Atypical Depression

Atypical depression is a term used to refer to either depression followed by stress or anxiety, or depression accompanied by a symptomatology of increased appetite, weight gain or hypersomnia. It is a clinical entity that shares many of the symptoms of major depression, but in the case of atypical depression an individual remains reactive to the stimuli of their environment, in the sense that their mood is still affected by them, positively of negatively.

This disorder is the result of mental processes.

Presentation

A characteristic feature of atypical depression is mood reactivity, namely the individual's ability to still respond positively to positive environmental stimuli. This characteristic is a factor that distinguishes atypical depression from a major depression or dysthymia. Patients affected by these conditions very rarely experience an elevated mood when something positive happens. Mood reactivity is termed "criterion A" for atypical depression.

Other than that, in order to diagnose an episode of atypical depression, at least two of the following symptoms must be present alongside mood reactivity ("criterion B"):

  • Excessive need for sleep (hypersomnia)
  • Increased appetite/weight gain
  • Leaden paralysis: The feeling of being so heavy one is unable to move, as though burdened with lead.
  • Interpersonal rejection sensitivity which causes problems in personal life or work, reacting excessively when one feels that they are being rejected.

Atypical depression is considered a "specifier" for major depression or dysthymic disorder, namely it is used to better evaluate the course of these conditions and characterize them. It is common for patients with atypical depression to have experienced at least one episode of major depression, usually at a young age.

Workup

Any recent or present episode of dysthymia or bipolar disorder can be termed as "bearing atypical characteristics" according to DSM-IV [10]. In order to achieve a successful and accurate diagnosis, a doctor must bear in mind that the feature distinctly distinguishing atypical depression from other psychiatric disorders is mood reactivity. A person is considered to be reactive, when they experience a mood elevation of at least 50% when a positive event takes place (a compliment, a raise, a date, etc.).

Treatment

Monoamine oxidase inhibitors (MAOIs), specifically phenelzine, have proven to address atypical depression with great efficacy. In spite of the existence of several FDA-licensed MAOIs for the treatment of major depression, phenelzine is the only drug that has received a clear indication for the treatment of atypical depression. Nevertheless, doctors tend to refrain from widely using MAOIs as first-line treatment, due to their possible interaction with diet-acquired tyramine, it could result in a life-threatening hypertensive crisis. Furthermore, there is always the risk of drug-drug interactions, which could trigger a serotonin syndrome. For these reasons, various other antidepressants are implemented as first-line treatments for atypical depression [12]. 

The use of MAOIs has assisted researchers in the so called psychopharmacological dissection of atypical depression, the classification of disease sub-categories based on the response to medication. A group of patients whose symptoms are aided by MAOIs in comparison to tricyclic antidepressants or electroconvulsive therapy has been a valid observation.

The existence of randomized clinical trials suggesting the use of selective serotonin reuptake inhibitors for this subtype (fluoxetine vs phenelzine, fluoxetine vs moclobemide, fluoxetine vs imipramine, fluoxetine vs nortriptyline and sertraline vs moclobemide) has also broken new ground. Fluoxetine has been proven to be effective for atypical depression, with patients responding positively at a rate of 65% [13].

Other types of medication that have shown effectiveness in the treatment of atypical depression according to open-label, randomized or controlled studies include hypericum, gepirone, modafinil, melatonin and GH. In addition to this, newer antidepressants like duloxetine, venlafaxine and mirtazapine may be used towards achieving a therapeutic result, but still remain an uninvestigated option.

During the acute phase of an atypical depression episode, a patient may also benefit more from cognitive therapy in contradistinction to pharmacologic treatment.

Prognosis

Atypical depression needs early intervention, which can help an individual manage their symptoms and minimize suffering. Comorbidities include somatization disorder, substance abuse (drugs, medications, etc.), cluster B and C personality disorders and increased anxiety.

Etiology

It is impossible to define the exact causes leading to atypical depression. Possible factors may involve:

  • Childhood trauma: Given the psychological sensitivity of a child, particularly in the early life, incidents such as the death of a parent or child abuse can lead to the individual being more prone to depression.
  • Incidents in adult life: Stress, financial issues, disease, dysfunctional interpersonal relationships or the death of a loved one can also trigger a depression.
  • Hereditary factors: Depression is more frequently observed in individuals whose blood relatives suffer from the same condition.
  • Biological factors: There has been a suggestion that depression may occur when neurotransmitters are dysfunctional.

Epidemiology

The characterization of "atypical" refers to the DSM criteria for other mood disorders. In this sense, atypical does not imply that a disorder is unusual or rare, but rather that it cannot be classified as an already existing mood disorder, even though they may share lots of common features. Atypical depression is, in reality, a common disorder [2].

Atypical depression was found to be affecting a 4.5% of women and a 1.2% of men in a study conducted in Zurich, Switzerland. Another research indicated the lifetime prevalence of the disorder to be amounting to a 0.7% [6].

Women are more frequently affected by this condition at a rate of 2:1 to 3:1 when compared to men. Some patients tend to display a chronic unmanageable course of major depression, rather than a typical depression [1]. Episodes start at a younger age [3] [4] and monozygotic twins usually both display the disorder, which suggests a possible genetic factor [5]. 

Sex distribution
Age distribution

Pathophysiology

The DSM-IV classification provides accurate characteristics and symptomatology for atypical depression, however, little is known about the actual mechanisms causing the condition. Therefore, data is limited to hypotheses.

Biological hypothesis

Hormonal axis

One study used a group of patients meeting the full atypical depression criteria, a group displaying mood reactivity as the only atypical symptom and a control group with no atypical symptoms. Desipramine (selective NRI (noradrenaline reuptake inhibitor)) was administered to all three groups, with the patients exhibiting the full set of atypical symptoms showing an increased cortisole response when compared to the others. This led to the suggestion that in patients with atypical depression, the noradrenaline system is less affected [7]. Furthermore, patients with atypical depression have been found to be free of corticotropin releasing hormone (CRH) hypersecretion, in contradistinction to patients suffering of typical depression. In fact, the CRH levels of atypical patients have been found to be lower even in comparison to healthy individuals [8].

Brain hemispheric bias

Atypical depression is distinct from its typical counterpart in the means of the brain region they originate. Atypical depression favors the right parietal lobe, whereas typical depression the left parietal lobe [9]. With reference to perfusion, increased right frontal lobe perfusion is seen in patients with atypical depression and typical depression exhibits diminished perfusion in all regions but the occipital lobe [10].

Psychological hypothesis

Parker et al [11] have suggested that atypical depression may indeed be a spectrum disorder, although their propositions have yet to be proven. Personality and temper evaluation of patients with both typical and atypical depression was used to determine the primary psychological triggers of atypical depression. Conclusions that were drawn, pointed out to the importance of interpersonal rejection sensitivity as a primary cause. People that generally tended to overreact to real or imagined rejection also went on to exhibit increased anxiety, hypersomnia and increased appetite. [11]   

Prevention

Given that there is no known cause for depression, one can simply follow advice on how to lead a stress-free life in order to reduce the chances of getting depressed:

  • Try to control the levels of stress. Recognize the situations you can influence and those you cannot. Try to evaluate the severity of a situation with a clear head, before panicking. 
  • Talk, people are social beings. You will see that sharing a problem with close people helps you to deal with it.
  • If you think you are depressed, consult an expert. Getting professional help early prevents a depression from settling firmly.
  • Consider the possibility of getting long-term professional help to prevent symptoms from re-emerging.

Summary

The DSM-IV defines atypical depression as a disorder characterized by symptoms of increased appetite and weight gain, excessive need for sleep, interpersonal rejection sensitivity, "leaden" paralysis and a reactive mood [1]. Episodes exhibiting the aforementioned characteristics occur during the course of longitudinal mood disorders (bipolar disorder, dysthymia or major depression). Therefore, in order to decisively diagnose an episode of atypical depression, a patient needs first of all to accurately meet the DSM specified criteria for a longitudinal mood disorder, atypical symptoms alone do not suffice to diagnose such an episode [1]. Atypical depression is viewed as a vital specifier, helping to manage patients with longitudinal mood disorders and better characterize the course of their condition. 

Given that such a disorder already exists, in order for an episode to be established as an atypical episode, the following criteria must be met [1]:

  • Mood reactivity to environmental stimuli and at least 2 other symptoms must dominate the most recent 2-week period of an episode related to major depression or bipolar disorder.
  • Mood reactivity to environmental stimuli and at least 2 other symptoms must be present in the most recent 2 years of a dysthymic disorder.

Atypical depression was established as a clinical entity in 1994, it was then that it was classified as  an “episode specifier” in DSM-IV classification.

Patient Information

Atypical depression is a type of the depression that has some different characteristics from its typical "counterpart". Even though the term atypical might strike one as odd, rare or unusual, this disorder is actually a very common one. Because depression is a factor that may lower the quality of your life and prevent you from doing many things you would normally like to do, it is important that you keep in mind the following signs, should you ever experience one of them:

  • Increased hunger, leading to weight gain
  • A need to sleep too much, more than usual
  • A feeling that your legs are heavy as though made from lead, that makes it unpleasant or difficult for you to move
  • Difficulty maintaining balanced relationships with friends or coworkers, because you feel too rejected or insulted all the time
  • Sudden mood enhancement when good news crop up, which is then followed by depressed feelings again

It is important to get professional help if you have the suspicion that you may have an atypical form of depression. It is nothing to be ashamed of, it is quite common, mostly among women, and it does not mean that you are faulty or irreparably damaged. Also, do keep in mind that such problems, if left untreated, may lead to complications that include:

  • Suicidal tendencies
  • Isolation
  • Phobias and panic disorder
  • Obesity and heart-related conditions or diabetes
  • Substance abuse
  • Dysfunctional relationships at work, in the family, at school which can further worsen the problems already present.

There are also many treatment options for atypical depression. Depending on the severity, patients may need medication, counseling or a combination of these. Do not hesitate to reach out to a psychologist, psychiatrist or other mental health expert, early intervention can help you get life back on track and continue living your life to a full extent.

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References

  1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association; 2000.
  2. Gillespie RD. The clinical differentiation of types of depression. Guy Hosp Rep. 1929;79: 306-344.
  3. Benazzi F. Testing DSM-IV definition of atypical depression. Ann Clin Psychiatry. 2003 Mar; 15 (1): 9-16
  4. Stewart JW, McGrath PJ, Quitkin FM. Do age of onset and course of illness predict different treatment outcome among DSM IV depressive disorders with atypical features? Neuropsychopharmacology. 2002 Feb; 26 (2): 237-45.
  5. Kendler KS, Eaves LJ, Walters EE, et al. The identifica-tion and validation of distinct depressive syndromes in a population-based sample of female twins. Arch Gen Psychiatry. 1996 May; 53 (5): 391-9.
  6. Horwath E, Johnson J, Weissman MM, et al. The validity of major depression with atypical features based on a com-munity study. J Affect Disord. 1992 Oct; 26 (2): 117-25
  7. McGinn LK, Asnis GM, Rubinson E. Biological and clinical validation of atypical depression. Psychiatry Res. 1996 Mar 29; 60 (2-3): 191-8
  8. Geracioti Jr TD, Loosen PT, Orth DN. Low cerebrospinal fluid corticotropin-releasing hormone concentrations in eucortisolemic depression. Biol Psychiatry. 1997 Aug 1; 42 (3): 165-74
  9. Bruder GE, Stewart JW, McGrath PJ, et al. Atypical de-pression: enhanced right hemispheric dominance for per-ceiving emotional chimeric faces. J Abnorm Psychology. 2002 Aug; 111 (3): 446-54
  10. Fountoulakis KN, Iacovides A, Gerasimou G, et al. The relationship of regional cerebral blood flow with subtypes of major depression. Prog Neuropsychopharmacology Biol Psychiatry. 2004 May; 28 (3): 537-46.
  11. Parker GB. Atypical depression: a valid subtype? J Clin Psychiatry. 2007; 68 Suppl. 3: 18-22
  12. Quitkin FM. Depression with atypical features: diagnostic validity, prevalence, and treatment. Prim Care Companion J Clin Psychiatry. 2002 Jun; 4 (3): 94-9
  13. Reimherr FW, Wood DR, Byerley B, et al. Characteristics of responde o fluoxetine. Psychopharmacol Bull. 1984; 20 (1): 70-2

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