Bipolar disorder in women: Contraception and preconception assessmen... http://www.uptodate.com/contents/bipolar-disorder-in-women-contrace...

Official reprint from UpToDate www.uptodate.com 2013 UpToDate

Bipolar disorder in women: Contraception and preconception assessment and counseling Author Victoria Hendrick, MD Disclosures All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Oct 2013. | This topic last updated: Ago 1, 2013. INTRODUCTION Bipolar patients who consider becoming pregnant should receive preconception counseling about the risks to the patient and her child. However, approximately one-half of all pregnancies in the United States are unplanned [1,2]. Thus, prepregnancy counseling is relevant to all female patients of reproductive age, regardless of their plans regarding pregnancy. In addition, contraception should be encouraged for patients who wish to avoid pregnancy. This topic reviews contraception and the preconception assessment and counseling of women with bipolar disorder. Indications for maintenance pharmacotherapy during pregnancy, selecting preconception and prenatal maintenance treatment for bipolar patients, and the teratogenic and postnatal effects of medications used for bipolar disorder are discussed separately. (See "Bipolar disorder in women: Indications for preconception and prenatal maintenance pharmacotherapy" and "Bipolar disorder in women: Preconception and prenatal maintenance pharmacotherapy" and "Bipolar disorder in adults: Teratogenic and postnatal risks of pharmacotherapy".) DEFINITION OF BIPOLAR DISORDER Bipolar disorder is a mood disorder that is characterized by episodes of mania (table 1), hypomania (table 2), and major depression (table 3), as well as mixed episodes (major depression concurrent with mania) [3]. The subtypes of bipolar disorder include bipolar I and bipolar II. Patients with bipolar I disorder experience manic and mixed episodes, and nearly always experience major depressive and hypomanic episodes. Bipolar II disorder is marked by at least one hypomanic episode, at least one major depressive episode, and the absence of manic and mixed episodes. Additional information about the clinical features and diagnosis of bipolar disorder is discussed separately. (See "Bipolar disorder in adults: Clinical features" and "Bipolar disorder in adults: Assessment and diagnosis", section on 'Diagnosis'.) CONTRACEPTION Bipolar patients who want to avoid pregnancy should receive information about contraceptive methods. Many female bipolar patients of childbearing age are treated with medications, but do not use contraception and are not trying to conceive. In a survey of 136 female patients receiving maintenance pharmacotherapy (including drugs that appear to be teratogenic), 41 percent did not use birth control [4]. Female bipolar patients should be encouraged to use long-acting reversible contraceptives, such as intrauterine devices or implants; these require much less attention from the user and are among the most effective methods. In particular, the copper intrauterine device will not interfere with concurrent medications, is nonhormonal, and can be effective for at least 10 years. Contraceptive techniques are discussed separately. (See "Overview of contraception".) It is not known if hormonal contraceptives affect the mood state of bipolar patients [5]. However, randomized trials have demonstrated that the estrogen receptor antagonist tamoxifen efficaciously treats mania [6-9]; this antimanic effect is discussed separately. (See "Bipolar disorder in adults: Pharmacotherapy for acute mania, mixed episodes, and hypomania", section on 'Other medications'.) Drug interactions between antiepileptics and hormonal contraceptives We suggest that bipolar patients treated with carbamazepine avoid hormonal contraception (oral, patch, and vaginal ring) and use a different form of birth control, such as an injectable contraceptive, implant, or intrauterine device (table 4). Carbamazepine may induce hepatic enzymes and increase metabolism of hormonal contraceptives, thus reducing their efficacy (table 4). However, a reasonable alternative is to use high-dose oral hormonal contraceptives and watch for spotting, which may indicate that the contraceptive is failing. Additional information about carbamazepine and hormonal contraception failure is discussed separately. (See "Overview of the management of epilepsy in adults", section on 'Oral contraceptive therapy'.) In addition, we suggest that bipolar patients treated with lamotrigine avoid estrogen containing contraceptives, which may increase lamotrigine clearance and reduce its efficacy for treating bipolar disorder [10]. However, a reasonable alternative includes prescribing higher doses of lamotrigine if an estrogen-based hormonal contraceptive is used. Additional information about drug-drug interactions between lamotrigine and oral contraception is discussed separately. (See "Pharmacology of antiepileptic drugs", section on 'Lamotrigine'.) Hormonal contraceptives can interact with drugs other than anticonvulsants (table 4). PRECONCEPTION ASSESSMENT The clinical assessment of bipolar patients who consider becoming pregnant includes a psychiatric and general medical history, mental status and physical examination, and focused laboratory tests [11-13]. The general preconception evaluation for all patients is discussed separately. (See "Preconception evaluation and counseling", section on 'Components of the preconception evaluation'.) The psychiatric history for bipolar patients should emphasize the following: Age Women should be aware that fertility declines and the risk of fetal chromosomal abnormalities rises with increasing age, especially after the mid-30s. Weight Many female bipolar patients are obese, which increases the risk of pregnancy complications (eg, gestational diabetes, preeclampsia, cesarean delivery, and fetal neural tube defects) [14]. (See "The impact of obesity on female fertility and pregnancy".) Clinicians should encourage patients to conceive at a normal body mass index (BMI), which is calculated from height and weight (calculator 1). Weight loss for overweight patients with dietary therapy, exercise, and other treatments is discussed separately. (See "Overview of therapy for obesity in adults".) Current status of bipolar disorder and course of illness, including current symptoms of a manic (table 1), hypomanic (table 2), major depressive (table 3), or mixed episode (major depression concurrent with mania or hypomania); number of prior mood episodes, particularly during the previous two to five years; and history of psychotic features (delusions and/or hallucinations) and suicidal ideation and behavior. Bipolar patients are encouraged to delay pregnancy until their illness is stable, and a long (eg, 2 years) duration of euthymia prior to conception is preferred. Medications Several medications used to treat bipolar disorder appear to be teratogenic, including valproate and carbamazepine, and to a lesser extent lithium. (See "Bipolar disorder in adults: Teratogenic and postnatal risks of pharmacotherapy".) Supplements Many patients do not realize that herbal supplements are potentially harmful to the fetus Substance abuse Drug, alcohol, and nicotine abuse is widespread among bipolar patients [15]. Women with bipolar disorder should be screened for their use of these substances, educated about the potential impact on the baby, and offered substance abuse treatment; these issues are discussed separately. (See "Overview of illicit drug use in pregnant women" and "Substance use disorders: Principles for recognition and assessment in general medical care" and "Psychosocial treatment of alcohol use disorder" and "Cannabis use disorder: Treatment, prognosis, and long-term medical effects" and "Treatment of opioid abuse and dependence" and "Treatment of cocaine use disorder in adults", section on 'Overview of treatment'.) Psychosocial functioning Psychosocial stressors (eg, domestic violence, marital conflict, inadequate social support, and financial problems) are likely to disrupt the patients stability and should be addressed before pregnancy The general medical history should emphasize the metabolic syndrome and diabetes, which commonly occur in bipolar patients and should be stabilized prior to attempting conception [14]. (See "The metabolic syndrome (insulin resistance syndrome or syndrome X)" and "Overview of medical care in adults with diabetes mellitus".) RISKS ASSOCIATED WITH PREGNANCY Although several risks are associated with pregnancy in bipolar patients, bipolar disorder is not a contraindication for pregnancy [16]. We encourage clinicians to include the spouse when discussing these risks with the patient, as well as other family members who may be called upon to support the patient during and after the pregnancy. Risk of adverse pregnancy and birth outcomes Adverse pregnancy and birth outcomes may occur more often in women with bipolar disorder regardless of treatment status, compared to women without bipolar disorder. A retrospective study of national registries compared outcomes in pregnant bipolar patients who were treated with mood stabilizers (antipsychotics, carbamazepine, lamotrigine, lithium, and/or valproate; N = 320), pregnant bipolar patients who were not treated with mood stabilizers (N = 554), and pregnant women without bipolar disorder who did not receive mood stabilizers (N = 331,263) [17]. The analyses controlled for potential confounders such as maternal age and substance use disorders; the primary findings included the following: Induced or planned caesarean delivery occurred in more treated and untreated bipolar patients than women without bipolar disorder (38 and 31 versus 21 percent) Preterm birth occurred in more treated and untreated bipolar patients than women without bipolar disorder (8 and 8 versus 5 percent) Adverse pregnancy and birth outcomes were comparable for treated and untreated bipolar patients Congenital defects The base rate for congenital defects in the offspring of patients with bipolar disorder appears to be no different than that of the general population, which is 2 to 5 percent [17-21]. However, some medications used to treat bipolar disorder appear to be teratogenic, including valproate and carbamazepine, and to a lesser extent lithium. The increased risk of malformations and adverse postnatal behavioral and developmental effects due to treatment of bipolar disorder during pregnancy is discussed separately, as are the general principles of teratology, genetic and environmental causes of birth defects, and the approach to congenital malformations. (See "Bipolar disorder in adults: Teratogenic and postnatal risks of pharmacotherapy" and "Principles of teratology" and "Genetic and environmental causes of birth defects" and "Approach to congenital malformations".) Risk of maternal mood episodes Clinicians should describe the risk of suffering bipolar mood episodes during pregnancy. As an example, a retrospective study in parous women with bipolar I disorder (N = 980) found that perinatal mood episodes had occurred in 56 percent, and among parous bipolar II patients, 40 percent [22]. Clinicians should also explain that pharmacotherapy may reduce this risk. In Section Editor Paul Keck, MD Deputy Editor David Solomon, MD

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addition, clinicians, patients, and family members are encouraged to develop prespecified contingency plans for treating mood episodes that occur during pregnancy [16]. Relapse during pregnancy Although bipolar patients often suffer mood episodes during pregnancy, it is not known if pregnancy changes the risk of recurrence. Some patients may experience fewer recurrences during pregnancy [23], whereas the course of illness in other pregnant patients remains unchanged or worsens [24,25]. Observational studies of pregnant bipolar patients have found the following rates of recurrence: Two prospective studies (N = 89 and 26) each found that at least one mood episode during pregnancy occurred in more than 70 percent of patients [24,26]; among patients in a third study (N = 41), episodes occurred in 24 percent [27] A retrospective study (N = 1120) found that a mood episode occurred during pregnancy in approximately 20 percent of patients [28] For pregnant bipolar patients, the risk of recurrence appears to be greatest during the first trimester. In a prospective observational study of 63 patients who suffered a mood episode, the timing was as follows [24]: First trimester 66.6 percent of patients Second trimester 23.8 percent Third trimester 9.5 percent The most common morbidity in pregnant bipolar patients is major depression [26,28]. In a prospective observational study of 81 mood episodes, the polarity was [24]: Major depression 42 percent of episodes Mixed (major depression concurrent with mania or hypomania) 32 percent Mania or hypomania 26 percent This finding is consistent with the observation that depression is the predominant mood state for bipolar patients in general [29,30]. Clinical factors that may be associated with relapse during pregnancy include [24,26]: Shorter period of clinical stability prior to conception Discontinuing pharmacotherapy between six months prior to conception and 12 weeks after conception Unplanned pregnancy Current psychiatric comorbidity Lifetime duration of bipolar disorder 5 years Following onset of bipolar disorder, history of at least one recurrent mood episode per year Relapse after discontinuing pharmacotherapy Maintenance treatment during pregnancy may protect bipolar patients against recurrent mood episodes [26]. In a prospective observational study, euthymic pregnant patients who either continued (N = 27) or discontinued (N = 62) pharmacotherapy were followed through the end of pregnancy [24]. Maintenance medications included lithium, valproate, lamotrigine, carbamazepine, olanzapine, quetiapine, and antidepressants, with some patients taking more than one drug. Among the results: Relapse occurred in significantly fewer patients who continued pharmacotherapy than patients who stopped pharmacotherapy (37 versus 86 percent) The proportion of time spent ill with a mood episode during pregnancy was significantly less in patients who continued pharmacotherapy than patients who stopped pharmacotherapy (9 versus 43 percent of weeks) Indications for maintenance pharmacotherapy during pregnancy, and selecting preconception and prenatal maintenance treatment for bipolar patients are discussed separately. (See "Bipolar disorder in women: Indications for preconception and prenatal maintenance pharmacotherapy" and "Bipolar disorder in women: Preconception and prenatal maintenance pharmacotherapy".) Recurrence of bipolar mood episodes in pregnant patients appears to be greater if medications are quickly discontinued [25]. In a prospective observational study of 62 patients who discontinued pharmacotherapy, the median time to recurrence was significantly shorter if medications were discontinued in less than 15 days, compared with tapering and stopping medications over 15 or more days (2 versus 22 weeks) [24]. This finding is consistent with other studies that have found that recurrence is more likely if stable maintenance pharmacotherapy for bipolar disorder is terminated over 1 to 14 days, compared with a more gradual taper [31-33]. Postpartum mood episodes The risk of bipolar mood episodes appears to be greater in the postpartum period than during pregnancy. A retrospective study of 1120 pregnancies in bipolar patients found that mood episodes occurred more than twice as often in the postpartum period (six months following live births) than during pregnancy [28]. A second retrospective study of 700 perinatal events in bipolar I patients found that more than 90 percent occurred in the postpartum period [22]. The risk of postpartum mood episodes is discussed separately. (See "Bipolar disorder in postpartum women: Epidemiology, clinical features, assessment, and diagnosis", section on 'Epidemiology'.) Inheriting bipolar disorder Bipolar patients who consider having children typically want information about the risk that offspring will inherit bipolar disorder. Bipolar disorder aggregates within families [34,35]. The estimated prevalence (risk) of bipolar disorder in children of families with one bipolar parent is 9 percent; the risk increases if onset of bipolar disorder in the parent was early (eg, 18 years), or if siblings or the other parent have the disorder [36,37]. By contrast, the estimated lifetime prevalence rate of bipolar disorder in the general population of the United States is 2 percent [38], and the cross-national (11 countries) rate is 1 percent [39]. There is considerable evidence that genes play a large role in the pathogenesis of bipolar disorder, based upon twin, family, and adoption studies [40,41]. As an example, a study of 30 monozygotic and 37 dizygotic twins in which one twin from each pair had bipolar disorder found that the concordance rate for bipolar disorder in the co-twin was eight times greater for monozygotic twins than dizygotic twins (40 versus 5 percent of the twin pairs) [42]. Genetic susceptibility appears to involve the interaction of many genes with small effects rather than a single gene with a major effect [36]. However, the risk of developing bipolar disorder probably involves environmental factors as well. This is indicated by the finding that the concordance rate of bipolar disorder in monozygotic twins is approximately 40 rather than 100 percent [42]. Additional information about the genetics of bipolar disorder is discussed separately. (See "Bipolar disorder in adults: Epidemiology and pathogenesis", section on 'Genetics'.) Prenatal infection and bipolar disorder It is not known if prenatal exposure to infectious agents is a risk factor for developing bipolar disorder, due to conflicting results across observational studies: One study compared 127 bipolar patients and 127 matched controls for antibodies to herpes simplex virus type 1 and 2, cytomegalovirus, and Toxoplasma gondii in blood drawn within one week of birth, and found no association between neonatal seropositivity and an increased risk of bipolar disorder [43]. However, a second study found that seropositivity to Toxoplasma gondii antibodies occurred more bipolar patients (N = 110) than healthy controls (N = 106) (77 versus 48 percent) [44]. In addition, a third study compared 92 adult bipolar patients and 722 matched controls for in utero exposure to influenza (based upon prospective, antenatal, clinical diagnoses of mothers), and found that gestational exposure to influenza at any time during pregnancy was four times greater in offspring with bipolar disorder, compared with controls [45]. Obstetric complications and bipolar disorder Obstetrical complications do not appear to play a role in the etiology of bipolar disorder. A meta-analysis of eight observational studies found that exposure to obstetric complications (eg, maternal anemia, rubella, prematurity, prolonged labor, and neonatal respiratory problems) was comparable for bipolar patients (N = 272) and healthy controls (N = 331) (31 versus 29 percent) [46]. In a subsequent retrospective observational study that compared 120 bipolar patients with 98 healthy controls, difficulties during delivery (eg, breech delivery, cesarean section, cord around the neck, and labor >24 hours) were comparable for patients and controls (66 and 57 percent) [47]. Risk of child developing other psychopathology The offspring of bipolar parents typically inherit psychopathology other than bipolar disorder, including [34,37,48-54]: Schizophrenia Schizoaffective disorder Unipolar major depressive disorder Substance use disorders Disruptive behavior disorders (oppositional defiant disorder and conduct disorder) Attention deficit hyperactivity disorder Anxiety disorders As an example, an observational study followed 108 bipolar offspring for 12 years from adolescence (mean age at study intake 17 years) to adulthood [55]. The lifetime prevalence of at least one psychiatric diagnosis was 72 percent. However, a diagnosis of bipolar I disorder, bipolar II disorder, or cyclothymic disorder was made in only 13 percent. By contrast, the lifetime prevalence of anxiety disorders, substance use disorders, and unipolar major depression was 25, 23, and 17 percent. Reducing risks Pregnancy outcomes may be improved in bipolar patients who: Achieve clinical stability prior to conception For bipolar patients who want to conceive, we suggest that they wait until they are clinically stable for at least 6 to 24 months [16]. A prospective observational study of 89 pregnant bipolar patients found that a short period of clinical stability between the most recent mood episode and conception was associated with recurrent mood episodes

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during pregnancy [24]. Use folic acid Folic acid is recommended for all women planning to conceive and is discussed separately. (See "Nutrition in pregnancy", section on 'Folic acid' and "Folic acid for prevention of neural tube defects" and "Management of epilepsy and pregnancy", section on 'Folic acid supplementation'.) Other preconception interventions that can reduce risks to a womans pregnancy are discussed separately. (See "Preconception evaluation and counseling", section on 'Interventions'.) FERTILITY Bipolar patients may have more difficulty conceiving than individuals without the disorder, but this is not established [56]. One study found that the fertility rate (defined as observed versus expected number of children) of 74 female and 60 male bipolar patients was significantly reduced in both sexes, both before and after onset of bipolar disorder [57]. Female bipolar patients may have difficulty conceiving because of ovulatory dysfunction (reflected by menstrual irregularities). A retrospective study found that patients who had yet to start pharmacotherapy (N = 295) were more likely to report menstrual cycle irregularities than controls (N = 619) (34 versus 22 percent) [10]. Menstrual cycle irregularities in some bipolar patients are due to medications, including: Antipsychotics Antipsychotics can increase prolactin levels, which can result in oligomenorrhea or amenorrhea and galactorrhea. Although hyperprolactinemia is more likely to occur with either risperidone or first generation antipsychotics, it has also been reported with other second generation antipsychotics, such as olanzapine and ziprasidone [10,58-60]. (See "Clinical manifestations and diagnosis of hyperprolactinemia".) Valproate Valproate use has been linked with polycystic ovarian syndrome (menstrual irregularities and hyperandrogenism) in bipolar patients [10,61]. (See "Clinical manifestations of polycystic ovary syndrome in adults".) Assessing menstrual cycle patterns before starting antipsychotics or valproate can help determine if medications are causing menstrual abnormalities that are observed after starting the drugs. Additional information about the evaluation, causes, and treatment of infertility is discussed separately. (See "Overview of infertility".) PRECONCEPTION AND PRENATAL PHARMACOTHERAPY For bipolar patients who plan to or do become pregnant, we suggest maintenance pharmacotherapy. (See "Bipolar disorder in women: Indications for preconception and prenatal maintenance pharmacotherapy" and "Bipolar disorder in women: Preconception and prenatal maintenance pharmacotherapy".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics and Beyond the Basics. The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on patient info and the keyword(s) of interest.) Basics topics (See "Patient information: Bipolar disorder (The Basics)" and "Patient information: Reducing the costs of medicines (The Basics)".) Beyond the Basics topics (See "Patient information: Bipolar disorder (manic depression) (Beyond the Basics)" and "Patient information: Reducing the costs of medicines (Beyond the Basics)".) These educational materials can be used as part of psychoeducational psychotherapy. (See "Bipolar disorder in adults: Maintenance treatment", section on 'Psychoeducation'.) The National Institute of Mental Health also has educational material explaining the symptoms, course of illness, and treatment of bipolar disorder in a booklet entitled "Bipolar Disorder," which is available online at the website http://www.nimh.nih.gov/health/publications/bipolar-disorder/complete-index.shtml or through a toll-free number, 866-615-6464. The web site also provides references, summaries of study results in language intended for the lay public, and information about clinical trials currently recruiting patients. More comprehensive information is provided in many books written for patients and family members, including The Bipolar Disorder Survival Guide: What You and Your Family Need to Know, written by David J. Miklowitz, PhD (published by The Guilford Press, 2002); An Unquiet Mind: A Memoir of Moods and Madness, written by Kay Jamison, PhD (published by Random House, 1995); and Treatment of Bipolar Illness: A Casebook for Clinicians and Patients, by RM Post, MD, and GS Leverich, LCSW (published by Norton Press, 2008). The Depression and Bipolar Support Alliance (http://www.dbsalliance.org or 800-826-3632) is a national organization that educates members about bipolar disorder and how to cope with it. Other functions include increasing public awareness of the illness and advocating for more research and services. The organization is administered and maintained by patients and family members, and has local chapters. The National Alliance on Mental Illness (http://www.nami.org or 800-950-6264) is a similarly structured organization devoted to education, support, and advocacy for patients with any mental illness. Bipolar disorder is one of their priorities. SUMMARY AND RECOMMENDATIONS Bipolar disorder is a mood disorder that is characterized by episodes of mania (table 1), hypomania (table 2), and major depression (table 3), as well as mixed episodes (major depression concurrent with mania or hypomania). (See 'Definition of bipolar disorder' above and "Bipolar disorder in adults: Assessment and diagnosis", section on 'Diagnosis'.) Bipolar patients who want to avoid pregnancy should receive information about contraceptive methods, especially long-acting reversible contraceptives. In addition, antiepileptics that are used to treat bipolar disorder may interact with hormonal contraception. Carbamazepine may render oral contraceptives ineffective, and conversely, oral contraceptives that include estrogen may reduce the effectiveness of lamotrigine. (See 'Contraception' above.) The clinical assessment of bipolar patients who consider becoming pregnant includes a psychiatric and general medical history, mental status and physical examination, and focused laboratory tests. The psychiatric history should emphasize age, body mass index (BMI) (calculator 1), current clinical status of bipolar disorder and course of illness, medications, supplements, substance abuse, and psychosocial functioning. (See 'Preconception assessment' above.) Adverse pregnancy and birth outcomes appear to be more common in women with bipolar disorder regardless of treatment status, compared to women without bipolar disorder. (See 'Risk of adverse pregnancy and birth outcomes' above.) The base rate for congenital defects in the offspring of patients with bipolar disorder appears to be no different than that of the general population, which is two to five percent. However, some medications used to treat bipolar disorder appear to be teratogenic, including valproate and carbamazepine, and to a lesser extent lithium. (See "Bipolar disorder in adults: Teratogenic and postnatal risks of pharmacotherapy" and "Principles of teratology".) Up to 70 percent of pregnant bipolar patients suffer at least one mood episode during pregnancy, but it is not known if pregnancy changes the risk of recurrence. The risk of recurrence appears to be greatest during the first trimester, and the most common morbidity is major depression. Risk factors for recurrence include a shorter period of clinical stability prior to conception, discontinuing pharmacotherapy (especially if medications are tapered and stopped in less than 15 days), unplanned pregnancy, current psychiatric comorbidity, lifetime duration of bipolar disorder 5 years, and history of at least one recurrent mood episode per year following onset of bipolar disorder. (See 'Relapse during pregnancy' above.) Bipolar disorder aggregates within families and there is evidence that genes are involved in the pathogenesis of the disorder. The estimated prevalence of bipolar disorder in children of families with one bipolar parent is 9 percent. By contrast, the estimated lifetime prevalence rate in the general population is 1 to 2 percent. (See 'Inheriting bipolar disorder' above.) In addition, the offspring of bipolar parents may inherit schizophrenia, schizoaffective disorder, unipolar major depressive disorder, substance use disorders, disruptive behavior disorders, attention deficit hyperactivity disorder, and anxiety disorders. (See 'Risk of child developing other psychopathology' above.) Pregnancy outcomes may be improved in bipolar patients who achieve clinical stability prior to conception and use folic acid. (See 'Reducing risks' above.) Bipolar patients may have more difficulty conceiving than individuals without the disorder, but this is not established. Antipsychotics and valproate can cause ovulatory dysfunction. (See 'Fertility' above.) Euthymic bipolar patients often receive maintenance pharmacotherapy prior to conception and during pregnancy. (See "Bipolar disorder in women: Preconception and prenatal maintenance pharmacotherapy".) Use of UpToDate is subject to the Subscription and License Agreement. Topic 15701 Version 9.0

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GRAPHICS DSM-IV-TR diagnostic criteria for mania
A. A distinct period of abnormally and persistently elevated, expansive, or irritable mood, lasting at least 1 week (or any duration if hospitalization is necessary). B. During the period of mood disturbance, three (or more) of the following symptoms have persisted (four if the mood is only irritable) and have been present to a significant degree:
1) Inflated self-esteem or grandiosity 2) Decreased need for sleep (eg, feels rested after only 3 hours of sleep) 3) More talkative than usual or pressure to keep talking 4) Flight of ideas or subjective experience that thoughts are racing 5) Distractibility (ie, attention too easily drawn to unimportant or irrelevant external stimuli) 6) Increase in goal-directed activity (either socially, at work or school, or sexuall y) or psychomotor agitation 7) Excessive involvement in pleasurable activities that have a high potential for pai nful consequences (eg, engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments)

C. The symptoms do not meet criteria for a mixed episode. D. The mood disturbance 1) is sufficiently severe to cause marked impairment in occupational functioning, usual social activities, or relationships with others, 2) necessitates hospitalization to prevent harm to self or others, or 3) has psychotic features. E. The symptoms are not due to the direct physiological effects of a substance (eg, a drug of abuse, a medication, or other treatment) or a general medical condition (eg, hyperthyroidism).
Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Text Revision, Fourth Edition (Copyright 2000). American Psychiatric Association.

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DSM-IV-TR diagnostic criteria for hypomania
A. A distinct period of persistently elevated, expansive, or irritable mood, lasting at least 4 days, that is clearly different from the usual nondepressed mood. B. During the period of mood disturbance, three (or more) of the following symptoms have persisted (four if the mood is only irritable) and have been present to a significant degree:
1) Inflated self-esteem or grandiosity 2) Decreased need for sleep (eg, feels rested after only 3 hours of sleep) 3) More talkative than usual or pressure to keep talking 4) Flight of ideas or subjective experience that thoughts are racing 5) Distractibility (ie, attention too easily drawn to unimportant or irrelevant external stimuli) 6) Increase in goal-directed activity (either socially, at work or school, or sexuall y) or psychomotor agitation 7) Excessive involvement in pleasurable activities that have a high potential for pai nful consequences (eg, engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments)

C. The episode is associated with an unequivocal change in functioning that is uncharacteristic of the person when not symptomatic. D. The disturbance in mood and the change in functioning are observable by others. E. The episode 1) is not severe enough to cause marked impairment in social or occupational functioning, 2) does not necessitate hospitalization, and 3) does not have psychotic features. F. The symptoms are not due to the direct physiological effects of a substance (eg, a drug of abuse, a medication, or other treatment) or a general medical condition (eg, hyperthyroidism). Note: Hypomanic-like episodes that are clearly caused by somatic antidepressant treatment (eg, medication, ECT, light therapy) should not count toward a diagnosis of bipolar II disorder.
Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Text Revision, Fourth Edition (Copyright 2000). American Psychiatric Association.

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DSM-IV-TR diagnostic criteria for major depression
A. Five (or more) of the following symptoms have been present during the same 2-week period, and represent a change from previous functioning. At least one of the symptoms is either depressed mood or loss of interest or pleasure.
(Note: Do not include symptoms that are clearly due to a general medical condition, or mood-incongruent delusions or hallucinations.) Depressed mood most of the day, nearly every day (or alternatively can be irritable mood in children and adolescents) Markedly diminished interest or pleasure in all, or almost all, activities, nearly every day Significant weight loss while not dieting, weight gain, or decrease or increase in appetite Insomnia or hypersomnia nearly every day Psychomotor agitation or retardation nearly every day Fatigue or loss of energy nearly every day Feelings of worthlessness or excessive or inappropriate guilt nearly every day Diminished ability to think or concentrate, or indecisiveness, nearly every day Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation wit hout a specific plan, or a suicide attempt or a specific plan for committing suicide

B. The symptoms do not meet criteria for a Mixed Episode. C. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. D. The symptoms are not due to the direct physiological effects of substance or a general medical condition. E. The symptoms are not better accounted for by Bereavement, ie, after the loss of a loved one, the symptoms persist for longer than two months or are characterized by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation.
Adapted from American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed, Text Revision. American Psychiatric Association, Washington, DC 2000.

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US Medical Eligibility Criteria for Contraceptive Use: Summary of classifications for hormonal contraceptive methods and intrauterine devices
Health-care providers can use the summary table as a quick reference guide to the classifications for hormonal contraceptive methods and intrauterine contraception and to compare classifications across these methods. See the full appendix for each method for clarifications to the numeric categories, as well as for summaries of the evidence and additional comments. BOX. Categories for classifying hormonal contraceptives and IUDs 1 = A condition for which there is no restriction for the use of the contraceptive method. 2 = A condition for which the advantages of using the method generally outweigh the theoretical or proven risks. 3 = A condition for which the theoretical or proven risks usually outweigh the advantages of using the method. 4 = A condition that represents an unacceptable health risk if the contraceptive method is used.

Condition

COC/P/R

POP

DMPA

Implants

LNG-IUD

Cu-IUD

Personal characteristics and reproductive history Pregnancy Age Not applicable* Menarche to <40 years = 1 40 years = 2 Not applicable* Menarche to <18 years = 1 18 to 45 years = 1 >45 years = 1 Parity a. Nulliparous b. Parous Postpartum (nonbreastfeeding women) a. <21 days b. 21 to 42 days i. With other risk factors for VTE (such as age 35 years, previous VTE, thrombophilia, immobility, transfusion at delivery, BMI 30, postpartum hemorrhage, postcesarean delivery, preeclampsia, or smoking) ii. Without other risk factors for VTE c. >42 days Postpartum (breastfeeding women ) a. <21 days b. 21 to <30 days i. With other risk factors for VTE (such as age 35 years, previous VTE, thrombophilia, immobility, transfusion at delivery, BMI 30 kg/m 2, postpartum hemorrhage, postcesarean delivery, preeclampsia, or smoking) ii. Without other risk factors for VTE c. 30 to 42 days i. With other risk factors for VTE (such as age 35 years, previous VTE, thrombophilia, immobility, transfusion at delivery, BMI 30, postpartum hemorrhage, postcesarean delivery, preeclampsia, or smoking) ii. Without other risk factors for VTE d. >42 days 2 1 1 1 2 1 1 1 3 1 1 1 3 2 2 2 3 2 2 2 4 2 2 2 1 1 1 1 2 1 1 1 3 1 1 1 4 1 1 1 1 1 1 1 1 1 1 1 2 1 2 1 Not applicable* Menarche to <18 years = 2 18 to 45 years = 1 >45 years = 2 Not applicable* Menarche to <18 years = 1 18 to 45 years = 1 >45 years = 1 4* Menarche to <20 years = 2 20 years = 1 4* Menarche to <20 years = 2 20 years = 1

Postpartum (breastfeeding or nonbreastfeeding women, including postcesarean delivery) a. <10 min after delivery of the placenta b. 10 min after delivery of the placenta to <4 weeks c. 4 weeks d. Puerperal sepsis Postabortion a. First trimester 1* 1* 1* 1* 1* 1* 1 4 1 4 2 2 1 2

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b. Second trimester c. Immediate postseptic abortion Past ectopic pregnancy History of pelvic surgery (see Postpartum, breastfeeding or nonbreastfeeding women, including postcesarean delivery) Smoking a. Age <35 years b. Age 35 years i. <15 Cigarettes/day ii. 15 Cigarettes/day Obesity a. 30 kg/m 2 BMI b. Menarche to <18 years and 30 kg/m 2 BMI History of bariatric surgery a. Restrictive procedures: decrease storage capacity of the stomach (vertical banded gastroplasty, laparoscopic adjustable gastric band, laparoscopic sleeve gastrectomy) b. Malabsorptive procedures: decrease absorption of nutrients and calories by shortening the functional length of the small intestine (Roux-en-Y gastric bypass, biliopancreatic diversion) Cardiovascular disease Multiple risk factors for arterial cardiovascular disease (such as older age, smoking, diabetes, and hypertension) Hypertension a. Adequately controlled hypertension

1* 1* 1 1

1* 1* 2 1

1* 1* 1 1

1* 1* 1 1

2 4 1 1

2 4 1 1

3 4

1 1

1 1

1 1

1 1

1 1

2 2

1 1

1 2

1 1

1 1

1 1

COCs: 3 P/R: 1

3/4*

2*

3*

2*

3*

1*

2*

1*

b. Elevated blood pressure levels (properly taken measurements) i. Systolic 140 to 159 mmHg or diastolic 90 to 99 mmHg ii. Systolic 160 mmHg or diastolic 100 mmHg c. Vascular disease History of high blood pressure during pregnancy (where current blood pressure is measurable and normal) Deep venous thrombosis (DVT)/pulmonary embolism (PE) a. History of DVT/PE, not on anticoagulant therapy i. Higher risk for recurrent DVT/PE (1 risk factors) History of estrogenassociated DVT/PE Pregnancyassociated DVT/PE Idiopathic DVT/PE Known thrombophilia, including antiphospholipid syndrome Active cancer (metastatic, on therapy, or within six months after clinical remission), excluding non-melanoma skin cancer History of recurrent DVT/PE 4 2 2 2 2 1 4 2 3 2 2 1 3 1 2 1 1 1

4 2

2 1

3 1

2 1

2 1

1 1

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ii. Lower risk for recurrent DVT/PE (no risk factors) b. Acute DVT/PE

c. DVT/PE and established on anticoagulant therapy for at least three months i. Higher risk for recurrent DVT/PE (1 risk factors) Known thrombophilia, including antiphospholipid syndrome Active cancer (metastatic, on therapy, or within six months after clinical remission), excluding non-melanoma skin cancer History of recurrent DVT/PE ii. Lower risk for recurrent DVT/PE (no risk factors) d. Family history (firstdegree relatives) e. Major surgery i. With prolonged immobilization ii. Without prolonged immobilization f. Minor surgery without immobilization Known thrombogenic mutations (eg, factor V Leiden; prothrombin mutation; protein S, protein C, and antithrombin deficiencies) Superficial venous thrombosis a. Varicose veins b. Superficial thrombophlebitis Current and history of ischemic heart disease Stroke (history of cerebrovascular accident) Known hyperlipidemias Valvular heart disease a. Uncomplicated b. Complicated (pulmonary hypertension, risk for atrial fibrillation, history of subacute bacterial endocarditis) Peripartum cardiomyopathy a. Normal or mildly impaired cardiac function (New York Heart Association Functional Class I or II: patients with no limitation of activities or patients with slight, mild limitation of activity) i. <6 months ii. 6 months b. Moderately or severely impaired cardiac function (New York Heart Association Functional Class III or IV: patients with marked limitation of activity or patients who should be at complete rest) Rheumatic diseases Systemic lupus erythematosus a. Positive (or unknown) antiphospholipid antibodies b. Severe thrombocytopenia c. Immunosuppressive treatment d. None of the above 2 2 2 2 2 2 2 2 2 2 2 2 2 1 1 1 2 2 3 2 2 2* 3* 2* 4 3 Initiation 3 Continuation 3 3 3 Initiation 1 Continuation 1 4 3 4 1 1 2 1 1 2 1 1 2 2 2 2 2 2 2 2 4 1 1 1 1 1 1 1 1 1 1 1 2 Initiation 4 2 Initiation 4 2/3* 2 2* 1 1 Continuation 3 Continuation 3 3 2* 3 1 1 Initiation 2 Initiation 2 2* 1 1 Continuation 3 Continuation 3 2 2* 1 1* Initiation 2 1 1 Continuation 3 1 1 1 1 4* 1 2* 1 2* 1 2* 1 2* 1 1* 4 2 2 1 2 1 2 1 2 1 1 1 3* 2 2 2 2 2 4* 2 2 2 2 2

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Rheumatoid arthritis a. On immunosuppressive therapy b. Not on immunosuppressive therapy Neurologic conditions Headaches a. Non-migrainous (mild or severe) b. Migraine i. Without aura
- Age <35 yrs - Age 35 yrs 2* 3* 3* 4* 1* 1* 2* 2* 2* 2* 2* 2* 2* 2* 2* 2*

Initiation 2 2 1 1 2/3* 2 1 1 2

Continuation 1 1

Initiation 2

Continuation 1 1

Initiation 1*

Continuation 2*

Initiation 1*

Continuation 1*

Initiation 1*

Continuation 1*

Initiation 1*

Continuation 1*

Initiation 1*

Continuation 1* 1*

2* 2*

2* 2*

1* 1*

ii. With aura (at any age) Epilepsy

4* 1*

4*

2* 1*

3*

2* 1*

3*

2* 1*

3*

2* 1

3*

1* 1

If on treatment, see Drug interactions section below Depressive disorders Depressive disorders 1* 1* 1* 1* 1* 1*

Reproductive tract infections and disorders Vaginal bleeding patterns a. Irregular pattern without heavy bleeding b. Heavy or prolonged bleeding (includes regular and irregular patterns) Unexplained vaginal bleeding (suspicious for serious condition) Before evaluation Endometriosis Benign ovarian tumors (including cysts) Severe dysmenorrhea Gestational trophoblastic disease a. Decreasing or undetectable beta-hCG levels b. Persistently elevated beta-hCG levels or malignant disease Cervical ectropion Cervical intraepithelial neoplasia Cervical cancer (awaiting treatment) Breast disease a. Undiagnosed mass b. Benign breast disease c. Family history of cancer d. Breast cancer i. Current ii. Past and no evidence of current disease for five years Endometrial hyperplasia Endometrial cancer 1 Ovarian cancer Uterine fibroids Anatomical abnormalities a. Distorted uterine cavity (any congenital or acquired uterine abnormality distorting the uterine cavity in a manner that is incompatible with IUD insertion) b. Other abnormalities (including cervical stenosis or cervical lacerations) not distorting the uterine cavity or interfering with IUD insertion Pelvic inflammatory disease (PID) 2 2 4 4 1 1 1 1 1 1 1 1 1 1 1 4 3 4 3 4 3 4 3 4 3 1 1 2* 1 1 2* 1 1 2* 1 1 2* 1 1 2 1 1 1 1 1 1 1 1 1 3 3 1 1 1 1 1 2 2* 1 1 2* 1 1 3* 1 1 3* 1 1 1 1* 2 2* 2 2* 2 2* Initiation 1 1* Continuation 1 2* 1 2*

Initiation

Continuation

Initiation

Continuation

4* 1 1

2*

4* 2 1

2*

1 2

1 1

1 2

1 2 Initiation

1 2 Continuation 2 Initiation 4

1 1 Continuation 2

1 Initiation 4

1 Continuation 2 1 2 Initiation 4

1 Continuation 2 1 2

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a. Past PID (assuming no current risk factors of STIs) i. With subsequent pregnancy ii. Without subsequent pregnancy b. Current PID STIs a. Current purulent cervicitis or chlamydial infection or gonorrhea b. Other STIs (excluding HIV and hepatitis) c. Vaginitis (including Trichomonas vaginalis and bacterial vaginosis) d. Increased risk for STIs HIV/AIDS 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1

Initiation

Continuation

Initiation

Continuation

1 2 4 Initiation 4

1 2 2* Continuation 2*

1 2 4 Initiation 4

1 2 2* Continuation 2*

1 1

1 1

1 1

1 1

2 2

2 2

2 2

2 2

2/3*

2/3*

Initiation High risk for HIV HIV infection AIDS 1 1 1 1 1 1 1 1 1 1 1 1 2 2 3 2

Continuation 2 2 2 2

Initiation 2 2 3 2

Continuation 2 2 2* 2

NOTE: If on treatment, drug interactions might exist between hormonal contraceptives, including LNG-IUD, and antiretroviral drugs; refer to the section on drug interactions below as there may be limitations to use of the method. Other infections Schistosomiasis a. Uncomplicated b. Fibrosis of the liver (if severe, see Cirrhosis) Tuberculosis a. Nonpelvic b. Pelvic 1* 1* 1* 1* 1* 1* 1* 1* 1 1 1 1 1 1 1 1

1 1 Initiation 1 4 Continuation 1 3 Initiation 1 4

1 1 Continuation 1 3

If on treatment, see Drug interactions section below Malaria Endocrine conditions Diabetes a. History of gestational disease b. Nonvascular disease i. Noninsulindependent ii. Insulin-dependent c. Nephropathy/retinopathy/ neuropathy d. Other vascular disease or diabetes of >20 years' duration Thyroid disorders a. Simple goiter b. Hyperthyroid c. Hypothyroid Gastrointestinal conditions Inflammatory bowel disease (IBD) (ulcerative colitis, Crohn disease) Gallbladder disease a. Symptomatic i. Treated by cholecystectomy ii. Medically treated iii. Current b. Asymptomatic History of cholestasis a. Pregnancy-related b. Past COC-related Viral hepatitis a. Acute or flare b. Carrier c. Chronic Cirrhosis a. Mild (compensated) b. Severe (decompensated) 1 4 1 3 1 3 1 3 1 3 1 1 Initiation 3/4* 1 1 2 3 Continuation 2 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2 1 2 1 2 1 2 1 1 2 3 3 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 1 1 1 1 2/3* 2 2 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2 2 3/4* 2 2 2 2 2 3 2 2 2 2 2 2 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1

3/4*

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Liver tumors a. Benign i. Focal nodular hyperplasia ii. Hepatocellular adenoma b. Malignant (hepatoma) Anemias Thalassemia Sickle cell disease Iron-deficiency anemia Solid organ transplantation Solid organ transplantation a. Complicated: graft failure (acute or chronic), rejection, cardiac allograft vasculopathy b. Uncomplicated Drug interactions Antiretroviral therapy a. Nucleoside reverse transcriptase inhibitors (NRTIs) b. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) c. Ritonavir-boosted protease inhibitors Anticonvulsant therapy a. Certain anticonvulsants (phenytoin, carbamazepine, barbiturates, primidone, topiramate, oxcarbazepine) b. Lamotrigine Antimicrobial therapy a. Broad-spectrum antibiotics b. Antifungals c. Antiparasitics d. Rifampicin or rifabutin therapy 1 1 3* 1 1 3* 1 1 1 1 1 2* 1 1 1 1 1 1 1 1 1 1 1 1 3* 1 1 1 1 1 3* 3* 1 2* 1 1 2* 2* 1 2* 2/3* 2* 2/3* 2* 1* 1 1 1 Initiation 2/3* Continuation 2* Initiation 2/3* Continuation 2* 2* 2 2 2 2 2 4 2 2 2 Initiation 3 Continuation 2 Initiation 3 Continuation 2 1 2 1 1 1 1 1 1 1 1 1 1 1 1 1 2 2 2 4 4 3 3 3 3 3 3 3 3 1 1 2 2 2 2 2 1

3*

3*

2*

2/3*

2*

2/3*

2*

COC: combined oral contraceptive; P: combined hormonal contraceptive patch; R: combined hormonal vaginal ring; POP: progestin-only pill; DMPA: depot medroxyprogesterone acetate; IUD: intrauterine device; LNG-IUD: levonorgestrel-releasing IUD; Cu-IUD: copper IUD; BMI: body mass index (weight [kg]/height [m 2]); DVT: deep venous thrombosis; VTE: venous thromboembolism; CHC: combined hormonal contraceptive; PE: pulmonary embolism; hCG: human chorionic gonadotropin; PID: pelvic inflammatory disease; STI: sexually transmitted infection; HI V: human immunodeficiency virus; AIDS: acquired immunodeficiency syndrome; NRTI: nucleoside reverse transcriptase inhibitor; NNRTI: non-nucleoside reverse transcriptase. * Consult the appendix for this contraceptive method for a clarification to this classification. Initiation refers to a condition already present when the contraceptive is begun. Continuation refers to a condition that develops after initiation of the method. Clarification: For women with other risk factors for VTE, these risk factors might increase the classification to a "4"; for example, smoking, deep venous thrombosis/pulmonary embolism, known thrombogenic mutations, and peripartum cardiomyopathy. The breastfeeding recommendations are divided by month in US Medical Eligibility Criteria for Contraceptive Use, 2010 . They have been divided by days for purposes of integration with the postpartum recommendations. Condition that exposes a woman to increased risk as a result of unintended pregnancy. Some studies suggest that women using progestin-only injectable contraception might be at increased risk for HIV acquisition; other studies do not show this association. CDC reviewed all available evidence and agreed that the data were not sufficiently conclusive to change current guidance. However, because of the inconclusive nature of the body of evidence on possible increased risk for HIV acquisition, women using progestin-only injectable contraception should be strongly advised to also always use condoms (male or female) and take other HIV preventive measures. References: 1. Update to CDC's U.S. Medical Eligibility Criteria for Contraceptive Use, 2010: Revised Recommendations for the Use of Contraceptive Methods During the Postpartum Period. MMWR Morb Mortal Wkly Rep 2011; 60:878. 2. Update to CDC's U.S. Medical Eligibility Criteria for Contraceptive Use, 2010: Revised Recommendations for the Use of Hormonal Contraception Among Women at High Risk for HIV Infection or Infected with HIV. MMWR Morb Mortal Wkly Rep 2012; 61:449. Reproduced with permission from: US Medical Eligibility Criteria for Contraceptive Use 2010, with data adapted from the World Health Organization Medical Eligibility Criteria for Contraceptive Use, 4th edition.

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