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Atypical depression

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 characterized 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.[4]

Atypical depression
Other namesDepression with atypical features
Atypical depression diagram.png
Depression subtypes
SymptomsLow mood, mood reactivity, hyperphagia, hypersomnia, leaden paralysis, interpersonal rejection sensitivity
Usual onsetTypically adolescence[1]
TypesPrimary anxious, primarily vegetative[1]
Risk factorsBipolar disorder, anxiety disorder, female sex[2]
Differential diagnosisMelancholic depression, anxiety disorder, bipolar disorder
Frequency15-29% of depressed patients[3]

Despite its name, "atypical" depression does not mean it is uncommon or unusual.[5] The reason for its name is twofold: (1) it was identified with its "unique" symptoms subsequent to the identification of melancholic depression and (2) its responses to the two different classes of antidepressants that were available at the time were different from melancholic depression (i.e., MAOIs had clinically significant benefits for atypical depression, while tricyclics did not).[6]

Atypical depression is four times more common in females than in males. [7] 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[8] 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.[4] Atypical depression has high comorbidity of anxiety disorders, carries more risk of suicidal behavior, and has distinct personality psychopathology and biological traits.[8] Atypical depression is more common in individuals with bipolar I,[8] bipolar II,[8][9] cyclothymia[8] and seasonal affective disorder.[4] Depressive episodes in bipolar disorder tend to have atypical features,[8] as does depression with seasonal patterns.[10]

Diagnostic CriteriaEdit

The DSM-IV-TR defines Atypical Depression as a subtype of major depressive disorder that presents with atypical features, characterized by:

  1. Mood reactivity (i.e., mood brightens in response to actual or potential positive events)
  2. 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.
  3. Criteria are not met for With Melancholic Features or With Catatonic Features during the same episode.


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. [11] 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. [12] 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.[13] Overall, rejection sensitivity is the most common symptom, and due to some studies forgoing this criterion, there is concern for underestimation of prevalence.[14]


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.[13]

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.[15]


Due to the differences in clinical presentation between atypical depression and melancholic depression, studies were conducted in the late 1900s to assess the therapeutic responsiveness of the available antidepressant pharmacotherapy in this subset of patients.[16]

Until the 2000s, Monoamine oxidase inhibitors (MAOI), such as the original iproniazid, were thought to be of superior efficacy compared to other antidepressants for the treatment of atypical depression. Since then, numerous studies and meta analyses have provided mixed results, throwing doubt on the idea of select agent superiority for the treatment of atypical depression. Regardless of the demonstrated superiority, treatment with MAOI requires a strict dietary restrictions with tyramine-containing foods and have many undesirable adverse effects such as hypertensive crisis. For such reasons, MAOI are rarely used as the preferred agent in the setting of atypical depression. Some evidence supports that cognitive behavioral therapy has equal efficacy to MAOI. [17] There currently do not exist robust guidelines for the treatment of atypical depression. [18]


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, generalized anxiety disorder, obsessive-compulsive disorder, and bipolar disorder.[4]

Recent research suggests that young people are more likely to suffer from hypersomnia while older people are more likely to suffer from polyphagia.[19]

Medication response differs between chronic atypical depression and acute melancholic depression. Some studies[20] suggest that the older class of antidepressants, monoamine oxidase inhibitors (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.[4] The wakefulness-promoting agent modafinil has shown considerable effect in combating atypical depression, maintaining this effect even after discontinuation of treatment.[21] 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.[citation needed]

See alsoEdit


  1. ^ a b Davidson JR, Miller RD, Turnbull CD, Sullivan JL (1982). "Atypical depression". Arch Gen Psychiatry. 39 (5): 527–34. doi:10.1001/archpsyc.1982.04290050015005. PMID 7092486.CS1 maint: multiple names: authors list (link)
  2. ^ Singh T, Williams K (2006). "Atypical depression". Psychiatry (Edgmont). 3 (4): 33–9. PMC 2990566. PMID 21103169.
  3. ^ Thase ME (2007). "Recognition and diagnosis of atypical depression". J Clin Psychiatry. 68 Suppl 8: 11–6. PMID 17640153.
  4. ^ a b c d e American Psychiatric Association. (2000). Mood Disorders. In Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.) Washington, DC: Author.[page needed]
  5. ^ "Atypical depression". Mayo Clinic. Retrieved 2013-06-23.
  6. ^ Cristancho, Mario. "Atypical Depression in the 21st Century: Diagnostic and Treatment Issues". Psychiatric Times. Retrieved 23 November 2013.
  7. ^ Dorota Łojko, et. al (2017). "Atypical depression: current perspectives, Neuropsychiatric Disease and Treatment
  8. ^ a b c d e f Singh T, Williams K (2006). "Atypical depression". Psychiatry. 3 (4): 33–9. PMC 2990566. PMID 21103169.
  9. ^ Perugi G, Akiskal HS, Lattanzi L, Cecconi D, Mastrocinque C, Patronelli A, Vignoli S, Bemi E (1998). "The high prevalence of 'soft' bipolar (II) features in atypical depression". Comprehensive Psychiatry. 39 (2): 63–71. doi:10.1016/S0010-440X(98)90080-3. PMID 9515190.
  10. ^ Juruena MF, Cleare AJ (2007). "Superposição entre depressão atípica, doença afetiva sazonal e síndrome da fadiga crônica" [Overlap between atypical depression, seasonal affective disorder and chronic fatigue syndrome]. Revista Brasileira de Psiquiatria (in Portuguese). 29 Suppl 1: S19–26. doi:10.1590/S1516-44462007000500005. PMID 17546343.
  11. ^ Dorota Łojko, et. al (2017). "Atypical depression: current perspectives, Neuropsychiatric Disease and Treatment
  12. ^ Tanvir Singh et. al (2006). "Atypical depression, Psychiatry (Edgmont).
  13. ^ a b Bosaipo, Nayanne Beckmann; Foss, Maria Paula; Young, Allan H.; Juruena, Mario Francisco (2017-02-01). "Neuropsychological changes in melancholic and atypical depression: A systematic review". Neuroscience & Biobehavioral Reviews. 73: 309–325. doi:10.1016/j.neubiorev.2016.12.014. ISSN 0149-7634.
  14. ^ Quitkin FM (2002). "Depression With Atypical Features: Diagnostic Validity, Prevalence, and Treatment". Prim Care Companion J Clin Psychiatry. 4 (3): 94–99. doi:10.4088/pcc.v04n0302. PMC 181236. PMID 15014736.
  15. ^ Łojko D, Rybakowski JK (2017). "Atypical depression: current perspectives". Neuropsychiatr Dis Treat. 13: 2447–2456. doi:10.2147/NDT.S147317. PMC 5614762. PMID 29033570.
  16. ^ Stewart, Jonathan W.; Thase, Michael E. (2007-04-15). "Treating DSM-IV Depression With Atypical Features". The Journal of Clinical Psychiatry. 68 (04): e10. doi:10.4088/jcp.0407e10. ISSN 0160-6689.
  17. ^ Mercier, MA (1992). "A pilot sequential study of cognitive therapy and pharmacotherapy of atypical depression". The Journal of Clinical Psychiatry. 53(5): 166-70.
  18. ^ Łojko, Dorota (2017). "Atypical depression: current perspectives". Neuropsychiatric Disease and Treatment.
  19. ^ Posternak MA, Zimmerman M (2001). "Symptoms of atypical depression". Psychiatry Research. 104 (2): 175–81. doi:10.1016/S0165-1781(01)00301-8. PMID 11711170.
  20. ^ Atypical depression: How is it different from 'regular' depression?
  21. ^ Vaishnavi S, Gadde K, Alamy S, Zhang W, Connor K, Davidson JR (2006). "Modafinil for atypical depression: effects of open-label and double-blind discontinuation treatment". Journal of Clinical Psychopharmacology. 26 (4): 373–8. doi:10.1097/ PMID 16855454.

External linksEdit

  1. Stewart JW, Quitkin FM, McGrath PJ, Klein DF (2005). "Defining the boundaries of atypical depression: evidence from the HPA axis supports course of illness distinctions". Journal of Affective Disorders. 86 (2–3): 161–7. doi:10.1016/j.jad.2005.01.009. PMID 15935235.
  2. Atypical Depression - Depression Central Mood Disorders & Treatment, Satish Reddy, MD., Editor (Formerly Dr. Ivan Goldberg's Depression Central)