While bipolar disorder affects both men and women, how the disorder is experienced and treated in both genders varies greatly. Women, for example, tend to experience more of the “rapid cycling” type of bipolar disorder.
Why is it that rapid cycling occurs more often in women? What other issues do women have to face with regards to having bipolar disorder? What should be the course of action for women (with bipolar disorder) who are contemplating pregnancy?
Types of Bipolar Disorder
There are several types of bipolar disorder. The main types include bipolar type I disorder, bipolar type II disorder, and cyclothymic disorder. Bipolar type I disorder is the “classic” form, and patients often experience at least one full or mixed episodes with major depressive episodes. Bipolar type II disorder is where patients have at least one milder form of mania and one major depressive episode. However, they never get a full manic or mixed episode. Bipolar II is more difficult to diagnose because some symptoms of hypomania may not be as apparent. Hypomania is described as a milder form of mania with less severe symptoms. The basic distinction between mania and hypomania is that mania can prevent a person from functioning on a day to day basis. That’s why it is so easy to overlook and misdiagnose a person as without bipolar disorder. Moreover, there are never any delusions in a hypomanic state. Lastly, in cyclothymic type of bipolar disorder, individuals suffer from many hypomanic and depressive symptoms (over 2 years, at least). It is interesting, however, that these symptoms are not severe enough or do not last long enough to be considered as a mood episode.
As told in its name, people with bipolar disorder have mood episodes that fall into two general categories: symptoms of mania and symptoms of depression. However, people diagnosed with bipolar disorder do not need to have symptoms of depression. In fact, people are often misdiagnosed with depression when bipolar disorder is actually the culprit. Thus, the symptoms of mania are key to the definition of having bipolar disorder. Symptoms of mania alone would be sufficient in diagnosing a person with bipolar disorder. The symptoms of mania include increased energy, activity, restlessness, racing thoughts, and rapid speech. The list continues with additional mania symptoms, such as excessive euphoria, extreme irritability and distractibility, decreased sleep requirement, uncharacteristically poor judgement, increased sexual drive, denial, and risky behavior. The symptoms of depression are also just as lengthy. These include persistent sad or empty mood, feelings of hopelessness, pessimism, guilt, worthlessness or hopelessness. Depression is also described as having decreased energy and thoughts of death or suicide. Overall, the specific symptoms and the severity of these mood episodes vary between individuals.
Bipolar Rapid Cycling in Women
Although bipolar illness is equally prevalent in both men and women, the course of the illness differs greatly between the sexes. This is especially true for conception and pregnancy, which affects both the course of the illness and the “treatment decisions that are made at various points in a woman’s life” (Leibenluft, 1997). A primary example of such a gender difference occurs with rapid cycling. As previously mentioned, rapid cycling is more prevalent in women. It is approximately three times more common in women than in men. Rapid cycling describes incidences where a bipolar patient experiences four or more episodes of mania, hypomania, or depression within a time period of a year (Leibenluft, 1997).
Why is rapid cycling bipolar disorder more common in women than in men? Three potential hypotheses to explain the higher prevalence of rapid cycling in women are hypothyroidism incidence, specific gonadal steroid effects, and the use of anti-depressant medications. First, more women encounter hypothyroidism than men do; however, there is not a general consensus on it being a primary cause of increased rapid cycling. Second, gonadal steroids, such as estrogen and progesterone, fluctuate throughout the menstrual cycle. Sixty-six percent of bipolar type I women had regular mood changes during either their menstrual or premenstrual phase of their cycle. They were more irritable and had increased anger outbursts (Blehar et al., 1998). These may set up women to frequent mood changes (especially prior to the menstrual cycle, as noted in the term “premenstrual syndrome”). Increased estrogen may cause women to develop hypercortisolism, which may increase the risk of depression. Stress levels are associated with cortisol level, so this may possibly be the reason for increased risk for depression.
People with bipolar disorder generally do not respond well to anti-depressant medications as the sole treatment. In fact, if taken alone, anti-depressant medications such as selective serotonin re-uptake inhibitors, tricyclics and monoamine oxidase inhibitors, may increase the manic episodes. They help alleviate the depression, but do not help the manic phases. Studies indicate that serotonin reuptake inhibitors and monoamine oxidase inhibitors are less likely to cause mania side effects, as compared with tricyclic antidepressants. Yet another study suggests that manic episodes caused by antidepressants are more moderate compared to those caused spontaneously. In addition, manic episodes caused by monoamine oxidase inhibitors are much milder than those caused by tricyclics or fluoxetine, also known as Prozac antidepressant (Leibenluft, 1998). This indicates that if a patient wanted to take antidepressants, then monoamine oxidases may be a better option. Again, there has not been enough evidence to suggest that any of the three hypotheses presented above is the absolute reason for increased rapid cycling in women with bipolar disorder. The treatments must be taken especially carefully, in order to account for all of the factors discussed.
The treatment of rapid cycling bipolar disorder is especially difficult. As mentioned above, treatment with anti-depressants may precipitate a switch to mania, but may also increase cycle frequency (Leibenluft, 1997). There needs to be more studies done in this area to confirm and treat these problems. However, the most helpful of all treatments is document daily what the moods are upon taking the appropriate drugs (anti-depressant/ antimanic). This will aid in the search for a better cure or prevention for both the short- and long-term treatment. It is probably best to minimize the use of anti-depressants and to maximize the use of mood-stabilizing agents. Mood-stabilizing agents are used to treat manic, hypomanic and mixed episodes and are used to prevent more mood episodes. This is not the absolute way, remember, because the use of mood-stabilizing agents is used primarily to treat mania. As with the problem of taking primarily anti-depressants, rapid cycling bipolar patients who use mainly mood-stabilizing agents will have severe depressive episodes. There is a trade-off between the use of either mood-stabilizing agents or anti-depressant drugs. Both decreases one problem while enhancing another. The absolute cure is still unknown.
Risks Associated with Bipolar Disorder in Women
Perhaps more significant a gender difference lies in the fact that women can give birth. Relatively little study has been done regarding the risks of bipolar disorder in the period during pregnancy. Sometimes it is difficult to distinguish bipolar symptoms from regular pregnancy symptoms. Pregnant women often do suffer from depression, depending on their environment and stresses. Nonetheless, it is unclear as to whether or not pregnancy increases or decreases bipolar symptoms. Some studies suggest that pregnancy may lessen symptoms: “In one study, 800f patients with affective illness (predominantly bipolar) experienced an improvement or a diminution of symptoms of their mood disorder during pregnancy” (Altshuler et al. 1998). At the same time, these studies are contradicted by other studies. For instance, in a study involving women with bipolar type I disorder, “…women reported manic mood changes, in each case occurring during pregnancy” (Blehar et al., 1998). Manic episodes and cycling seemed to occur exclusively during pregnancy.
Although the reason for this point is unclear, it is apparent pregnancy also poses a question of relapse, which has an important effect on women and the fetus that they are carrying. The fetus can be at risk due to lack of attention to prenatal care, if the woman is not treated for the psychiatric illness. Precipitated episodes in the absence of treatment may be very detrimental to both parties involved. Secondly, the woman would be at risk because with each successive episode, the length of time to following episodes gets smaller. That is, the woman could have manic and depressive episodes more often. This would neither be beneficial to the woman or her child. The effect on the fetus due to many mood episodes is unclear (Viguera et al., 1998). “During pregnancy, a woman’s glomerular filtration rate increases” (Llewellyn et al., 1998). This means that any medication that she takes, such as lithium (discussed below), will be excreted more rapidly. This is very dangerous because if she does not have enough medication in her system, she can fall into relapse. A dilemma arises in that if she increases her medication amount, she may be exposing her fetus to grave side effects and even danger (discussed below). Moreover, during labor, it is important that women remain fully hydrated. Since the period of time for delivery varies with each individual, a pregnant woman can become very dehydrated. When a woman gets dehydrated, the serum medication concentrations will increase (Llewellyn et al., 1998). This is the opposite effect of the increase in glomerulus filtration. Nonetheless, both situations are dangerous and can be very toxic to the woman and indirectly to the fetus.
As varying as the symptoms of bipolar disorder, per individual, so are the treatments. It is very important that bipolar pregnant women get the appropriate care and treatment that they need, in order to properly care for themselves as well as for the child that they are carrying. In treating pregnant women who have bipolar disorder, there exist several clinical problems. There are several drugs or chemicals that are used to treat bipolar disorder. However, such drugs have been shown to cause clinical problems. Drugs that are antimanic agents, such as lithium, valproic acid, and carbamazepine, all have teratogenic effects. Prenatal exposure to lithium increases risk for cardiovascular malformations (Viguera et al., 1998; Llewellyn et al., 1998). With lithium use, cardiovascular abnormalities such as Ebstein’s anomaly may result. This risk in the infant is “400 more common if the mother was being treated with lithium during pregnancy” (WWW1). Ebstein’s anomaly is a cardiovascular malformation where the right ventricle has hypoplasia and there is downward placement of the tricuspid valve into the right ventricle (Viguera et al., 1998). In addition, lithium use during the first trimester of pregnancy increases the risk for Ebstein’s anomaly dramatically. Since lithium can cross the placenta, it is particularly risky because fetal serum concentration is similar to that of the mother (Llewellyn et al., 1998). Moreover, lithium can also cause cardiac arrhythmia, where the heart beats are asynchronous, irregular, or especially slow. Often physicians will counsel their patients to terminate the pregnancy.
Early reports urged the change from lithium use to that of carbamazepine and valproic acid. However, these carbamazepine and valproic acid have been shown to cause defects in the fetus. They have teratogenic effects. Rates of neural tube defects due to carbamazepine and valproic acid exposure has been estimated to be about 1 percent and 3-5%, respectively (Viguera et al., 1998). Studies now suggest that carbamazepine and valproic acid treatment for pregnant bipolar patients may cause even more severe fetal defects than lithium. In addition to the neural defects, carbamazepine and valproic acid exposure to the fetus is associated with craniofacial abnormalities and cognitive dysfunction, if given late in pregnancy. At least with the damage caused by lithium, early detection and surgery can repair the effects. Another study believes that giving pregnant women folate reduces the neural tube defects (Viguera et al., 1998). Nonetheless, studies now show that lithium may be the lesser harmful of the three.
Other treatments are now being discovered to treat bipolar disorder. Yet, newer anticonvulsant agents such as gabapentin and lamotrigine seem to have contradicting effects. Newer antidepressants, such as bupropion, supposedly have good response rates and low risk for manic episodes or rapid cycling. However, as with all new medications, bupropion studies have been met with mixed results (Leibenluft, 1998). Apparently, patients had to discontinue use of bupropion because upon its use, patients occasionally switched to hypomania. Another possible treatment for bipolar disorder is electroconvulsive therapy. This should be considered for as an alternative medication for bipolar depression. In comparison of medication effectiveness, specifically that of monoamine oxidase inhibitors and tricyclics, electroconvulsive therapy seems to be more effective. Five out of seven studies show that electroconvulsive therapy is more useful (Leibenluft, 1998). As with all treatments so far discussed, there exists a drawback in using electroconvulsive therapy. It seems that electroconvulsive therapy is capable of alleviating depression symptoms of bipolar disorder, but there is a possibility that patients will switch into mania or hypomania.
In the use of anti-manic treatment, some studies suggest periodic use and disuse of drugs for pregnant women. For example, some women discontinue taking these drugs for the first trimester of pregnancy. This may decrease the defects mentioned above. These women then use the drugs in later trimesters. How exactly does this work? Data shows that there is increased risk for relapse upon abrupt discontinuation of medications. Gradual, as opposed to rapid, discontinuation may have a more positive effect for pregnant women with respect to relapse. However, although gradual discontinuation is most ideal for pregnant women, the fetus may be exposed to these antimanic agents for a longer period of time–a time that is critical for organogenesis, or the development of the organs. Teratogenic risks are also quite high at this time. The risk of relapse is especially high in women with a greater number of prior mood episodes. Low lithium circulation also increases the risk of relapse; thereafter, there is an increased suicide risk (Viguera et al., 1998).
Viguera et al. (1998) also describes possible treatment guidelines for women with varying episodes. Bipolar patients with a history of one episode of mania and usually function well should be able to discontinue lithium before conception. Those who have moderate illness (2-3 episodes) could take either of two paths. First, the patient may choose to gradually discontinue lithium before conception. If they find that they are unable to handle this, lithium may be easily resumed. Or, they could wait until they find out that they are pregnant. This way, the patient minimizes exposure during placental implantation. Thus, these critical factors must be considered before beginning treatment of pregnant women suffering from bipolar disorder. Women with the most severe forms of bipolar disorder (i.e. more than four episodes) should continue to use lithium throughout the first and second trimesters. They should use lithium treatment before as well as during pregnancy. This is because they are most prone to have severe manic-depressive episodes in the absence of medication treatment. As emphasized before, this would be very detrimental to both the mother and fetus. In general, all women who use lithium during the first trimester of pregnancy should get a level II ultrasound at 18 to 20 weeks gestation (Llewellyn et al., 1998). This is to check for cardiac abnormalities.
An even more critical period in a pregnant woman’s life is during the postpartum period, after the woman has given birth. This is because the postpartum period of a woman’s life is one of especially high risk. Relatively more studies have been done on bipolar disorder during the postpartum period as opposed to during the actual pregnancy. The relapse from bipolar disorder during the postpartum period has been estimated between 33% (Altshuler et al., 1998). Since some women do suffer from depression after giving birth, it is especially crucial to be aware of the possibility of elevated depression. During the postpartum period, women often feel the need to commit suicide, because the depressive episodes seem to dominate (Blehar et al., 1997). Postpartum psychotic episodes vary and they can be very severe. This has to be noted in order to prevent the mother’s suicide or infanticide of the newborn. Moreover, postpartum relapse can be greatly decreased by five-fold when lithium is taken right before birth (within 48 hours of delivery) and continued throughout the postpartum period (Viguera et al., 1998).
Altshuler, L.L., Henrick V., Cohen, L.S. Course of mood and anxiety disorders during pregnancy and the postpartum period. Journal of Clinical Psychiatry 59 Suppl 2: 29-33 (1998).
Blehar, M.C., DePaulo J.R. Jr., Gershon, E.S., Reich, T., Simpson, S.G., Nurnberger, J.I. Jr. Women with bipolar disorder: findings from the NIMH Genetics Initiative sample. PsychopharmacologyBulletin 34(3): 239-243 (1998).
Leibenluft, E. Issues in the treatment of women with bipolar illness. Journal of Clinical Psychiatry 58 Suppl 15: 5-11 (1997).
Llewellyn, A., Stowe, Z. N., Strader, J.R. Jr. The use of lithium and management of women with bipolar disorder during pregnancy and lactation. Journal of Clinical Psychiatry59 Suppl 6: 57-64, discussion 65 (1998).
Viguera, A.C., Cohen, L.S. The course and management of bipolar disorder during pregnancy. Psychopharmacology Bulletin 34(3): 339-46 (1998).