atypical depression

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.

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.{{cite journal | vauthors = Łojko D, Rybakowski JK | title = Atypical depression: current perspectives | journal = Neuropsychiatric Disease and Treatment | volume = 13 | pages = 2447–2456 | year = 2017 | pmid = 29033570 | pmc = 5614762 | doi = 10.2147/NDT.S147317 | doi-access = free }}

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.{{cite journal | vauthors = Stewart JW, Thase ME | title = Treating DSM-IV depression with atypical features | journal = The Journal of Clinical Psychiatry | volume = 68 | issue = 4 | pages = e10 | date = April 2007 | pmid = 17474800 | doi = 10.4088/jcp.0407e10 }} 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.{{Cite web|url=https://adaa.org/resources-professionals/practice-guidelines-mdd|title=Clinical Practice Review for Major Depressive Disorder {{!}} Anxiety and Depression Association of America, ADAA|website=adaa.org|access-date=2019-11-22}} Bupropion, a norepinephrine–dopamine reuptake inhibitor (NDRI), 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.{{cite journal |vauthors=Vaishnavi S, Gadde K, Alamy S, Zhang W, Connor K, Davidson JR |date=August 2006 |title=Modafinil for atypical depression: effects of open-label and double-blind discontinuation treatment |journal=Journal of Clinical Psychopharmacology |volume=26 |issue=4 |pages=373–378 |doi=10.1097/01.jcp.0000227700.263.75.39 |pmid=16855454 |s2cid=19370803}}

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 (e.g., some aged cheese, certain types of wine, tap beer and fava beans) causing a hypertensive crisis{{cite book | vauthors = Burns C, Kidgron A | chapter = Biochemistry, Tyramine |date=2021 |url=http://www.ncbi.nlm.nih.gov/books/NBK563197/| title =StatPearls |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=33085344 }} 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.{{cite journal | vauthors = Grady MM, Stahl SM | title = Practical guide for prescribing MAOIs: debunking myths and removing barriers | journal = CNS Spectrums | volume = 17 | issue = 1 | pages = 2–10 | date = March 2012 | pmid = 22790112 | doi = 10.1017/S109285291200003X | s2cid = 206312008 }} 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.{{cite journal | vauthors = Nair NP, Ahmed SK, Kin NM | title = Biochemistry and pharmacology of reversible inhibitors of MAO-A agents: focus on moclobemide | journal = Journal of Psychiatry & Neuroscience | volume = 18 | issue = 5 | pages = 214–225 | date = November 1993 | pmid = 7905288 | pmc = 1188542 }}

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.

One pilot study suggested that psychotherapy or 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.{{cite journal | vauthors = Mercier MA, Stewart JW, Quitkin FM | title = A pilot sequential study of cognitive therapy and pharmacotherapy of atypical depression | journal = The Journal of Clinical Psychiatry | volume = 53 | issue = 5 | pages = 166–170 | date = May 1992 | pmid = 1592844 }} 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.{{Cite web|url=https://www.psychiatry.org/patients-families/psychotherapy|title=What is Psychotherapy?|website=www.psychiatry.org|access-date=2019-11-21}}

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.{{cite journal | vauthors = Bienvenüe A, Vidal M, Sainte-Marie J, Philippot J | title = Kinetics of phospholipid transfer between liposomes (neutral or negatively charged) and high-density lipoproteins: a spin-label study of early events | journal = Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism | volume = 835 | issue = 3 | pages = 557–66 | date = July 1985 | pmid = 2990566 | doi = 10.1016/0005-2760(85)90125-0 | url = }}

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.{{cite journal | vauthors = Bosaipo NB, Foss MP, Young AH, Juruena MF | title = Neuropsychological changes in melancholic and atypical depression: A systematic review | journal = Neuroscience and Biobehavioral Reviews | volume = 73 | pages = 309–325 | date = February 2017 | pmid = 28027956 | doi = 10.1016/j.neubiorev.2016.12.014 | s2cid = 3983515 }} Overall, rejection sensitivity is the most common symptom, and due to some studies forgoing this criterion, there is concern for underestimation of prevalence.{{cite journal | vauthors = Quitkin FM | title = Depression With Atypical Features: Diagnostic Validity, Prevalence, and Treatment | journal = Primary Care Companion to the Journal of Clinical Psychiatry | volume = 4 | issue = 3 | pages = 94–99 | date = June 2002 | pmid = 15014736 | pmc = 181236 | doi = 10.4088/pcc.v04n0302 }}

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.{{cite journal | vauthors = Pae CU, Tharwani H, Marks DM, Masand PS, Patkar AA | title = Atypical depression: a comprehensive review | journal = CNS Drugs | volume = 23 | issue = 12 | pages = 1023–1037 | date = December 2009 | pmid = 19958040 | doi = 10.2165/11310990-000000000-00000 | s2cid = 40284568 }} 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.{{cite journal | vauthors = West ED, Dally PJ | title = Effects of iproniazid in depressive syndromes | journal = British Medical Journal | volume = 1 | issue = 5136 | pages = 1491–1494 | date = June 1959 | pmid = 13651775 | pmc = 1993720 | doi = 10.1136/bmj.1.5136.1491 }}

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 (e.g., borderline personality disorder, avoidant personality disorder).{{Additional citation needed|date=June 2022}}

Recent research suggests that young people are more likely to experience hypersomnia while older people are more likely to experience polyphagia.{{cite journal | vauthors = Posternak MA, Zimmerman M | title = Symptoms of atypical depression | journal = Psychiatry Research | volume = 104 | issue = 2 | pages = 175–181 | date = November 2001 | pmid = 11711170 | doi = 10.1016/S0165-1781(01)00301-8 | s2cid = 11514430 }}

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.{{cite web|url=https://www.mayoclinic.org/diseases-conditions/atypical-depression/symptoms-causes/syc-20369747|title=Atypical depression - Symptoms and Causes|publisher=Mayo Clinic|access-date=18 March 2020}} While the more modern SSRIs and SNRIs are usually quite effective in this illness, the tricyclic antidepressants typically are not. 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.{{cite journal | vauthors = Hunsley J, Elliott K, Therrien Z | title = The efficacy and effectiveness of psychological treatments for mood, anxiety, and related disorders. | journal = Canadian Psychology | date = August 2014 | volume = 55 | issue = 3 | pages = 161–176 | doi = 10.1037/a0036933 }}

{{Portal|Psychiatry}}

• Masked depression
• Treatment-resistant depression

{{Reflist|refs=

{{cite journal | vauthors = Singh T, Williams K | title = Atypical depression | journal = Psychiatry | volume = 3 | issue = 4 | pages = 33–39 | date = April 2006 | pmid = 21103169 | pmc = 2990566 }}}}

1. {{cite journal | vauthors = Stewart JW, Quitkin FM, McGrath PJ, Klein DF | title = Defining the boundaries of atypical depression: evidence from the HPA axis supports course of illness distinctions | journal = Journal of Affective Disorders | volume = 86 | issue = 2–3 | pages = 161–167 | date = June 2005 | pmid = 15935235 | doi = 10.1016/j.jad.2005.01.009 | doi-access = free }}

{{Medical resources

| DiseasesDB =

| ICD10 = {{ICD10|F|32|8|f|30}}

| ICD9 = {{ICD9|296.2x}}

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{{Mental and behavioral disorders|selected = mood}}

Category:Major depressive disorder