bipolar disorder in pregnant women - treatment of major depression.pdf

8/13/2019 Bipolar disorder in pregnant women - Treatment of major depression.pdf

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Official reprint from UpToDate

www.uptodate.com2013 UpToDate

AuthorVictoria Hendrick, MD

Section EditorPaul Keck, MD

Deputy EditorDavid Solomon, MD

Bipolar disorder in pregnant women: Treatment of major depression

Disclosures

All topics are updated as new evidence becomes available and ourpeer 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.

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]:

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

(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".)

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

olar disorder in pregnant women: Treatment of major depression http://www.uptodate.com/contents/bipolar-disorder-in-pregnant-women...

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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 lamotrigineas first line

treatment, based upon efficacy in a meta-analysis of randomized trials that excluded pregnant pat ients [14]. Up to40 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 quetiapineappear 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 fluoxetineplus olanzapineor lamotrigine plus lithium,

and prenatal treatment with monotherapy is preferable to treatment with drug combinations due to concerns about

teratogenic effects.

The efficacy oflamotrigine, quetiapine, fluoxetineplus olanzapine, and lamotrigine plus lithium; reproductive safety

profile of these drugs; and the dose schedule, side effects (table 4and 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 fluoxetineplusolanzapineor 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 lamotrigineat the same time that quetiapineis 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 ofquetiapine. (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

oflamotrigineand 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 fluoxetineplus olanzapineand the combination of lamotrigine


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and lithiumappear 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].

Fluoxetineplus 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 pregnantpatients 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 (Lexi-

Interact 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.

Lamotrigineplus lithium For pregnant patients with bipolar major depression who do not respond to or

tolerate fluoxetineplus 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 4and 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 (Lexi-

Interact 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 oflamotrigine, quetiapine, fluoxetineplus 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 everythree 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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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. Usingpsychotherapy 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 5 to 6 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. Beyondthe Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written

at the 10 to 12 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.)

These educational materials can be used as part of psychoeducational psychotherapy. (See "Bipolar disorder in

adults: Maintenance treatment", section on 'Psychoeducation'.)

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'.)

th th

th th

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 theBasics)"and "Patient information: Reducing the costs of medicines (Beyond the Basics)".)


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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 KayJamison, 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.orgor 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.orgor 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

Use of UpToDate is subject to the Subscription and License Agreement.

Topic 82788 Version 4.0

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 lamotrigineas 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 lamotrigineor cannot tolerate it,

we suggest quetiapinerather than other medications (Grade 2C). (See 'Treatment resistance'above.)

Pregnant patients with refractory bipolar major depression that does not respond to lamotrigineorquetiapine

are often treated with fluoxetineplus 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.)


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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 thefollowing 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 irr itability,

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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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 Systemic side effects Neurotoxic side effects

Carbamazepine Nausea, vomiting, diarrhea,

hyponatremia, rash, pruritus

Drowsiness, dizziness, blurred or

double vision, lethargy, headache

Clobazam Increased salivation, nausea,

vomiting, constipation

Somnolence, aggression, irritability,

ataxia, insomnia

Ethosuximide Nausea, vomiting Sleep disturbance, drowsiness,

hyperactivity

Ezogabine Nausea, fatigue, change in color of

urine, dysuria, urinary hesitancy,

weight gain

Dizziness, somnolence, confusion,

vertigo, blurred or double vision,

tremor, abnormal coordination,

inattention, memory impairment

Felbamate Nausea, vomiting, anorexia, weight

loss

Insomnia, dizziness, headache, ataxia

Gabapentin Infrequent Somnolence, dizziness, ataxia

Lacosamide Nausea, vomiting, fatigue Ataxia, dizziness, headache, diplopia

Lamotrigine Rash, nausea Dizziness, tremor, diplopia

Levetiracetam Infection Fatigue, somnolence, dizziness,

agitation, anxiety, irritability,

depression

Oxcarbazepine Nausea, rash, hyponatremia Sedation, headache, dizziness,

vertigo, ataxia, diplopia

Perampanel Weight gain, fatigue, nausea Dizziness, somnolence, irritability,

gait disturbance, falls, aggression,

mood alteration

Phenytoin Gingival hypertrophy, rash Confusion, slurred speech, double

vision, ataxia

Pregabalin Weight gain, peripheral edema, dry

mouth

Dizziness, somnolence, ataxia,

tremor

Primidone,

phenobarbital

Nausea, rash Alteration of sleep cycles, sedation,

lethargy, behavioral changes,

hyperactivity, ataxia, tolerance,

dependence

Rufinamide Nausea, vomiting, fatigue Dizziness, somnolence, headache

Tiagabine Abdominal pain 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 Weight gain, nausea, vomiting, hair

loss, easy bruising

Tremor, dizziness

Vigabatrin Vision loss 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 Side effects*

Carbamazepine Agranulocytosis, SJS/TEN, aplastic anemia, hepatic failure, dermatitis/rash,

serum sickness, pancreatitis, lupus syndrome

Clobazam Respiratory depression, SJS/TEN

Ethosuximide Agranulocytosis, SJS/TEN, aplastic anemia, hepatic failure, dermatitis/rash,

serum sickness

Ezogabine Urinary retention, urinary tract infection, QT prolongation, psychosis

Felbamate Aplastic anemia, liver failure

Gabapentin Multiorgan hypersensitivity

Lacosamide Prolonged PR interval, atrioventricular block, multiorgan hypersensitivity,

neutropenia

Lamotrigine SJS/TEN, multiorgan hypersensitivity, aseptic meningitis

Levetiracetam SJS/TEN, pancytopenia, psychosis

Oxcarbazepine SJS/TEN, multiorgan hypersensitivity

Phenytoin Agranulocytosis, SJS/TEN, aplastic anemia, hepatic failure, dermatitis/rash,

serum sickness, adenopathy, pseudolymphoma, neuropathy, ataxia, lupus-

syndrome, hirsuitism

Pregabalin Angioedema, hypersensitivity reactions, rhabdomyolysis

Primidone,

phenobarbital

Agranulocytosis, SJS/TEN, hepatic failure, dermatitis/rash, serum sickness,

connective tissue contractures (eg, Duputrens)

Rufinamide SJS/TEN, dermatitis/rash, shortened QT interval

Tiagabine SJS/TEN, nonconvulsive status epilepticus

Topiramate Acute myopia and glaucoma; kidney stones; oligohydrosis and hyperthermia

which primarily occur in children

Valproate Agranulocytosis, SJS/TEN, aplastic anemia, hepatic failure, dermatitis/rash,

serum sickness, pancreatitis, polycystic ovary syndrome

Vigabatrin MRI abnormalities, depression, weight gain

Zonisamide Rash, SJS/TEN, aplastic anemia, agranulocytosis, nephrolithiasis; in children,

fever and hyperhidrosis

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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