Bipolar II Disorder

Bipolar II disorder is a mood disorder characterized by the alternation of at least one major depressive episode and at least one hypomanic episode, in the absence of any manic episodes. It is considered a less “flamboyant” form compared to bipolar I disorder, but not less severe: subjective suffering and long-term functional impact can be even greater due to the greater duration and frequency of depressive phases.

Often overlooked or diagnosed late, bipolar II disorder falls within the bipolar spectrum and is distinct from cyclothymia due to the severity and duration of the episodes. Diagnosis requires careful clinical and differential evaluation, as the hypomanic episode may be mistaken for a moment of well-being or high functioning.

Etiology and Risk Factors

The etiology of bipolar II disorder is multifactorial and, in many respects, overlaps with that of bipolar I disorder, with some specific features:

• Genetic factors: family history is a major factor, with strong familial aggregation of mood disorders. Twin studies suggest a heritability of about 70%.
• Neurotransmitter alterations: fluctuations in serotonin, dopamine, and norepinephrine levels are implicated in both depressive and hypomanic phases.
• Circadian rhythm dysregulation: alterations in the sleep-wake cycle have been shown to trigger both hypomanic and depressive episodes.
• Neuroinflammation and neuroplasticity: there is evidence of neuroanatomical changes (such as reduced amygdala volume and alterations in the prefrontal cortex) and BDNF disturbances, similar to what is observed in major depressive disorders.

Major risk factors for the development of bipolar II disorder include:

• Family history of bipolar disorder, especially type II or mood disorders with cyclicity
• Early onset of depression, particularly during adolescence
• Recurrent major depressive disorder not responsive to antidepressant therapy
• Use of antidepressants without mood stabilizers, which may trigger a hypomanic episode in predisposed individuals
• History of sleep disorders, substance abuse, or chronic stressful events

Diagnosis is often delayed because the hypomanic episode is not recognized as pathological by either the patient or relatives, being mistaken for a "good" or particularly productive phase.

Clinical Manifestations and Diagnosis

Bipolar II disorder clinically presents with alternating major depressive episodes and hypomanic episodes. The absence of manic episodes clearly distinguishes this condition from bipolar I disorder.

The major depressive episode shows the characteristics described in the dedicated section (see here): depressed mood, anhedonia, sleep and appetite disturbances, suicidal ideation, psychomotor retardation or agitation, guilt, etc. These episodes represent the most disabling and frequent component in the course of the disorder.

According to the DSM-5, the diagnosis of Bipolar II Disorder requires at least one major depressive episode and at least one hypomanic episode, with a complete absence of manic episodes.

The diagnostic criteria are as follows:

• Presence of at least one major depressive episode: the criteria for a major depressive episode must be met, lasting at least two weeks and having a significant impact on functioning.
• Presence of at least one hypomanic episode: the criteria for a hypomanic episode must be met, lasting at least four days, with symptoms similar to those of a manic episode but milder and without marked impairment.
• Absence of manic episodes: there must never have been a manic episode during the patient's lifetime. If one occurs, the diagnosis becomes Bipolar I Disorder.
• Exclusion of other causes: symptoms must not be due to the effects of substances (e.g., drugs or medications) or general medical conditions.
• Functional impact: the depressive episode or the alternation of the two episodes must cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

The diagnosis can only be made retrospectively, once the hypomanic episode is identified after evaluating the clinical course. An initial misdiagnosis of major depressive disorder is common.

Useful tools include structured interviews (SCID), screening questionnaires (MDQ), and thorough anamnesis involving family members.

Treatment, Prognosis, and Complications

The treatment of bipolar II disorder must be continuous, personalized, and aimed at both managing acute episodes and preventing relapses.

• Mood stabilizers: lithium is the first-line drug, effective in preventing both depressive and hypomanic relapses. Other options include lamotrigine (especially effective for preventing depression), valproate, and carbamazepine.
• Atypical antipsychotics: especially quetiapine and lurasidone for depressive phases. Olanzapine may be used for refractory hypomania.
• Antidepressants: should be avoided as monotherapy. If used, they must always be combined with a mood stabilizer to prevent hypomanic switching.
• Psychotherapy: psychoeducation, cognitive-behavioral therapy, and family interventions are essential.

Prognosis is variable but often underestimated. Depressive episodes tend to be more frequent, prolonged, and severe than hypomanic ones. The disorder has a significant impact on quality of life, with high rates of:

• Hospitalizations
• Suicidal ideation and behavior
• Psychiatric comorbidities (anxiety disorders, substance use disorders)

Therapeutic adherence, early diagnosis, and psychoeducational support are crucial factors for reducing relapse risk and improving global functioning.

Main complications of bipolar II disorder include:

• High suicide risk: comparable or even higher than in bipolar I disorder, especially during depressive phases
• Delayed or incorrect diagnosis: leading to inappropriate treatment
• Medical comorbidities: obesity, metabolic, and cardiovascular disorders
• Relational and professional crises
• Progression to more severe forms of bipolar disorder if untreated

References
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