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August 4, 2005

Bipolar Disorder in Women

A major review article in the Australian and New Zealand Journal of Psychiatry discusses special considerations for women who have bipolar disorder. There are several gender differences that differentiate diagnosis and treatment of bipolar disorder for men vs. women.

The authors of the review included relevant literature from the Medline, Psychinfo, and Pubmed databases. They examined studies from 1966 to the present day, and included over 100 references in their published article.

Among their findings were the following points:

Concerning prevalence, diagnosis, and presentation of bipolar disorder in women:

--Although bipolar I is equally prevalent among men and women, bipolar II (characterized by milder, 'hypomanic' episodes, but a greater burden of depression) is more commonly reported in women

--Women with bipolar disorder tend to report more episodes of depression than men. Women also experience more 'mixed' episodes (an episode which has simultaneous features of both mania and depression

--Women are almost three times more likely than men to have a comorbid diagnosis. Two of the most common comorbid disorders for women with bipolar were alcoholism and anxiety disorder.

--Women are more likely to be rapid-cyclers (experience for or more episodes per year) than men. Proposed explanations for this include: effects of gonadal steroids (estrogen or testosterone), hypothyroidism (more common in women), and greater use of antidepressant medication in women, which has been reported to cause episodes of mania in people with bipolar disorder.

Concerning the effects of female hormones (menstrual cycle) on bipolar disorder:

--Menstrual cycle hormones (fluctuations in estrogen and progesterone, which can act on the activity of neurotransmitters serotonin, noradrenaline, and GABA) may exacerbate bipolar symptoms in women. Two studies reported that a65% of women with bipolar disorder report worse mood symptoms during their menstrual cycle. Other studies did not support this finding, however.

Concerning pregnancy in women with bipolar disorder:

--Pregnancy represents a period of increased risk for women with bipolar disorder. Two studies found that about half of women with bipolar disorder reported a worsening of their symptoms during pregnancy. The post-partum period is also recognized in literature as a time of highly increased risk for an affective and/or psychotic episode. Relapse rates for women with bipolar disorder within 3-6 months of childbirth are reported to be as high as 67-82%. Moreover, the risk of psychosis increases from 10-20% in women with bipolar disorder during the post-partum period.

Dr. Terence Ketter, who recently spoke about bipolar disorder at the Stanford University Schizophrenia and Bipolar Education Day, also acknowledged that bipolar women in the post-partum period are at highly increased risk for experiencing an episode. He also mentioned, "although the books won't tell you things...in my clinical experience, women say it is the worst episode they have ever had." (See Dr. Ketter's full lecture from the Stanford Education Day.)

The authors found from their literature review that "use of lithium reduces the risk of relapse fivefold if re-instituted shortly before delivery (at about week 36), or within 48 hours of delivery and is continued into the post-partum period." However, they also cautioned: "as neonatal toxicity can occur, careful monitoring of maternal lithium levels needs to occur during and immediately after delivery."

--Other interventions mentioned by the authors to decrease the risk of the post-partum period included planning for extra support, especially at night, to ensure that the mother is allowed adequate periods of uninterrupted sleep. Irregular sleep patterns have been shown to have serious effects on mood in people with bipolar disorder.

As far as treatments for women during the post-partum period, the authors suggested that ECT may be the treatment of choice. Antidepressants (the risk for inducing mania notwithstanding) may also be considered; breast-feeding mothers can minimize exposure of their infant to medication by taking their pills immediately after breast-feeding, and then waiting 7-11 hours before breast-feeding again (using formula as needed). Small studies of the effects of antipsychotics on breast-feeding infants are inconclusive; the authors suggest that "if antipsychotics need to be used in a mother committed to breast-feeding, the infant should be closely monitored for side-effects such as somnolence, tremor, and rigidity).

--The article reiterated the risks of taking mood stabilizers or antipsychotics during pregnancy, due to their increased birth defect rates. The first trimester is a particularly risky period, when an infant's major organs are forming. Of the medications specifically mentioned in the review (lithium, sodium valproate, carbamazepine, and lamotrigine), lamotrigine showed the lowest risk of birth defects. However, the sample sizes used to study this drug were small, and therefore the findings need to be replicated. Women should always discuss their options with their doctors before planning a pregnancy.


Concerning medication considerations for women:

--Hormone flucuations during the menstrual cycle can effect a woman's metabolic rate, which subsequently can effect her blood levels of medication. This may result in periods of exacerbated symptoms and/or worse side-effect burden during certain periods of the menstrual cycle. The authors suggested that women may need a lower dose of lithium from men.

--the bipolar medication carbamazepine may reduce the effectiveness of oral contraceptives. It is important that young women who may depend on the protection of oral contraceptives be informed of this risk. Options include taking a higher dose of the oral contraceptive, or using barrier or other alternate methods.

Source: "Considerations in the management of bipolar disorder in women" Aust N Z J Psychiatry. 2005 Aug;39(8):662-73.

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