May 2019 By PsychDB.com

Bipolar I Disorder

Bipolar I Disorder is a mental disorder characterized by episodes of highly elevated mood, known as mania. Mania in the context of bipolar disorder has a very high recurrence rate (95%) if untreated.

Prevalence

The lifetime prevalence for bipolar I disorder is approximately 1%, with equal gender distribution. Men typically have more manic episodes and females have more depressive/rapid cycling episodes. The typical age of onset is at age 20. 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.[1]

Risk Factors

Patients with a diagnosis of bipolar disorder often have a history of anxiety or panic disorder in childhood. Bipolar disorder is one of the most heritable conditions. Most of the studies put the concordance rate among identical twins at 50 to 60 percent.

Misdiagnosis

Bipolar disorder is often misdiagnosed or undiagnosed. Part of the challenge is patients can present with multiple depressive episodes prior to the onset of a manic episode.[2] Patients often fail (unintentionally) to report hypomanic/manic episodes as well.

For a diagnosis of bipolar I disorder, it is necessary to meet the following criteria for a manic episode. The manic episode may have been preceded by and may be followed by hypo-manic or major depressive episodes. Criteria A-D constitute a manic episode. At least one lifetime manic episode is required for the diagnosis of bipolar I disorder.

Criterion A

A distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased goal-directed activity or energy, lasting at least 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:

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

Mnemonic

The mnemonic DIG FAST can be used to remember the criteria for bipolar I and II disorder.[3]

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

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 major 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 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.

With melancholic features

  • 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

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

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

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

With peripartum onset

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

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.

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

Comparison

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

Psychometric Scales for Bipolar Disorder

Name Young Mania Rating Scale (YMRS)
Rater Clinician
Description Most frequently utilized to assess manic symptoms. 11 items on the patient’s subjective report over the last 48 hours plus clinical observations.[4] Takes 15–30 minutes to complete.
Download YMRS Download
Name Mood Disorder Questionnaire (MDQ)
Rater Patient
Description The MDQ screens for Bipolar Spectrum Disorder, (which includes Bipolar I, Bipolar II and unspecified bipolar disorder). There are 13 self-rated questions. It has a 90% specificity and 70% sensitivity for eventual diagnosis of bipolar disorder.[5]
Download MDQ Download
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.[6] 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. It has a 90% specificity and 70% sensitivity for eventual diagnosis of bipolar disorder.[7] MDQ Download

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.[8]

Medical Etiologies

  • Neurologic
    • Dementia
    • Head injury
    • CNS tumor
    • Multiple sclerosis
    • Stroke
    • Epilepsy
    • Wilson’s disease
  • Sleep apnea
  • Vitamin B12 deficiency
  • Endocrine
    • Hypo or hyperthyroidism
    • Hypercortisolemia
  • Infectious
    • HIV
    • Syphilis
    • Lyme disease
    • Viral encephalitis
  • Toxic
    • Medications (corticosteroids, amphetamines, and other sympathomimetics, L-DOPA)
    • Other substances

Late-Life Bipolar Disorder

Patients with late-life onset of bipolar disorder are a diverse group with high rates of neurologic comorbidities. Therefore, a comprehensive assessment should be done in these patients.[9] The differential diagnosis should be broad and include cerebrovascular disease, frontotemporal dementia, epilepsy, central nervous system infections, head injuries, tumours, endocrine disorders, vitamin deficiencies, dementia, and medication side effects (corticosteroids).[10]

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.[11] Bipolar disorder also contributes to cognitive dysfunction, in particular with 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.[12][13]

  • TSH, CBC, liver function, renal function, electrolytes, calcium, folate, B12, ECH
  • Neuroimaging when there are neurological symptoms, abrupt/late onset, or presentation is different from typical episodes.

Medication

General Principles in the Pharmacological Treatment of Bipolar Disorder

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.[14][15] 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 on an antipsychotic for acute mania, they can be transitioned to a mood stabilizer for long-term management. Adherence to pharmacological treatment of bipolar I disorder remains challenging; 1 in 3 patients will be unable to adhere to treatment.[16] Any patients presenting with mania who have been taking antidepressants or stimulants should have these medications discontinued to reduce the risk of prolonging a manic episode.
In Canada, aripiprazole and lurasidone are the only antipsychotics indicated for children and adolescents with schizophrenia or bipolar disorder.

The following treatment guidelines are based on the 2013 Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) Guidelines.[17]

First-line treatment for various phases of bipolar disorder

Mania Lithium, all antipsychotics (most evidence for olanzapine, quetiapine)
Maintenance Lithium, valproic acid, lamotrigine
Depression Lithium, lurasidone, olanzapine, quetiapine
Acute Mania

Acute Mania

1st line Monotherapy: lithium, divalproex, divalproex ER (Extended-Release), olanzapine, risperidone, quetiapine, quetiapine XR, aripiprazole, ziprasidone, asenapine, paliperidone ER

Adjunctive therapy with lithium or divalproex: risperidone, quetiapine, olanzapine, aripiprazole, asenapine
2nd line Monotherapy: carbamazepine, carbamazepine ER, ECT, haloperidol

Combination therapy: lithium + divalproex
3rd line Monotherapy: chlorpromazine, clozapine, oxcarbazepine, tamoxifen, cariprazine

Combination therapy: lithium or divalproex + haloperidol, lithium + carbamazepine, adjunctive tamoxifen
Not recommended Monotherapy: gabapentin, topiramate, lamotrigine, verapamil, tiagabine

Combination therapy: risperidone + carbamazepine, olanzapine + carbamazepine
Maintenance

Maintenance Therapy

1st line Monotherapy: lithium, lamotrigine (limited efficacy in preventing mania), divalproex, olanzapinea, quetiapine, risperidone LAI, aripiprazole

Adjunctive therapy with lithium or divalproex: quetiapine, risperidone LAI, aripiprazoleb, ziprasidone
2nd line Monotherapy: carbamazepine, palideridone ER

Combination therapy: lithium + divalproex, lithium + carbamazepine, lithium or divalproex + olanzapine, lithium + risperidone, lithium + lamotrigine, olanzapine + fluoxetine
3rd line Monotherapy: asenapine

Adjunctive therapy: phenytoin, clozapine, ECT, topiramate, omega-3-fatty acids, oxcarbazepine, gabapentin, asenapine
Not recommended Monotherapy: gabapentin, topiramate, or antidepressants

Adjunctive therapy: flupenthixol
Depression
Remember the “Ls” for bipolar depression: Lithium, Lurasidone, Lamotrigine

Acute Bipolar I Depression

1st line Monotherapy: lithium, lamotrigine, quetiapine, quetiapine XR, lurasidone[18]

Combination therapy: (1) lithium or divalproex + SSRI, (2) olanzapine + SSRI, (3) lithium + divalproex, (4) lithium or divalproex + bupropion
2nd line Monotherapy: divalproex, lurasidone

Combination therapy: (1) quetiapine + SSRI, (2) adjunctive modafinil, lithium or divalproex + lamotrigine, lithium or divalproex + lurasidone
3rd line Monotherapy: carbamazepine, olanzapine, ECT

Combination therapy: lithium + carbamazepine, lithium + pramipexole, lithium or divalproex + venlafaxine, lithium + MAOI, lithium or divalproex or AAP + TCA, lithium or divalproex or carbamazepine + SSRI + lamotrigine, quetiapine + lamotrigine
Not recommended Monotherapy: gabapentin, aripiprazole, ziprasidone

Combination therapy: adjunctive ziprasidonec, adjunctive levetiracetam

Antidepressants in Bipolar Depression

The role of antidepressants in bipolar depression continues to be controversial. SSRIs (other than paroxetine) and bupropion could be used as first-line treatments in conjunction with a mood stabilizer for acute short term treatment of bipolar depression, with the goal of tapering and discontinuing the antidepressant 6–8 weeks after full remission of depression. Several other key points to consider include:
  • Tricyclic antidepressants and venlafaxine should be avoided as they are associated with an increased risk of manic switch.
  • Antidepressants should not be used to treat a current mixed episode or in patients with a history of rapid cycling.
  • Monotherapy with antidepressants is not recommended for bipolar depression.

The STEP-BD trial showed that adjunctive treatment with antidepressants does not appear to improve clinical outcomes in people with bipolar disorder taking a mood stabilizer.[19] Other more recent studies have shown that combined antidepressant plus mood stabilizer therapy may reduce new depressive episodes.[20]

Psychotherapy

Psychotherapies in combination with medications have been shown to be helpful in both in the treatment of acute depressive episodes and also as long-term maintenance treatment, including decreased relapse rates, mood fluctuations, need for medications, and hospitalizations, as well as increased functioning and medication adherence. Treatments include Interpersonal and Social Rhythm Theory (IPSRT) and Cognitive Behavioural Therapy (CBT).

ECT

Electroconvulsive Therapy (ECT) is a second line treatment for bipolar mania, and third line treatment for bipolar depression. It is well-tolerated and safe.

Nutrition

Coenzyme Q10, likely due to its antioxidant and anti-inflammatory properties, has been found to improve symptoms of bipolar depression.[21]