Bipolar II Disorder

Last edited on February 13, 2022

Epidemiology

Bipolar II has a similar prevalence as bipolar I disorder, with a prevalence of 0.8% in the United States, and 0.3% internationally.^[1]
- The combined prevalence rates of all forms of bipolar disorders (bipolar I, II, and unspecified) is 1.8%.^[2]
The average age of onset is in the mid-20s, which is later than bipolar I disorder, but earlier than major depressive disorder.
Females are more diagnosed than males.

Prognosis

Although by definition hypomania is less severe than mania (bipolar I), the disability associated with bipolar II actually is similar to that of bipolar I. The economic burden of bipolar II is actually four times greater than that of bipolar I, because individuals spend as much time symptomatic (but predominantly with depressive symptoms) as those with bipolar I disorder.^[3]
- Typically, the hypomanic episodes in bipolar II do not themselves cause impairment.
- Individuals with a rapid cycling pattern typically have a worse prognosis. Individuals who are married, have higher levels of education, and fewer years of illness have better recovery.^[4]
- The rates of completed suicide are also similar between bipolar II and bipolar I. 1 in 25 individuals will have completed suicide over the lifetime of the illness. Importantly, 1/3 of individuals with bipolar II disorder report a lifetime history of a suicide attempt (about similar as bipolar I). However, the lethality of attempts are actually higher in bipolar II.^[5]
Many individuals may experience several episodes of depression before their first hypomanic episode.
Between 5 to 15% of individuals with bipolar II disorder will ultimately have a manic episode, which changes the diagnosis to bipolar I disorder.

Comorbidity

60% of individuals have 3 or more comorbid mental disorders, with anxiety disorders and substance use disorders being the highest.
Approximately 40% of individuals have at least one lifetime diagnosis of an eating disorder, with binge eating disorder being more common than bulimia and anorexia nervosa.

Risk Factors

The risk for developing bipolar II is highest among relatives of individuals with bipolar II disorder.
Genetic factors may also be involved.

For a critical review of the diagnostic validity of bipolar II disorder, see:

Criterion A

Criteria have been met for at least 1 hypomanic episode and at least 1 major depressive episode.

Criterion B

There has never been a manic episode.

Criterion C

The occurrence of the hypomanic episode(s) and major depressive episode(s) is not better explained by schizoaffective disorder, schizophrenia, schizophreniform disorder, delusional disorder, or other specified or unspecified schizophrenia spectrum and other psychotic disorder.

Criterion D

The symptoms of depression or the unpredictability caused by frequent alternation between periods of depression and hypomania causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Criterion A

A distinct period of abnormally and persistently elevated, expansive, or irritable mood AND
Abnormally and persistently increased activity or energy, lasting at least 4 consecutive days and present most of the day, nearly every day.

Criterion B

During the period of mood disturbance and increased energy and activity, at least 3 of the following symptoms have persisted (4 symptoms if the mood is only irritable), represent a noticeable change from usual behaviour, and have been present to a significant degree:

Distractibility (i.e. - attention too easily drawn to unimportant or irrelevant external stimuli), as reported or observed.
Indiscretion, characterized by excessive involvement in activities that have a high potential for painful consequences (e.g. - unrestrained buying sprees, sexual behaviours, or foolish business investments).
Grandiosity or inflated self-esteem.
Flight of ideas or subjective experience that thoughts are racing.
Activity (goal-directed) increasing (e.g. - either socially, at work or school, or sexually) or psychomotor agitation.
Sleep decreased (e.g. - feels rested after only 3 hours of sleep).
Talkative (more than usual or pressure to keep talking)

Mnemonic

The mnemonic DIGFAST can be used to remember the criteria for bipolar I and II disorder.^[6]

D - Distractibility
I - Indiscretion
G - Grandiosity

F - Flight of ideas
A - Activity increased
S - Sleep decreased
T - Talkativeness

Criterion C

The episode is associated with an unequivocal change in functioning that is uncharacteristic of the individual when not symptomatic.

Criterion D

The disturbance in mood and the change in functioning are observable by others.

Criterion E

No marked social or occupational impairment.
There is never hospitalization.
No psychotic features (if there are psychotic features, the episode is, by definition, manic).

Criterion F

The episode is not attributable to the physiological effects of a substance (e.g. - a drug of abuse, a medication or other treatment) or another medical condition.

What If There is an Antidepressant-induced Hypomania?

A full hypomanic episode that emerges during antidepressant treatment (e.g. - 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 1 or 2 symptoms (particularly increased irritability, edginess, or agitation following antidepressant use) are not taken as sufficient for diagnosis of a hypomanic episode, nor necessarily indicative of a true bipolar disorder.

Episode Specifier

Specify current or most recent episode:

Hypomanic
Depressed

Severity Specifier

Mild: Few, if any, symptoms in excess of those required to make the diagnosis are present, the intensity of the symptoms is distressing but manageable, and the symptoms result in minor impairment in social or occupational functioning.
Moderate: The number of symptoms, intensity of symptoms, and/or functional impairment are between those specified for “mild” and “severe.”
Severe: The number of symptoms is substantially in excess of that required to make the diagnosis, the intensity of the symptoms is seriously distressing and unmanageable, and the symptoms markedly interfere with social and occupational functioning.

Remission Specifier

In partial remission: Symptoms of the immediately previous manic, hypomanic, or depressive episode are present, but full criteria are not met, or there is a period lasting less than 2 months without any significant symptoms of a manic, hypomanic, or major depressive episode following the end of such an episode.
In full remission: During the past 2 months, no significant signs or symptoms of the disturbance were present.

With anxious distress

At least 2 of the following symptoms during the majority of days of the current or most recent episode of mania, hypomania, or depression:
- (1) Feeling keyed up or tense
- (2) Feeling unusually restless
- (3) Difficulty concentrating because of worry
- (4) Fear that something awful may happen
- (5) Feeling that the individual might lose control of himself or herself
Severity:
- Mild: 2 symptoms
- Moderate: 3 symptoms
- Moderate-severe: 4 or 5 symptoms
- Severe: 4 or 5 symptoms and with motor agitation

Note: Anxious distress has been noted as a prominent feature of both bipolar and major depressive disorder in both primary care and specialty mental health settings. High levels of anxiety have been associated with higher suicide risk, longer duration of illness, and greater likelihood of treatment nonresponse. As a result, it is clinically useful to specify accurately the presence and severity levels of anxious distress for treatment planning and monitoring of response to treatment.

With mixed features

The mixed features specifier can apply to the current manic, hypomanic, or depressive episode in bipolar I or bipolar II disorder:

Manic or hypomanic episode, with mixed features:

A. Full criteria are met for a manic episode or hypomanic episode, and at least 3 of the following symptoms are present during the majority of days of the current or most recent episode of mania or hypomania:
- (1) Prominent dysphoria or depressed mood as indicated by either subjective report (e.g. - feels sad or empty) or observation made by others (e.g. - appears tearful)
- (2) Diminished interest or pleasure in all, or almost all, activities (as indicated by either subjective account or observation made by others)
- (3) Psychomotor retardation nearly every day (observable by others and not merely subjective feelings of being slowed down)
- (4) Fatigue or loss of energy
- (5) Feelings of worthlessness or excessive or inappropriate guilt (not merely self-reproach or guilt about being sick)
- (6) Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide
B. Mixed symptoms are observable by others and represent a change from the person’s usual behavior
C. For individuals whose symptoms meet full episode criteria for both mania and depression simultaneously, the diagnosis should be manic episode, with mixed features, due to the marked impairment and clinical severity of full mania
D. The mixed symptoms are not attributable to the physiological effects of a substance (e.g. - a drug of abuse, a medication, other treatment)

Depressive episode, with mixed features:

A. Full criteria are met for a major depressive episode, and at least 3 of the following manic/hypomanic symptoms are present during the majority of days of the current or most recent episode of depression:
- (1) Elevated, expansive mood
- (2) Inflated self-esteem or grandiosity
- (3) More talkative than usual or pressure to keep talking
- (4) Flight of ideas or subjective experience that thoughts are racing.
- (5) Increase in energy or goal-directed activity (either socially, at work or school, or sexually)
- (6) Increased or excessive involvement in activities that have a high potential for painful consequences (e.g. - engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments)
  - (7) Decreased need for sleep (feeling rested despite sleeping less than usual; to be contrasted with insomnia)
B. Mixed symptoms are observable by others and represent a change from the person’s usual behavior
C. For individuals whose symptoms meet full episode criteria for both mania and depression simultaneously, the diagnosis should be manic episode, with mixed features
D. The mixed symptoms are not attributable to the physiological effects of a substance (e.g. - a drug of abuse, a medication, or other treatment)

Note: Mixed features associated with a major depressive episode have been found to be a significant risk factor for the development of bipolar I or bipolar II disorder. As a result, it is clinically useful to note the presence of this specifier for treatment planning and monitoring of response to treatment.

With rapid cycling

This specifier (can be applied to bipolar I or bipolar II disorder). There is presence of at least 4 mood episodes in the previous 12 months that meet the criteria for manic, hypomanic, or major depressive episode.

Note: The essential feature of a rapid-cycling bipolar disorder is the occurrence of at least 4 mood episodes during the previous 12 months. These episodes can occur in any combination and order. The episodes must meet both the duration and symptom number criteria for a major depressive, manic, or hypomanic episode and must be demarcated by either a period of full remission or a switch to an episode of the opposite polarity. Manic and hypomanic episodes are counted as being on the same pole. Episodes are demarcated by either partial or full remissions of at least 2 months or a switch to an episode of the opposite polarity (e.g. - major depressive episode to manic episode). Except for the fact that they occur more frequently, the episodes that occur in a rapid-cycling pattern are no different from those that occur in a non-rapid cycling pattern. Mood episodes that count toward defining a rapid-cycling pattern exclude those episodes directly caused by a substance (e.g. - cocaine, corticosteroids) or another medical condition.

Hypothyroidism, antidepressant use, and substance use is associated with rapid cycling. So assessing thyroid function, stopping any offending antidepressants, stimulants, and other psychotropics that might contribute to cycling is critical!

With melancholic features

See main article: Melancholic Depression

A. 1 of the following is present during the most severe period of the current episode:
- (1) Loss of pleasure in all, or almost all, activities
- (2) Lack of reactivity to usually pleasurable stimuli (does not feel much better, even temporarily, when something good happens)
B. 3 or more of the following:
- (1) A distinct quality of depressed mood characterized by profound despondency, despair, and/or moroseness or by so-called empty mood,
- (2) Depression that is regularly worse in the morning
- (3) Early-morning awakening (i.e. - at least 2 hours before usual awakening)
- (4) Marked psychomotor agitation or retardation
- (5) Significant anorexia or weight loss
- (6) Excessive or inappropriate guilt

With atypical features

See main article: Atypical Depression

This specifier can be applied when these features predominate during the majority of days of the current or most recent major depressive episode.

A. Mood reactivity (i.e. - mood brightens in response to actual or potential positive events)
B. 2 or more of the following:
- (1) Significant weight gain or increase in appetite
- (2) Hypersomnia
- (3) Leaden paralysis (i.e. - heavy, leaden feelings in arms or legs)
- (4) A long-standing pattern of interpersonal rejection sensitivity (not limited to episodes of mood disturbance) that results in significant social or occupational impairment
C. Criteria are not met for “with melancholic features” or “with catatonia” during the same episode

With psychotic features

See main article: Psychotic Depression

Delusions or hallucinations are present at any time in the episode. If psychotic features are present, specify if mood-congruent or mood-incongruent:

With mood-congruent psychotic features:
- The content of all delusions and hallucinations is consistent with the typical depressive themes of personal inadequacy, guilt, disease, death, nihilism, or deserved punishment
With mood-incongruent psychotic features:
- The content of the delusions or hallucinations does not involve typical depressive themes of personal inadequacy, guilt, disease, death, nihilism, or deserved punishment, or the content is a mixture of mood-incongruent and mood-congruent themes

With catatonia

See main article: Catatonia

This specifier can apply to an episode of mania or depression if catatonic features are present during most of the episode.

With peripartum onset

See main article: Peripartum and Postpartum Depression

This specifier can be applied to the current or, if the full criteria are not currently met for a mood episode, most recent episode of mania, hypomania, or major depression in bipolar I or bipolar II disorder if onset of mood symptoms occurs during pregnancy or in the 4 weeks following delivery.

With seasonal pattern

See main article: Seasonal Affective Disorder (SAD)

This specifier applies to the lifetime pattern of mood episodes. The essential feature is a regular seasonal pattern of at least 1 type of episode (i.e. - mania, hypomania, or depression). The other types of episodes may not follow this pattern. For example, an individual may have seasonal manias, but his or her depressions do not regularly occur at a specific time of year.

A. There has been a regular temporal relationship between the onset of manic, hypomanic, or major depressive episodes and a particular time of the year (e.g. - in the fall or winter) in bipolar I or bipolar II disorder. Do not include cases in which there is an obvious effect of seasonally related psychosocial stressors (e.g. - regularly being unemployed every winter).
B. Full remissions (or a change from major depression to mania or hypomania or vice versa) also occur at a characteristic time of the year (e.g. - depression disappears in the spring)
C. In the last 2 years, the individual’s manic, hypomanic, or major depressive episodes have demonstrated a temporal seasonal relationship, as defined above, and no non-seasonal episodes of that polarity have occurred during that 2-year period.
D. Seasonal manias, hypomanias, or depressions (as described above) substantially outnumber any nonseasonal manias, hypomanias, or depressions that may have occurred over the individual’s lifetime.

Psychometric Scales for Bipolar Disorder

Name	Rater	Description	Download
Young Mania Rating Scale (YMRS)	Clinician	Most frequently utilized to assess manic symptoms. 11 items on the patient’s subjective report over the last 48 hours plus clinical observations.^[7] Takes 15–30 minutes to complete.	YMRS Download
Mood Disorder Questionnaire (MDQ)	Patient	The MDQ screens for bipolar spectrum disorder, (which includes Bipolar I, Bipolar II and unspecified bipolar disorder). There are 13 self-rated questions. Although the original study claimed a 90% specificity and 70% sensitivity for an eventual diagnosis of bipolar disorder, more recent studies show that the MDQ risks falsely identifying individuals with bipolar disorder.^[8]^[9]^[10] For example, borderline personality disorder, PTSD, substance use disorder, and childhood abuse are associated with false positives on the MDQ. More recent studies have shown that the positive predictive value of the MDQ is only around 55%.^[11]	MDQ Download

Major depressive disorder
- Perhaps the most challenging differential diagnosis to consider is major depressive disorder, which may be accompanied by hypomanic or manic symptoms that do not meet full criteria (i.e. - either fewer symptoms or a shorter duration than required for a hypomanic episode). This is especially true in evaluating individuals with symptoms of irritability, which may be associated with either major depressive disorder or bipolar II disorder. A hypomanic episode should not be confused with the several days of euthymia and restored energy or activity that may follow remission of a major depressive episode. Conversely, once a hypomanic episode has been confirmed, the diagnosis becomes by bipolar II disorder, and never returns back to major depressive disorder.
Cyclothymic disorder
- In cyclothymic disorder, there are numerous periods of hypomanic symptoms and numerous periods of depressive symptoms that do not meet symptom or duration criteria for a major depressive episode or a true hypomanic episode. Bipolar II disorder is distinguished from cyclothymic disorder by the presence of one or more major depressive episodes. If a major depressive episode occurs after the first 2 years of cyclothymic disorder, the additional diagnosis of bipolar II disorder is given.
Schizophrenia spectrum and other related psychotic disorders
- Bipolar II disorder must be distinguished from psychotic disorders (e.g. - schizoaffective disorder, schizophrenia, and delusional disorder). These disorders are all characterized by periods of psychotic symptoms that occur in the absence of prominent mood symptoms. Other helpful considerations include the accompanying symptoms, previous course, and family history.

Panic disorder or other anxiety disorders
- Anxiety disorders need to be considered in the differential diagnosis and may frequently be present as co-occurring disorders.
Substance use disorders and substance/medication induced hypomania
- Substance use disorders and substance/medication-induced mood episodes should also be ruled out prior to the diagnosis of bipolar II disorder.
Attention-deficit/hyperactivity disorder
- Attention-deficit/hyperactivity disorder (ADHD) may be misdiagnosed as bipolar II disorder, especially in adolescents and children. Many symptoms of ADHD, such as rapid speech, racing thoughts, distractibility, and less need for sleep, overlap with the symptoms of hypomania. The “double counting” of both ADHD and bipolar II symptoms can be avoided if the clinician clarifies whether the symptoms represent a distinct episode and if the noticeable increase over baseline required for the diagnosis of bipolar II disorder is present.
Personality disorders (especially borderline personality disorder)
- The same convention as applies for ADHD also applies when evaluating an individual for a personality disorder such as borderline personality disorder, since mood lability and impulsivity are common in both personality disorders and bipolar II disorder. Symptoms must represent a distinct episode, and the noticeable increase over baseline required for the diagnosis of bipolar II disorder must be present. A diagnosis of a personality disorder should not be made during an untreated mood episode unless the lifetime history supports the presence of a personality disorder.
Other bipolar disorders
- Diagnosis of bipolar II disorder should be differentiated from bipolar I disorder by carefully considering whether there have been any past episodes of mania and from other specified and unspecified bipolar and related disorders by confirm ing the presence of fully syndromal hypomania and depression.

Primer

Bipolar I Disorder is a mental disorder characterized by episodes of highly elevated or irritable mood, known as mania. Individuals may also present with decreased sleep, grandiosity, talkativeness, racing thoughts, and indiscretion or risk-taking behaviours. In some presentations, one's mood can shift very quickly between mania, anger, irritability, and/or depression, indicating a “mixed features” presentation of bipolar disorder.

Epidemiology

The lifetime prevalence for bipolar I disorder is approximately 0.6%, with equal gender distribution.^[12] Men typically have more manic episodes and females have more depressive/rapid cycling episodes.
- Bipolar I disorder is more common in high income (1.4%) than low income (0.7%) countries. Separated, divorced, or widowed individuals have higher rates of bipolar I disorder.
- The combined prevalence rates of all forms of bipolar disorders (bipolar I, II, and unspecified) is 1.8%.^[13]
The typical age of onset is at age 20 (in the US), and closer to age 29 (in European countries)
- Evidence suggests that age of onset for bipolar disorder has a trimodal distribution pattern, with distinct groups represented by onset in late teens, mid 20s, and early 40s.^[14]

Prognosis

With treatment, up to 25% of patients will experience a relapse of symptoms, compared to up to 40% for those on placebo. Risk factors for relapse include young age of onset, psychotic features, rapid cycling, comorbid substance use, and comorbid anxiety.^[15]
- More than 90% of individuals with a single manic episode will go onto have another mood episode
- About 60% of manic episodes happen right before a depressive episode
Between 6 to 7% of individuals will die by suicide, and suicide is a significant cause of bipolar disorder mortality.^[16] Individuals are at highest risk during and following hospital admission, and over 70% of suicide deaths occur during depressive and mixed episodes. As a result, comprehensive suicide risk assessments should be done.^[17]
Females are more likely to experience rapid cycling and mixed features, and have higher lifetime rates of eating disorders and alcohol use disorder.^[18]
Cognitive deficits (attention, processing speed, executive function) in bipolar disorder are similar to that of schizophrenia, but less severe.^[19]^[20]
Factors associated with good prognosis are: good treatment adherence, lack of early childhood adversity, higher age of onset, good social supports, the absence of rapid cycling, and absence of personality disorders.
Factors associated with poor prognosis are: male gender, mixed episodes/features, rapid cycling, co-morbid anxiety disorder, co-morbid substance abuse, co-morbid personality disorder, and/or obesity.^[21]

Comorbidity

Bipolar disorder is most comorbid with anxiety disorders, substance use disorders, personality disorders, and impulse-control disorders (oppositional defiant disorder, conduct disorder, and ADHD).^[22]

Risk Factors

Individuals with a diagnosis of bipolar disorder often have a history of anxiety disorder in childhood.
Bipolar disorder is one of the most heritable psychiatric disorders (between 79-93%) which is higher than diseases such as breast cancer.
Monozygotic (identical) twins have 40–45% concordance rates (i.e. - percent chance that the other twins will have bipolar disorder if one has it).^[23]
Depressive episodes often precede manic episodes. Individuals with the following depression factors are at higher risk for having bipolar disorder: early age of illness onset (<age 25), highly recurrent depressive episodes, a family history of bipolar disorder, depression with psychotic features, atypical features such as hypersomnia and increased appetite, leaden paralysis, psychomotor agitation, postpartum depression or psychosis, and antidepressant induced irritability.^[24]

Relative Risk Factors in Bipolar Disorder

Barnett, J. H et al. (2009). The genetics of bipolar disorder. Neuroscience, 164(1), 331-343.

Risk Factor	Risk
Monozygotic twin affected	40-45%
1st degree relative affected	9%

DSM-5 Diagnostic Criteria

See also: Zimmerman, M. et al. (2008). Is bipolar disorder overdiagnosed?. Journal of Clinical Psychiatry, 69(6), 935-940.

Criterion A

Criteria have been met for at least 1 manic episode (see Manic Episode Criteria below)

Criterion B

The occurrence of the manic and major depressive episode(s) is not better explained by schizoaffective disorder, schizophrenia, schizophreniform disorder, delusional disorder, or other specified or unspecified schizophrenia spectrum and other psychotic disorder.

Manic Episode Criteria

Note: Criteria A to D constitute a manic episode. At least 1 lifetime manic episode is required for the diagnosis of bipolar I disorder. The manic episode may have been preceded by and may be followed by hypomanic or major depressive episodes.

Criterion A

A distinct period of abnormally and persistently elevated, expansive, or irritable mood AND
Abnormally and persistently increased activity or energy, lasting at least 1 week and present most of the day, nearly every day (or any duration if hospitalization is necessary).

Criterion B

During the period of mood disturbance and increased energy and activity, at least 3 of the following symptoms have persisted (4 symptoms if the mood is only irritable), represent a noticeable change from usual behaviour, and have been present to a significant degree:

Distractibility (i.e. - attention too easily drawn to unimportant or irrelevant external stimuli), as reported or observed.
Indiscretion, characterized by excessive involvement in activities that have a high potential for painful consequences (e.g. - unrestrained buying sprees, sexual behaviours, or foolish business investments).
Grandiosity or inflated self-esteem.
Flight of ideas or subjective experience that thoughts are racing.
Activity (goal-directed) increasing (e.g. - either socially, at work or school, or sexually) or psychomotor agitation.
Sleep decreased (e.g. - feels rested after only 3 hours of sleep).
Talkative (more than usual or pressure to keep talking)

Mnemonic

The mnemonic DIGFAST can be used to remember the criteria for bipolar I and II disorder.^[25]

D - Distractibility
I - Indiscretion
G - Grandiosity
F - Flight of ideas
A - Activity increased
S - Sleep decreased
T - Talkativeness

Criterion 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.

Criterion D

The episode is not attributable to the physiological effects of a substance (e.g. - a drug of abuse, a medication, other treatment) or to another medical condition.

What If There Is A Medication-induced Mania?

Manic symptoms that are attributable to the physiological effects of a drug of abuse (e.g. - cocaine or amphetamines), medication or treatment side effect (e.g. - steroids, L-dopa, antidepressants, stimulants), or another medical condition do not count toward the diagnosis of bipolar I disorder. However, a fully syndromal manic episode that arises during treatment (e.g. - with an antidepressant, electroconvulsive therapy, or light therapy) or drug of abuse, and persists beyond the physiological effect of the inducing agent (i.e. - after a medication or substance is fully out of the individual’s system or the effects of electroconvulsive therapy would be expected to have dissipated completely) is sufficient evidence for a manic episode diagnosis, and therefore a bipolar I disorder diagnosis.

Specifiers

Episode Specifier

Current or most recent episode manic
Current or most recent episode hypomanic
Current or most recent episode depressed
Current or most recent episode unspecified

Severity Specifier

Mild: Few, if any, symptoms in excess of those required to make the diagnosis are present, the intensity of the symptoms is distressing but manageable, and the symptoms result in minor impairment in social or occupational functioning.
Moderate: The number of symptoms, intensity of symptoms, and/or functional impairment are between those specified for “mild” and “severe.”
Severe: The number of symptoms is substantially in excess of that required to make the diagnosis, the intensity of the symptoms is seriously distressing and unmanageable, and the symptoms markedly interfere with social and occupational functioning.

Remission Specifier

In partial remission: Symptoms of the immediately previous manic, hypomanic, or depressive episode are present, but full criteria are not met, or there is a period lasting less than 2 months without any significant symptoms of a manic, hypomanic, or major depressive episode following the end of such an episode.
In full remission: During the past 2 months, no significant signs or symptoms of the disturbance were present.

With anxious distress

At least 2 of the following symptoms during the majority of days of the current or most recent episode of mania, hypomania, or depression:
- (1) Feeling keyed up or tense
- (2) Feeling unusually restless
- (3) Difficulty concentrating because of worry
- (4) Fear that something awful may happen
- (5) Feeling that the individual might lose control of himself or herself
Severity:
- Mild: 2 symptoms
- Moderate: 3 symptoms
- Moderate-severe: 4 or 5 symptoms
- Severe: 4 or 5 symptoms and with motor agitation

Note: Anxious distress has been noted as a prominent feature of both bipolar and major depressive disorder in both primary care and specialty mental health settings. High levels of anxiety have been associated with higher suicide risk, longer duration of illness, and greater likelihood of treatment nonresponse. As a result, it is clinically useful to specify accurately the presence and severity levels of anxious distress for treatment planning and monitoring of response to treatment.

With mixed features

The mixed features specifier can apply to the current manic, hypomanic, or depressive episode in bipolar I or bipolar II disorder:

Manic or hypomanic episode, with mixed features:

A. Full criteria are met for a manic episode or hypomanic episode, and at least 3 of the following symptoms are present during the majority of days of the current or most recent episode of mania or hypomania:
- (1) Prominent dysphoria or depressed mood as indicated by either subjective report (e.g. - feels sad or empty) or observation made by others (e.g. - appears tearful)
- (2) Diminished interest or pleasure in all, or almost all, activities (as indicated by either subjective account or observation made by others)
- (3) Psychomotor retardation nearly every day (observable by others and not merely subjective feelings of being slowed down)
- (4) Fatigue or loss of energy
- (5) Feelings of worthlessness or excessive or inappropriate guilt (not merely self-reproach or guilt about being sick)
- (6) Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide
B. Mixed symptoms are observable by others and represent a change from the person’s usual behavior
C. For individuals whose symptoms meet full episode criteria for both mania and depression simultaneously, the diagnosis should be manic episode, with mixed features, due to the marked impairment and clinical severity of full mania
D. The mixed symptoms are not attributable to the physiological effects of a substance (e.g. - a drug of abuse, a medication, other treatment)

Depressive episode, with mixed features:

A. Full criteria are met for a major depressive episode, and at least 3 of the following manic/hypomanic symptoms are present during the majority of days of the current or most recent episode of depression:
- (1) Elevated, expansive mood
- (2) Inflated self-esteem or grandiosity
- (3) More talkative than usual or pressure to keep talking
- (4) Flight of ideas or subjective experience that thoughts are racing.
- (5) Increase in energy or goal-directed activity (either socially, at work or school, or sexually)
- (6) Increased or excessive involvement in activities that have a high potential for painful consequences (e.g. - engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments)
  - (7) Decreased need for sleep (feeling rested despite sleeping less than usual; to be contrasted with insomnia)
B. Mixed symptoms are observable by others and represent a change from the person’s usual behavior
C. For individuals whose symptoms meet full episode criteria for both mania and depression simultaneously, the diagnosis should be manic episode, with mixed features
D. The mixed symptoms are not attributable to the physiological effects of a substance (e.g. - a drug of abuse, a medication, or other treatment)

Note: Mixed features associated with a major depressive episode have been found to be a significant risk factor for the development of bipolar I or bipolar II disorder. As a result, it is clinically useful to note the presence of this specifier for treatment planning and monitoring of response to treatment.

With rapid cycling

This specifier (can be applied to bipolar I or bipolar II disorder). There is presence of at least 4 mood episodes in the previous 12 months that meet the criteria for manic, hypomanic, or major depressive episode.

Note: The essential feature of a rapid-cycling bipolar disorder is the occurrence of at least 4 mood episodes during the previous 12 months. These episodes can occur in any combination and order. The episodes must meet both the duration and symptom number criteria for a major depressive, manic, or hypomanic episode and must be demarcated by either a period of full remission or a switch to an episode of the opposite polarity. Manic and hypomanic episodes are counted as being on the same pole. Episodes are demarcated by either partial or full remissions of at least 2 months or a switch to an episode of the opposite polarity (e.g. - major depressive episode to manic episode). Except for the fact that they occur more frequently, the episodes that occur in a rapid-cycling pattern are no different from those that occur in a non-rapid cycling pattern. Mood episodes that count toward defining a rapid-cycling pattern exclude those episodes directly caused by a substance (e.g. - cocaine, corticosteroids) or another medical condition.

Hypothyroidism, antidepressant use, and substance use is associated with rapid cycling. So assessing thyroid function, stopping any offending antidepressants, stimulants, and other psychotropics that might contribute to cycling is critical!

With melancholic features

See main article: Melancholic Depression

A. 1 of the following is present during the most severe period of the current episode:
- (1) Loss of pleasure in all, or almost all, activities
- (2) Lack of reactivity to usually pleasurable stimuli (does not feel much better, even temporarily, when something good happens)
B. 3 or more of the following:
- (1) A distinct quality of depressed mood characterized by profound despondency, despair, and/or moroseness or by so-called empty mood,
- (2) Depression that is regularly worse in the morning
- (3) Early-morning awakening (i.e. - at least 2 hours before usual awakening)
- (4) Marked psychomotor agitation or retardation
- (5) Significant anorexia or weight loss
- (6) Excessive or inappropriate guilt

With atypical features

See main article: Atypical Depression

This specifier can be applied when these features predominate during the majority of days of the current or most recent major depressive episode.

A. Mood reactivity (i.e. - mood brightens in response to actual or potential positive events)
B. 2 or more of the following:
- (1) Significant weight gain or increase in appetite
- (2) Hypersomnia
- (3) Leaden paralysis (i.e. - heavy, leaden feelings in arms or legs)
- (4) A long-standing pattern of interpersonal rejection sensitivity (not limited to episodes of mood disturbance) that results in significant social or occupational impairment
C. Criteria are not met for “with melancholic features” or “with catatonia” during the same episode

With psychotic features

See main article: Psychotic Depression

Delusions or hallucinations are present at any time in the episode. If psychotic features are present, specify if mood-congruent or mood-incongruent:

With mood-congruent psychotic features:
- The content of all delusions and hallucinations is consistent with the typical depressive themes of personal inadequacy, guilt, disease, death, nihilism, or deserved punishment
With mood-incongruent psychotic features:
- The content of the delusions or hallucinations does not involve typical depressive themes of personal inadequacy, guilt, disease, death, nihilism, or deserved punishment, or the content is a mixture of mood-incongruent and mood-congruent themes

With catatonia

See main article: Catatonia

This specifier can apply to an episode of mania or depression if catatonic features are present during most of the episode.

With peripartum onset

See main article: Peripartum and Postpartum Depression

This specifier can be applied to the current or, if the full criteria are not currently met for a mood episode, most recent episode of mania, hypomania, or major depression in bipolar I or bipolar II disorder if onset of mood symptoms occurs during pregnancy or in the 4 weeks following delivery.

With seasonal pattern

See main article: Seasonal Affective Disorder (SAD)

This specifier applies to the lifetime pattern of mood episodes. The essential feature is a regular seasonal pattern of at least 1 type of episode (i.e. - mania, hypomania, or depression). The other types of episodes may not follow this pattern. For example, an individual may have seasonal manias, but his or her depressions do not regularly occur at a specific time of year.

A. There has been a regular temporal relationship between the onset of manic, hypomanic, or major depressive episodes and a particular time of the year (e.g. - in the fall or winter) in bipolar I or bipolar II disorder. Do not include cases in which there is an obvious effect of seasonally related psychosocial stressors (e.g. - regularly being unemployed every winter).
B. Full remissions (or a change from major depression to mania or hypomania or vice versa) also occur at a characteristic time of the year (e.g. - depression disappears in the spring)
C. In the last 2 years, the individual’s manic, hypomanic, or major depressive episodes have demonstrated a temporal seasonal relationship, as defined above, and no non-seasonal episodes of that polarity have occurred during that 2-year period.
D. Seasonal manias, hypomanias, or depressions (as described above) substantially outnumber any nonseasonal manias, hypomanias, or depressions that may have occurred over the individual’s lifetime.

Pediatric Bipolar

Screening and Rating Scales

Psychometric Scales for Bipolar Disorder

Name	Rater	Description	Download
Young Mania Rating Scale (YMRS)	Clinician	Most frequently utilized to assess manic symptoms. 11 items on the patient’s subjective report over the last 48 hours plus clinical observations.^[28] Takes 15–30 minutes to complete.	YMRS Download
Mood Disorder Questionnaire (MDQ)	Patient	The MDQ screens for bipolar spectrum disorder, (which includes Bipolar I, Bipolar II and unspecified bipolar disorder). There are 13 self-rated questions. Although the original study claimed a 90% specificity and 70% sensitivity for an eventual diagnosis of bipolar disorder, more recent studies show that the MDQ risks falsely identifying individuals with bipolar disorder.^[29]^[30]^[31] For example, borderline personality disorder, PTSD, substance use disorder, and childhood abuse are associated with false positives on the MDQ. More recent studies have shown that the positive predictive value of the MDQ is only around 55%.^[32]	MDQ Download

Pathophysiology

Genetics

Genome Wide Association Studies (GWAS) suggest that the ANK3 (ankyrin G) and CACNA1C (alpha 1C subunit of the L-type voltage-gated calcium channel) genes may be involved in the pathogenesis of bipolar disorder. Both of these genes for for ion channels, and suggest that channelopathies may play a role in the development of bipolar disorder.^[33] Other candidate genes for bipolar disorder include:

G30 (DAAO) and G72 genes located on chromosome 13q-32 (associated with mood symptoms)
BDNF gene on chromosome 11 p13-15 region (associated with cognitive impairment and rapid cycling)
COMT gene on chromosome 22q (associated with psychotic symptoms)
XBP1 gene on chromosome 22q12 (underexpressed in bipolar disorder)
DISC1 gene
CLOCK and BMAL1 gene polymorphisms

Neuroimaging

Some of the abnormalities found in patients with bipolar disorder involve the fronto-limbic network, including subcortical structures such as the hippocampus, amygdala and striatum. Some cortical regions are hypothesized to be involved as well.^[34]
MRI neuroimaging studies have found:
- Smaller hippocampus, amygdala, thalamus and anterior cingulate regions
- Larger ventricles
- Increased white matter hyperintensities
- Widespread cortical thinning
- Cortical thickening in those on lithium, and thinning in those on anticonvulsants
Functional neuroimaging studies have shown that there is hyperconnectivity in the default mode network, salience network, and central executive network.

Differential Diagnosis

It is important to keep your differential diagnosis broad to avoid overdiagnosis and misdiagnosis of bipolar disorder. Common comorbidities such as substance use disorders, impulse control disorders, anxiety disorders, and personality disorders such as borderline personality disorder have a significant symptom overlap with bipolar disorder.

Major depressive disorder or persistent depressive disorder
- Major depressive disorder may also be accompanied by hypomanic or manic symptoms (but have fewer symptoms or for a shorter duration than required for mania or hypomania criteria). When the individual presents in an episode of major depression, one must depend on corroborating history regarding past episodes of mania or hypomania. Symptoms of irritability may be associated with either major depressive disorder or bipolar disorder, adding to diagnostic complexity.
Other bipolar disorders (e.g. - bipolar II)
- Diagnosis of bipolar I disorder is differentiated from bipolar II disorder by determining whether there have been any past episodes of mania. Other specified and unspecified bipolar and related disorders should be differentiated from bipolar I and II disorders by considering whether either the episodes involving manic or hypomanic symptoms or the episodes of depressive symptoms fail to meet the full criteria for those conditions. Bipolar disorder due to another medical condition may be distinguished from bipolar I and II disorders by identifying, based on best clinical evidence, a causally related medical condition.
Bipolar or related disorder due to another medical condition
- Episodes are judged to be a consequence of a medical condition such as traumatic brain injury, brain tumours such as frontal lobe meningiomas, multiple sclerosis, stroke, Cushing's disease, Wilson's disease or hyperthyroidism. Onset or exacerbation of mood coincides with that of the medical condition.
Substance‐ or medication‐induced mood disorder
- Mood episodes are determined to be a consequence of a substance such as an illicit/recreational drug, or a medication (stimulants, steroids, L‐dopa or antidepressants) or toxin exposure. Episodes may also be related to intoxication or withdrawal. Substance use disorders may manifest with substance/medication-induced manic symptoms that should be distinguished from bipolar I disorder; response to mood stabilizers during a substance/medication-induced mania may not necessarily be diagnostic for bipolar disorder. There may be substantial overlap since individuals with bipolar I disorder may overuse substances during an episode. A primary diagnosis of bipolar disorder must be established based on symptoms that remain once substances are no longer being used.
Cyclothymic disorder
- Hypomanic symptoms do not meet the full criteria for a hypomanic episode, and depressive symptoms do not meet the criteria for a major depressive episode.
Disruptive mood dysregulation disorder (DMDD)
- In individuals with severe irritability, particularly children and adolescents, care must be taken to apply the diagnosis of bipolar disorder only to those who have a clear episode of mania or hypomania. This means a distinct time period and duration, in which the irritability was clearly different from the individual's baseline and also accompanied by the onset of Criterion B symptoms. When a child's irritability is persistent and severe, the diagnosis of disruptive mood dysregulation disorder would be more appropriate. When any child is being assessed for mania, it is essential that the symptoms represent a clear change from the child's typical behavior.

Psychotic disorders
- Periods of psychotic symptoms in the absence of prominent mood symptoms. Consider onset, accompanying symptoms, pervious course and family history.
Generalized anxiety disorder, panic disorder, posttraumatic stress disorder, or other anxiety disorders
- Anxiety disorders need to be considered as either the primary disorder or a comorbid disorder. A careful history and psychiatric interview is needed to differentiate generalized anxiety disorder from bipolar disorder, since anxious ruminations may be mistaken for racing thoughts. Similarly, efforts to minimize anxious feelings may be misinterpreted by the clinician as impulsive behavior. Similarly, symptoms of posttraumatic stress disorder (PTSD) must be differentiated from bipolar disorder. It is helpful to assess the episodic nature of the symptoms described, as well as to consider symptom triggers to help differentiate between the disorders.
Attention-deficit/hyperactivity disorder (ADHD)
- ADHD may be misdiagnosed as bipolar disorder, especially in adolescents and children. Many symptoms overlap with the symptoms of mania, such as rapid speech, racing thoughts, distractibility, and decreased need for sleep. One can avoid “double counting” symptoms toward both ADHD and bipolar disorder if the clinician clarifies whether the symptom(s) represents a distinct episode as opposed to the child's baseline personality/symptoms.
Personality disorders (can still co-occur with bipolar disorder)
- A diagnosis of a personality disorder should not be made during an untreated mood episode. Symptoms must represent a distinct episode, and the noticeable increase over baseline required for the diagnosis of bipolar disorder must be present.
- Borderline personality disorder
  - Instability of interpersonal relationships, self‐image and mood, with marked impulsivity and a central theme of intense abandonment fears. Borderline personality disorder has an early onset and long‐standing course. True euphoria and prolonged well‐functioning intervals are extremely rare.
  - Individuals with bipolar disorder are more likely to have a family history of bipolar illness, whereas self-harm and past sexual abuse are more likely in borderline personality disorder.^[35]
- Narcissistic personality disorder
  - Grandiosity, need for admiration and lack of empathy of early onset. Grandiosity not associated with mood changes or functional impairments.
- Antisocial personality disorder
  - Early onset of disregard for, and violation of, the rights of others, which does not occur only in the context of a manic episode.
Obstructive sleep apnea
Vitamin B12 deficiency
Endocrine dysfunction
- Hypo or hyperthyroidism
- Hypercortisolemia
Infectious etiologies
- Infectious causes such as HIV, neurosyphilis, Lyme disease, and viral/autoimmune encephalitis can also present with neuropsychiatric symptoms that appear to be mania/hypomania.

Bipolar I vs. Bipolar II

There are key differences in the diagnostic criteria between bipolar I and bipolar II disorder. The table below outlines these differences.

Comparison of Bipolar I vs. Bipolar II

	Bipolar I	Bipolar II
Diagnostic Criteria	manic episode only	hypomanic episode + depressive episode
Length	> `7` days	> `4` days
Impairment	Severe	Minor to none
Hospitalization	Possible	No
Psychosis	Possible	No

Mixed Features: Mania and Hypomania Symptoms Can Also Occur During Depressive Episodes!

See also: Depression with psychomotor excitation is not just a "major depressive episode" -- Nassir Ghaemi
Patients with bipolar I and bipolar II disorder experiencing active depressive episodes can also have concomitant manic/hypomanic symptoms at the same time – most commonly distractibility, flight of ideas, racing thoughts, and psychomotor agitation (least common).^[36]

Bipolar vs. Depression

Since bipolar disorder often presents first with a depressive episode, individuals may be misdiagnosed with major depressive disorder instead of bipolar disorder. Patients often fail (unintentionally) to report hypomanic/manic episodes as well. A missed diagnosis of bipolar disorder can result in the worse prognosis and inadequate treatment.^[37]^[38]

Features of Depression that May Increase Suspicion of a Bipolar vs Unipolar Illness

Adapted from: Mitchell, P. B. et al (2008). Diagnostic guidelines for bipolar depression: a probabilistic approach. Bipolar disorders, 10(1p2), 144-152.

Feature	Suggests Bipolar	Suggests Unipolar Depression
Symptomatology and Mental State Signs	• Hypersomnia and/or increased daytime napping • Hyperphagia and/or increased weight • Other “atypical” depressive symptoms such as leaden paralysis • Psychomotor retardation • Psychotic features and/or pathological guilt • Lability of mood, irritability, psychomotor agitation, racing thoughts	• Initial insomnia/reduced sleep • Appetite and/or weight loss • Normal activity levels • Somatic complaints
Course of Illness	• Early onset of first depression (<25 years) • Multiple prior episodes (≥5 episodes)	• Late onset of first depression (>25 years) • Long duration of current episode (>6 months)
Family History	• Positive family history of bipolar disorder	• Negative family history of bipolar disorder

Late-Life Bipolar Disorder

Patients with late-life onset bipolar disorder are a diverse group with high rates of neurologic comorbidities. Therefore, a comprehensive assessment should be done in these patients.^[39]
- The differential diagnosis should be broad and include stroke and cerebrovascular disease, dementias such as frontotemporal dementia, epilepsy, central nervous system infections, traumatic brain injuries, tumours, endocrine disorders, vitamin deficiencies, and medication side effects (e.g. - corticosteroid-induced mania).^[40]
In the elderly who are diagnosed bipolar disorder, there are more mixed episodes with less severity, but longer duration of illness. There is also increased mortality risk due to cardiovascular and physical comorbidity.^[41]
Bipolar disorder also contributes to cognitive dysfunction, in particular executive dysfunction, slower processing speed, and visuospatial dysfunction (separate from any Alzheimer's pathology).
Treatment with anticonvulsants confers a higher risk of cognitive impairment, when compared with lithium. Consistent with treatment for bipolar disorder of all ages, lithium is a better treatment option than valproic acid.^[42]^[43]

Investigations

Baseline investigations should include: CBC, fasting glucose, fasting lipid profile (TC, vLDL, LDL, HDL, TG), platelets, electrolytes and extended electrolytes (calcium, magnesium, phosphate), liver enzymes, serum bilirubin, prothrombin time and partial thromboplastin time, urinalysis, serum creatinine, eGFR, thyroid‐stimulating hormone (TSH)
If there is a history of substance use: urine drug screen
If history of renal disease: 24h creatinine clearance
If older >40 years or if indicated: electrocardiogram
If woman of childbearing age: pregnancy test, prolactin

Neuroimaging

Neuroimaging should be ordered if there are neurological findings, an abrupt or late age of onset, or if the presentation is different from typical episodes of mania (if the individual has had previous episodes of mania).
MRI findings generally show:
- Smaller hippocampus, amygdala, thalamus and anterior cingulate regions
- Larger ventricles
- Increased White matter hyperintensities
- Widespread cortical thinning
- Cortical thickening in those on lithium and thinning in those on anticonvulsants

Treatment

Medication

Lithium remains the gold-standard for treatment in all phases of bipolar I disorder, and atypical antipsychotics play an important role in treating acute mania.^[44]^[45]
- This is especially true for those who display a classical euphoric grandiose mania, have a family history of bipolar disorder, and/or have a family history of good lithium response.
Otherwise, picking a mood stabilizer depends on patient factors, their medical history, and other drug interaction factors.
- There are some patient factors that may help clinicians choose one mood stabilizer over another (see table below)
Adherence to pharmacological treatment of bipolar I disorder remains challenging; 1 in 3 patients will be unable to adhere to treatment long-term.^[46]
Any individual presenting with mania who are also on antidepressants or stimulants should have these medications discontinued to reduce the risk of prolonging a manic episode.

Mood Stabilizers and Predictors of Outcomes

Adapted from: Yatham, L. et al. (2018). 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 disorders, 20(2), 97–170.

Medication	Use If	Possible Adverse Events
Lithium	• Classical euphoric grandiose mania (elated mood in the absence of depressive symptoms) • Classical mania‐depression‐euthymia course • Fewer prior episodes of illness • Family history of bipolar and/or lithium response	Renal impairment, thyroid dysfunction, worsening of psoriasis
Valproate	• Both classical and dysphoric mania (mixed features) • Predominant irritable or dysphoric mood • Comorbid substance use • History of traumatic brain injury	Teratogen, and PCOS
Carbamazepine	• History of traumatic brain injury • Comorbid anxiety and substance use • Schizoaffective disorder with mood-incongruent delusions • Negative family history of bipolar disorder	Teratogen, hepatic CYP enzyme autoinduction, risk of SJS/TEN as well
Lamotrigine	• Predominant depressive symptoms (remember that lamotrigine does not treat mania!) • Comorbid anxiety	Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)

For Women of Childbearing Age...

Contraceptive counselling and medication risks must be included as part of the comprehensive treatment plan for bipolar disorder. This is for two reasons:

Contraception efficacy: many of the treatments used in bipolar disorder, especially anticonvulsants (such as carbamazepine, topiramate, and lamotrigine) can significantly reduce the effectiveness of oral contraceptives (OCPs), and increase the risk for unintended pregnancy. On the flipside, OCPs can also reduce the efficacy of medications like lamotrigine.
Teratogenicity: valproate products (valproic acid, divalproex) have high teratogenic potential and also increase the risk for developmental disorders in infants exposed to valproate in utero. Thus, women on valproate products should be on contraception, and informed about the risks of using valproate during pregnancy. Additionally, individuals wishing to become pregnant should work with their clinician to switch off from valproate.

See also main article: Obstetric and Fetal Pharmacology

Acute Mania

About 50% of patients will have significant improvement on monotherapy within 3 to 4 weeks.
- However, combination therapies tend to work faster compared to monotherapy.
Atypical antipsychotics are frequently used for management of acute mania due to its rapid onset of action and various forms of administration.
- Once a patient is stabilized on an antipsychotic for acute mania, they can be transitioned to a mood stabilizer for long-term management.^[47]

Pharmacological Treatments for Acute Mania in Bipolar I

Adapted from: Yatham, L. et al. (2018). 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 disorders, 20(2), 97–170.

1st line	Monotherapy: lithium, quetiapine (dose range 400 to 800 mg)^[48], divalproex, asenapine, aripiprazole, paliperidone (>6mg), risperidone, cariprazine Combination therapy: quetiapine + Li/DVP, aripiprazole + Li/DVP, risperidone + Li/DVP, asenapine + Li/DVP
2nd line	Monotherapy: olanzapine, carbamazepine, ziprasidone, haloperidol, ECT Combination therapy: olanzapine + Li/DVP, lithium + DVP
3rd line	Monotherapy: chlorpromazine, clonazepam, clozapine Combination therapy: Carbamazepine/oxcarbazepine + Li/DVP, haloperidol + Li/DVP, rTMS, tamoxifen, tamoxifen + Li/DVP
Not recommended	Allopurinol, eslicarbazepine/licarbazepine, gabapentin, lamotrigine, Omega-3 fatty acids, topiramate, valnoctamide, zonisamide

Li = lithium, DVP = divalproex

Maintenance

If a patient was treated with both an atypical antipsychotic plus a mood stabilizer (lithium/divalproex) during an episode of acute mania, the benefits of still being on an antipsychotic 6 months after reponse is unclear. Therefore the risks and benefits of using an antipsychotics beyond the 6 month mark should be reassessed in conjunction with the patient.
Olanzapine should not be used as a first line medication due to the risks of metabolic syndrome.

Pharmacological Treatments for Maintenance Therapy in Bipolar I Disorder

Adapted from: Yatham, L. et al. (2018). 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 disorders, 20(2), 97–170.

1st line	Monotherapy: lithium, quetiapine, divalproex, lamotrigine (limited efficacy in preventing mania), asenapine, aripiprazole, aripiprazole OM (once monthly) Combination therapy: quetiapine + Li/DVP, aripiprazole + Li/DVP
2nd line	Monotherapy: olanzapine, risperidone LAI, carbamazepine, paliperidone (>6 mg) Adjunctive therapy: risperidone LAI Combination therapy: lurasidone + Li/DVP, ziprasidone + Li/DVP
3rd line	Combination therapy: aripiprazole + lamotrigine, olanzapine + fluoxetine Adjunctive therapy: clozapine, gabapentin
Not recommended	Monotherapy: perphenazine, tricyclic antidepressants

Li = lithium, DVP = divalproex

Depression

Mnemonic for Bipolar Depression Medications

Remember the 3 “L's” for bipolar depression: Lithium, Lurasidone, Lamotrigine.

Patients with acute bipolar I depression who are not on any treatment, should generally start quetiapine monotherapy.^[49]
For those already on lithium with a breakthrough depressive episode, adding adjunctive lurasidone, lamotrigine, or quetiapine would be a reasonable first step.^[50]
Lamotrigine monotherapy is not recommended for patients with frequent manic episodes because it has limited efficacy in preventing manic episodes.^[51]

Pharmacological Treatments for Acute Bipolar I Depression

Adapted from: Yatham, L. et al. (2018). 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 disorders, 20(2), 97–170.

1st line	Monotherapy: quetiapine (target dose: 300 mg/day), lithium (target level: 0.8-1.2 meq/L), lamotrigine (minimum dose: 200 mg), lurasidone Combination therapy: lurasidone + Li/DVP Adjunctive therapy: lamotrigine
2nd line	Monotherapy: divalproex, ECT, cariprazine Combination therapy: olanzapine-fluoxetine (combination pill) Adjunctive therapy: SSRIs/bupropion
3rd line	Monotherapy: carbamazepine, olanzapine Adjunctive therapy: aripiprazole, armodafinil, asenapine, eicosapentaenoic acid (EPA), ketamine (IV), light therapy ± total sleep deprivation, levothyroxine, modafinil, N‐acetylcysteine, pramipexole, repetitive transmagnetic stimulation (rTMS), SNRI/MAOI
Not recommended	Monotherapy: antidepressant, aripiprazole Combination therapy: lamotrigine + folic acid Adjunctive therapy: mifepristone

Li = lithium, DVP = divalproex

Should Antidepressants Be Used in Bipolar I Depression?

Antidepressants should never be used as a single monotherapy treatment for bipolar I depression
Antidepressants should also never be used to treat a current mixed episode or in patients with a history of rapid cycling, even if the patient is on a mood stabilizer.
In general, there is very weak evidence for the use of antidepressants and bipolar I depression.
- For certain patients, antidepressants could be used in conjunction with a mood stabilizer for acute short term treatment of bipolar depression, with the goal of tapering and discontinuing the antidepressant 6 to 8 weeks after full remission of depressive symptoms.

For a deeper dive into the literature, the STEP-BD trial showed that adjunctive treatment with antidepressants does not improve clinical outcomes in people with bipolar disorder taking a mood stabilizer.^[52] Recent randomized clinical trials have shown that antidepressants may worsen outcomes in maintenance treatment of bipolar disorder as well.^[53]

Summary

Pharmacological Treatments for Various Phases of Bipolar Disorder

Adapted from: Yatham, L. et al. (2018). 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 disorders, 20(2), 97–170.

	Acute Mania	Acute Depression	Mania Prevention	Depression Prevention	Prevention of Any Mood Episode
Lithium	Yes¹	Yes²	Yes¹	Yes¹	Yes¹
Quetiapine	Yes¹	Yes¹	Yes¹	Yes¹	Yes¹
Divalproex	Yes¹	Yes¹	Yes³	Yes¹	Yes¹
Lamotrigine	No!	Yes¹	Yes²	Yes¹	Yes¹
Asenapine	Yes¹	No data	Yes²	Yes²	Yes²
Aripiprazole	Yes¹	Not recommended!	Yes²	No	Yes²
Paliperidone	Yes¹	No	Yes²	No data	Yes²
Olanzapine*	Yes¹	Yes¹	Yes¹	Yes¹	Yes¹

* = Olanzapine is generally no longer first-line given significant metabolic side effects. 1 = Level 1 evidence, 2 = Level 2 evidence, 3 = Level 3 evidence

Psychotherapy

No evidence exists for specific psychosocial interventions in acute mania. However, after treatment of mania, adding psychosocial interventions in addition to medication treatment is very important.
- In fact, on average, adjunctive psychosocial interventions reduce recurrence rates by about 15%.^[54]
Psychosocial interventions can decrease relapse rates, mood fluctuations, need for medications, hospitalizations, and increase functioning and medication adherence.
Psychoeducation is a first-line treatment in maintenance therapy, and includes providing information about the course of illness, treatments, and coping strategies for both the patient and the family. Psychoeducation can also be delivered in individual or group settings.^[55]

Adjunctive Psychological Treatments in Bipolar Disorder

Adapted from: Yatham, L. et al (2018). 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 disorders, 20(2), 97-170.

	Mania	Maintenance	Bipolar Depression
1st line	None	• Psychoeducation (PE)	None
2nd line	None	• Cognitive behavioural therapy (CBT) • Family-focused therapy (FFT)	• Cognitive behavioural therapy (CBT) • Family-focused therapy (FFT)
3rd line	None	• Interpersonal and social rhythm therapy (IPSRT) • Peer support	• Interpersonal and social rhythm therapy (IPSRT)
Insufficient evidence	None	Cognitive and functional remediation, dialectical behavioural therapy (DBT), family/caregiver interventions, mindfulness‐based cognitive therapy (MBCT), online interventions	Psychoeducation, cognitive and functional remediation, dialectical behavioural therapy (DBT), family/caregiver interventions, mindfulness‐based cognitive therapy (MBCT), online interventions

ECT

See main article: Electroconvulsive Therapy (ECT)

Electroconvulsive therapy is a second line treatment for bipolar mania and bipolar (I and II) depression. It is well-tolerated and safe, and may be useful in cases where rapid resolution of symptoms is required, such as in pregnancy where there is concern about maternal/fetal well-being.

Nutrition

Coenzyme Q10, likely due to its antioxidant and anti-inflammatory properties, has been found to improve symptoms of bipolar depression.^[56]

Guidelines

See also: Parker, G. B., Graham, R. K., & Tavella, G. (2017). Is there consensus across international evidence‐based guidelines for the management of bipolar disorder?. Acta Psychiatrica Scandinavica, 135(6), 515-526.

Bipolar Disorder Guidelines

Guideline	Location	Year	PDF	Website
Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD)	Canada, International	2018	PDF	Link
American Psychiatric Association (APA)	USA	2002	PDF	• Guideline (2002) • Guideline Watch (2005) • Quick Reference
National Institute for Health and Care Excellence (NICE)	UK	2014	PDF	Link
British Association for Psychopharmacology (BAP)	UK	2016	PDF	Link
Royal Australian and New Zealand College of Psychiatrists (RANZCP)	AUS, NZ	2015	PDF	Link

Resources

For Patients

The Bipolar Disorder Survival Guide, Second Edition: What You and Your Family Need to Know

For Providers

Articles

Research

¹⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

²⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

³⁾ Yatham, L. N., Kennedy, S. H., Parikh, S. V., Schaffer, A., Bond, D. J., Frey, B. N., ... & Berk, M. (2018). 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 disorders, 20(2), 97-170.

⁴⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

⁵⁾ Yatham, L. N., Kennedy, S. H., Parikh, S. V., Schaffer, A., Bond, D. J., Frey, B. N., ... & Berk, M. (2018). 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 disorders, 20(2), 97-170.

⁶⁾ Mnemonics in a mnutshell: 32 aids to psychiatric diagnosis. Current Psychiatry. 2008 October;7(10):27-33

⁷⁾ Young, R. C., Biggs, J. T., Ziegler, V. E., & Meyer, D. A. (1978). A rating scale for mania: reliability, validity and sensitivity. The British Journal of Psychiatry, 133(5), 429-435.

⁸⁾ Paterniti, S., & Bisserbe, J. C. (2018). Factors associated with false positives in MDQ screening for bipolar disorder: Insight into the construct validity of the scale. Journal of affective disorders, 238, 79-86.

⁹⁾ Hirschfeld, R. M., Holzer, C., Calabrese, J. R., Weissman, M., Reed, M., Davies, M., ... & Tierce, J. (2003). Validity of the mood disorder questionnaire: a general population study. American Journal of Psychiatry, 160(1), 178-180.

¹⁰⁾ Hirschfeld, R. M., Williams, J. B., Spitzer, R. L., Calabrese, J. R., Flynn, L., Keck Jr, P. E., ... & Zajecka, J. (2000). Development and validation of a screening instrument for bipolar spectrum disorder: the Mood Disorder Questionnaire. American journal of psychiatry, 157(11), 1873-1875.

¹¹⁾ Paterniti, S., & Bisserbe, J. C. (2018). Factors associated with false positives in MDQ screening for bipolar disorder: Insight into the construct validity of the scale. Journal of affective disorders, 238, 79-86.

¹²⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

¹³⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

¹⁴⁾ Bellivier, F., Golmard, J. L., Rietschel, M., Schulze, T. G., Malafosse, A., Preisig, M., ... & Leboyer, M. (2003). Age at onset in bipolar I affective disorder: further evidence for three subgroups. American Journal of Psychiatry, 160(5), 999-1001.

¹⁵⁾ Yatham, L. N., Kennedy, S. H., Parikh, S. V., Schaffer, A., Bond, D. J., Frey, B. N., ... & Berk, M. (2018). 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 disorders, 20(2), 97-170.

¹⁶⁾ American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.

¹⁷⁾ Yatham, L. N., Kennedy, S. H., Parikh, S. V., Schaffer, A., Bond, D. J., Frey, B. N., ... & Berk, M. (2018). 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 disorders, 20(2), 97-170.

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²¹⁾ Yatham, L. N., Kennedy, S. H., Parikh, S. V., Schaffer, A., Bond, D. J., Frey, B. N., ... & Berk, M. (2018). 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 disorders, 20(2), 97-170.

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²⁴⁾ Yatham, L. N., Kennedy, S. H., Parikh, S. V., Schaffer, A., Bond, D. J., Frey, B. N., ... & Berk, M. (2018). 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 disorders, 20(2), 97-170.

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³¹⁾ Hirschfeld, R. M., Williams, J. B., Spitzer, R. L., Calabrese, J. R., Flynn, L., Keck Jr, P. E., ... & Zajecka, J. (2000). Development and validation of a screening instrument for bipolar spectrum disorder: the Mood Disorder Questionnaire. American journal of psychiatry, 157(11), 1873-1875.

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³⁴⁾ Guzman, F. Lithium’s Mechanism of Action: An Illustrated Review

³⁵⁾ Ghaemi, S. N., Dalley, S., Catania, C., & Barroilhet, S. (2014). Bipolar or borderline: a clinical overview. Acta Psychiatrica Scandinavica, 130(2), 99-108.

³⁶⁾ Goldberg, J. F., Perlis, R. H., Bowden, C. L., Thase, M. E., Miklowitz, D. J., Marangell, L. B., Calabrese, J. R., Nierenberg, A. A., & Sachs, G. S. (2009). Manic symptoms during depressive episodes in 1,380 patients with bipolar disorder: findings from the STEP-BD. The American journal of psychiatry, 166(2), 173–181.

³⁷⁾ Lish, J. D., Dime-Meenan, S., Whybrow, P. C., Price, R. A., & Hirschfeld, R. M. (1994). The National Depressive and Manic-depressive Association (DMDA) survey of bipolar members. Journal of affective disorders, 31(4), 281-294.

³⁸⁾ Yatham, L. N., Kennedy, S. H., Parikh, S. V., Schaffer, A., Bond, D. J., Frey, B. N., ... & Berk, M. (2018). 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 disorders, 20(2), 97-170.

³⁹⁾ Prabhakar, D., & Balon, R. (2010). Late-onset bipolar disorder: a case for careful appraisal. Psychiatry (Edgmont), 7(1), 34.

⁴⁰⁾ Carlino, A. R., Stinnett, J. L., & Kim, D. R. (2013). New onset of bipolar disorder in late life. Psychosomatics, 54(1), 94-97.

⁴¹⁾ Sajatovic, M., & Chen, P. (2011). Geriatric bipolar disorder. Psychiatric Clinics, 34(2), 319-333.

⁴²⁾ Balance Investigators. (2010). Lithium plus valproate combination therapy versus monotherapy for relapse prevention in bipolar I disorder (BALANCE): a randomised open-label trial. The Lancet, 375(9712), 385-395.

⁴³⁾ Smith, E. G., Austin, K. L., Kim, H. M., Eisen, S. V., Kilbourne, A. M., Miller, D. R., ... & Valenstein, M. (2015). Mortality associated with lithium and valproate treatment of US Veterans Health Administration patients with mental disorders. The British Journal of Psychiatry, 207(1), 55-63.

⁴⁴⁾ Yatham, Lakshmi N., et al. "Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013." Bipolar disorders 15.1 (2013): 1-44.

⁴⁵⁾ Lähteenvuo, M., Tanskanen, A., Taipale, H., Hoti, F., Vattulainen, P., Vieta, E., & Tiihonen, J. (2018). Real-world effectiveness of pharmacologic treatments for the prevention of rehospitalization in a Finnish nationwide cohort of patients with bipolar disorder. JAMA psychiatry.

⁴⁶⁾ Woods, S. W. (2000). The economic burden of bipolar disease. The Journal of clinical psychiatry.

⁴⁷⁾ Yatham, L. N., Kennedy, S. H., Parikh, S. V., Schaffer, A., Bond, D. J., Frey, B. N., ... & Berk, M. (2018). 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 disorders, 20(2), 97-170.

⁴⁸⁾ Muneer, A. (2015). Pharmacotherapy of bipolar disorder with quetiapine: a recent literature review and an update. Clinical Psychopharmacology and Neuroscience, 13(1), 25.

⁴⁹⁾ Yatham, L. N., Kennedy, S. H., Parikh, S. V., Schaffer, A., Bond, D. J., Frey, B. N., ... & Berk, M. (2018). 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 disorders, 20(2), 97-170.

⁵⁰⁾ Yatham, L. N., Kennedy, S. H., Parikh, S. V., Schaffer, A., Bond, D. J., Frey, B. N., ... & Berk, M. (2018). 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 disorders, 20(2), 97-170.

⁵¹⁾ Yatham, L. N., Kennedy, S. H., Parikh, S. V., Schaffer, A., Bond, D. J., Frey, B. N., ... & Berk, M. (2018). 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 disorders, 20(2), 97-170.

⁵²⁾ Sachs, G. S., Nierenberg, A. A., Calabrese, J. R., Marangell, L. B., Wisniewski, S. R., Gyulai, L., ... & Ketter, T. A. (2007). Effectiveness of adjunctive antidepressant treatment for bipolar depression. New England Journal of Medicine, 356(17), 1711-1722.

⁵³⁾ Ghaemi, S. N., Whitham, E. A., Vohringer, P. A., Barroilhet, S. A., Amerio, A., Sverdlov, O., & Patkar, A. A. (2021). Citalopram for Acute and Preventive Efficacy in Bipolar Depression (CAPE-BD): a randomized, double-blind, placebo-controlled trial. The Journal of Clinical Psychiatry, 82(1), 0-0.

⁵⁴⁾ Yatham, L. N., Kennedy, S. H., Parikh, S. V., Schaffer, A., Bond, D. J., Frey, B. N., ... & Berk, M. (2018). 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 disorders, 20(2), 97-170.

⁵⁵⁾ Yatham, L. N., Kennedy, S. H., Parikh, S. V., Schaffer, A., Bond, D. J., Frey, B. N., ... & Berk, M. (2018). 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 disorders, 20(2), 97-170.

⁵⁶⁾ Mehrpooya, M., Yasrebifar, F., Haghighi, M., Mohammadi, Y., & Jahangard, L. (2018). Evaluating the Effect of Coenzyme Q10 Augmentation on Treatment of Bipolar Depression: A Double-Blind Controlled Clinical Trial. Journal of clinical psychopharmacology, 38(5), 460-466.

For Women of Childbearing Age...

Contraceptive counselling and medication risks must be included as part of the comprehensive treatment plan for bipolar disorder. This is for two reasons:

Contraception efficacy: many of the treatments used in bipolar disorder, especially anticonvulsants (such as carbamazepine, topiramate, and lamotrigine) can significantly reduce the effectiveness of oral contraceptives (OCPs), and increase the risk for unintended pregnancy. On the flipside, OCPs can also reduce the efficacy of medications like lamotrigine.
Teratogenicity: valproate products (valproic acid, divalproex) have high teratogenic potential and also increase the risk for developmental disorders in infants exposed to valproate in utero. Thus, women on valproate products should be on contraception, and informed about the risks of using valproate during pregnancy. Additionally, individuals wishing to become pregnant should work with their clinician to switch off from valproate.

See also main article: Obstetric and Fetal Pharmacology

Hypomania

Since hypomania by definition means an individual is not hospitalized, it causes no to minimal functional impairment and may even be associated with “better-than-normal” function.
- Thus, treatment should only be considered when the symptoms are frequent, severe, or significantly impairing. Common treatments include medications used in bipolar I disorder, such as lithium, divalproex, and/or atypical antipsychotics.

Maintenance

Pharmacological Treatments for Maintenance Therapy in Bipolar II (Not Bipolar I!) Disorder

Adapted from: Yatham, L. et al. (2018). 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 disorders, 20(2), 97–170.

1st line	Monotherapy: quetiapine, lithium, lamotrigine
2nd line	Monotherapy: venlafaxine
3rd line	Monotherapy: carbamazepine, divalproex, escitalopram, fluoxetine, other antidepressants, risperidone*

Li = lithium, DVP = divalproex, * = Use of risperidone is mainly for prevention of hypomania

Depression

Pharmacological Treatments for Bipolar II (Not Bipolar I!) Depression

Adapted from: Yatham, L. et al. (2018). 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 disorders, 20(2), 97–170.

1st line	Monotherapy: quetiapine
2nd line	Monotherapy: lithium, lamotrigine, sertraline, venlafaxine, ECT Adjunctive therapy: bupropion
3rd line	Monotherapy: divalproex, fluoxetine^a, tranylcypromine, ziprasidone^b Adjunctive therapy: agomelatine, bupropion, eicosapentaenoic acid (EPA), ketamine (IV or sublingual), N-acetylcysteine, pramipexole, T3/T4 thyroid hormones
Not recommended	Paroxetine

Li = lithium, DVP = divalproex, a = For patients with pure depression (non-mixed), b = For patients with depression and mixed hypomania

Should Antidepressants Be Used in Bipolar II Depression?

Similar to the concerns about the use of antidepressants in Bipolar I depression, there is also controversy about the use of antidepressants in Bipolar II depression. The most recent recommendations from the Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines suggest that antidepressant only be used for Bipolar II patients that present with a pure depressive syndrome, and be avoided in those who present with mixed symptoms, or have a history of antidepressant-induced hypomania. Additionally, the patient should be warned to monitor for early warning signs of hypomania.

No evidence exists for specific psychosocial interventions in acute mania. However, after treatment of mania, adding psychosocial interventions in addition to medication treatment is very important.
- In fact, on average, adjunctive psychosocial interventions reduce recurrence rates by about 15%.^[2]
Psychosocial interventions can decrease relapse rates, mood fluctuations, need for medications, hospitalizations, and increase functioning and medication adherence.
Psychoeducation is a first-line treatment in maintenance therapy, and includes providing information about the course of illness, treatments, and coping strategies for both the patient and the family. Psychoeducation can also be delivered in individual or group settings.^[3]

Adjunctive Psychological Treatments in Bipolar Disorder

Adapted from: Yatham, L. et al (2018). 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 disorders, 20(2), 97-170.

	Mania	Maintenance	Bipolar Depression
1st line	None	• Psychoeducation (PE)	None
2nd line	None	• Cognitive behavioural therapy (CBT) • Family-focused therapy (FFT)	• Cognitive behavioural therapy (CBT) • Family-focused therapy (FFT)
3rd line	None	• Interpersonal and social rhythm therapy (IPSRT) • Peer support	• Interpersonal and social rhythm therapy (IPSRT)
Insufficient evidence	None	Cognitive and functional remediation, dialectical behavioural therapy (DBT), family/caregiver interventions, mindfulness‐based cognitive therapy (MBCT), online interventions	Psychoeducation, cognitive and functional remediation, dialectical behavioural therapy (DBT), family/caregiver interventions, mindfulness‐based cognitive therapy (MBCT), online interventions

See also: Parker, G. B., Graham, R. K., & Tavella, G. (2017). Is there consensus across international evidence‐based guidelines for the management of bipolar disorder?. Acta Psychiatrica Scandinavica, 135(6), 515-526.

Bipolar Disorder Guidelines

Guideline	Location	Year	PDF	Website
Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD)	Canada, International	2018	PDF	Link
American Psychiatric Association (APA)	USA	2002	PDF	• Guideline (2002) • Guideline Watch (2005) • Quick Reference
National Institute for Health and Care Excellence (NICE)	UK	2014	PDF	Link
British Association for Psychopharmacology (BAP)	UK	2016	PDF	Link
Royal Australian and New Zealand College of Psychiatrists (RANZCP)	AUS, NZ	2015	PDF	Link

¹⁾ Yatham, L. N., Kennedy, S. H., Parikh, S. V., Schaffer, A., Bond, D. J., Frey, B. N., ... & Berk, M. (2018). 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 disorders, 20(2), 97-170.

²⁾ Yatham, L. N., Kennedy, S. H., Parikh, S. V., Schaffer, A., Bond, D. J., Frey, B. N., ... & Berk, M. (2018). 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 disorders, 20(2), 97-170.

³⁾ Yatham, L. N., Kennedy, S. H., Parikh, S. V., Schaffer, A., Bond, D. J., Frey, B. N., ... & Berk, M. (2018). 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 disorders, 20(2), 97-170.

Bipolar II Disorder

Table of Contents

Primer

Epidemiology

Prognosis

Comorbidity

Risk Factors

DSM-5 Diagnostic Criteria

Criterion A

Criterion B

Criterion C

Criterion D

Hypomanic Episode Criteria

Criterion A

Criterion B

Mnemonic

Criterion C

Criterion D

Criterion E

Criterion F

What If There is an Antidepressant-induced Hypomania?

Specifiers

Episode Specifier

Severity Specifier

Remission Specifier

With anxious distress

With mixed features

With rapid cycling

With melancholic features

With atypical features

With psychotic features

With catatonia

With peripartum onset

With seasonal pattern

Screening and Rating Scales

Psychometric Scales for Bipolar Disorder

Differential Diagnosis

Bipolar I versus Bipolar II

Table of Contents

Primer

Epidemiology

Prognosis

Comorbidity

Risk Factors

Relative Risk Factors in Bipolar Disorder

DSM-5 Diagnostic Criteria

Criterion A

Criterion B

Manic Episode Criteria

Criterion A

Criterion B

Mnemonic

Criterion C

Criterion D

What If There Is A Medication-induced Mania?

Specifiers

Episode Specifier

Severity Specifier

Remission Specifier

With anxious distress

With mixed features

With rapid cycling

With melancholic features

With atypical features

With psychotic features

With catatonia

With peripartum onset

With seasonal pattern

Pediatric Bipolar

Screening and Rating Scales

Psychometric Scales for Bipolar Disorder

Pathophysiology

Genetics

Neuroimaging

Differential Diagnosis

Bipolar I vs. Bipolar II

Comparison of Bipolar I vs. Bipolar II

Mixed Features: Mania and Hypomania Symptoms Can Also Occur During Depressive Episodes!

Bipolar vs. Depression

Features of Depression that May Increase Suspicion of a Bipolar vs Unipolar Illness