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.


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.

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 (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 (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 an antidepressant-induced mania?

A full manic 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 manic episode and, therefore, a bipolar I diagnosis.


The mnemonic DIG FAST can be used to remember the criteria for bipolar I and II disorder.[2]

  • D Distractability
  • I Indiscretion
  • G Grandiosity
  • F Flight of Ideas
  • A Activity increased
  • S Sleep decreased
  • T Talkativeness

Episode specifiers


  • 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 specifiers


  • With psychotic features
  • In partial remission
  • In full remission
  • Unspecified

Additional specifiers

Specify if:

  • With anxious distress
  • With mixed features
  • With rapid cycling
  • With melancholic features
  • With atypical features
  • With mood-congruent psychotic features
  • With mood-incongruent psychotic features
  • With catatonia
  • With peripartum onset
  • With seasonal pattern

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


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 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.[3] Takes 15–30 minutes to complete. YMRS 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.[4]

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.[5] 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).[6]


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.[7]

General Treatment Principles

Lithium remains the gold-standard for treatment in all phases of bipolar I.[8] 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.

First-line treatment for various phases of bipolar disorder

Mania Lithium, antipsychotics (olanzapine, quetiapine)
Maintenance Lithium, valproic acid, lamotrigine
Depression Lithium, lurasidone
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 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
Remember the “Ls” for bipolar depression: Lithium, Lurasidone, Lamotrigine

Acute Bipolar I Depression

1st line Monotherapy: lithium, lamotrigine, quetiapine, quetiapine XR, lurasidone[9]

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.[10]