Recognizing Crucial Differentiating Features When Diagnosing Bipolar Disorder Vs. PMDD

Caffeine Withdrawl Syndrome
Caffeine Withdrawl Syndrome

Premenstrual syndrome (PMS) is an extremely common condition, affecting up to 85% of menstruating women.1 Between 2% and 10% of women experience severely disabling and incapacitating symptoms.1,2 Although more than 200 symptoms are associated with PMS, irritability, tension, and dysphoria are the most prominent and consistently described.3 Women whose affective symptoms are especially severe may meet criteria for premenstrual dysphoric disorder (PMDD).3

PMS is cyclical, with symptoms arising during the luteal phase of the menstrual cycle and lasting until the onset of menstrual flow, when symptoms typically abate.3 During the follicular phase prior to ovulation, estrogen levels rise, while during the luteal phase following ovulation, progesterone levels rise. Immediately before the onset of menstruation, estrogen and progesterone levels both decrease.4

Estrogen is considered to exert a generally positive effect on serotonergic neurons and on their cortical postsynaptic targets, thereby conferring some protection against depression.5 However, estrogen levels may be less implicated in premenstrual depression than hormonal fluctuation. Depression in women particularly occurs at times of hormonal flux (i.e., prior to menstruation, following childbirth, and during menopause).6

Bipolar disorder and severe premenstrual syndrome (PMS) have many similar symptoms. Both are characterized by cycling moods, including severe depression.6 Because of the overlap in symptoms, severe PMS is often misdiagnosed as bipolar disorder. In an article titled "Severe Premenstrual Syndrome and Bipolar Disorder: A Tragic Confusion,"6 author Studd points out that severe PMS is frequently treated with psychotropic medications, such as antidepressants and mood stabilizing antiepileptic agents, rather than therapies designed to suppress cyclical hormonal changes. He describes this confusion as "tragic" because these inappropriate therapies are often ineffective and can be damaging. According to Studd, effective treatment utilizes transdermal estradiol or gonadotropin-releasing hormone (GnRH) analogues, which suppress ovulation. He notes that "It has been observed that longstanding 'bipolar depression' . . . often disappears when the cyclical premenstrual nature of the condition is treated by suppression of ovarian cycles."

Studd cautions that the diagnosis of hormone-responsive depression should be made through the patient's history and not through the measurement of hormonal levels, since hormonal levels in premenopausal women are typically normal. Instead, he suggests eight items in the patient's history that point to hormonally based depression:

1. A history of mild or severe PMS as a teenager

2. Relief of depressive symptoms during pregnancy

3. Postpartum depression, with new-onset or newly recurring depressive symptoms

4. Recurrence of premenstrual depression following resumption of menstruation after delivery

5. Worsening of premenstrual depression with age, blending into the menopausal transition and becoming less cyclical thereafter

6. Coexistence of cyclical somatic symptoms, such as menstrual migraine, bloating, or mastalgia, which are not associated with bipolar disorder

7. Runs of 5 to 20 euthymic days per month

8. Recurrent episodes of depression, often severe and related to menstrual periods, but without episodes of mania

Beyond the patient's personal history, family history can shed light on the origin of depressive symptoms. If the mother and sisters also suffer from PMS and postnatal depression, it can be suggestive of a familial hormonal basis for the symptoms. Alternatively, a history of bipolar disorder and suicide in male relatives would suggest mixed etiology.

Studd notes that there may be "premenstrual exacerbations of all mood disorders, and therefore cases of comorbidity and overlap between conditions may occur." Even so, "elimination of the endocrine causes of mood swings will facilitate effective treatment by [utilizing] a combination of estrogens and antidepressants." This will ensure that hormonal causes are addressed on their own terms, even if the depression also requires treatment with antidepressant agents.

1. ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologists. Number 15, April 2000. Premenstrual syndrome. Obstet Gynecol. 2000;95:1–9.

2. Steiner M, Born L. Diagnosis and treatment of premenstrual dysphoric disorder: an update. Int Clin Psychopharmacol. 2000;15(suppl 3):S5–17.

3.Dickerson LM, Mazyck PJ, Hunter MH. Premenstrual syndrome. Am Fam Physician. 2003;67(8):1743–1752.

4. Zukov I, Ptácek R, Raboch J, et al. Premenstrual dysphoric disorder—review of actual findings about mental disorders related to menstrual cycle and possibilities of their therapy. Prague Med Rep. 2010;111(1):12–24.

5. Wise DD, Felker MA, Stahl SM. Tailoring treatment of depression for women across the reproductive lifecycle: the importance of pregnancy, vasomotor symptoms, and other estrogen-related events in psychopharmacology. CNS Spectr. 2008;13(8):647–655,658–662.

6. Studd J. Severe premenstrual syndrome and bipolar disorder: a tragic confusion. Menopause Int. 2012;18(2):82–6.
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