Atypical depression
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Atypical depression is defined in the '' DSM IV'' as depression that shares many of the typical symptoms of
major depressive disorder Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Intro ...
or
dysthymia Dysthymia ( ), also known as persistent depressive disorder (PDD), is a mental and behavioral disorder, specifically a disorder primarily of mood, consisting of similar cognitive and physical problems as major depressive disorder, but with lo ...
but is characterized by improved mood in response to positive events. In contrast to those with atypical depression, people with
melancholic depression Melancholic depression, or depression with melancholic features, is a DSM-IV and DSM-5 subtype of clinical depression. Signs and symptoms Requiring at least one of the following symptoms: * Anhedonia (the inability to find pleasure in positive t ...
generally do not experience an improved mood in response to normally pleasurable events. Atypical depression also often features significant weight gain or an increased appetite,
hypersomnia Hypersomnia is a neurological disorder of excessive time spent sleeping or excessive sleepiness. It can have many possible causes (such as seasonal affective disorder) and can cause distress and problems with functioning. In the fifth edition ...
, a heavy sensation in the limbs, and interpersonal rejection sensitivity that results in significant social or occupational impairment.American Psychiatric Association. (2000). Mood Disorders. In Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.) Washington, DC: Author. 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.,
MAOI Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, especia ...
s 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 features of atypical depression tend to report an earlier age of onset (e.g. while in high school) of their depressive episodes. These episodes tend to be more chronic than those of major depressive disorder 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 with anxiety disorders, carries more risk of suicidal behavior, and has distinct personality psychopathology and biological traits. Atypical depression is more common in individuals with
bipolar I Bipolar I disorder (BD-I; pronounced "type one bipolar disorder") is a type of bipolar spectrum disorder characterized by the occurrence of at least one manic episode, with or without mixed or psychotic features. Most people also, at other tim ...
,
bipolar II Bipolar II disorder (BP-II) is a mood disorder on the bipolar spectrum, characterized by at least one episode of hypomania and at least one episode of major depression. Diagnosis for BP-II requires that the individual must never have experience ...
,
cyclothymia Cyclothymia ( ), also known as cyclothymic disorder, psychothemia/psychothymia, bipolar III, affective personality disorder and cyclothymic personality disorder, is a mental and behavioural disorder that involves numerous periods of symptoms of ...
or
seasonal affective disorder Seasonal affective disorder (SAD) is a mood disorder subset, in which people who have normal mental health throughout most of the year exhibit depressive symptoms at the same time each year. Common symptoms include sleeping too much, having li ...
. Depressive episodes in bipolar disorder tend to have atypical features, as does depression with seasonal patterns.


Pathophysiology

Significant overlap between atypical and other forms of depression has been observed, though studies suggest that there are differentiating factors within the various pathophysiological models of depression. In the endocrine model, evidence suggests the
HPA axis HPA may refer to: Organizations * Harry Potter Alliance, a charity * Halifax Port Authority, Canada * Hamburg Port Authority, Germany * Hawaii Preparatory Academy, a school in Hawaii, US * Health Protection Agency, UK * Heerespersonalamt, the Ger ...
is hyperactive in
melancholic depression Melancholic depression, or depression with melancholic features, is a DSM-IV and DSM-5 subtype of clinical depression. Signs and symptoms Requiring at least one of the following symptoms: * Anhedonia (the inability to find pleasure in positive t ...
, 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 ''Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition'' (DSM-5), is the 2013 update to the '' Diagnostic and Statistical Manual of Mental Disorders'', the taxonomic and diagnostic tool published by the American Psychiatri ...
''). The ''DSM-5'' defines atypical depression as a subtype of
major depressive disorder Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Intro ...
that presents with "atypical features", characterized 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 Melancholic depression, or depression with melancholic features, is a DSM-IV and DSM-5 subtype of clinical depression. Signs and symptoms Requiring at least one of the following symptoms: * Anhedonia (the inability to find pleasure in positive t ...
, 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 Mirtazapine, sold under the brand name Remeron amongst others, is an Atypical antidepressant, atypical antidepressant, and as such is used primarily to treat Depression (mood), depression. Its effects may take up to four weeks, but can also man ...
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 drug Sympathomimetic drugs (also known as adrenergic drugs and adrenergic amines) are stimulant compounds which mimic the effects of endogenous agonists of the sympathetic nervous system. Examples of sympathomimetic effects include increases in heart ...
s, as well as the risk of
serotonin syndrome Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain serotonergic medications or drugs. The degree of symptoms can range from mild to severe, including a potentiality of death. Symptoms in mild cases include high ...
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 Moclobemide, sold under the brand names Amira, Aurorix, Clobemix, Depnil and Manerix among others, is a reversible inhibitor of monoamine oxidase A (RIMA) drug primarily used to treat depression and social anxiety. It is not approved for use in ...
, which carry a much lower risk of tyramine potentiation and have fewer interactions with other drugs.
Tricyclic antidepressant Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants, which is important for the management of depression. They are second-line drugs next to SSRIs. TCAs were discovered in the early 1950s and wer ...
s (TCAs) were also used prior to the year 2000 for atypical depression, but were not as efficacious as MAOIs, and have fallen out of favor with prescribers due to the less tolerable side effects of TCAs and more adequate therapies being available. One pilot study suggested that psychotherapy such as cognitive behavioral therapy (CBT) may have equal efficacy to MAOIs for a subset of patients with atypical depression, although the sample size was small and statistical significance was not reached. These are talk therapy sessions with psychiatrists to help the individual identify troubling thoughts or experiences that may affect their mental state, and develop corresponding coping mechanisms for each identified issue.


Epidemiology

True
prevalence In epidemiology, prevalence is the proportion of a particular population found to be affected by a medical condition (typically a disease or a risk factor such as smoking or seatbelt use) at a specific time. It is derived by comparing the number o ...
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

Atypical depression was first thought of as a disorder separate from typical depression in 1959, when doctors E.D. West and P. J. Dally were studying the effects of iproniazid, an MAOI, on patients with depression. They found consistencies among the patients who responded well to the drug in comparison to those who didn't. These patients, who were displaying symptoms of "anxiety hysteria with secondary depression", responded notably well to the iproniazid. 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 have anxiety disorders, (such as
generalized anxiety disorder Generalized anxiety disorder (GAD) is a mental and behavioral disorder, specifically an anxiety disorder characterized by excessive, uncontrollable and often irrational worry about events or activities. Worry often interferes with daily function ...
, obsessive-compulsive disorder), bipolar disorder, or
personality disorder Personality disorders (PD) are a class of mental disorders characterized by enduring maladaptive patterns of behavior, cognition, and inner experience, exhibited across many contexts and deviating from those accepted by the individual's culture ...
s (such as borderline personality disorder,
avoidant personality disorder Avoidant personality disorder (AvPD) is a Cluster C personality disorder characterized by excessive social anxiety and inhibition, fear of intimacy (despite an intense desire for it), severe feelings of inadequacy and inferiority, and an overre ...
). Recent research suggests that young people are more likely to experience
hypersomnia Hypersomnia is a neurological disorder of excessive time spent sleeping or excessive sleepiness. It can have many possible causes (such as seasonal affective disorder) and can cause distress and problems with functioning. In the fifth edition ...
while older people are more likely to experience
polyphagia Polyphagia or hyperphagia is an abnormally strong, incessant sensation of hunger or desire to eat often leading to overeating. In contrast to an increase in appetite following exercise, polyphagia does not subside after eating and often leads to ...
. Medication response differs between chronic atypical depression and acute
melancholic depression Melancholic depression, or depression with melancholic features, is a DSM-IV and DSM-5 subtype of clinical depression. Signs and symptoms Requiring at least one of the following symptoms: * Anhedonia (the inability to find pleasure in positive t ...
. Some studies suggest that the older class of antidepressants, monoamine oxidase inhibitors (
MAOI Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, especia ...
s), may be more effective at treating atypical depression. While the more modern
SSRI Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs increase the extracellul ...
s and SNRIs are usually quite effective in this illness, the
tricyclic antidepressant Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants, which is important for the management of depression. They are second-line drugs next to SSRIs. TCAs were discovered in the early 1950s and wer ...
s typically are not. The
wakefulness-promoting agent Eugeroics (originally "eugrégorique" or "eugregoric"), also known as wakefulness-promoting agents and wakefulness-promoting drugs, are a class of drugs that promote wakefulness and alertness. They are medically indicated for the treatment of cer ...
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 Buspirone, sold under the brand name Buspar, among others, is a medication primarily used to treat anxiety disorders, particularly generalized anxiety disorder. Benefits support its short-term use. It is taken by mouth, and it may take up to fo ...
, bupropion, or
aripiprazole Aripiprazole, sold under the brand names Abilify and Aristada among others, is an atypical antipsychotic. It is primarily used in the treatment of schizophrenia and bipolar disorder. Other uses include as an add-on treatment in major depressiv ...
. Psychotherapy, whether alone or in combination with medication, is also an effective treatment in individual and group settings.


See also

*
Masked depression Masked depression (MD) was a proposed form of atypical depression The paper is accompanied with an abstract in English. in which somatic symptoms or behavioural disturbances dominate the clinical picture and disguise the underlying affective diso ...
*
Treatment-resistant depression Treatment-resistant depression is a term used in psychiatry to describe people with major depressive disorder (MDD) who do not respond adequately to a course of appropriate antidepressant medication within a certain time. Definitions of treatment- ...


References


External links

# {{Mental and behavioral disorders, selected = mood Major depressive disorder