appetite in adults. Modafinil is sometimes used successfully as an off-label treatment option.

Before the year 2000, monoamine oxidase inhibitors (MAOIs) were shown to be of superior efficacy compared to other antidepressants for the treatment of atypical depression, and were used as first-line treatment for this clinical presentation. This class of medication fell in popularity with the advent of the aforementioned selective agents, due to concerns of interaction with tyramine-rich foods (such as some aged cheese, certain types of wine, tap beer and fava beans) causing a hypertensive crisis and some – but not all – sympathomimetic drugs, as well as the risk of serotonin syndrome when concomitantly used with serotonin reuptake agents. Despite these concerns, they are still used in treatment-resistant cases, when other options have been exhausted, and usually show greater rates of remission compared to previous pharmacotherapies. They are also generally better tolerated by many patients. There are also newer selective and reversible MAOIs, such as moclobemide, which carry a much lower risk of tyramine potentiation and have fewer interactions with other drugs.

Tricyclic antidepressants (TCAs) were also used prior to the year 2000 for atypical depression, but were not as efficacious as MAOIs, and have fallen out of favour with prescribers due to the less tolerable side effects of TCAs and more adequate therapies being available.

Some evidence supports that psychotherapy such as cognitive behavioural therapy (CBT) has equal efficacy to MAOI. These are talk therapy sessions with psychiatrists to help the individual identify troubling thoughts or experiences that may have affected their mental state, and develop corresponding coping mechanisms for each identified issue.

No robust guidelines for the treatment of atypical depression currently exist.

Epidemiology

True prevalence of atypical depression is difficult to determine. Several studies conducted in patients diagnosed with a depressive disorder show that about 40% exhibit atypical symptoms, with four times more instances found in female patients. Research also supports that atypical depression tends to have an earlier onset, with teenagers and young adults more likely to exhibit atypical depression than older patients. Patients with atypical depression have shown to have higher rates of neglect and abuse in their childhood as well as alcohol and drug disorders in their family. Overall, rejection sensitivity is the most common symptom, and due to some studies forgoing this criterion, there is concern for underestimation of prevalence.

Research

In general, atypical depression tends to cause greater functional impairment than other forms of depression. Atypical depression is a chronic syndrome that tends to begin earlier in life than other forms of depression – usually beginning in the teenage years. Similarly, patients with atypical depression are more likely to suffer from personality disorders and anxiety disorders such as borderline personality disorder, avoidant personality disorder, generalised anxiety disorder, obsessive-compulsive disorder, and bipolar disorder.

Recent research suggests that young people are more likely to suffer from hypersomnia while older people are more likely to suffer from polyphagia.

Medication response differs between chronic atypical depression and acute melancholic depression. Some studies suggest that the older class of antidepressants, MAOIs, may be more effective at treating atypical depression. While the more modern SSRIs and SNRIs are usually quite effective in this illness, the tricyclic antidepressants typically are not. The wakefulness-promoting agent modafinil has shown considerable effect in combating atypical depression, maintaining this effect even after discontinuation of treatment. Antidepressant response can often be enhanced with supplemental medications, such as buspirone, bupropion, or aripiprazole. Psychotherapy, whether alone or in combination with medication, is also an effective treatment in individual and group settings.

What is Melancholic Depression?

Introduction

Melancholic depression, or depression with melancholic features, is a DSM-IV and DSM-5 subtype of clinical depression.

Refer to Melancholia.

Signs and Symptoms

Requiring at least one of the following symptoms:

  • Anhedonia (the inability to find pleasure in positive things).
  • Lack of mood reactivity (i.e. mood does not improve in response to positive events).

And at least three of the following:

  • Depression that is subjectively different from grief or loss.
  • Severe weight loss or loss of appetite.
  • Psychomotor agitation or retardation.
  • Early morning awakening.
  • Guilt that is excessive.
  • Worse mood in the morning.

Melancholic features apply to an episode of depression that occurs as part of either major depressive disorder or bipolar disorder I or II.

Causes

The causes of melancholic-type major depressive disorder are believed to be mostly biological factors; some may have inherited the disorder from their parents. Sometimes stressful situations can trigger episodes of melancholic depression, though this is a contributing cause rather than a necessary or sufficient cause. People with psychotic symptoms are also thought to be more susceptible to this disorder. It is frequent in old age and often unnoticed by some physicians who perceive the symptoms to be a part of dementia. Major depressive disorder, melancholic or otherwise, is a separate condition that can be comorbid with dementia in the elderly.

Treatment

Melancholic depression is often considered to be a biologically based and particularly severe form of depression. Treatment involves antidepressants, electroconvulsive therapy, or other empirically supported treatments such as cognitive behavioural therapy and interpersonal therapy for depression. A 2008 analysis of a large study of patients with unipolar major depression found a rate of 23.5% for melancholic features. It was the first form of depression extensively studied, and many of the early symptom checklists for depression reflect this.

Incidence

The incidence of melancholic depression has been found to increase when the temperature and/or sunlight are low. According to the DSM-IV, the “melancholic features” specifier may be applied to the following only:

  • Major depressive episode, single episode.
  • Major depressive episode, recurrent episode.
  • Bipolar I disorder, most recent episode depressed.
  • Bipolar II disorder, most recent episode depressed.

What is Melancholia?

Introduction

Melancholia (from Greek: µέλαινα χολή melaina chole “black bile”, “blackness of the bile”; compare also: lugubriousness, from Latin lugere, “to mourn”; moroseness, from Latin morosus, “self-will or fastidious habit”; wistfulness, from obsolete English whist; and saturnineness, from Latin Sāturnīnus, “under the influence of the planet Saturn”) is a condition characterised by extreme depression, bodily complaints, and sometimes hallucinations and delusions.

Melancholia as a concept derived from ancient or pre-modern medicine, which regarded melancholy as one of the four temperaments matching the four humours. Until the 19th century, medical doctors regarded “melancholia” as having physical symptoms as well as mental ones, and medicine classified melancholic conditions as such by their perceived common cause – an excess of black bile. At times, received wisdom associated all forms of mental illness with the concept of mis-balanced humours, with some mental disease deemed to be caused by a combination of excess black bile and a disorder of one of the other humours.

Despite there being a variety of mental and physical symptoms to this condition, clinicians in the 20th century came to attach the term “melancholia” almost exclusively to depression. As such, “melancholia” is the historical predecessor of the modern mental-health diagnosis of “clinical depression”, and the term currently characterises a subtype of major depression known as melancholic depression.

Background

Early History

The name “melancholia” comes from the old medical belief of the four humours: disease or ailment being caused by an imbalance in one or more of the four basic bodily liquids, or humours. Personality types were similarly determined by the dominant humour in a particular person. According to Hippocrates and subsequent tradition, melancholia was caused by an excess of black bile, hence the name, which means “black bile”, from Ancient Greek μέλας (melas), “dark, black”, and χολή (kholé), “bile”; a person whose constitution tended to have a preponderance of black bile had a melancholic disposition. In the complex elaboration of humourist theory, it was associated with the earth from the Four Elements, the season of autumn, the spleen as the originating organ and cold and dry as related qualities. In astrology it showed the influence of Saturn, hence the related adjective saturnine.

Melancholia was described as a distinct disease with particular mental and physical symptoms in the 5th and 4th centuries BC. Hippocrates, in his Aphorisms, characterised all “fears and despondencies, if they last a long time” as being symptomatic of melancholia. Other symptoms mentioned by Hippocrates include: poor appetite, abulia, sleeplessness, irritability, agitation. The Hippocratic clinical description of melancholia shows significant overlaps with contemporary nosography of depressive syndromes (6 symptoms out of the 9 included in DSM diagnostic criteria for a Major Depressive).

In addition to the symptoms Hippocrates identified, the first century physician Galen believed the condition included fixed delusions. The second century’s Aretaeus of Cappadocia also believed that melancholia involved both a state of anguish, and a delusion.

In the 10th century Persian physician Al-Akhawayni Bokhari described melancholia as a chronic illness caused by the impact of black bile on the brain. He described melancholia’s initial clinical manifestations as “suffering from an unexplained fear, inability to answer questions or providing false answers, self-laughing and self-crying and speaking meaninglessly, yet with no fever.”

In Middle-Ages Europe, the humoral, somatic paradigm for understanding sustained sadness lost primacy in front of the prevailing religious perspective. Sadness came to be a vice (λύπη in the Greek vice list by Evagrius Ponticus, tristitia vel acidia in the 7 vice list by Gregorius Magnus). When a patient could not be cured of the disease it was thought that the melancholia was a result of demonic possession.

In his study of French and Burgundian courtly culture, Johan Huizinga noted that “at the close of the Middle Ages, a sombre melancholy weighs on people’s souls.” In chronicles, poems, sermons, even in legal documents, an immense sadness, a note of despair and a fashionable sense of suffering and deliquescence at the approaching end of times, suffuses court poets and chroniclers alike: Huizinga quotes instances in the ballads of Eustache Deschamps, “monotonous and gloomy variations of the same dismal theme”, and in Georges Chastellain’s prologue to his Burgundian chronicle, and in the late fifteenth-century poetry of Jean Meschinot. Ideas of reflection and the workings of imagination are blended in the term merencolie, embodying for contemporaries “a tendency”, observes Huizinga, “to identify all serious occupation of the mind with sadness”.

Painters were considered by Vasari and other writers to be especially prone to melancholy by the nature of their work, sometimes with good effects for their art in increased sensitivity and use of fantasy. Among those of his contemporaries so characterised by Vasari were Pontormo and Parmigianino, but he does not use the term of Michelangelo, who used it, perhaps not very seriously, of himself. A famous allegorical engraving by Albrecht Dürer is entitled Melencolia I. This engraving has been interpreted as portraying 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 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. His concept of melancholia includes all mental illness, which he divides into different types. Burton wrote in the 17th century that music and dance were critical in treating mental illness.

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.

In the Encyclopédie of Diderot and d’Alembert, the causes of melancholia are stated to be similar to those that cause Mania: “grief, pains of the spirit, passions, as well as all the love and sexual appetites that go unsatisfied.”

English Art Movement

During the later 16th and early 17th centuries, a curious cultural and literary cult of melancholia arose in England. In an influential 1964 essay in Apollo, art historian Roy Strong traced the origins of this fashionable melancholy to the thought of the popular Neoplatonist and humanist Marsilio Ficino (1433–1499), who replaced the medieval notion of melancholia with something new:

Ficino transformed what had hitherto been regarded as the most calamitous of all the humours into the mark of genius. Small wonder that eventually the attitudes of melancholy soon became an indispensable adjunct to all those with artistic or intellectual pretentions.

The Anatomy of Melancholy (The Anatomy of Melancholy, What it is: With all the Kinds, Causes, Symptomes, Prognostickes, and Several Cures of it… Philosophically, Medicinally, Historically, Opened and Cut Up) by Burton, was first published in 1621 and remains a defining literary monument to the fashion. Another major English author who made extensive expression upon being of an melancholic disposition is Sir Thomas Browne in his Religio Medici (1643).

Night-Thoughts (The Complaint: or, Night-Thoughts on Life, Death, & Immortality), a long poem in blank verse by Edward Young was published in nine parts (or “nights”) between 1742 and 1745, and hugely popular in several languages. It had a considerable influence on early Romantics in England, France and Germany. William Blake was commissioned to illustrate a later edition.

In the visual arts, this fashionable intellectual melancholy occurs frequently in portraiture of the era, with sitters posed in the form of “the lover, with his crossed arms and floppy hat over his eyes, and the scholar, sitting with his head resting on his hand” – descriptions drawn from the frontispiece to the 1638 edition of Burton’s Anatomy, which shows just such by-then stock characters. These portraits were often set out of doors where Nature provides “the most suitable background for spiritual contemplation” or in a gloomy interior.

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”.

A similar phenomenon, though not under the same name, occurred during the German Sturm und Drang movement, with such works as The Sorrows of Young Werther by Goethe or in Romanticism with works such as Ode on Melancholy by John Keats or in Symbolism with works such as Isle of the Dead by Arnold Böcklin. In the 20th century, much of the counterculture of modernism was fuelled by comparable alienation and a sense of purposelessness called “anomie”; earlier artistic preoccupation with death has gone under the rubric of memento mori. The medieval condition of acedia (acedie in English) and the Romantic Weltschmerz were similar concepts, most likely to affect the intellectual.

Modern Understandings

In the 18th to 19th centuries, the concept of “melancholia” became almost solely about abnormal beliefs, and lost its attachment to depression and other affective symptoms.

Melancholia was a category that “the well-to-do, the sedentary, and the studious were even more liable to be placed in the eighteenth century than they had been in preceding centuries.”

In the 20th century, “melancholia” lost its attachment to abnormal beliefs, and in common usage became entirely a synonym for depression.

In the early 20th century, some believed there was distinct condition called involutional melancholia, a low mood disorder affecting people of advanced age.

In 1996, Gordon Parker and Dusan Hadzi-Pavlovic described “melancholia” as a specific disorder of movement and mood. They are attaching the term to the concept of “endogenus depression” – depression caused by internal forces rather than environmental influences. They have developed the “Sydney Melancholia Prototype Index” which they believe has an 80% accuracy rate of being able to differentiate endogenus and non-endogenus depression. They believe that the two conditions benefit from different treatment.

In 2006, MA Taylor and M Fink similarly defined melancholia as a systemic disorder that is identifiable by depressive mood rating scales, verified by the present of abnormal cortisol metabolism (abnormal dexamethasone suppression test), and validated by rapid and effective remission with ECT or tricyclic antidepressant agents. They believe it has many forms, including retarded depression, psychotic depression and postpartum depression. They consider that it is characterised by depressed mood, abnormal motor functions, and abnormal vegetative signs.