Treatment Issues for Bipolar Disorder in Women

Treating women with bipolar disorder (BD) requires some special considerations, explained Laura Miller, MD, during a recent presentation at the 2012 US Psychiatric & Mental Health Congress. Miller reviewed treatment issues across the lifespan of women-from puberty and menstruation to sexuality to issues in menopause-and shared practical tips and clinical consideration with attendees.

Issues Associated With Menstruation
Miller, professor at Harvard Medical School and Director of the Women's Mental Health Divisionin the Department of Psychiatry at Brigham and Women's Hospital, said the hormonal changes associated with the menstrual cycle and menopause can complicate treatment and disease course. For instance, in a retrospective study of 2524 women, 65.1% of women with bipolar type I and 70.5% with bipolar type II reported increased premenstrual mood symptoms. Only 33.7% of women without BD reported increased mood symptoms.¹ She added that there are a number of well-documented cases showing a clear exacerbation of mood symptoms associated with the menstrual cycle.

Not only is it possible for the hormonal changes to impact mood, but the hormones can also impact pharmacokinetics of the mood stabilizing medications, she said. There have been case reports of dramatic changes in lithium’s potency across the menstrual cycle. Miller explained she witnessed this in one of her patients who was extremely vigilant with medications. The woman reported mild psychotic symptoms and mania several days prior to menstruation, so Miller investigated the patient’s lithium levels. She found that the lithium level was 0.6 just before menstruation and 1.1 after menstruation, further demonstrating the menstrual cycle’s impact on pharmacokinetics.

The impact runs both ways, Miller added, with BD also impacting the menstrual cycle. Women with BD often report menstrual irregularities. Miller acknowledged that some, although not all, could be attributed to the medications used in treating the disorder. Valproate, risperidone, and haloperidol, for example, can impact the cycle and cause irregular menstruation. However, she suggested chatting with your patient about their cycle before initiating treatment to get a baseline status.

Perimenopause and Menopause
Menopause and perimenopause are also vulnerable times for women with BD, Miller said, with research pointing to an exacerbation of symptoms during this time in a woman’s life. For example, in a STEP-BD study (N = 164) of women aged 45 years old to 55 years old who were perimenopausal, researchers found an increased risk for exacerbation of depressive symptoms.2 These researchers postulated the increased risk may be due to hormonal fluctuations,  changes in sleep, changes in midlife roles, and losses experienced during this time of life. Another study found increased frequency of depressive episodes and total mood episodes in women with BD who were perimenopausal.3 More studies are needed to better understand what’s happening here, Miller said.

Sexuality and Contraception
BD also impacts sexuality, Miller explained. Unlike with other psychiatric disorders, women with BD report increased interest in sex. This can often lead to unwanted intercourse, increased risk for sexually transmitted diseases, and increased risk for unwanted pregnancy. As such, Miller said it very important to talk to patients about safe sex practices, especially since contraception and mood stabilizers do not always work well together. In fact, the World Health Organization recommends avoiding combined oral contraceptives, transdermal patches, vaginal rings, and progesterone-only pills. Instead, they suggest considering depot medroxyprogesterone acetate, levonorgestrel implants, IUDs, or combined injectables. The WHO also notes the importance of condom use.

While the WHO takes this conservative approach, Miller said other organizations are less stringent and simply suggest patients increase the dose of oral contraception to ensure its efficacy. However, she cautioned, these recommendations are not empirically based, as there is no data.

On the other side of the coin, contraceptive use can also decrease the level of mood stabilizers and alter their effectiveness. Lamotrogine and valproate are especially vulnerable to the impact of contraceptives, she said. This becomes truly problematic for patients during the “placebo” portion of the cycle, as the medication levels rise, resulting in the patient’s levels going up and down in a matter of days.

Men Versus Women With BD: Gender Differences
In general, there are relatively few gender differences between men and women with BD, Miller said, especially in comparison with gender differences found in other psychiatric disorders. Symptoms in men with BD tend to be more associated with mania (eg, increased sex drive) while women symptoms are generally more associated with depressive episodes (eg, weight gain, sleep disturbances). Indeed, there seems to be a consensus that women are more likely to express depressive symptoms; she pointed to a 7 year study (N = 711) that demonstrated women were depressed in 35.6% of visits while men were depressed in 28.7% of visits.4 While early onset tends to occur more often in men, she said there is no dramatic difference. Episodes also tend to last longer in women, she explained, and time to recurrence is shorter in women.

In terms of comorbidities, men are more likely to have conduct disorder and ADHD, while women are more likely to have PTSD, phobias, anxiety, or eating disorders.

Perhaps the most clinically challenge difference is in receiving the diagnosis. Miller said it takes longer to recognize and correctly diagnose women with BD than men BD, causing delayed treatment.

References:1. Payne JL, Roy PS, Murphy-Eberenz K, Weismann MM, Swartz KL, et al. Reproductive cycle-associated mood symptoms in women with major depression and bipolar disorder. J Affect Disord. 2007;99(1-3):221-9.
2. Marsh WK, Ketter TA, Rasgon NL. Increased depressive symptoms in menopausal age women with bipolar disorder: age and gender comparison. J Psychiatr Res. 2009;43(8):798-802.
3. Marsh WK, Templeton A, Ketter TA, Rasgon NL. Increased frequency of depressive episodes during the menopausal transition in women with bipolar disorder: preliminary report. J Psychiatr Res. 2008; 42(3):247-51.
4. Altshuler LL, Kupka RW, Hellemann G, Frye MA, Sugar CA, et al. Gender and depressive symptoms in 711 patients with bipolar disorder evaluated prospectively in the Stanley Foundation bipolar treatment outcome network. Am J Psychiatry. 2010;167(6):708-15.