Psychiatric Annals

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Treatment Challenges of Atypical Depression: A Case Report

Heather Greenspan, MD; Asad Hussain, MD; Onyechi Aginah, MD; Padmaja Sajja, BS; Umair Randhawa, BS; Omkar Purohit, BS; M. Haroon Burhanullah, MD

Symptoms such as mood reactivity, hyperphagia, hypersomnia, leaden paralysis, and interpersonal rejection sensitivity are classified as atypical features of a major depressive episode. If these symptoms are concurrent with an episode of hypomania, the patient would be diagnosed with having a depressive episode in the continuum of bipolar II disorder. Because patients may have subsequent depressive episodes for years without any symptoms of hypomania, and because they can function unequivocally within the community due to the nature of the disorder, the diagnosis of a bipolar disorder often gets misclassified as one of a unipolar etiology. Most evidence-based literature states the complexity of this diagnosis due to the subtlety of the presenting symptoms, and it is usually only with a thorough patient history that a clinician can diagnose a patient with bipolar II disorder when the chief complaint is atypical depression.

An integrative approach to classifying the depression in terms of polarity requires the clinician to consider the longitudinal course of the patient’s illness; the tendency for depression to recur; the onset, prominence, and severity of depressive episodes; and whether there is a family history of bipolar disorder. It is essential to distinguish between unipolar and bipolar depression in order to treat current episodes and prevent further depressive episodes. The first-line treatment for unipolar depression with atypical features is monoamine oxidase inhibitors (MAOIs), whereas first-line treatment for bipolar depression is a mood stabilizer that may be augmented with an antidepressant.


A 42-year-old white woman carries the diagnoses of panic disorder with agoraphobia and major depressive disorder with atypical features. She has been following up at the out-patient clinic for more than 2 years with stable and baseline depression without suicidal intent or behavior. The patient’s medication had originally been stabilized on sertraline and aripiprazole, which was initiated for augmentation of unipolar depression. However, the patient’s unipolar depression had not improved during the past 2 years, prompting her current psychiatrist to ask further questions to categorize her depressive symptoms with the hope of finding a better treatment plan. The patient had reported some features of atypical depression (hypersomnia, hyperphagia, and mood reactivity) without leaden paralysis.

The current first-line therapy for atypical depression is an MAOI, but because of the many dietary and drug restrictions and rate of treatment failure for this class of drugs,1 it was decided not to place the patient on this therapy. After doing a literature review of evidence-based medicine, the outpatient psychiatrist recognized that atypical features are more common in bipolar depression (versus unipolar depression) and that these features may lie on the spectrum of bipolar disorder. Thus, the psychiatrist decided to prescribe a mood stabilizer to treat the atypical features in this patient. The dosage of aripiprazole was up-titrated to a dose that was indicated for bipolar disorder.

The patient responded well to the medication adjustment, reporting a marked decrease in depressed mood and a reduction of the parameters of the aforementioned atypical features. The psychiatry resident continued to follow-up with the patient on a monthly basis in the outpatient setting and continued her on the same pharmacotherapy. At the time of this writing, the patient was doing well, was compliant with treatment, and has experienced a step-wise reduction of symptoms.


The relationship among atypical depression, bipolar II disorder, and borderline personality disorder remains unclear.2 A significant body of knowledge suggests a considerable overlap in clinical manifestations and psychotherapeutic responses, and also the difficulty among psychiatrists in making distinct diagnostic entities.

The category “atypical depression” includes a large subset of depression states characterized by reactive mood, a pattern of stable interpersonal sensitivity (exaggerated vulnerability to feeling hurt by criticism or rejection that leads to difficulties in interpersonal relationships, creating a personal life characterized by being easily hurt, having many romantic partners, and experiencing frequent breakups), and reverse vegetative symptoms such as increased appetite and hypersomnia.

The Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR)3 defines atypical depression as a subtype of major depressive disorder with atypical features, characterized by:

  • Mood reactivity (ie, mood brightens in response to actual or potential positive events).
  • At least two of the following:
    • - Significant weight gain or increase in appetite;

    • - Hypersomnia (sleeping too much, as opposed to the insomnia present in melancholic depression.

    • - Leaden paralysis (ie, heavy, leaden feelings in 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 melancholic depression or catatonic depression during the same episode.

Other significant facts about atypical depression include the following:4

  • It tends to cause greater functional impairment than other forms of depression. Women are more likely to be affected.
  • It is a chronic syndrome and tends to begin early in life, usually in teenage years.
  • Patients with atypical depression are more likely to suffer from other psychiatric syndromes (eg, panic disorder, social phobia, body dysmorphic disorder).
  • Patients often have intense cravings for carbohydrates. A mineral supplement (chromium picolinate) assuages these cravings.


It is evident that effective therapeutic response in patients with atypical depression depends on the diagnostic accuracy of the clinician. Although MAOIs have been the prescribed drugs of choice, their use is limited by their dietary restrictions and safety profiles. A consensus exists that because atypical depression lies on the spectrum of bipolar disorder and may predict the future diagnosis of bipolar disorder,5 mood stabilizers should be considered as therapy for atypical depression. Psychosocial interventions,6 such as behavioral activation, should also be assessed as a non-psychopharmacological option for patients with atypical depression.


  1. Cohen LJ, Sclar DA. Issues in adherence to treatment with monoamine oxidase inhibitors and the rate of treatment failure. J Clin Psychiatry. 2012;73(Suppl 1):31–36. doi:10.4088/JCP.11096su1c.05 [CrossRef]
  2. Perugi G, Fornaro M, Akiskal HS. Are atypical depression, borderline personality disorder and bipolar II disorder overlapping manifestations of a common cyclothymic diathesis?World Psychiatry. 2011;10(1):45–51.
  3. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders [text revision]. 4th ed. Washington, DC: American Psychiatric Association; 2000.
  4. Singh T, William K. Atypical depression. Psychiatry (Edgmont). 2006; 3(4):33–39.
  5. Benazzi F. Depression with DSM-IV atypical features: a marker for bipolar II disorder. Eur Arch Psychiatry Clin Neurosci. 2000;250(1):53–55. doi:10.1007/s004060050010 [CrossRef]
  6. Weinstock LM, Munroe M, Brown IM. Behavioral activation for the treatment of atypical depression:a pilot open trial. Behav Modif. 2011;35(4):403–424. doi:10.1177/0145445511405646 [CrossRef]

Heather Greenspan, MD, is Academic Chief Psychiatry Resident, Bergen Regional Medical Center. Asad Hussain, MD, is PGY-3 Psychiatry Resident at Bergen Regional Medical Center. Onyechi Aginah, MD, is a graduate of the College of Medicine, University of Ibadan, Nigeria. Padmaja Sajja, BS, is a medical student at Ross University. Umair Randhawa, BS, is a medical student at Ross University. Omkar Purohit, BS, is a medical student at Ross University. M. Haroon Burhanullah is PGY-4 Psychiatry Resident at Bergen Regional Medical Center.

Address correspondence to: Heather Greenspan, MD, Bergen Regional Medical Center, 230 East Ridgewood Avenue, Paramus, NJ 07652; email:

Disclosure: The authors have no relevant financial relationships to disclose.


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