Bipolar Disorder in Pregnant Women - Treatment of Major Depression PDF

Bipolar disorder in pregnant women: Treatment of major depression
http://www.uptodate.com/contents/bipolar-disorder-in-pregnant-women...
Official reprint from UpToDate www.uptodate.com 2013 UpToDate
Bipolar disorder in pregnant women: Treatment of major depression 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: Nov 16, 2013. INTRODUCTION Medications are commonly used to treat pregnant patients, including those with bipolar major depression [1]. At least one prescription drug is taken by more than 60 percent of pregnant patients [2], and psychotropic drugs are taken by 21 to 33 percent [3,4]. This topic discusses treatment of pregnant patients with bipolar major depression. Treatment of manic and hypomanic episodes during pregnancy, prenatal maintenance pharmacotherapy for bipolar disorder, the teratogenic and postnatal risks of pharmacotherapy for bipolar disorder, and the general treatment of bipolar major depression are discussed separately. (See "Bipolar disorder in pregnant women: Treatment of mania and hypomania".) (See "Bipolar disorder in women: Preconception and prenatal maintenance pharmacotherapy".) (See "Bipolar disorder in adults: Teratogenic and postnatal risks of pharmacotherapy".) (See "Bipolar disorder in adults: Pharmacotherapy for acute depression".) DEFINITION OF BIPOLAR DISORDER Bipolar disorder is characterized by episodes of mania (table 1), hypomania (table 2), and major depression (table 3) [5]. The subtypes of bipolar disorder include bipolar I and bipolar II. Patients with bipolar I disorder experience manic 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 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'.) INDICATIONS Pharmacotherapy is indicated for pregnant patients with bipolar major depression that is characterized by [6]: Suicidal or homicidal ideation or behavior Aggressive behavior Psychotic features (delusions or hallucinations) Poor judgement that places the patient or others at imminent risk of being harmed Moderate to severe impairment of social or occupational functioning GENERAL PRINCIPLES AND MANAGEMENT Bipolar mood episodes during pregnancy are usually treated by perinatal or general psychiatrists in collaboration with obstetricians and primary care clinicians [4,7-10]. For pregnant patients with bipolar major depression, treatment is based upon randomized trials that excluded pregnant patients [11-14], as well as observational studies, birth registries, and clinical experience [15]. Additional information about the general principles and management of treating bipolar mood episodes during pregnancy are discussed separately, as is the general treatment of bipolar major depression. (See "Bipolar disorder in pregnant women: Treatment of mania and hypomania", section on 'Management' and "Bipolar disorder in adults: Pharmacotherapy for acute depression".) Duration of individual drug trial We suggest treating pregnant patients with bipolar major depression for six to eight weeks before determining whether a specific drug is beneficial, based upon the duration of most randomized 1 de 14 02/12/2013 04:41 Section Editor Paul Keck, MD Deputy Editor David Solomon, MD
trials (which excluded pregnant patients) [11-13,16]. Response is defined as stabilizing the patients safety and substantial improvement in the number, intensity, and frequency of symptoms. SELECTING TREATMENT Bipolar major depression during pregnancy is typically treated with pharmacotherapy because it is easier to administer, more widely available, and more acceptable to patients than electroconvulsive therapy (ECT). However, refractory patients may benefit from ECT. First line treatment For pregnant patients with bipolar major depression, we suggest lamotrigine as first line treatment, based upon efficacy in a meta-analysis of randomized trials that excluded pregnant patients [14]. Up to 40 to 50 percent of patients may respond (defined as stabilizing the patients safety and substantial improvement in the number, intensity, and frequency of symptoms). In addition, the reproductive safety profile of lamotrigine is generally regarded as favorable [4,17,18]. The efficacy of lamotrigine and quetiapine appear to be comparable, but there is more experience using lamotrigine during pregnancy than quetiapine. In addition, there is more evidence supporting the efficacy of lamotrigine compared with fluoxetine plus olanzapine or lamotrigine plus lithium, and prenatal treatment with monotherapy is preferable to treatment with drug combinations due to concerns about teratogenic effects. The efficacy of lamotrigine, quetiapine, fluoxetine plus olanzapine, and lamotrigine plus lithium; reproductive safety profile of these drugs; and the dose schedule, side effects (table 4 and table 5) (including life-threatening skin rash), and pharmacology of lamotrigine are discussed separately. (See "Bipolar disorder in adults: Pharmacotherapy for acute depression" and "Bipolar disorder in adults: Teratogenic and postnatal risks of pharmacotherapy" and "Bipolar disorder in adults: Maintenance treatment", section on 'Lamotrigine' and "Pharmacology of antiepileptic drugs", section on 'Lamotrigine'.) Treatment resistance For pregnant patients with bipolar major depression who do not respond to lamotrigine or cannot tolerate it, we suggest quetiapine [19], based upon randomized trials that excluded pregnant patients [20-23]. Up to 50 to 60 percent of patients may respond (defined as stabilizing the patients safety and substantial improvement in the number, intensity, and frequency of symptoms). In addition, other studies suggest that quetiapine is not associated with teratogenic effects [24], and use of quetiapine for bipolar major depression during pregnancy is consistent with practice guidelines from the United Kingdom National Institute for Health and Clinical Excellence [25,26]. There is more evidence supporting the efficacy of lamotrigine compared with fluoxetine plus olanzapine or lamotrigine plus lithium, and prenatal treatment with monotherapy is preferable to treatment with drug combinations due to concerns about teratogenic effects. We generally taper and discontinue lamotrigine at the same time that quetiapine is started and titrated up. Lamotrigine is usually tapered by the same amount for each dose decrease over a one to two week period. As an example, lamotrigine 200 mg per day is decreased by 50 mg per day every three to four days. Second-generation antipsychotics may cause metabolic complications (eg, hyperglycemia and obesity) that are associated with risks to the mother and fetus [27,28]. These risks are discussed separately, as are monitoring of metabolic parameters in pregnant patients taking second-generation antipsychotics and the efficacy, dose, reproductive safety, pharmacology, and side effects of quetiapine. (See "Bipolar disorder in women: Preconception and prenatal maintenance pharmacotherapy", section on 'Metabolic complications' and "Bipolar disorder in adults: Pharmacotherapy for acute depression" and "Bipolar disorder in adults: Teratogenic and postnatal risks of pharmacotherapy", section on 'Second-generation' and "Second-generation antipsychotic medications: Pharmacology, administration, and comparative side effects", section on 'Quetiapine'.) Refractory patients Pregnant patients with bipolar major depression often do not respond to sequential trials of lamotrigine and quetiapine. For these refractory patients, we suggest tapering and discontinuing quetiapine over one to two weeks at the same time that another medication regimen is started and titrated up. (Response is defined as stabilizing the safety of the patient and others, as well as substantial improvement in the number, intensity, and frequency of symptoms.) Quetiapine is generally tapered by the same amount for each dose decrease. As an example, quetiapine 600 mg per day is decreased by 50 to 100 mg per day, every one to two days. We suggest using the following treatments in sequence for pregnant patients with refractory bipolar major depression, based upon their efficacy in randomized trials (which excluded pregnant patients), reproductive safety profiles, and adverse effects. Although the benefit of fluoxetine plus olanzapine and the combination of lamotrigine
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and lithium appear to be comparable, neither fluoxetine nor olanzapine appear to be associated with teratogenic effects. By contrast, lithium is generally regarded as teratogenic [29-31]. The proportion of patients who respond to any of the following treatment regimens may be as high as approximately 50 percent, based upon trials in nonpregnant patients [11,12]. Fluoxetine plus olanzapine Fluoxetine plus olanzapine is efficacious for bipolar major depression in nonpregnant patients [12,32]. However, second-generation antipsychotics, especially olanzapine, may cause metabolic complications (eg, hyperglycemia and obesity) that are associated with risks to the mother and fetus [27,28]. These risks are discussed separately, as are monitoring of metabolic parameters in pregnant patients taking second-generation antipsychotics and the efficacy, dose, reproductive safety, pharmacology, and side effects of fluoxetine and olanzapine. (See "Bipolar disorder in women: Preconception and prenatal maintenance pharmacotherapy", section on 'Metabolic complications' and "Bipolar disorder in adults: Teratogenic and postnatal risks of pharmacotherapy" and "Selective serotonin reuptake inhibitors: Pharmacology, administration, and side effects" and "Second-generation antipsychotic medications: Pharmacology, administration, and comparative side effects" and "Bipolar disorder in adults: Pharmacotherapy for acute depression".) Specific medication interactions that can occur may be determined using the drug interactions tool (LexiInteract Online) included in UpToDate. This tool can be accessed from the online search page or through the individual drug information topics in the section on Drug Interactions. Lamotrigine plus lithium For pregnant patients with bipolar major depression who do not respond to or tolerate fluoxetine plus olanzapine, we suggest lamotrigine plus lithium [11]. Fluoxetine plus olanzapine are usually tapered and discontinued concurrently over a period of one week, and subsequently lamotrigine and lithium are started and titrated up. Fluoxetine is generally tapered by the same amount for each dose decrease, as is olanzapine. As an example, fluoxetine 40 mg per day is decreased by 10 mg per day every two days, and olanzapine 15 mg per day is decreased by 5 mg per day every three days. Although lithium is generally regarded as teratogenic due to increased risks of cardiac defects (eg, Ebsteins anomaly) [29-31], many authorities consider the absolute risk small [1,4,18,33,34]. The reproductive safety profile of lamotrigine is generally regraded as favorable [4,17,18], based primarily upon studies of patients with epilepsy. (See "Bipolar disorder in adults: Teratogenic and postnatal risks of pharmacotherapy", section on 'Lithium' and "Risks associated with epilepsy and pregnancy", section on 'Lamotrigine'.) The dose schedule, side effects (table 4 and table 5) (including life-threatening skin rash), and pharmacology of lamotrigine are discussed separately; as are the use of lithium during pregnancy, dose, use of serum concentrations to establish the proper dose, side effects, and pharmacology of lithium. (See "Bipolar disorder in adults: Maintenance treatment", section on 'Lamotrigine' and "Pharmacology of antiepileptic drugs", section on 'Lamotrigine' and "Bipolar disorder in women: Preconception and prenatal maintenance pharmacotherapy", section on 'Refractory patients' and "Bipolar disorder in adults and lithium: Pharmacology, administration, and side effects".) Specific medication interactions that can occur may be determined using the drug interactions tool (LexiInteract Online) included in UpToDate. This tool can be accessed from the online search page or through the individual drug information topics in the section on Drug Interactions. Electroconvulsive therapy (ECT) For refractory pregnant patients with bipolar major depression that does not respond to sequential trials of lamotrigine, quetiapine, fluoxetine plus olanzapine, and lamotrigine plus lithium, we suggest electroconvulsive therapy (ECT). Lamotrigine and lithium are tapered and discontinued over a period of one to two weeks prior to starting ECT. Lamotrigine is generally tapered by the same amount for each dose decrease, as is lithium. As an example, lamotrigine 200 mg per day is decreased by 50 mg per day every three to four days, and lithium 1200 mg per day is tapered by 300 mg per day every three to four days. Reviews have found that ECT is efficacious and safe for patients with bipolar major depression who are not
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pregnant [35,36], as well as patients who are pregnant [37,38]; ECT is thus recommended by several practice guidelines [7,39-42]. The efficacy, adverse maternal and fetal effects, and reproductive safety of ECT are discussed separately, as is the technique for performing ECT during pregnancy. (See "Bipolar disorder in postpartum women: Treatment", section on 'Electroconvulsive therapy (ECT)' and "Bipolar disorder in pregnant women: Treatment of mania and hypomania", section on 'Electroconvulsive therapy' and "Bipolar disorder in adults: Teratogenic and postnatal risks of pharmacotherapy", section on 'Electroconvulsive therapy' and "Technique for performing electroconvulsive therapy (ECT) in adults", section on 'Pregnancy'.) ADJUNCTIVE TREATMENT Psychotherapy For pregnant patients with bipolar major depression who are treated with pharmacotherapy, we suggest adjunctive psychotherapy based upon randomized trials in nonpregnant patients [2,6,43]. As an example, a one-year randomized trial compared intensive psychotherapy plus pharmacotherapy with brief psychoeducation plus pharmacotherapy in 293 nonpregnant patients with bipolar major depression [44]. Intensive psychotherapy consisted of family therapy, cognitive-behavioral therapy, or interpersonal and social rhythm therapy, with up to 30 sessions (50 minutes each) administered over nine months; brief psychoeducation included three 50-minute sessions instructing patients about the clinical features and treatment of bipolar disorder. Recovery occurred in more patients who received adjunctive intensive psychotherapy compared with brief psychoeducation (64 versus 52 percent), and outcome did not differ significantly among the three intensive therapies. Using psychotherapy is also supported by randomized trials in pregnant patients with unipolar major depression [45], and is consistent with treatment guidelines [26]. Omega-3 fatty acids For pregnant patients with bipolar major depression, dietary supplementation with omega-3 fatty acids (eg, eicosapentaenoic acid 1 to 2 grams per day) as adjunctive treatment is reasonable, based upon limited evidence in meta-analyses of randomized trials (which excluded pregnant patients) [46,47] and the apparent lack of serious side effects. In addition, prenatal intake of omega-3 fatty acid supplements may have modest beneficial effects on fetal neurodevelopment, and do not have known harmful effects. The efficacy of omega-3 fatty acids and the risks and benefits during pregnancy are discussed separately. (See "Bipolar disorder in adults: Pharmacotherapy for acute depression" and "Risks and benefits of fish consumption and fish oil supplements during pregnancy".) RESIDUAL INSOMNIA Bipolar major depression in pregnant patients often includes insomnia, which may persist despite resolution of the depressive syndrome. For patients with residual insomnia, we suggest behavioral therapy, including education about sleep hygiene (table 6) and stimulus control (table 7). Patients unresponsive to behavior therapy typically receive additional treatment with low dose doxepin. Treatment of insomnia is discussed separately. (See "Treatment of insomnia".) 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'.)
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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 characterized by episodes of mania (table 1), hypomania (table 2), and major depression (table 3). (See 'Definition of bipolar disorder' above and "Bipolar disorder in adults: Assessment and diagnosis", section on 'Diagnosis'.) Pharmacotherapy is indicated for pregnant patients with bipolar major depression that is characterized by (see 'Indications' above): Suicidal or homicidal ideation or behavior Aggressive behavior Psychotic features (delusions or hallucinations) Poor judgement that places the patient or others at imminent risk of being harmed Moderate to severe impairment of social or occupational functioning An individual drug trial for pregnant patients with bipolar major depression typically lasts six to eight weeks before determining whether treatment is beneficial. (See 'General principles and management' above.) For pregnant patients with bipolar major depression, we suggest lamotrigine as first line treatment rather than other medications (Grade 2C). (See 'First line treatment' above.) For pregnant patients with bipolar major depression who do not respond to lamotrigine or cannot tolerate it, we suggest quetiapine rather than other medications (Grade 2C). (See 'Treatment resistance' above.) Pregnant patients with refractory bipolar major depression that does not respond to lamotrigine or quetiapine are often treated with fluoxetine plus olanzapine, lamotrigine plus lithium, or electroconvulsive therapy. (See 'Refractory patients' above.) For pregnant patients with bipolar major depression who are treated with pharmacotherapy, we suggest adjunctive psychotherapy (Grade 2B). (See 'Psychotherapy' above.) Use of UpToDate is subject to the Subscription and License Agreement. Topic 82788 Version 4.0
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GRAPHICS DSM-5 diagnostic criteria for manic episode

A. A distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased goal-directed activity or energy, lasting at least one week and present most of the day, nearly every day (or any duration if hospitalization is necessary). B. During the period of mood disturbance and increased energy or activity, three (or more) of the following symptoms (four if the mood is only irritable) are present to a significant degree and represent a noticeable change from usual behavior: 1) Inflated self-esteem or grandiosity. 2) Decreased need for sleep (eg, feels rested after only three 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), as reported or observed. 6) Increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation (ie, purposeless non-goal-directed activity). 7) Excessive involvement in activities that have a high potential for painful consequences (eg, engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments). C. The mood disturbance is sufficiently severe to cause marked impairment in social or occupational functioning or to necessitate hospitalization to prevent harm to self or others, or there are psychotic features. D. The episode is not attributable to the physiological effects of a substance (eg, a drug of abuse, a medication, other treatment) or to another medical condition. NOTE: A full manic episode that emerges during antidepressant treatment (eg, medication, electroconvulsive therapy) but persists at a fully syndromal level beyond the physiological effect of that treatment is sufficient evidence for a manic episode and, therefore, a bipolar I diagnosis.
NOTE: Criteria A through D constitute a manic episode. At least one lifetime manic episode is required for the diagnosis of bipolar I disorder.
Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (Copyright 2013). American Psychiatric Association. All Rights Reserved.
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DSM-5 diagnostic criteria for hypomanic episode

A. A distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased activity or energy, lasting at least four consecutive days and present most of the day, nearly every day. B. During the period of mood disturbance and increased energy and activity, three (or more) of the following symptoms (four if the mood is only irritable) have persisted, represent a noticeable change from usual behavior, and have been present to a significant degree: 1) Inflated self-esteem or grandiosity. 2) Decreased need for sleep (eg, feels rested after only three 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), as reported or observed. 6) Increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation. 7) Excessive involvement in activities that have a high potential for painful 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 individual when not symptomatic. D. The disturbance in mood and the change in functioning are observable by others. E. The episode is not severe enough to cause marked impairment in social or occupational functioning or to necessitate hospitalization. If there are psychotic features, the episode is, by definition, manic. F. The episode is not attributable to the physiological effects of a substance (eg, a drug of abuse, a medication, or other treatment). NOTE: A full hypomanic episode that emerges during antidepressant treatment (eg, medication, electroconvulsive therapy) but persists at a fully syndromal level beyond the physiological effect of that treatment is sufficient evidence for a hypomanic episode diagnosis. However, caution is indicated so that one or two symptoms (particularly increased irritability, edginess, or agitation following antidepressant use) are not taken as sufficient for a diagnosis of a hypomanic episode, nor necessarily indicative of a bipolar diathesis.
NOTE: Criteria A through F constitute a hypomanic episode. Hypomanic episodes are common in bipolar I disorder but are not required for the diagnosis of bipolar I disorder.
Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (Copyright 2013). American Psychiatric Association. All Rights Reserved.
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DSM-5 diagnostic criteria for bipolar major depression

A. Five (or more) of the following symptoms have been present during the same two-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure. NOTE: Do not include symptoms that are clearly attributable to another medical condition. 1) Depressed mood most of the day, nearly every day, as indicated by either subjective report (eg, feels sad, empty, hopeless) or observations made by others (eg, appears tearful). (NOTE: In children and adolescents can be irritable mood.) 2) Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation) 3) Significant weight loss when not dieting or weight gain (eg, a change of more than 5 percent of body weight in a month), or decrease or increase in appetite nearly every day. (NOTE: In children, consider failure to make expected weight gain.) 4) Insomnia or hypersomnia nearly every day 5) Psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down) 6) Fatigue or loss of energy nearly every day 7) Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick) 8) Diminished ability to think or concentrate, or indecisiveness, nearly every day (either by their subjective account or as observed by others) 9) Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide B. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. C. The episode is not attributable to the direct physiological effects of a substance or to another medical condition. NOTE: Criteria A through C represent a major depressive episode. NOTE: Responses to a significant loss (eg, bereavement, financial ruin, losses from a natural disaster, a serious medical illness or disability) may include the feelings of intense sadness, rumination about the loss, insomnia, poor appetite, and weight loss noted in Criterion A, which may resemble a depressive episode. Although such symptoms may be understandable or considered appropriate to the loss, the presence of a major depressive episode in addition to the normal response to a significant loss should also be carefully considered. This decision inevitably requires the exercise of clinical judgement based on the individual's history and the cultural norms for the expression of distress in the context of loss. D. The occurence of the major depressive episode is not better explained by schizoaffective disorder, schizophrenia, schizophreniform disorder, delusional disorder, or other specified and unspecified schizophrenia spectrum and other psychotic disorders. Specify: With anxious distress With mixed features With rapid cycling With melancholic features With atypical features With psychotic features
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With catatonia With peripartum onset With seasonal pattern

Adapted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (Copyright 2013). American Psychiatric Association. All Rights Reserved.
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Common side effects of antiepileptic drugs

Drug
Carbamazepine Clobazam Ethosuximide Ezogabine
Systemic side effects

Nausea, vomiting, diarrhea, hyponatremia, rash, pruritus Increased salivation, nausea, vomiting, constipation Nausea, vomiting Nausea, fatigue, change in color of urine, dysuria, urinary hesitancy, weight gain
Neurotoxic side effects

Drowsiness, dizziness, blurred or double vision, lethargy, headache Somnolence, aggression, irritability, ataxia, insomnia Sleep disturbance, drowsiness, hyperactivity Dizziness, somnolence, confusion, vertigo, blurred or double vision, tremor, abnormal coordination, inattention, memory impairment Insomnia, dizziness, headache, ataxia Somnolence, dizziness, ataxia Ataxia, dizziness, headache, diplopia Dizziness, tremor, diplopia Fatigue, somnolence, dizziness, agitation, anxiety, irritability, depression Sedation, headache, dizziness, vertigo, ataxia, diplopia Dizziness, somnolence, irritability, gait disturbance, falls, aggression, mood alteration
Felbamate Gabapentin Lacosamide Lamotrigine Levetiracetam
Nausea, vomiting, anorexia, weight loss Infrequent Nausea, vomiting, fatigue Rash, nausea Infection
Oxcarbazepine Perampanel
Nausea, rash, hyponatremia Weight gain, fatigue, nausea
Phenytoin Pregabalin Primidone, phenobarbital
Gingival hypertrophy, rash Weight gain, peripheral edema, dry mouth Nausea, rash
Confusion, slurred speech, double vision, ataxia Dizziness, somnolence, ataxia, tremor Alteration of sleep cycles, sedation, lethargy, behavioral changes, hyperactivity, ataxia, tolerance, dependence
Rufinamide Tiagabine
Nausea, vomiting, fatigue Abdominal pain
Dizziness, somnolence, headache Dizziness, lack of energy, somnolence, nausea, nervousness, tremor, difficulty concentrating
Topiramate
Weight loss, paresthesias
Fatigue, nervousness, difficulty concentrating, confusion, depression, anorexia, language problems, anxiety, mood problems, tremor
Valproate Vigabatrin
Weight gain, nausea, vomiting, hair loss, easy bruising Vision loss
Tremor, dizziness Drowsiness, fatigue, dizziness
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Zonisamide
Nausea, anorexia
Somnolence, dizziness, ataxia, confusion, difficulty concentrating, depression
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Rare but serious side effects of AEDs*

Drug
Carbamazepine Clobazam Ethosuximide Ezogabine Felbamate Gabapentin Lacosamide Lamotrigine Levetiracetam Oxcarbazepine Phenytoin
Side effects*
Agranulocytosis, SJS/TEN, aplastic anemia, hepatic failure, dermatitis/rash, serum sickness, pancreatitis, lupus syndrome Respiratory depression, SJS/TEN Agranulocytosis, SJS/TEN, aplastic anemia, hepatic failure, dermatitis/rash, serum sickness Urinary retention, urinary tract infection, QT prolongation, psychosis Aplastic anemia, liver failure Multiorgan hypersensitivity Prolonged PR interval, atrioventricular block, multiorgan hypersensitivity, neutropenia SJS/TEN, multiorgan hypersensitivity, aseptic meningitis SJS/TEN, pancytopenia, psychosis SJS/TEN, multiorgan hypersensitivity Agranulocytosis, SJS/TEN, aplastic anemia, hepatic failure, dermatitis/rash, serum sickness, adenopathy, pseudolymphoma, neuropathy, ataxia, lupussyndrome, hirsuitism Angioedema, hypersensitivity reactions, rhabdomyolysis Agranulocytosis, SJS/TEN, hepatic failure, dermatitis/rash, serum sickness, connective tissue contractures (eg, Duputrens) SJS/TEN, dermatitis/rash, shortened QT interval SJS/TEN, nonconvulsive status epilepticus Acute myopia and glaucoma; kidney stones; oligohydrosis and hyperthermia which primarily occur in children Agranulocytosis, SJS/TEN, aplastic anemia, hepatic failure, dermatitis/rash, serum sickness, pancreatitis, polycystic ovary syndrome MRI abnormalities, depression, weight gain Rash, SJS/TEN, aplastic anemia, agranulocytosis, nephrolithiasis; in children, fever and hyperhidrosis
Pregabalin Primidone, phenobarbital Rufinamide Tiagabine Topiramate Valproate Vigabatrin Zonisamide
AEDs: antiepileptic drugs; SJS: Stevens-Johnson sydrome; TEN: toxic epidermal necrolysis. * As a class, AEDs have been associated with an increased risk of suicidal ideation and suicidal behavior.
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Sleep hygiene: Ten basic rules for a good night's sleep

Sleep only as much as you need to feel rested and then get out of bed Keep a regular sleep schedule Avoid forcing sleep Exercise regularly for at least 20 minutes, preferably 4 to 5 hours before bedtime Avoid caffeinated beverages after lunch Avoid alcohol near bedtime: no "night cap" Avoid smoking, especially in the evening Do not go to bed hungry Adjust bedroom environment Deal with your worries before bedtime
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Stimulus control therapy rules

1. Go to bed only when sleepy. 2. Do not watch television, read, eat, or worry while in bed. Use bed only for sleep and sex. 3. Get out of bed if unable to fall asleep within twenty minutes and go to another room. Return to bed only when sleepy. Repeat this step as many times as necessary throughout the night. 4. Set an alarm clock to wake up at a fixed time each morning including weekends. 5. Do not take a nap during the day.
Data from: Bootzin, RR, Perlis, ML. Nonpharmacologic treatments of insomnia. J Clin Psychiatry 1992; 53:37.
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Bipolar Disorder in Pregnant Women - Treatment of Major Depression PDF

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