Bipolar Disorder - ClinicalKey

20/10/21 15:24 Bipolar Disorder - ClinicalKey
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bipolar resultados Buscar
RESEÑA CLÍNICA
Trastorno bipolar
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Actualizado el 8 de octubre de 2021 . Copyright Elsevier BV. Reservados todos los derechos.
Sinopsis
Key Points Acción urgente

Bipolar disorder (ie, manic-depressive illness) is a condition El suicidio y la agresión
in which the afflicted person experiences clear episodic mood requieren hospitalización 1
changes, in combination with cognitive, behavioral, and
physiologic changes Las siguientes condiciones
requieren una intervención
Episodic for most patients, with recurrent episodes urgente:
Patient must experience at least 1 episode of mania or Pacientes maníacos

hypomania during their lifetime to meet diagnostic criteria bipolares con síntomas
graves, que incluyen: 1
Diagnosis involves history, physical examination, and mental
status examination; based on DSM-5 criteria 1 Delirio
Management of bipolar disorder is directly related to the Psicosis severa

episode (depression or mania) and the severity of that phase;
involves a combination of medication, psychotherapy, and Suicidal or homicidal
possible electroconvulsive therapy ideation or attempts
Always evaluate patients for suicidality, acute psychosis, Violent behavior

chronic psychosis, and other unstable and dangerous
Substance withdrawal
conditions
or intoxication
Treatment includes medication options, such as lithium,
Bipolar depressive
divalproex, and antipsychotics 2
patients with severe
symptoms, including: 1
https://clinicalkey.unicartagenaproxy.elogim.com/#!/content/clinical_overview/67-s2.0-7a27f11d-0277-4550-95ff-f941ff23d0ec#treatment-heading-26 1/35
Antidepressants may precipitate mania and contribute to

Severe delusions
rapid cycling and therefore should be avoided if mood
stabilizers are not maximized; antidepressants (selective Visual or auditory
serotonin reuptake inhibitors are favored) do not work well hallucinations
for bipolar depression
Confusion
Electroconvulsive therapy offers rapid and effective
management of mania and depression; may be considered for Catatonic behavior
severe and treatment-resistant bipolar depression, severe
mania during pregnancy, psychosis, suicidality, and catatonia
3
Psychotherapy, psychoeducation, and family intervention should be used to restore normal

functioning, prevent recurrence, and increase treatment compliance 3 4
Factors that worsen prognosis include earlier age at onset, multiple relapses, mixed episodes
and/or rapid cycling, and comorbid conditions, especially substance use
Factors associated with moderate to high risk of relapse include severity of illness and strong
family history of bipolar disorder
Pitfalls
This disorder has a high risk of suicide 3 5
Disorder is often unrecognized for years; suspect bipolar disorder if there is no response to
antidepressants
Antidepressants can precipitate mania and contribute to rapid cycling and therefore should be
avoided during maintenance-stage treatment; they are also far less effective than in unipolar
depression
Coexisting psychiatric conditions (eg, anxiety, insomnia, attention-deficit/hyperactivity

disorder) can significantly impact the treatment of bipolar disorder; refer patient for specialty
care
Terminology
Clinical Clarification
Bipolar disorder (ie, manic-depressive illness) is a condition in which the afflicted person
experiences clear episodic mood changes, in combination with cognitive, behavioral, and
physiologic changes
Episodic for most patients, with recurrent episodes
Some patients have frequent episodes; most will experience several episodes over the course
of their lifetime
Patient must experience at least 1 episode of mania or hypomania during their lifetime to meet
diagnostic criteria 6 7
Mania is characterized by a distinct period of abnormal and persistently elevated, expansive,

or irritable mood and abnormally and persistently increased activity and energy lasting at
least 1 week; associated with 3 of the following symptoms (4 if the mood is only irritable):
Distractibility
Increased activity/psychomotor agitation
Grandiosity or inflated self-esteem
Flight of ideas or racing thoughts
Excessive involvement in activities with potential for painful consequences, such as sexual
indiscretions
Decreased sleep
Patient is talkative or has pressured speech
Mania is distinguished from hypomania by duration and severity
Duration: 7 days (mania) versus 4 days (hypomania); however, if patient is hospitalized or

if the episode has psychotic features, 1 day is sufficient to diagnose mania
Severity: marked impairment and/or psychosis, potentially resulting in hospitalization
Classification
Bipolar I disorder 6 7
DSM-5 criteria have been met for at least 1 manic episode in patient's lifetime
Manic episode may have been preceded or followed by hypomanic or major depressive
episodes
Occurrence of the manic and major depressive episode(s) cannot be better explained by
schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or
other schizophrenia spectrum or psychotic disorders
Bipolar II disorder 6 7
DSM-5 criteria have been met for at least 1 hypomanic episode and at least 1 major
depressive episode in patient's lifetime
No history of manic episodes
Occurrence of the hypomanic and major depressive episode(s) cannot be better explained by
schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or
other schizophrenia spectrum or psychotic disorders
Depressive symptoms or unpredictability caused by frequent alternation between periods of

hypomania and depression causes clinically significant distress or impairment in social,
occupational, or other important areas of functioning
Cyclothymic disorder 6
Mood disorder consisting of subthreshold depressive and hypomanic periods
Patient must be symptomatic for minimum of 2 years and have no more than 2 months
without symptoms
Bipolar mixed states involve symptoms of both mania and depression, either simultaneously
or in rapid sequence
Diagnosis
Clinical Presentation
History
Encourage the patient to be accompanied by a relative or caretaker to obtain a corroborative
history; patients often have limited recall or insight about symptoms during episodes
Family history of bipolar disorder (first-degree relative)
History of:
Mood swings
Episodes of overactivity and disinhibition
Other episodic and sustained behavioral changes
Substance use
Potential mental and physical comorbidities, especially those associated with impulsivity (eg,
HIV, hepatitis C, motor vehicle accidents)
Symptoms in manic phase 8
Inflated self-opinion
Decreased need for sleep
Poor appetite and weight loss
Racing speech, flight of ideas, and impulsiveness
Distractibility
Increased activity level
Excessive involvement in pleasurable activities
Poor financial management
Excessive irritability
Symptoms in depressive phase 8
Feelings of sadness or hopelessness
Loss of interest in pleasurable or usual activities
Insomnia or hypersomnia
Sense of guilt or low self-esteem
Difficulty concentrating
Negative thoughts about the future
Weight loss or gain
Talk of suicide or death
Suicidal ideation
Physical examination
Mental status examination
Appearance
Depressed episode
Poor to no eye contact
Slow movement
Psychomotor retardation
Speaking in low tones or slowly
Hypomanic episode
Busy, active, and involved
Manic episode
Hyperactive and hypervigilant
Clothes put on in a hurry; disorganized
Clothes are often too bright and colorful; uncharacteristic for patient
Affect/mood
Depressed episode: sad, depressed
Hypomanic episode: elevated, expansive
Manic episode
Joyous, elated, jubilant, and euphoric
Irritable
Hard to interrupt
Thought content
Depressed episode: sadness, hopelessness, death, and suicide
Hypomanic episode: forward-thinking and optimistic attitude
Manic episode
Expansive and overly optimistic thinking; may display excessive self-confidence; no

insight into potential painful consequences
Flight of ideas
Perceptions and thought content
Depressed episode: may experience hallucinations and delusions
Hypomanic episode: no hallucinations or delusions
Manic episode: may experience hallucinations and delusions
Insight and judgment
Often no insight; judgment is impaired, leading to unwise decisions, particularly if manic
Self-destruction/suicidality
Depressed episode: associated with high rate of suicide
Homicidality/violence/aggression/accidents
Manic episode: aggressive, intolerant, highly demanding, and violently assertive
Causes and Risk Factors
Causes
Unknown
Risk factors and/or associations
Age
3
3
Mean age of onset is 21 years
Sex
Bipolar I disorder: equal distribution among males and females 8
Bipolar II disorder: may be more common in females 1 8
Genetics
Family history is a major risk factor 1
Ethnicity/race
More common among black populations 1
Other risk factors/associations

Stress (eg, bereavement, marital difficulties, sleep disturbances) 9
Pregnancy 9
Multiple sclerosis 9
Traumatic brain injury 9
Alcohol or drug use
Physical illness
Attention-deficit/hyperactivity disorder
Conduct disorder
Anxiety disorders
Treatment with corticosteroids
Diagnostic Procedures
Primary diagnostic tools 1 9

Diagnosis involves history, physical examination, and mental status examination; based on
DSM-5 criteria
Other questionnaires and scales may be used to assist with diagnosis
There are no specific diagnostic laboratory tests to confirm diagnosis of bipolar disorder
Imaging
Other diagnostic tools
Differential Diagnosis
Most common
Major depressive disorder Chronic and relapsing mental disorder, characterized by
(Related: Major Depressive pervasive sad mood and loss of pleasure in most activities
Disorder) (anhedonia) persisting for at least 2 weeks
Involves the presence of 1 or more major depressive episodes

without history of mania or hypomania
Presence of mania or hypomania is the cardinal feature that

distinguishes bipolar disorder from major depressive
disorder
Carefully screen patients with major depression for bipolar

disorder
Patients with bipolar disorder do not respond well to

antidepressants; therefore, differentiation is crucial
Distinction between anxious depression and bipolar disorder

with mixed features can be difficult
Differentiated from bipolar disorder based on clinical history
Substance-induced mood Characterized by significantly elevated or depressed mood

disorder that develops after using medications or illicit substances (eg,
stimulants, alcohol), resulting in psychosocial impairment
Mood symptoms among nonbipolar persons are typically

confined to, and change in parallel with, periods of substance
intoxication or withdrawal 9
Differentiated by clinical history and urine toxicology
Schizophrenia 1 Psychiatric disorder with prominent psychosis as core

clinical feature
Characterized by significant distortion in thinking,

perception, speech, and behavior
May cause altered mood including manialike phases and

depressive symptoms, particularly when acutely psychotic
Differentiated from bipolar disorder by the presence of

psychotic symptoms outside of mood episodes 9
Hyperthyroidism Clinical state induced by excessive production and secretion

of thyroid hormones by an overactive thyroid gland
Mood disturbance (eg, emotional lability, depression) results

from increased thyroid hormone levels
TSH measurement is the most sensitive test; decreased (ie,

suppressed) TSH level is positive test result
Free T₄ level is high in most cases of overt hyperthyroidism
T₃ level is often elevated to a greater extent than T₄ level in

severe hyperthyroidism
Differentiated with thyroid function tests (decreased TSH

level with elevated T₄ and T₃ levels)
Hypothyroidism Disorder caused by inadequate synthesis and secretion of

thyroid hormone
Causes depression by producing a functional decrease in

noradrenergic transmission
TSH level is elevated
Total or free T₄ level is low
Serum T₃ level remains within the general reference range

until severe stages of hypothyroidism and is therefore
unlikely to be helpful in the diagnosis of most cases
Differentiated with thyroid function tests (elevated TSH level

with decreased T₄ level)
Multiple sclerosis (Related: Chronic, demyelinating autoimmune disease (central

Multiple Sclerosis) nervous system) with subacute neurologic impairment
May cause depression (common) and euphoria (less common)
MRI shows effects in brain and spinal cord, such as plaques

and cerebral atrophy; most sensitive imaging modality for
diagnosing spinal cord disease
Cerebrospinal fluid analysis is no longer routine; may be

useful if MRI results are nondiagnostic or MRI is
unavailable; cerebrospinal fluid is evaluated for oligoclonal
bands and intrathecal IgG
Differentiated from bipolar disorder based on clinical

findings consistent with multiple sclerosis, MRI of the
brain/spinal cord, and, in some cases, examination of
cerebrospinal fluid
Cushing syndrome 1 Characterized by high levels of cortisol resulting from

inflated adrenal cortisol production or long-term
glucocorticoid therapy
May cause psychological symptoms, including emotional

lability and depression
Elevated 24-hour urinary cortisol level suggests Cushing

syndrome and distinguishes from bipolar disorder
Differentiated by elevated 24-hour urinary cortisol level

(more than 3-4 times greater than upper reference limit)
Treatment
Goals
Primary goals are to limit number of lifetime episodes by stabilizing mood, reduce intensity of
current episode, and return patient to normal psychosocial functioning 1
As early as possible, identify new episodes and control functional impairments
Promote stress management, regular activity, and normal sleep patterns 3
Educate patient about bipolar disorder to ensure treatment adherence
Disposition
Admission criteria 1
Suicidal ideation or suicide attempts require psychiatric hospital admission
Patients with bipolar mania experiencing severe symptoms, including:
Delirium
Severe psychosis
Suicidal or homicidal ideation or attempts
Violent behavior
Substance withdrawal or intoxication
Catatonic symptoms
Patients with bipolar depression experiencing severe symptoms, including:
Severe delusions
Severe psychosis (eg, visual or auditory hallucinations)
Confusion
Catatonic behavior
Patients with bipolar mixed state
Patients who are unable to care for themselves
Recommendations for specialist referral

In patients presenting with depression, if overactivity or disinhibited behavior is reported as
lasting for 4 or more days, consider referral for specialist mental health assessment 1
Psychiatric consultation is required for: 1
Any patient with suspected bipolar disorder, particularly if manic
Violent or severe psychosis
Delirium
Suicidality or homicidality
Severe depression
Comorbid substance use
Electroconvulsive therapy in patients with severe or treatment-resistant mania 3 or psychotic

or refractory depression
Pregnancy; should be planned in consultation with psychiatrist to discuss risks and benefits
of therapeutic options 1
Addiction psychiatrist consultation is recommended for substance withdrawal or use 1
Treatment Options
Management of bipolar disorder is directly related to the episode (depression or mania) and the
severity of that phase; involves a combination of medication, psychotherapy, and possible
electroconvulsive therapy 9 12
Chronic disease management requires collaborative care efforts between primary care provider
and psychiatrist, patient education regarding medications, and family involvement regarding
issues (eg, supervision)
Patients must be protected from risks of their illness (eg, self-harm, self-neglect, malnutrition,
exhaustion, substance use, risky behavior) 9
Address dangerous behavior that may put others at risk (eg, aggressiveness, reckless driving,
inappropriate sexual advances) 9
General approach to care should include the following considerations:
Treatment goals
Achieving remission when patient is in an acute mood episode
Preventing new mood episodes
Mainstay of treatment for bipolar disorder involves mood stabilizers; often, 2 mood stabilizers
must be used
Some second-generation antipsychotics have mood stabilizing properties
Antipsychotic dosing for depression is often lower than for mania
Antidepressants do not work well for bipolar depression; may precipitate mania and
contribute to rapid cycling 9
Treatment of acute bipolar mania 2
First line monotherapy options include lithium, quetiapine, divalproex, asenapine,

aripiprazole, paliperidone, risperidone, and cariprazine
Adjunctive therapy with lithium or divalproex can include risperidone, quetiapine,

asenapine, and aripiprazole
Second line monotherapy options include olanzapine, carbamazepine, ziprasidone,

haloperidol, and electroconvulsive therapy
Second line combination therapy includes lithium plus divalproex
Do not use antiepileptic drugs other than divalproex or carbamazepine; lamotrigine,

gabapentin, and topiramate are not effective
Treatment of acute bipolar depression 2
First line monotherapy options include quetiapine, lithium, lamotrigine, and lurasidone
Lurasidone and lamotrigine are also recommended as first line adjunctive treatments
Second line therapy options include monotherapy with divalproex, adjunctive use of
antidepressant therapy (selective serotonin reuptake inhibitors or bupropion) with lithium-
divalproex, cariprazine, olanzapine-fluoxetine, and electroconvulsive therapy
2
2
Maintenance therapy
First line monotherapy options include lithium, quetiapine, divalproex, lamotrigine,

asenapine, and aripiprazole
Adjunctive therapy with lithium or divalproex can include quetiapine or aripiprazole
Second line monotherapy options include olanzapine, risperidone, carbamazepine, and

paliperidone
Second line adjunctive therapy can include ziprasidone or lurasidone
Treatment for mixed states is similar to that for manic states; atypical antipsychotics generally
have similar efficacy for different types of mania 9
Antidepressants may precipitate mania and contribute to rapid cycling and therefore should be
avoided if mood stabilizers are not maximized; antidepressants do not work well for bipolar
depression 9
Selective serotonin reuptake inhibitors are favored over MAOIs and tricyclic antidepressants 3
Selective serotonin reuptake inhibitors are contraindicated during a manic phase; withdraw
immediately if manic symptoms develop 3
Most guidelines suggest avoiding antidepressants in long-term treatment where possible 9
Electroconvulsive therapy offers rapid and effective management of mania and depression; may
be considered for severe and treatment-resistant bipolar depression, severe mania during
pregnancy, psychosis, suicidality, and catatonia 3
Psychotherapy, psychoeducation, and family intervention should be used to restore normal

functioning, prevent recurrence, and increase treatment adherence 3 4
Interpersonal and social rhythm therapy can be used to help create routines and improved sleep 9
Patients starting treatment for acute bipolar mania, hypomania, or mixed episodes should be
reassessed every 1 to 2 weeks for at least 6 weeks 8
Patients with severe mania who are not hospitalized should be reassessed every 2 to 5 days until
symptoms improve 8
Absence of any significant symptoms of mania or depression for 2 months is considered full
remission; assessment for relapse should continue periodically 8
Drug therapy
1 13 14
1 13 14
Lithium
Lithium Carbonate Oral capsule; Children 6 years†: 15 to 20 mg/kg/day PO given in 3 to 4

divided doses initially; adjust as needed weekly to achieve target concentration. Range of
dosing: 15 to 60 mg/kg/day PO given in 3 to 4 divided doses. An approximate dose range of
10 to 30 mg/kg/day PO, in divided doses, provides serum lithium levels of 0.6 to 1.1 mEq/L
and is suggested in a consensus guideline, but the guideline does not differentiate between
acute and maintenance therapy. Individualize dosage based on severity of disease, patient
response, and serum lithium concentrations. Serum lithium concentrations above 1.5
mEq/L are generally associated with toxicity.
Lithium Carbonate Oral capsule; Children and Adolescents 7 years and older and weighing
20 kg to 30 kg: RECOMMENDED INITIAL DOSE: 300 mg PO 2 times per day. Obtain serum
lithium concentrations after 3 days (12 hours after the last oral dose) and regularly until
stabilization. Titrate dose by 300 mg weekly to desired effect. In patients at risk for lithium
toxicity, consider a lower starting dose and titrate slowly; frequently assess serum lithium
concentration and monitor for toxicity. TITRATION FOR ACUTE MANIA: Titrate to serum
concentrations between 0.8 and 1.2 mEq/L. Usual dose range: 600 mg to 1,500 mg per day
PO, given in divided doses. Monitor clinical status and serum lithium concentrations
regularly until the patient is stabilized. MAINTENANCE THERAPY: Titrate to serum
lithium concentrations between 0.8 and 1 mEq/L. Usual dose range: 600 mg to 1,200 mg per
day PO, given in divided doses. Monitor clinical status and serum lithium concentrations;
adjust patient's dosage and therapeutic monitoring schedule accordingly. Max: Maximum
dose has not been established for either acute mania or for maintenance therapy. Serum
lithium concentrations above 1.5 mEq/L are generally associated with toxicity. An
approximate pediatric weight-based dose range of 10 to 30 mg/kg/day PO, in divided doses,
provides serum lithium concentrations of 0.6 to 1.1 mEq/L and has been suggested in a
consensus guideline. Individualize dosage based upon the nature and severity of disease,
patient response, and serum lithium concentrations.
Lithium Carbonate Oral capsule; Children and Adolescents 7 years and older and weighing
more than 30 kg: RECOMMENDED INITIAL DOSE: 300 mg PO 3 times per day. Obtain
serum lithium concentrations after 3 days (12 hours after the last oral dose) and regularly
until stabilization. Titrate by 300 mg every 3 days to the desired effect. In patients at risk for
lithium toxicity, consider a lower starting dose and titrate slowly; frequently assess serum
lithium level and monitor for toxicity. TITRATION FOR ACUTE MANIA: Titrate to serum
concentrations between 0.8 and 1.2 mEq/L. Usual dose range: 600 mg PO 2 or 3 times per
day. Monitor clinical status and serum lithium concentrations regularly until stabilization.
MAINTENANCE THERAPY: Titrate to serum lithium concentrations between 0.8 and 1
mEq/L. Usual dose range: 300 to 600 mg PO 2 or 3 times per day. Monitor lithium
concentrations and clinical response; adjust the patient's dosage and therapeutic monitoring
schedule accordingly. Max: Maximum dose has not been established for either acute mania
or for maintenance therapy. Individualize dosage regimen. Serum lithium concentrations
above 1.5 mEq/L are generally associated with toxicity.
Lithium Carbonate Oral capsule; Adults: RECOMMENDED INITIAL DOSE: 300 mg PO 3

times per day. Obtain serum lithium concentrations after 3 days (12 hours after the last oral
dose) and regularly until stabilization. Titrate by 300 mg every 3 days to the desired effect. In
patients at risk for lithium toxicity, such as geriatric patients, consider a lower starting dose
and titrate slowly; frequently assess serum lithium concentration and monitor for toxicity.
TITRATION FOR ACUTE MANIA: Titrate to serum concentrations between 0.8 and 1.2
mEq/L. Usual dosage range: 600 mg PO 2 or 3 times per day. Monitor clinical status and
serum lithium concentrations regularly until stabilization. MAINTENANCE THERAPY:
Titrate to serum lithium concentrations between 0.8 and 1 mEq/L. Usual dosage range: 300
to 600 mg PO 2 or 3 times per day. Monitor lithium concentrations and clinical response;
adjust the patient's dosage and therapeutic monitoring schedule accordingly. Max:
Maximum dose has not been established for either acute mania or for maintenance therapy.
Individualize dosage regimen. Serum lithium concentrations above 1.5 mEq/L are generally
associated with toxicity.
Antiepilépticos 1
Utilizado como estabilizadores del estado de ánimo
Divalproex
No ofrezca medicamentos que contengan valproato a mujeres en edad fértil para un tratamiento a
largo plazo o para tratar un episodio agudo 1
Se debe evitar el divalproex durante el embarazo debido al riesgo elevado de defectos del tubo neural
(hasta un 5%), una incidencia aún mayor de otras anomalías congénitas y la evidencia de un retraso
significativo en el desarrollo neurológico en niños de 3 años y una pérdida promedio de 9 puntos de
CI 2
Divalproex de liberación retardada
Tableta gastrorresistente de Divalproex Sodium; Niños † y adolescentes †: uso no establecido del

todo. En 1 estudio pequeño (n = 34; edad media 12,3 años) abierto, se dosificó divalproex de 15 a 20
mg / kg / día por vía oral, con una dosis inicial de 250 a 500 mg por vía oral el día 1 y aumentada
hasta la dosis completa. más de 1 semana. Los incrementos de dosis se guiaron por la
tolerabilidad, las concentraciones séricas mínimas (50 mcg / mL a 120 mcg / mL) y el progreso
clínico.
Tableta gastrorresistente de Divalproex Sodium; Adultos: inicialmente, 750 mg / día VO, en dosis
divididas. Aumente la dosis lo más rápidamente posible a la dosis efectiva más baja que produzca
el efecto clínico deseado o las concentraciones séricas deseadas. Máx: 60 mg / kg / día.
Alternativamente, se ha demostrado que 20 mg / kg / día VO en dosis divididas producen una
respuesta clínicamente significativa dentro de los 3 días en algunos casos. En otras evaluaciones,
se demostró que 30 mg / kg / día durante 2 días, seguido de 20 mg / kg / día, eran seguros y
eficaces.
Divalproex de liberación prolongada
Divalproex Sodium Tableta oral de liberación prolongada; Adultos: Inicialmente, 25 mg / kg / día

VO administrados una vez al día. Aumente la dosis lo más rápido posible para lograr el efecto
clínico deseado o el rango de concentraciones plasmáticas. Máx: 60 mg / kg / día.
Lamotrigina
Nota: la lamotrigina se metaboliza predominantemente por conjugación con ácido glucurónico. Los
fármacos que se sabe que inducen o inhiben la glucuronidación pueden afectar el aclaramiento
aparente de lamotrigina. Tenga en cuenta al prescribir lamotrigina; se recomiendan ajustes de dosis.
15
Lamotrigina, tableta oral; Niños † y adolescentes † de 12 años en adelante: la seguridad y la eficacia

no están completamente establecidas; mayor riesgo de erupción cutánea grave en pacientes
pediátricos. Sin embargo, la titulación lenta puede ayudar a minimizar la aparición de erupciones. En
un pequeño estudio abierto en adolescentes con depresión bipolar (n = 19; 12 a 17 años; 12 mujeres, 7
hombres), los pacientes recibieron lamotrigina durante 8 semanas. En pacientes que no recibieron
valproato, la dosis se tituló de la siguiente manera (administrada en 1 o 2 dosis diarias PO): 25 mg /
día durante 2 semanas; luego 50 mg / día durante 2 semanas; luego 100 mg / día (con dosis
posteriores aumentadas en 25 mg / semana según la necesidad clínica). La dosis final objetivo en
pacientes que no tomaban valproato fue de 100 a 200 mg / día por vía oral con una dosis final media
informada de 132 +/- 31 mg al día. Puede ser necesario evitar la coadministración de ciertos
medicamentos o puede ser necesario ajustar la dosis; revisar las interacciones de los medicamentos.
Lamotrigina, tableta oral; Adultos: durante las semanas 1 a 2, inicie la terapia con 25 mg por vía oral
una vez al día; durante las semanas 3 a 4, administre 50 mg por vía oral una vez al día; durante la
semana 5, administre 100 mg VO una vez al día; durante la semana 6 a la 7 y en adelante, administre
200 mg por vía oral una vez al día. Puede ser necesario evitar la coadministración de ciertos
medicamentos o puede ser necesario ajustar la dosis; revisar las interacciones de los medicamentos.
No se recomienda el tratamiento de episodios maníacos agudos o mixtos, ya que no se ha establecido
la eficacia.
Carbamazepina
Tableta masticable de carbamazepina; Niños † de 6 a 12 años: faltan ensayos clínicos amplios y bien
controlados para el trastorno bipolar pediátrico. En un estudio abierto de 6 semanas en pacientes
pediátricos de 8 años y mayores, la dosis inicial fue de 15 mg / kg / día VO en 3 dosis divididas
durante 1 semana, con evaluación de la concentración sérica, luego titulada hasta que la
concentración sérica fue de 7 a 10 mcg. / mL. Los algoritmos de las guías clínicas pediátricas incluyen
una recomendación de carbamazepina como una opción para el tratamiento de primera línea en
monoterapia (etapa 1) del trastorno bipolar no psicótico I (maníaco o mixto) en pacientes pediátricos
de 6 a 17 años.
Carbamazepine Oral tablet; Adolescents†: Large, well-controlled, clinical trials for

pediatric bipolar disorder are lacking. In adolescents, doses of 200 mg PO twice daily have
been used. Increase dose every 3 to 4 days to achieve a serum carbamazepine

concentration of 8 to 12 mcg/mL. Usual daily dose range is 600 to 1600 mg/day PO in
divided doses. In a 6-week open label study of pediatric patients 8 years and older, the
initial dose was 15 mg/kg/day PO in 3 divided doses for 1 week, with serum concentration
assessment, then titrated until serum concentration was 7 to 10 mcg/mL. Clinical
pediatric guideline algorithms include a recommendation of carbamazepine as one
choice for first line monotherapy (Stage 1) treatment of nonpsychotic bipolar disorder I
(manic or mixed) in pediatric patients 6 to 17 years.
Carbamazepine Oral tablet; Adults: Initially, 200 mg PO twice daily. Increase every 3 to 4
days to achieve a serum carbamazepine concentration of 8 to 12 mcg/mL. Usual daily dose
range is 600 to 1600 mg/day PO in divided doses. Used as monotherapy or as adjunct
therapy with lithium.
Antipsychotics 1
Indicated in mania or mixed episode with or without psychotic features and in depressive
patients with psychotic features
Aripiprazole 16
Aripiprazole Oral tablet; Children and Adolescents 10 years and older: ACUTE OR
MAINTENANCE THERAPY: Initially, 2 mg PO once daily. Titrate to 5 mg once daily after
2 days, and then titrate to a target dose of 10 mg/day after an additional 2 days.
Subsequent increases should occur in increments of 5 mg/day. Use lowest effective dose.
Max: 30 mg/day PO. Periodically reassess the need for continued maintenance therapy.
ORAL SOLUTION DOSING: Substitute for the tablet on a mg-per-mg basis, up to 25 mg.
Patients receiving 30 mg tablets should receive 25 mg of the solution due to enhanced
absorption of the solution at higher dosages. ADJUSTMENTS: Coadministration of
certain drugs may need to be avoided or dosage adjustments may be necessary; review
drug interactions. In patients classified as CYP2D6 poor metabolizers (CYP2D6 PMs),
reduce the initial oral aripiprazole dose to one-half of the usual dose, then adjust the dose
according to clinical response. In patients classified as CYP2D6 PMs who are receiving a
strong CYP3A4 inhibitor, reduce the oral aripiprazole dose to one-quarter of the usual
dose. When the CYP3A4 inhibitor is withdrawn, increase to the original dose (i.e., one-half
of the usual dose).
Aripiprazole Oral tablet; Adults: INITIAL MONOTHERAPY DOSING FOR ACUTE OR

MAINTENANCE TREATMENT: 15 mg/day PO. INITIAL DOSING FOR ACUTE OR
MAINTENANCE TREATMENT AS ADJUNCT THERAPY TO LITHIUM OR
VALPROATE: 10 to 15 mg/day PO. The recommended target dose as monotherapy or
adjunct therapy to lithium or valproate is 15 mg/day. May titrate if needed/tolerated. Use
the lowest effective dose. Max: 30 mg/day PO. Periodically reassess the need for continued
therapy. ORAL SOLUTION DOSING: Substitute for the tablet on a mg-per-mg basis, up
to 25 mg. Patients receiving 30 mg tablets should receive 25 mg of the solution due to
enhanced absorption of the solution at higher dosages. ADJUSTMENTS:

Coadministration of certain drugs may need to be avoided or dosage adjustments may be
necessary; review drug interactions. In patients classified as CYP2D6 poor metabolizers
(CYP2D6 PMs), reduce the initial oral aripiprazole dose to one-half of the usual dose, then
adjust the dose according to clinical response. In patients classified as CYP2D6 PMs who
are receiving a strong CYP3A4 inhibitor, reduce the oral aripiprazole dose to one-quarter
of the usual dose. When the CYP3A4 inhibitor is withdrawn, increase to the original dose
(i.e., one-half of the usual dose).
Haloperidol 17
Oral
Haloperidol Oral tablet; Adults: Doses of up to 10 mg to 25 mg PO every 4 to 6 hours

have been recommended.
Intramuscular
Haloperidol Lactate Solution for injection; Adults: Doses of up to 5 mg to 10 mg IM

every 4 to 6 hours have been recommended.
Lurasidone
Lurasidone Hydrochloride Oral tablet; Children and Adolescents 10 years and older:
Initially, 20 mg/day PO as monotherapy taken with food (at least 350 calories). After 1
week, may increase the dose based on response. Effective range: 20 mg/day to 80 mg/day
as monotherapy. Max: 80 mg/day PO. Periodically re-evaluate the need for continued
treatment. Coadministration of certain drugs may need to be avoided or dosage
adjustments may be necessary; review drug interactions.
Lurasidone Hydrochloride Oral tablet; Adults: Initially, 20 mg/day PO once daily with
food (at least 350 calories) as monotherapy or as adjunctive therapy to lithium or
valproate. Effective dose range: 20 to 120 mg/day. Max: 120 mg/day PO. Higher end of
dose range (i.e., 80 to 120 mg/day) may not provide additional benefit vs. lower doses.
Coadministration of certain drugs may need to be avoided or dosage adjustments may be
necessary; review drug interactions.
Olanzapine 18 19
For treatment of bipolar disorder (bipolar I disorder), including mania or mixed episodes
Olanzapine Oral tablet; Adolescents: ACUTE TREATMENT OF MANIC OR MIXED

EPISODES (MONOTHERAPY): Initially, 2.5 or 5 mg PO once daily, with a target dose of
10 mg/day. Titrate in increments/decrements of 2.5 or 5 mg, at no less than 24 hour
intervals. Effective dose range: 2.5 to 20 mg/day; the mean dose was 8.9 mg/day PO
during clinical trials. Not FDA-approved in adolescents as adjunct treatment to lithium
or valproate. MAINTENANCE (MONOTHERAPY): Responding adolescents should

generally continue treatment, at the lowest dose needed to maintain remission.
Periodically reassess the need for continued treatment. MAX (ALL USES): 20 mg/day
PO.
Olanzapine Oral tablet; Adults: ACUTE TREATMENT OF MANIC OR MIXED

EPISODES (MONOTHERAPY): Initially, 10 to 15 mg PO once daily is recommended.
May titrate in increments/decrements of 5 mg, at no less than 24 hour intervals.
ADJUNCT THERAPY TO LITHIUM OR VALPROATE FOR ACUTE MANIC OR
MIXED EPISODES: Initially, 10 mg PO once daily. Effective antimanic dosage range: 5
to 20 mg/day PO in combination with lithium or valproate. MAINTENANCE
TREATMENT (MONOTHERAPY): Effective dose range of 5 to 20 mg/day PO. Re-
evaluate periodically to assess the need for continued therapy. MAX (ALL USES): 20
mg/day PO. Debilitated or geriatric patients may require lower total daily dosages. In
all cases, the lowest effective dosage should be determined.
For treatment of acute agitated behavior related to bipolar mania
Olanzapine Solution for injection; Children† and Adolescents† 12 years and older: Not
FDA approved, safety and efficacy have not been established in controlled clinical trials.
Data are limited. Off-label use has been reported as effective but is reserved for when
non-pharmacologic treatment fails or oral treatment is refused. SUGGESTED INITIAL
DOSING: 10 mg IM for adolescents as a single dose; a lower dose of 5 to 7.5 mg IM may
be given if clinical factors warrant. Give 5 mg IM for children 12 years and younger as a
single dose. Limited experience in those less than 12 years. POST-DOSE: Patients
should remain recumbent if drowsy or dizzy after injection until exam indicates no
postural hypotension and/or bradycardia. Sedation is a common side effect. LIMITS:
Repeat dosing generally not recommended; if needed, do not give a second dose more
frequently than 2 hours after the initial dose or 4 hours after the second dose. MAX: 30
mg/day IM in adolescents. Convert to oral therapy as soon as possible if long term
treatment is indicated.
Olanzapine Solution for injection; Adults: ADULTS NOT AT RISK FOR

HYPOTENSION: 10 mg IM as a single initial dose. A lower dose of 5 to 7.5 mg IM may
be given if clinical factors warrant. A dose of 5 mg IM should be considered for
geriatric patients. DEBILITATED ADULTS, THOSE AT RISK FOR HYPOTENSION,
THOSE WITH FACTORS FOR SLOWED DRUG METABOLISM (e.g., females, non-
smokers), OR THOSE PHARMACODYNAMICALLY SENSITIVE TO OLANZAPINE: A
dose of 2.5 mg IM should be considered. Patients should remain recumbent if drowsy
or dizzy after injection until examination has indicated that they are not experiencing
postural hypotension and/or bradycardia. POST-DOSE: Keep patient recumbent if
drowsy or dizzy after injection until exam has indicated no postural hypotension
and/or bradycardia. REPEAT DOSING: Subsequent doses up to 10 mg IM may be given
if necessary. However, efficacy of repeat doses has not been evaluated. LIMITS: The
safety of total daily doses greater than 30 mg IM or 10 mg IM given more frequently
than 2 hours after the initial dose and 4 hours after the second dose has not been
evaluated. Convert to oral therapy as soon as feasible.
Quetiapine 19
For acute treatment of mania and for maintenance therapy after stabilization
Quetiapine Fumarate Oral tablet; Children and Adolescents 10 years and older: 25 mg
PO twice daily on Day 1, 50 mg PO twice daily on Day 2, 100 mg PO twice daily on Day
3, 150 mg PO twice daily on Day 4, and 200 mg PO twice daily beginning Day 5. Range:
400 mg/day to 600 mg/day based upon response and tolerability. If needed, administer
in 3 divided doses per day to help with medication tolerance. Adjust dose in
increments 100 mg/day or less. Maximum: 600 mg/day PO. If maintenance therapy is
needed, use lowest effective dose and periodically re-evaluate need for continued
adjustments may be necessary; review drug interactions. RE-INITIATION OF
TREATMENT: If therapy is discontinued for less than 1 week and subsequently re-
initiated, the same dose/schedule may be used without titration. If therapy has been
discontinued for more than 1 week, follow the initial titration schedule.
Quetiapine Fumarate Oral tablet; Adults: Initially, 50 mg PO twice daily on Day 1 for
adults not at risk for hypotension. Increase in increments of up to 100 mg/day in two
divided doses as tolerated to 400 mg/day on Day 4. If needed, may further titrate up to
800 mg/day by Day 6 in increments of no greater than 200 mg/day. The recommended
dosage range for acute mania is 400 mg/day to 800 mg/day (monotherapy or as an
adjunct to lithium or divalproex). Consider a slower titration and a lower target dose in
debilitated patients or those at risk for hypotension. Max: 800 mg/day PO, in two
divided doses. Coadministration of certain drugs may need to be avoided or dosage
adjustments may be necessary; review drug interactions. Clinical trials excluded
patients with rapid cycling or mixed features. Periodically re-assess to determine the
need for ongoing treatment. Efficacy of quetiapine as monotherapy for maintenance
treatment has not been formally evaluated; therefore, use as an adjunct to lithium or
divalproex. During clinical trials, patients were generally continued on the same dose
on which they were stabilized during the acute phase of treatment. RE-INITIATION OF
TREATMENT: If therapy is discontinued for less than 1 week and subsequently re-
initiated, the same dose/schedule may be used without titration. If therapy has been
discontinued for more than 1 week, follow the initial titration schedule.
Quetiapine Fumarate Oral tablet; Geriatric Adults: Initially, 25 mg PO twice daily.

Increase the dose in increments of 50 mg/day depending upon individual response and
tolerability. The dosage range for acute mania in younger adults is 400 mg/day to 800
mg/day as monotherapy or as an adjunct to lithium or divalproex. Max: 800 mg/day PO,
in two divided doses. Consider a slow rate of dose titration and a lower target dose in
debilitated patients or patients at risk for hypotension. Coadministration of certain
drugs may need to be avoided or dosage adjustments may be necessary; review drug
interactions. Clinical trials excluded patients with rapid cycling or mixed features.
Periodically re-assess to determine the need for ongoing treatment. Efficacy of
quetiapine as monotherapy for maintenance treatment of bipolar disorder has not been
formally evaluated; therefore, when instituting maintenance therapy, use as an adjunct
to lithium or divalproex. During clinical trials, patients were generally continued on
the same dose on which they were stabilized during the acute phase of treatment. RE-
INITIATION OF TREATMENT: If therapy is discontinued for less than 1 week and
subsequently re-initiated, the same dose/schedule may be used without titration. If
therapy has been discontinued for more than 1 week, follow the initial titration
schedule.
For treatment of bipolar depression during depressive episodes of bipolar I or bipolar II

disorder
Quetiapine Fumarate Oral tablet; Adults: Dosing is once daily at bedtime, regardless of
immediate-release or extended-release oral dosage forms. Initially, 50 mg PO at
bedtime on Day 1, then 100 mg PO at bedtime on Day 2, 200 mg PO at bedtime on Day
3, and 300 mg PO once daily at bedtime beginning on Day 4. Bipolar depression Max:
300 mg/day PO. Consider slower titration and a lower target dose in debilitated patients
or patients at risk for hypotension, such as the elderly. Coadministration of certain
interactions. RE-INITIATION OF TREATMENT: If it has been less than 1 week, the
same dose/schedule may be used without titration. If therapy has been discontinued for
more than 1 week, follow the initial titration schedule.
For treatment of rapid-cycling bipolar disorder
Quetiapine Fumarate Oral tablet; Adults: In clinical trials for bipolar disorder for FDA-
approval, patients with rapid-cycling or mixed episodes were excluded. However,
quetiapine has been studied in rapid-cycling adult patients. In an open-label study, 50
mg PO once daily was added to an existing regimen of lithium, valproate, and/or
carbamazepine; quetiapine was then titrated to response. Initial titration from 50
mg/day PO to a mean dose 720 mg/day for mania and 183 mg/day for depression was
used. Final average doses were 360 mg/day for manic patients and 117 mg/day for
depressed patients, respectively. In another study, the initial 50 mg PO once daily dose
was titrated to a target range of 150 mg/day to 200 mg/day PO; mean target dose: 196
mg/day (dose range: 25 mg/day to 900 mg/day). Coadministration of certain drugs may
need to be avoided or dosage adjustments may be necessary; review drug interactions.
Risperidone 19
For treatment of mania or mixed episodes
Risperidone Oral tablet; Children and Adolescents 10 to 17 years: Initially, 0.5 mg PO

once daily as monotherapy. May give in divided doses to increase tolerability. Adjust by
0.5 mg/day to 1 mg/day at intervals of at least 24 hours to target dose range of 1 mg/day
to 2.5 mg/day PO. Doses above 2.5 mg/day do not appear to provide additional
therapeutic benefits and may result in more adverse events. Doses above 6 mg/day have
not been studied. Safety and efficacy of risperidone as adjunct treatment to lithium or
valproate in pediatric patients have not been established. Individualize and use the
lowest effective dosage. In general, pharmacological treatment is continued beyond
acute stabilization; however, there are no systematically obtained data to support the
use of risperidone in longer-term treatment (i.e., beyond 3 weeks). Periodically re-assess
the need for continued treatment. Coadministration of certain drugs may need to be
avoided or dosage adjustments may be necessary; review drug interactions.
Risperidone Oral tablet; Adults: Initially, 2 mg/day to 3 mg/day PO once daily as

monotherapy or as an adjunct to lithium or valproate. If needed, adjust the dose by 1
mg/day at intervals of no less than 24 hours. A dose range of 1 mg/day to 6 mg/day PO
was found effective in clinical trials; higher doses were not studied. Individualize
according to response and tolerability. Slower titration or divided daily doses may be
needed in some patients. Use the lowest effective dosage. In general, treatment is
continued beyond acute stabilization. Periodically re-assess the need for continued
adjustments may be necessary; review drug interactions.
Risperidone Oral tablet; Geriatric Adults: Initially, 0.5 mg PO twice per day followed by
careful titration. If needed, adjust the dose by 1 mg/day at intervals of no less than 24
hours. Slower titration or divided doses may be needed in geriatric patients due to the
potential for impaired renal function and an increase in drug toxicity. A dose range of 1
mg/day to 6 mg/day PO was found effective in clinical trials in younger adults; higher
doses were not studied. Individualize according to response and tolerability. Use the
lowest effective dosage. In general, treatment is continued beyond acute stabilization.
Periodically re-assess the need for continued treatment. Coadministration of certain
interactions.
For maintenance treatment of bipolar I disorder as monotherapy or adjunct therapy to

lithium or valproate
Risperidone Suspension for injection, Extended Release; Adults: Establish tolerability

with oral risperidone prior to converting to IM extended-release risperidone (Risperdal
Consta) in patients who have never received risperidone. Then, initiate Risperdal
Consta at 25 mg IM every 2 weeks. Oral risperidone (or another antipsychotic) should
be given with the first injection of Risperdal Consta, and continued for 3 weeks to
ensure adequate therapeutic plasma concentrations from Risperdal Consta. Some
patients may benefit from doses of 37.5 mg to 50 mg IM every 2 weeks.
Coadministration of certain drugs may need to be avoided or dosage adjustments may
be necessary; review drug interactions. GERIATRIC PATIENTS: The recommended
geriatric dose is 25 mg IM once every 2 weeks; however, similar to younger adults,
doses up to 50 mg IM every 2 weeks may be needed in select patients. Instruct geriatric

patients on orthostasis prevention and consider monitoring orthostatic vital signs in
at-risk patients. OTHER ADJUSTMENTS: An initial dose of 12.5 mg may be
appropriate for those with renal impairment, hepatic impairment, a history of poor
tolerability to psychotropic medications, or regimens with potential drug interactions
with risperidone; however, efficacy of the 12.5 mg dose has not been established. Max:
50 mg IM every 2 weeks.
Ziprasidone
For treatment of acute mania or for mixed episodes with or without psychotic features as
monotherapy
Ziprasidone Hydrochloride Oral capsule; Adults: FOR ACUTE MANIA OR MIXED

EPISODES AS MONOTHERAPY: Initially, 40 mg PO twice daily with food. On day 2 of
treatment, increase to 60 or 80 mg PO twice a day. Thereafter, adjust dose based on
tolerability and efficacy within the range 40 to 80 mg PO twice a day. In flexible-dose
clinical trials, the mean daily dose administered was approximately 120 mg/day.
MAINTENANCE TREATMENT AS AN ADJUNCT TO LITHIUM OR VALPROATE:
Continue at the same dose on which the patient was initially stabilized, within the
range of 40 to 80 mg PO twice daily. Periodically re-evaluate the need for continued
treatment.
Asenapine
Asenapine Sublingual tablet; Children and Adolescents 10 years and older: ACUTE
TREATMENT OF MANIC OR MIXED EPISODES (MONOTHERAPY): Initially, 2.5 mg
sublingually twice daily. Thereafter, the dose may be increased to 5 mg sublingually twice
daily after 3 days, and then increased to 10 mg sublingually twice daily after an additional
3 days. The dose should be adjusted based on individual response and tolerability within
the recommended dose range of 2.5 mg to 10 mg sublingually twice daily. MAX: 20
mg/day. The safety of doses greater than 10 mg twice daily has not been evaluated in
clinical trials. Pediatric patients may be more sensitive to dystonia when the escalation
schedule is not followed. Periodically re-evaluate the need for continued treatment.
Continued treatment beyond the acute episode is generally recommended. Asenapine is
not FDA-approved in pediatric patients as adjunct therapy to lithium or valproate for the
acute treatment of manic or mixed episodes or as maintenance treatment, either as
monotherapy or adjunct therapy.
Asenapine Sublingual tablet; Adults: ACUTE TREATMENT OF MANIC OR MIXED

EPISODES (MONOTHERAPY): Initially, 5 mg to 10 mg sublingually twice daily.
Responding patients should usually continue treatment beyond the acute episode.
ADJUNCT THERAPY TO LITHIUM OR VALPROATE FOR THE ACUTE TREATMENT
OF MANIC OR MIXED EPISODES: 5 mg sublingually twice daily initially. May increase
to 10 mg sublingually twice daily based upon response and tolerability. Responding
patients should usually continue treatment beyond the acute episode. MAINTENANCE
TREATMENT (MONOTHERAPY): Initially, continue the asenapine dose from
stabilization. In those receiving 10 mg sublingually twice daily, may decrease to 5 mg
sublingually twice daily on an individual basis. Periodically re-evaluate to assess the need
for continued treatment. MAX: 20 mg/day sublingually.
Paliperidone
Paliperidone Oral tablet, extended-release; Adults: Use not established; not FDA-
approved. 6 mg PO once daily initially; some response may be evident within a few days.
Some patients may need 3 mg PO once daily initially. May adjust dose by 3 mg/day at
intervals of at least 2 days to response and tolerability. Data suggest that 12 mg/day PO
may be the most effective dose after titration. Max: 12 mg PO once daily. Considered a
monotherapy option for manic or mixed episodes per some expert guidelines.
Cariprazine
Cariprazine Oral capsule; Adults: Initially, 1.5 mg PO once daily with or without food.
Increase to 3 mg PO once daily on Day 2. Make further dose adjustments (1.5 mg to 3 mg
increments) for response and tolerability; consider the long half-life of the drug.
Recommended range: 3 mg to 6 mg PO once daily. Max: 6 mg/day PO. Coadministration
of certain drugs may need to be avoided or dosage adjustments may be necessary; review
drug interactions.
Antidepressants 1 3
Far less effective (often ineffective) in bipolar depression compared with unipolar depression
Do not prescribe without optimal mood stabilization
Sudden discontinuation results in worsening of symptoms
Exercise caution; use of antidepressants can cause hypomania or mania (including mixed
features)
Selective serotonin reuptake inhibitors
Fluoxetine-olanzapine combination product
Olanzapine, Fluoxetine Hydrochloride Oral capsule; Children and Adolescents 10 years

and older: Olanzapine 3 mg/fluoxetine 25 mg PO once daily in the evening initially,
with a recommended target dose after titration within the approved dosing range (e.g.,
olanzapine 6 to 12 mg and fluoxetine 25 to 50 mg PO once daily). Max:
olanzapine/fluoxetine 12 mg/50 mg per day.
Olanzapine, Fluoxetine Hydrochloride Oral capsule; Adults: Initially, olanzapine 6

mg/fluoxetine 25 mg PO once daily in the evening; titrate as needed. PATIENTS
PREDISPOSED TO HYPOTENSIVE REACTIONS, OR WITH THE POTENTIAL FOR
REDUCED METABOLISM OF OLANZAPINE OR FLUOXETINE (e.g., FEMALE, NON-
SMOKER), OR PHARMACODYNAMICALLY SENSITIVE TO OLANZAPINE: Initially,
olanzapine 3 mg/fluoxetine 25 mg to olanzapine 6 mg/fluoxetine 25 mg PO once daily
in the evening, with cautious dose escalation. USUAL DOSE RANGE: olanzapine 6 to 12
mg and fluoxetine 25 to 50 mg PO once daily. Max: olanzapine/fluoxetine 18 mg/75 mg
PO per day.
Olanzapine, Fluoxetine Hydrochloride Oral capsule; Geriatric Adults: Olanzapine 3

mg/fluoxetine 25 mg to olanzapine 6 mg/fluoxetine 25 mg PO once daily each evening
initially. Titrate with caution. USUAL ADULT DOSE RANGE: olanzapine 6 to 12 mg
and fluoxetine 25 to 50 mg PO once daily. Adult Max: olanzapine/fluoxetine 18 mg/75
mg per day.
Sertraline 20
Off-label dosing for children and adolescents
Sertraline Hydrochloride Oral tablet; Children 6 to 11 years†: 12.5 mg to 25 mg/day

PO initially. Begin with a low dose and titrate gradually in 12.5 to 25 mg/day
increments at 4-week intervals until clinical response is achieved; some studies
report titration in 25 mg to 50 mg/day increments as often as every 1 to 2 weeks. A
dose of 50 mg/day PO is considered effective in some patients. Max: 200 mg/day PO.
Sertraline Hydrochloride Oral tablet; Children and Adolescents 12 to 17 years†: 25 to

50 mg/day PO initially. Begin with a low dose and titrate gradually in 12.5 to 25
mg/day increments at 4-week intervals until clinical response is achieved; some
studies report titration in 25 mg to 50 mg/day increments as often as every 1 to 2
weeks. A dose of 50 mg/day PO is considered effective in some patients. Max: 200
mg/day PO.
Sertraline Hydrochloride Oral tablet; Adults: 50 mg PO once daily. A lower initial

dose (25 mg PO once daily) may be used to minimize adverse effects. May increase at
intervals of not less than 1 week. May initiate sertraline capsules in patients who
have taken 100 mg or 125 mg for at least 1 week. Max: 200 mg/day PO.
Citalopram 21
Off-label dosing for children and adolescents
Citalopram Hydrobromide Oral tablet; Children and Adolescents 7 to 17 years: 10

mg PO once daily initially. Some experts recommend initial doses of 20 mg/day PO
in those 12 years and older. Clinical guidelines recommend to start with a low dose
and titrate gradually, in 10 mg/day increments at 4-week intervals until clinical
response is achieved. Some studies titrate as often as every week. A dose of 20 mg/day
PO is considered effective. Max: 40 mg/day in the general population and 20 mg/day
in poor metabolizers of CYP2C19 due to the potential for QT prolongation.
Coadministration of certain drugs may need to be avoided or dosage adjustments
may be necessary; review drug interactions.
Citalopram Hydrobromide Oral tablet; Adults 60 years and younger: Initially, 20 mg

PO once daily; may increase to 40 mg PO once daily after 1 week if clinically
indicated. Max: 40 mg/day in the general population and 20 mg/day in poor
metabolizers of CYP2C19 due to the potential for QT prolongation.
Coadministration of certain drugs may need to be avoided or dosage adjustments
may be necessary; review drug interactions.
Citalopram Hydrobromide Oral tablet; Adults older than 60 years: 20 mg PO once

daily is the recommended and maximum daily dosage. Coadministration of certain
interactions.
Bupropion
Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]; Children† and

Adolescents† 6 years and older: Dosage not established. Suggested dosage ranges from
1.4 to 6 mg/kg/day PO, titrated upward slowly and administered in divided doses. In
trials, the average effective dose is roughly 3 mg/kg/day PO; the maximum dosage is
generally 250 to 300 mg/day PO. Safety data are not extensive; most patients have also
been diagnosed with ADHD.
Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]; Adults: Initially,

100 mg PO twice daily; titrate after 3 days to 100 mg PO 3 times per day if needed; no
single dose should exceed 150 mg.
Nondrug and supportive care

Psychotherapy
Cognitive behavioral therapy 22 23
Used as an adjunctive therapy in patients with bipolar disorder (during remission from
manic episodes) who are also on prophylactic treatment; however, it is most effective in
management of depression
Modification of distorted cognition aids in reducing mood dysfunction
Includes:
Cognitive restructuring skills
Identifying and replacing maladaptive thoughts with adaptive thoughts
Integrating pleasurable events to reduce inactivity
Interpersonal and social rhythm therapy 9
Indicated for patients with bipolar disorder in remission from manic episodes, who are also
on prophylactic treatment
Helps to build better relationships, focusing on resolution of patient problems and

prevention of recurrence
Assists in maintaining consistent sleep/wake cycle and exercise activity
Family-focused psychotherapy 22
Should be provided for family members or couples dealing with bipolar disorder
Helps identify and reduce stress within the family
Lifestyle 1
Maintain regular sleep schedule
Treat insomnia aggressively; do not use trazodone for insomnia because it can induce
switching to mania
Avoid alcohol and drugs
Follow consistent exercise program
Minimize stress
Psychoeducation 1 22
Helps patient to understand behavioral and biologic risk factors that worsen the condition and
aid in preventing recurrence
Obtain consent of the patient to involve family members or others in psychoeducation process
Should emphasize:
Recognition of warning signs of mood swings
Avoidance of substance use and regulation of sleep pattern
Procedures
Electroconvulsive therapy 1 3
General explanation
Most rapid and effective treatment for mania and bipolar depression
Risk of mood destabilization or switching to mania is prevented by appropriate monitoring of

the patient closely after therapy
Indication
Severe and treatment-resistant bipolar depression
Severe mania during pregnancy (although careful discussion of risks and benefits is crucial)
Psychosis
Suicidality
Catatonia
Patient preference for electroconvulsive therapy
Comorbidities 1 24
Substance use disorders, including nicotine use (Related: Tobacco Use Disorder and Smoking
Cessation)
Include addiction treatment with treatment of bipolar disorder
Coexisting psychiatric conditions, such as anxiety, suicidality, and attention-

deficit/hyperactivity disorder
May significantly impact treatment of bipolar disorder; refer patient for psychiatric
evaluation and management
Special populations
Women
Premenstrual and postpartum exacerbation in women with bipolar disorder causes

increased depressive and manic episodes, in addition to high recurrence
Pregnant patients
Psychosocial strategies are preferred over medications in the first trimester as this period
involves highest risk for teratogenicity; if medications are necessary, preference should be
given to monotherapy, using lowest effective dose 2
Drugs containing valproate taken in pregnancy can cause malformations in 11% of infants
and developmental disorders in 30% to 40% of children after birth; valproate treatment
must not be used in girls and women—including young girls prepuberty—unless alternative
treatments are not suitable and terms of the pregnancy prevention program are met 1
Avoid divalproex during pregnancy owing to elevated risk of neural tube defects (up to 5%),
even higher incidences of other congenital abnormalities, and evidence of significant
neurodevelopmental delay in children at age 3 years and average loss of 9 IQ points 2
Monitoring
Absence of any significant symptoms of mania or depression for 2 months is considered full
remission; periodically continue to assess for relapse 8
When treating with lithium: 1
Measure plasma lithium concentration every 3 months for first year
After first year, measure plasma lithium concentrations every 6 months; measure every
3 months for patients in any of the following groups:
Older patients
Patients taking drugs that interact with lithium
Patients who are at risk of impaired renal or thyroid function, who have raised calcium
levels, or other complications
Patients with poor symptom control
Patients with poor adherence
Patients whose last plasma lithium concentration was 0.8 mmol/L or higher
Monitor lithium dose and plasma lithium concentrations more frequently if urea levels and
creatinine levels become elevated, or if estimated GFR falls over 2 or more tests; evaluate rate
of deterioration of renal function
Monitor patients at every appointment for symptoms of neurotoxicity (eg, paresthesia,

ataxia, tremor, cognitive impairment); can occur at therapeutic levels
Complications and Prognosis
Complications
Risk of drug or alcohol use
Risk of suicide; 5 in untreated bipolar disorder, 10% to 15% 3
Increased risk of death from cerebrovascular accidents
Malnutrition and self-neglect are more common among elderly patients
Prognosis
Risk of recurrence in the year after a mood episode is 50% and greater than 70% at 4 years 12
Factors associated with a mild to moderate increased risk of relapse include poor psychosocial
support, poor occupational advancement, long duration of illness, depressive symptoms,
comorbidity, psychotic features, mixed bipolar disorder, and early or late age of onset
Factors associated with moderate to high risk of relapse include severe illness and strong
family history of bipolar disorder
Factors that improve prognosis:
Stable sleep/wake cycles
Better adherence to treatment
Having fewer comorbid conditions, such as substance use disorder
Addition of psychosocial/psychotherapeutic intervention
Factors that worsen prognosis:
Earlier age at onset
Multiple relapses
Mixed episodes and/or rapid cycling
Comorbid conditions, especially substance use disorder
Screening and Prevention
Prevention
Consider genetic counseling in patients with bipolar disorder who are planning pregnancy
owing to high genetic risk 3
REFERENCIAS
1: National Institute for Health and Care Excellence: Bipolar Disorder: Assessment and Management.
Clinical guideline CG185. NICE website. Published September 2014. Updated April 2018. Accessed January
6, 2020. https://www.nice.org.uk/guidance/cg185
Ver en el Artículo | Referencia cruzada (https://www.nice.org.uk/guidance/cg185)
2: Yatham LN et al: Canadian Network for Mood and Anxiety Treatments (CANMAT) and International
Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder.
Bipolar Disord. 20(2):97-170, 2018
Ver en el Artículo | Referencia cruzada (https://pubmed.ncbi.nlm.nih.gov/29536616)
3: American Psychiatric Association: Practice guideline for the treatment of patients with bipolar disorder
(revision). Am J Psychiatry 159(4 Suppl):1-50, 2002
4: Colom F et al: Group psychoeducation for stabilised bipolar disorders: 5-year outcome of a randomised
clinical trial. Br J Psychiatry. 194(3):260-5, 2009
5: Plans L et al: Association between completed suicide and bipolar disorder: a systematic review of the
literature. J Affect Disord. 242:111-22, 2019
6: American Psychiatric Association: Bipolar and related disorders. In: Diagnostic and Statistical Manual of
Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Association; 2013:123-39
Ver en el Artículo
7: American Psychiatric Association: Supplement to Diagnostic and Statistical Manual of Mental Disorders,
Fifth Edition. APA website. Published September 2016. Accessed January 2, 2020.
https://dsm.psychiatryonline.org/pb-assets/dsm/update/DSM5Update2016.pdf
Ver en el Artículo | Referencia cruzada (https://dsm.psychiatryonline.org/pb-
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8: Department of Veteran Affairs et al: Clinical Practice Guideline: Management of Bipolar Disorder in
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Bipolar Disorder - ClinicalKey

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20/10/21 15:24 Bipolar Disorder - ClinicalKey

Todos Volver adisease

Key Points Acción urgente

Patient must experience at least 1 episode of mania or Pacientes maníacos

Management of bipolar disorder is directly related to the Psicosis severa

Always evaluate patients for suicidality, acute psychosis, Violent behavior

Antidepressants may precipitate mania and contribute to

Psychotherapy, psychoeducation, and family intervention should be used to restore normal

Coexisting psychiatric conditions (eg, anxiety, insomnia, attention-deficit/hyperactivity

Episodic for most patients, with recurrent episodes

Mania is characterized by a distinct period of abnormal and persistently elevated, expansive,

Increased activity/psychomotor agitation

Grandiosity or inflated self-esteem

Flight of ideas or racing thoughts

Patient is talkative or has pressured speech

Mania is distinguished from hypomania by duration and severity

Duration: 7 days (mania) versus 4 days (hypomania); however, if patient is hospitalized or

Severity: marked impairment and/or psychosis, potentially resulting in hospitalization

No history of manic episodes

Depressive symptoms or unpredictability caused by frequent alternation between periods of

Mood disorder consisting of subthreshold depressive and hypomanic periods

Family history of bipolar disorder (first-degree relative)

Episodes of overactivity and disinhibition

Other episodic and sustained behavioral changes

Symptoms in manic phase 8

Decreased need for sleep

Poor appetite and weight loss

Racing speech, flight of ideas, and impulsiveness

Increased activity level

Excessive involvement in pleasurable activities

Poor financial management

Symptoms in depressive phase 8

Feelings of sadness or hopelessness

Loss of interest in pleasurable or usual activities

Sense of guilt or low self-esteem

Negative thoughts about the future

Weight loss or gain

Talk of suicide or death

Poor to no eye contact

Speaking in low tones or slowly

Busy, active, and involved

Hyperactive and hypervigilant

Clothes put on in a hurry; disorganized

Depressed episode: sad, depressed

Hypomanic episode: elevated, expansive

Joyous, elated, jubilant, and euphoric

Depressed episode: sadness, hopelessness, death, and suicide

Hypomanic episode: forward-thinking and optimistic attitude

­Expansive and overly optimistic thinking; may display excessive self-confidence; no

Perceptions and thought content

Depressed episode: may experience hallucinations and delusions

Hypomanic episode: no hallucinations or delusions

Manic episode: may experience hallucinations and delusions

Insight and judgment

Often no insight; judgment is impaired, leading to unwise decisions, particularly if manic

Depressed episode: associated with high rate of suicide

Manic episode: aggressive, intolerant, highly demanding, and violently assertive

Causes and Risk Factors

Risk factors and/or associations

Bipolar II disorder: may be more common in females 1 8

Other risk factors/associations

Traumatic brain injury 9

Alcohol or drug use

Treatment with corticosteroids

Expansive and overly optimistic thinking; may display excessive self-confidence; no