Bipolar Women Research Articles

Prophylactic treatment of bipolar disorder in pregnancy and breastfeeding: focus on emerging mood stabilizers

Bipolar disorders are reported to have a high incidence during childbearing years and the need may arise to start or continue a pharmacological treatment during pregnancy and the postpartum period. In the last few years several investigations have evaluated the efficacy of emerging mood-stabilizing agents in the treatment of bipolar disorders, such as lamotrigine, olanzapine, risperidone, quetiapine, aripiprazole and ziprasidone. A number of studies, which examined the use of oxcarbazepine, point to its potential usefulness in prophylactic treatment. The aim of this review is to compare information from the literature on the safety of lamotrigine, oxcarbazepine, risperidone, olanzapine, and quetiapine to the safety data on classic mood stabilizers during pregnancy and the postpartum period. A computerized search carried out from 1980 to April 5, 2006 led to the summarization of the results. (References were updated after acceptance and prior to publication.) Emerging mood stabilizers show uncertain safety parameters in pregnancy and lactation. Limited information on lamotrigine and oxcarbazepine does not suggest a clear increase in teratogenicity, while olanzapine appears to be associated with a higher risk of metabolic complications in pregnant women. Data about risperidone and quetiapine are still inconclusive. Finally, the literature on the safety of these compounds in breastfeeding is anecdotal. Untreated pregnant bipolar women are at an increased risk of poor obstetrical outcomes and relapse of affective symptoms. On the other hand, classic antiepileptic drugs are well-known human teratogens, whereas data on lithium are partially ambiguous. The safety of emerging mood stabilizers in pregnancy and breastfeeding has not been examined extensively. Therefore, when approaching bipolar disorder, if possible, each episode must be considered separately.

Grossesse, allaitement et thymorégulateurs : éléments de décisions et règles pour la pratique

Introduction The high prevalence of bipolar affective disorder, the early age of onset and the even sex ratio imply that numerous women of childbearing age raise the question of mood stabilisers during pregnancy and breast feeding. Literature findings Some data suggest that giving appropriate answers to bipolar women who want to have children is an unmet need. We reviewed the risks and therapeutic options of this period of life in women with bipolar disorder. The generally accepted idea that pregnancy protects from relapses in bipolar disorders may be untrue and even deceitful. Lithium is the only mood stabiliser that can be prescribed in some cases during the first three months of pregnancy. Discussion and guide lines We give explicit criteria that allow to consider this option : a severe illness prior to lithium prescription, a highly favourable outcome since initiation of lithium, no relapse during the last 18 months. When such conditions are satisfied, a reflection of the patient and at best of the couple must be proposed and associated with very complete information, both oral and written when possible, on the risks and benefits of the interruption and/or continuation of lithium. The teratogenic risks with anticonvulsants have been demonstrated and their prescription during the first three months of pregnancy should be avoided. Besides, there is some concern about the psycho-motor development of children born from women who were under anticonvulsants during pregnancy. The more recent mood stabilisers are not recommended either due to insufficient data. Breast feeding is not recommended under lithium, but seems safe under carbamazepine or valproate and its derivatives.

Reproductive function and risk for PCOS in women treated for bipolar disorder

This study examined the reproductive function and prevalence of polycystic ovary syndrome (PCOS) in women with bipolar disorder taking antimanic medications. Women aged 18-45 treated for bipolar disorder and not taking steroid contraceptives were recruited to complete questionnaires about their menstrual cycle and to provide blood samples for measurement of a range of reproductive endocrine and metabolic hormone levels. Eighty women participated in completing the questionnaires and 72 of them provided blood samples. Fifty-two of the 80 women (65%) reported current menstrual abnormalities, 40 of which (50%) reported one or more menstrual abnormalities that preceded the diagnosis of bipolar disorder. Fifteen women (38%) reported developing menstrual abnormalities since treatment for bipolar disorder, 14 of which developed abnormalities since treatment with valproate (p = 0.04). Of the 15 patients reporting menstrual abnormalities since starting medication, 12 (80%) reported changes in menstrual flow (heavy or prolonged bleeding) and five (33%) reported changes in cycle frequency. No significant differences were observed between women receiving or not receiving valproate in mean levels of free or total serum testosterone levels. This was true for the total sample and for the sub-group without preexisting menstrual problems. However, within the valproate group, duration of use was significantly correlated with free testosterone levels (r = 0.33, p = 0.02). Three of the 50 women (6%) taking VPA, and 0% of the 22 taking other antimanic medications, met criteria for PCOS (p = 0.20). Other reproductive and metabolic values outside the normal range across treatment groups included elevated 17 alpha-OH progesterone levels, luteinizing hormone: follicle-stimulating hormone ratios, homeostatic model assessment (HOMA) values, and low estrogen and dehydroepiandrosterone sulfate (DHEAS) levels. Preexisting menstrual abnormalities predicted higher levels of 17 alpha-OH progesterone, free testosterone, and estrone as well as development of new menstrual abnormalities. Body mass index (BMI) was significantly positively correlated with free testosterone levels and insulin resistance (HOMA) across all subjects, regardless of medication used. Rates of menstrual disturbances are high in women with bipolar disorder and, in many cases, precede the diagnosis and treatment for the disorder. Treatment with valproate additionally contributes significantly to the development of menstrual abnormalities and an increase in testosterone levels over time. A number of bipolar women, regardless of type of medication treatment received, have reproductive and metabolic hormonal abnormalities, yet the etiology of such abnormalities requires further study. Women with preexisting menstrual abnormalities may represent a group at risk for development of reproductive dysfunction while being treated for bipolar disorder.

Association between the TRAX/DISC locus and both bipolar disorder and schizophrenia in the Scottish population

The Translin-associated factor X/Disrupted in Schizophrenia 1 (TRAX/DISC) region was first implicated as a susceptibility locus for schizophrenia by analysis of a large Scottish family in which a t(1;11) translocation cosegregates with schizophrenia, bipolar disorder and recurrent major depression. We now report evidence for association between bipolar disorder and schizophrenia and this locus in the general Scottish population. A systematic study of linkage disequilibrium in a representative sample of the Scottish population was undertaken across the 510 kb of TRAX and DISC1. SNPs representing each haplotype block were selected for case-control association studies of both schizophrenia and bipolar disorder. Significant association with bipolar disorder in women P=0.00026 (P=0.0016 in men and women combined) was detected in a region of DISC1. This same region also showed nominally significant association with schizophrenia in both men and women combined, P=0.0056. Two further regions, one in TRAX and the second in DISC1, showed weaker evidence for sex-specific associations of individual haplotypes with bipolar disorder in men and women respectively, P<0.01. Only the association between bipolar women and DISC1 remained significant after correction for multiple testing. This result provides further supporting evidence for DISC1 as a susceptibility factor for both bipolar disorder and schizophrenia, consistent with the diagnoses in the original Scottish translocation family.

Valproate Use Related to PCOS In 10% of Bipolar Women

Valproate Use Related to PCOS In 10% of Bipolar Women

Valproate-associated reproductive and metabolic abnormalities: are epileptic women at greater risk than bipolar women?

Objective: Evidence indicates that valproate (VPA) may have an adverse impact on reproductive endocrine and metabolic functions in women with epilepsy. This study explores whether the association of VPA with reproductive endocrine abnormalities is applicable to women with bipolar disorder (BD) or is unique to women with epilepsy. Methods: Thirty female patients aged 18–40 years with a DSM-IV diagnosis of BD (15 on lithium monotherapy and 15 on VPA monotherapy or VPA in combination with lithium therapy) and 15 with idiopathic generalized epilepsy (IGE) on VPA monotherapy were evaluated for reproductive endocrine functioning and metabolic parameters. Results: The menarche age, mean length of menstrual cycle and mean length of menses were not significantly different between groups. None of the bipolar patients on lithium, three (20%) of the bipolar patients on VPA and seven (47%) of the epileptic patients on VPA reported menstrual disturbances. Hirsutism scores of the epilepsy group were significantly higher than those bipolar women, regardless of treatment. Serum total testosterone levels were significantly higher in patients (both with BD and with IGE) treated with VPA than in those treated with lithium. Serum FSH levels were significantly lower and LH-to-FSH ratio was significantly higher in patients with epilepsy than in patients with BD, regardless of treatment. The weight parameters and lipid values investigated did not differ significantly between the groups. Conclusion: The study supports the conclusion that VPA may be associated with menstrual abnormalities and increased total testosterone levels in both bipolar and epileptic patients although women with BD did not show clinical features of hyperandrogenism (menstrual abnormalities, hirsutism and truncal obesity) as did frequently as women with epilepsy.

A Preliminary Study of the Relationship Between Clozapine-Induced Weight Gain and Menstrual Irregularities in Schizophrenic, Schizoaffective, and Bipolar Women

A Preliminary Study of the Relationship Between Clozapine-Induced Weight Gain and Menstrual Irregularities in Schizophrenic, Schizoaffective, and Bipolar Women

Association study between novel promoter variants at the 5-HT2C receptor gene and human patients with bipolar affective disorder

Two recently described adjacent DNA polymorphisms [(GT)12–18 and (CT)4–5] in the 5′-regulatory region of 5-HT2C receptor gene were analysed in a sample of 88 bipolar patients and 162 controls, all of Spanish origin. Statistical analyses revealed no overall allele or genotype associations with the disease. A haplotype analyses between the (GT)12–18/(CT)4–5 motif and a Cys23Ser variant of the 5-HT2C gene (which had previously been genotyped in the same sample) showed similar distributions between cases and controls. Only a slight increase of s-Ser23 haplotype was found in the subgroup of bipolar women with family history of psychiatric illness (OR=1.24 [95%CI: 1.12–1.38]).

Gender and Bipolar Illness

For major depression and schizophrenia, gender differences have been reported in symptom expression and course of illness. Gender differences in bipolar disorder are becoming increasingly apparent, but have been less studied. Research data on these differences will help determine whether gender is important in influencing illness variables such as course, symptom expression, and likelihood of comorbidity. Charts of 131 patients (63 women and 68 men) with a DSM-IV diagnosis of bipolar disorder admitted to the University of California Los Angeles Mood Disorders Program over a 3-year period were reviewed to gather data on demographic variables and course of illness and to assess differences in the illness across genders. No significant gender differences were found in the rate of bipolar I or bipolar II diagnoses, although women were overrepresented in the latter category. Also, no significant gender differences emerged in age at onset, number of depressive or manic episodes, and number of hospitalizations for depression. Women, however, had been hospitalized significantly more often than men for mania. Further, whereas bipolar men were significantly more likely than bipolar women to have a comorbid substance use disorder, women with bipolar disorder had 4 times the rate of alcohol use disorders and 7 times the rate of other substance use disorders than reported in women from community-derived samples. For bipolar disorder, course of illness variables such as age at onset and number of affective episodes of each polarity do not seem to differ across genders. Women, however, may be more likely than men to be hospitalized for manic episodes. While both men and women with the illness have high rates of comorbidity with alcohol and other substance use disorders, women with bipolar disorder are at a particularly high risk for comorbidity with these conditions.

Diagnosis and treatment of bipolar disorder in pregnant women

Bipolar disorder is relatively rare in obstetrics and gynecology (ob/gyn) practice compared with depressive and anxiety disorders, but there is a high risk for poor outcomes for patients and their offspring. Ob/Gyn physicians are assuming increasing responsibility for the care of these patients in today’s managed care environment, working independently or in collaboration with a psychiatrist. The clinical presentation of bipolar patients may include mania and/or depression, in addition to more minor mood fluctuations that accompany the emotional and physical changes of pregnancy. The key issue in the differential diagnosis is to rule out medical, surgical, medication, and substance etiologies of mania that are potentially reversible. Indications for routine, urgent, and emergent referrals to a psychiatrist are reviewed. Treatment for bipolar women considering pregnancy includes prepregnancy planning education, involving the patient, family, psychiatrist, ob/gyn physician, and maternal-fetal medicine specialist. Treatment for pregnant bipolar women includes an individualized risk/benefit assessment regarding medication, monitoring levels and adherence to medication if it is used, ongoing patient education, and collaboration between the ob/gyn physician, maternal-fetal medicine specialist, and psychiatrist.

Preliminary, open-label study of topiramate in rapid cycling bipolar women

Preliminary, open-label study of topiramate in rapid cycling bipolar women

Prevalence of migraine in bipolar disorder

Background: this study was undertaken to estimate the prevalence of migraine in people suffering from bipolar affective disorder. Methods: a headache questionnaire incorporating the newly introduced International Headache Society (IHS) criteria was given to 117 patients on the Dunedin Bipolar Research Register. Results: a total of 81 (69%) completed the questionnaire, out of which 21 (25.9%) reported migraine headaches. 25% of bipolar men and 27% of bipolar women suffered from migraine. Conclusions: these rates are higher than those reported in the general population with the rate for bipolar men being almost five-times higher than expected. An increased risk of suffering form migraine was particularly noted in bipolar patients with an early onset of the disorder. This may represent a more severe form of bipolar affective disorder.

Rapid cycling in women and men with bipolar manic-depressive disorders.

This study investigated risks for rapid cycling, as defined by DSM-IV, in women and men with bipolar disorders. The results of 10 studies with a total of 2,057 bipolar patients were meta-analyzed by pooled contingency methods. The proportions of women and men among rapid-cycling cases averaged 72% and 28%, respectively, but the risk of rapid cycling was inconsistently more frequent among women (29.6%) than among men (16.5%). The mean number of episodes per year was much higher in rapid-cycling patients before and during lithium treatment but was similar in rapid-cycling men and women. Rapid cycling was only moderately, and inconsistently, more common in bipolar women than men.

Recurrence in affective disorder. II. Effect of age and gender.

The risk of recurrence in affective disorder has been found to increase with each new episode. It is unclear whether it is universal without regard to gender, age and type of disorder. Survival analysis was used to estimate the risk of recurrence in a case-register study including all hospital admissions with primary affective disorder in Denmark from 1971-1993. In this period 20,350 first-admission patients had been discharged with a diagnosis of affective disorder, depressive or manic/cyclic type. The risk of recurrence increased with the number of previous episodes regardless of the combination of gender, age and type of disorder. Initially in the course of illness, unipolar and bipolar women experienced an equal greater risk of recurrence than men. The risk of recurrence after the first episode was increased for middle-aged and older unipolar women compared with the risk for younger women, while after all other episodes younger age at first episode increased the risk of recurrence. The course of severe unipolar and bipolar disorder seems to be progressive in nature irrespective of gender, age and type of disorder.

Eye movements and psychopathology in schizophrenia and bipolar disorder.

The aim of this study was to examine multivariate patterns of relationships between oculomotor performance, psychopathology, and neuropsychology. Performance on smooth pursuit and saccadic eye movement tasks was assessed in three DSM-III-R diagnosis-based groups of subjects; normal (N = 55), schizophrenic (N = 29), and bipolar disorder (N = 26) and analyzed in relation to age, gender, scale for the Assessment of Negative Symptoms, Scale for the Assessment of Positive Symptoms, and Brief Psychiatric Rating Scale scores, Shipley intelligence quotient, and Wisconsin Card Sorting Test Performance. The greatest difference was a higher proportion of errors in the antisaccade task in the schizophrenic and bipolar groups, which was related to worse Wisconsin Card Sorting Test performance and was not accounted for by gender, age, education, or intelligence quotient. A significant gender and bipolar interaction showed bipolar women to have worse antisaccade performance. Abnormal smooth pursuit was more specific to schizophrenia. Antisaccade task and sine wave root-mean-square error were correlated in bipolar but not schizophrenic subjects. Scale for the Assessment of Negative Symptoms and Scale for the Assessment of Positive Symptoms scores had independent associations with the antisaccade task. Faster reaction times in the schizophrenic group to antisaccade errors were observed, suggesting an abnormality in visual attention processing and perhaps sensory gating functions. These results confirm abnormal smooth pursuit in schizophrenia and suggests that impairments in saccadic function are less specific to diagnostic group. Oculomotor performance and psychopathology seem related in complex ways to age, gender, intelligence quotient, and executive neuropsychological and possibly visual attention functions.

Postpartum Prophylaxis for Women With Bipolar Disorder

Cohen, Lee S.; Sichel, Deborah A.; Robertson, Laura M.; Heckscher, Elizabeth; Rosenbaum, Jerrold F. Author Information

Women with bipolar illness: clinical and research issues.

The purpose of this article is to review the literature concerning gender differences in the course of bipolar illness and discuss issues relevant to the treatment of women with the illness. The literature concerning the following topics is reviewed: gender differences in the course of bipolar illness; effects of the female reproductive cycle on the course of bipolar illness; special considerations in the treatment of bipolar women (focusing on the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-thyroid axes); and hypotheses to explain the greater prevalence of rapid cycling among bipolar women than among bipolar men. Data clearly indicate that rapid cycling is more common among bipolar women. Data also suggest that bipolar women may have more depressive episodes (and fewer manic episodes) and may be more likely to suffer from mixed (as opposed to pure) mania than bipolar men. While it is clear that bipolar women are at high risk for postpartum episodes, the effects of other reproductive system events (i.e., puberty, menstrual cycle, pregnancy, menopause, use of oral contraceptives or hormone replacement therapy) on the course or treatment of bipolar illness have received little systematic study. It is unclear whether women are at higher risk than men for developing lithium-induced hypothyroidism. Higher rates of hypothyroidism, greater use of antidepressants, and gonadal steroid effects are possible explanations for the greater prevalence of rapid cycling among bipolar women. Gender differences in bipolar illness and the effects of the female reproductive system on the course and treatment of the illness deserve more study. The importance of a longitudinal approach to these questions is emphasized.

Managing Bipolar Disorder

Two recent reports describe the difficulties of managing bipolar disorder. The first retrospective naturalistic study of 27 women diagnosed with bipolar disorder demonstrates the value of prophylactically treating bipolar women during the immediate postpartum period. Only one of 14 women who either continued medication or started prophylactic medication within 48 hours after delivery relapsed within the first three postpartum months, versus 8 of 13 women who did not take medication. Although the two …

Postpartum prophylaxis for women with bipolar disorder.

The postpartum period has typically been considered a time of heightened vulnerability for development of affective disorders, and women with bipolar disorder have consistently demonstrated vulnerability to puerperal worsening of mood. This retrospective study examined the extent to which mood-stabilizing agents provide prophylactic benefit to bipolar women during the postpartum period. The clinical course of 27 women meeting the DSM-III-R criteria for bipolar disorder was followed during pregnancy and the postpartum period. Information regarding severity of illness (as measured by number of episodes of mania, depression, or both) was obtained, in addition to data on pharmacotherapy (if any) received before, during, and after pregnancy. The extent to which the prophylactic use of antimanic agents minimized the risk of relapse was explored. Only one of the 14 patients taking prophylactic agents during the acute puerperium relapsed within the first 3 months postpartum, while eight of the 13 who did not receive antimanic drugs showed evidence of recurrent affective instability during those 3 months. A survival analysis indicated that the women receiving prophylactic treatment with mood stabilizers maintained well-being significantly longer than the women who did not receive such treatment. Women with bipolar disorder appear to benefit from puerperal prophylaxis with mood stabilizers. Consistent with results of earlier studies, postpartum prophylaxis was associated with lower rates of relapse into affective disorders. The findings have implications for the early identification and treatment of subgroups of women at particular risk for puerperal illness.

Psychosocial outcomes of children of unipolar depressed, bipolar, medically ill, and normal women: A longitudinal study.

The psychosocial functioning of children of unipolar depressed, bipolar, medically ill, and psychiatrically normal women was studied over a 2-year period. Ninety-six children aged 8-16 years were assessed at 6-month intervals on Child Behavior Checklist behavior problems, social competence, internalizing and externalizing behaviors, academic performance, and school behavior. The children of unipolar mothers showed significantly poorer functioning on all measures as compared with the other 3 groups of children, including bipolar offspring. A greater proportion of children in the unipolar group also had relatively chronic, clinically significant problems in psychosocial functioning. Children of bipolar women did not differ from children of psychiatrically normal women. Results are discussed in terms of the consequences of children's continuing exposure to maternal depression and attendant stressors, as well as the contribution of social and academic difficulties to a vicious cycle of maladjustment.