What are the diagnostic criteria and treatment options for bipolar disorder?

Bipolar Disorder Diagnostic Criteria and Treatment

Diagnostic Criteria

Bipolar disorder is diagnosed based on DSM-IV-TR criteria requiring distinct episodes of mania or hypomania with specific duration requirements: manic episodes must last at least 7 days (or any duration if hospitalization is required), while hypomanic episodes must last at least 4 days. 1, 2

Bipolar I Disorder

• Requires at least one manic or mixed episode lasting ≥7 days, representing a marked departure from baseline functioning 2
• Depressive episodes are not required for diagnosis, though most patients experience them during their lifetime 2
• A manic episode involves abnormally and persistently elevated, expansive, or irritable mood with increased energy/activity, decreased need for sleep without fatigue, racing thoughts, pressured speech, grandiosity, and excessive involvement in pleasurable activities with high potential for harmful consequences 2

Bipolar II Disorder

• Requires periods of major depression and hypomania (≥4 days duration) with no history of full manic or mixed episodes 2
• Hypomanic episodes have similar symptoms to mania but are less severe, do not cause marked impairment in functioning, and do not require hospitalization 2

Mixed Episodes

• A period lasting ≥7 days where symptoms for both manic and depressive episodes are met simultaneously, involving both elevated mood/increased energy and depressive symptoms occurring together 2

Bipolar Disorder NOS

• Used for youths with manic symptoms lasting hours to <4 days, or those with chronic manic-like symptoms representing their baseline functioning 1
• These patients are significantly impaired but do not meet full duration criteria for bipolar I or II 1

Key Diagnostic Features

Essential Assessment Elements

• Look for distinct, spontaneous periods of mood changes associated with sleep disturbances and psychomotor activation 1
• Obtain histories of depression and family histories of mood disorders 1
• Manic grandiosity and irritability must present as marked changes in mental/emotional state rather than reactions to situations, temperamental traits, or anger outbursts 1
• The illness must be evident and impairing in different realms of life, not isolated to one setting 1

Duration and Pattern Recognition

• Use a life chart to characterize the course of illness, patterns of episodes, severity, and treatment response—this longitudinal perspective is critical because acute phase symptoms are often confused with other disorders 1
• Changes in energy, activity, and sleep patterns should be assessed in addition to mood symptoms 2
• A longitudinal history, rather than solely cross-sectional assessment, is necessary for accurate diagnosis 2

Special Considerations in Youth

• Children and adolescents may present differently than adults, with more irritability, mixed states, and rapid cycling 2
• DSM-IV-TR criteria, including duration criteria, should be followed when diagnosing mania or hypomania in children and adolescents 1
• Manic-like symptoms of irritability and emotional reactivity may be found in disruptive behavior disorders, PTSD, and pervasive developmental disorders—distinguish these from true bipolar disorder 1
• Changes in mood, energy, and behavior in juvenile bipolar disorder are often more labile and erratic rather than persistent, with high rates of comorbidity, especially with ADHD and disruptive behavior disorders 2

Comorbidity Assessment

• Youths with suspected bipolar disorder must be carefully evaluated for suicidality, comorbid disorders (including substance abuse), psychosocial stressors, and medical problems 1

Treatment Options

First-Line Pharmacotherapy

First-line therapy includes mood stabilizers (lithium, valproate, lamotrigine) and atypical antipsychotics (quetiapine, aripiprazole, asenapine, lurasidone, cariprazine). 3

Mood Stabilizers

• Lithium, valproate, and lamotrigine are recommended for long-term treatment 3
• Carbamazepine is also an option for mood stabilization 4
• Bipolar I depressions should initially be treated with a mood stabilizer; antidepressant monotherapy is contraindicated 4

Atypical Antipsychotics

• Quetiapine, aripiprazole, asenapine, lurasidone, and cariprazine are recommended 3
• Some are associated with weight gain, which is an important consideration 3
• Olanzapine (5-20 mg/day) is FDA-approved for acute manic or mixed episodes in adults and adolescents (ages 13-17), with efficacy established in multiple controlled trials 5
• Olanzapine combined with lithium or valproate is superior to lithium or valproate alone for inadequately controlled manic or mixed symptoms 5

Acute Episode Management

Manic Episodes in Adults

• Start olanzapine at 5-10 mg once daily orally, with target of 10 mg/day within several days 5
• Alternative: start at 10 or 15 mg once daily 5
• For adjunct therapy with lithium or valproate, start olanzapine at 10 mg once daily 5

Manic Episodes in Adolescents

• Start olanzapine at 2.5-5 mg once daily, with target of 10 mg/day 5
• Efficacy established in a 3-week trial with flexible dosing 2.5-20 mg/day (mean modal dose 10.7 mg/day) 5

Acute Agitation

• Intramuscular olanzapine 10 mg (5 mg or 7.5 mg when clinically warranted) for agitation associated with schizophrenia and bipolar I mania 5
• Assess for orthostatic hypotension prior to subsequent dosing (maximum 3 doses 2-4 hours apart) 5

Depressive Episodes

For bipolar depression, start with a mood stabilizer; more severe or "breakthrough" episodes often require a concomitant antidepressant such as bupropion or an SSRI. 4

Combination Therapy for Bipolar Depression

• The first FDA-approved treatment specifically for bipolar depression is olanzapine combined with fluoxetine 4
• In adults: start at 5 mg olanzapine with 20 mg fluoxetine once daily 5
• In children and adolescents: start at 2.5 mg olanzapine with 20 mg fluoxetine once daily 5
• Olanzapine monotherapy is not indicated for depressive episodes associated with bipolar I disorder 5

Refractory Depression

• For refractory depressive episodes, venlafaxine, tranylcypromine (MAOI), and ECT are most widely recommended 4

Maintenance Treatment

• Responding patients should be continued beyond acute response at the lowest dose needed to maintain remission, with periodic reassessment to determine need for maintenance treatment 5
• Maintenance efficacy in adolescents can be extrapolated from adult data along with pharmacokinetic comparisons 5
• The optimal duration of maintenance antidepressant therapy has not been established empirically and should be determined case-by-case 4

Treatment Considerations

Dosing Adjustments

• Lower starting doses are recommended in debilitated or pharmacodynamically sensitive patients, those with predisposition to hypotensive reactions, or with potential for slowed metabolism 5
• Olanzapine may be given without regard to meals 5
• When using olanzapine with fluoxetine, dosage adjustments should be made with individual components according to efficacy and tolerability 5

Common Pitfalls

• Antidepressants are not recommended as monotherapy for bipolar disorder 3
• More than 50% of patients with bipolar disorder are not adherent to treatment 3
• Diagnosis and optimal treatment are often delayed by a mean of approximately 9 years following an initial depressive episode 3
• Misdiagnosis as major depressive disorder delays initiation of appropriate therapy and worsens prognosis 4

Monitoring Requirements

• Monitor for metabolic syndrome (37% prevalence), obesity (21%), and type 2 diabetes (14%) in patients with bipolar disorder 3
• Assess suicide risk continually—annual suicide rate is approximately 0.9% in bipolar disorder versus 0.014% in general population 3
• Mood symptoms, psychosocial functioning, and suicide risk must be continually reevaluated, with treatment plan adjustments as necessary 6