Atypical depression

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Atypical depression
Other namesDepression with atypical features
Depression subtypes
SymptomsLow mood, mood reactivity, hyperphagia, hypersomnia, leaden paralysis, interpersonal rejection sensitivity
Complicationsrisk of self harm
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]

Atypical depression is defined in the DSM-IV as depression that shares many of the typical symptoms of major depressive disorder or dysthymia but is characterized by improved mood in response to positive events. In contrast to those with atypical depression, people with melancholic depression 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, a heavy sensation in the limbs, and interpersonal rejection sensitivity that results in significant social or occupational impairment.[4]

Despite its name, "atypical" depression does not mean it is uncommon or unusual.[5] 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., 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 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[2] 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 with anxiety disorders, carries more risk of suicidal behavior, and has distinct personality psychopathology and biological traits.[2] Atypical depression is more common in individuals with bipolar I,[2] bipolar II,[2][8] cyclothymia[2] or seasonal affective disorder.[4] Depressive episodes in bipolar disorder tend to have atypical features,[2] as does depression with seasonal patterns.[9]


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 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.[10]

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.[11]


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", 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 for depression with melancholic features or catatonic features must not be met during the same episode.


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.[12] 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.[13] Bupropion, a norepinephrine reuptake inhibitor, may be uniquely suited to treat the atypical depression symptoms of lethargy and increased appetite in adults.[13] Modafinil is sometimes used successfully as an off-label treatment option.[14]

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[15] 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.[16] 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.[17]

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 favor with prescribers due to the less tolerable side effects of TCAs and more adequate therapies being available.[12]

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.[18] These are talk therapy sessions with psychiatrists or clinical psychologists to help the individual identify troubling thoughts or experiences that may affect their mental state, and develop corresponding coping mechanisms for each identified issue.[19]


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.[20]

[7] 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.[2] 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.[10] Overall, rejection sensitivity is the most common symptom, and due to some studies forgoing this criterion, there is concern for underestimation of prevalence.[21]


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.[22] 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.[23]

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, obsessive-compulsive disorder and social anxiety disorder), bipolar disorder, or personality disorders (such as borderline personality disorder, avoidant personality disorder).[4][additional citation(s) needed]

Recent research suggests that young people are more likely to experience hypersomnia while older people are more likely to experience polyphagia.[24]

Medication response differs between chronic atypical depression and acute melancholic depression. Some studies suggest that the older class of antidepressants, monoamine oxidase inhibitors (MAOIs), may be more effective at treating atypical depression.[25] 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.[14] 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.[26]

See also[edit]


  1. ^ a b Davidson JR, Miller RD, Turnbull CD, Sullivan JL (May 1982). "Atypical depression". Archives of General Psychiatry. 39 (5): 527–534. doi:10.1001/archpsyc.1982.04290050015005. PMID 7092486.
  2. ^ a b c d e f g h Singh T, Williams K (April 2006). "Atypical depression". Psychiatry. 3 (4): 33–39. PMC 2990566. PMID 21103169.
  3. ^ Thase ME (2007). "Recognition and diagnosis of atypical depression". The Journal of Clinical Psychiatry. 68 (Suppl 8): 11–16. 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 M (2012-11-20). "Atypical Depression in the 21st Century: Diagnostic and Treatment Issues". Psychiatric Times. Psychiatric Times Vol 28 No 1. 28 (1). Archived from the original on 2013-12-02. Retrieved 23 November 2013.
  7. ^ a b Łojko D, Rybakowski JK (2017). "Atypical depression: current perspectives". Neuropsychiatric Disease and Treatment. 13: 2447–2456. doi:10.2147/NDT.S147317. PMC 5614762. PMID 29033570.
  8. ^ Perugi G, Akiskal HS, Lattanzi L, Cecconi D, Mastrocinque C, Patronelli A, et al. (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.
  9. ^ Juruena MF, Cleare AJ (May 2007). "[Overlap between atypical depression, seasonal affective disorder and chronic fatigue syndrome]" [Overlap between atypical depression, seasonal affective disorder and chronic fatigue syndrome]. Revista Brasileira de Psiquiatria (in Portuguese). 29 (Suppl 1): S19–S26. doi:10.1590/S1516-44462007000500005. PMID 17546343.
  10. ^ a b Bosaipo NB, Foss MP, Young AH, Juruena MF (February 2017). "Neuropsychological changes in melancholic and atypical depression: A systematic review". Neuroscience and Biobehavioral Reviews. 73: 309–325. doi:10.1016/j.neubiorev.2016.12.014. PMID 28027956. S2CID 3983515.
  11. ^ Łojko D, Rybakowski JK (2017). "Atypical depression: current perspectives". Neuropsychiatric Disease and Treatment. 13: 2447–2456. doi:10.2147/NDT.S147317. PMC 5614762. PMID 29033570.
  12. ^ a b Stewart JW, Thase ME (April 2007). "Treating DSM-IV depression with atypical features". The Journal of Clinical Psychiatry. 68 (4): e10. doi:10.4088/jcp.0407e10. PMID 17474800.
  13. ^ a b "Clinical Practice Review for Major Depressive Disorder | Anxiety and Depression Association of America, ADAA". Retrieved 2019-11-22.
  14. ^ a b Vaishnavi S, Gadde K, Alamy S, Zhang W, Connor K, Davidson JR (August 2006). "Modafinil for atypical depression: effects of open-label and double-blind discontinuation treatment". Journal of Clinical Psychopharmacology. 26 (4): 373–378. doi:10.1097/ PMID 16855454. S2CID 19370803.
  15. ^ Burns C, Kidgron A (2021). "Biochemistry, Tyramine". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 33085344.
  16. ^ Grady MM, Stahl SM (March 2012). "Practical guide for prescribing MAOIs: debunking myths and removing barriers". CNS Spectrums. 17 (1): 2–10. doi:10.1017/S109285291200003X. PMID 22790112. S2CID 206312008.
  17. ^ Nair NP, Ahmed SK, Kin NM (November 1993). "Biochemistry and pharmacology of reversible inhibitors of MAO-A agents: focus on moclobemide". Journal of Psychiatry & Neuroscience. 18 (5): 214–225. PMC 1188542. PMID 7905288.
  18. ^ Mercier MA, Stewart JW, Quitkin FM (May 1992). "A pilot sequential study of cognitive therapy and pharmacotherapy of atypical depression". The Journal of Clinical Psychiatry. 53 (5): 166–170. PMID 1592844.
  19. ^ "What is Psychotherapy?". Retrieved 2019-11-21.
  20. ^ Bienvenüe A, Vidal M, Sainte-Marie J, Philippot J (July 1985). "Kinetics of phospholipid transfer between liposomes (neutral or negatively charged) and high-density lipoproteins: a spin-label study of early events". Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism. 835 (3): 557–66. doi:10.1016/0005-2760(85)90125-0. PMID 2990566.
  21. ^ Quitkin FM (June 2002). "Depression With Atypical Features: Diagnostic Validity, Prevalence, and Treatment". Primary Care Companion to the Journal of Clinical Psychiatry. 4 (3): 94–99. doi:10.4088/pcc.v04n0302. PMC 181236. PMID 15014736.
  22. ^ Pae CU, Tharwani H, Marks DM, Masand PS, Patkar AA (December 2009). "Atypical depression: a comprehensive review". CNS Drugs. 23 (12): 1023–1037. doi:10.2165/11310990-000000000-00000. PMID 19958040. S2CID 40284568.
  23. ^ West ED, Dally PJ (June 1959). "Effects of iproniazid in depressive syndromes". British Medical Journal. 1 (5136): 1491–1494. doi:10.1136/bmj.1.5136.1491. PMC 1993720. PMID 13651775.
  24. ^ Posternak MA, Zimmerman M (November 2001). "Symptoms of atypical depression". Psychiatry Research. 104 (2): 175–181. doi:10.1016/S0165-1781(01)00301-8. PMID 11711170. S2CID 11514430.
  25. ^ "Atypical depression - Symptoms and Causes". Mayo Clinic. Retrieved 18 March 2020.
  26. ^ Hunsley J, Elliott K, Therrien Z (August 2014). "The efficacy and effectiveness of psychological treatments for mood, anxiety, and related disorders". Canadian Psychology. 55 (3): 161–176. doi:10.1037/a0036933.

External links[edit]

  1. Stewart JW, Quitkin FM, McGrath PJ, Klein DF (June 2005). "Defining the boundaries of atypical depression: evidence from the HPA axis supports course of illness distinctions". Journal of Affective Disorders. 86 (2–3): 161–167. doi:10.1016/j.jad.2005.01.009. PMID 15935235.