What is the risk of hypomania in a patient with bipolar type II disorder taking an antidepressant (AD) only?

From the Guidelines

Patients with bipolar II disorder should not be treated with antidepressant monotherapy due to the significant risk of hypomania. The use of antidepressants alone in bipolar II disorder can trigger a switch from depression to an elevated mood state, leading to hypomania 1. Instead, the recommended first-line treatment for bipolar II depression is typically a mood stabilizer, such as lithium, lamotrigine, or valproic acid, either alone or in combination with an antidepressant. Some key points to consider when treating bipolar II disorder include:

• If an antidepressant is necessary, it should always be used in conjunction with a mood stabilizer to minimize the risk of hypomania.
• Common antidepressants used include SSRIs like fluoxetine or sertraline, or SNRIs like venlafaxine, which should be started at a low dose and titrated slowly while monitoring for signs of hypomania.
• Clinicians should educate patients about the signs of hypomania, such as decreased need for sleep, increased goal-directed activity, or racing thoughts, and instruct them to contact their healthcare provider immediately if these symptoms occur.
• The risk of antidepressant-induced hypomania in bipolar II disorder is due to the medication's potential to trigger a switch from depression to an elevated mood state, which is inherent to the nature of bipolar disorder, where mood regulation is already impaired 1. Key considerations for treatment include:
• Mood stabilizers help to prevent this switch by dampening the excessive neuronal excitability associated with manic and hypomanic episodes.
• The combination of olanzapine and fluoxetine is approved for bipolar depression in adults, but this should not be taken to imply that antidepressants can be used alone in bipolar II disorder.
• Other agents with some support for efficacy in adult studies include carbamazepine and antipsychotic agents, but these should be used with caution and under close monitoring for signs of hypomania or other adverse effects 1.

From the FDA Drug Label

It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric

The risk of hypomania in a patient with bipolar type II disorder taking an antidepressant (AD) only is not directly quantified in the provided drug labels. However, it is mentioned that treating a major depressive episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder 2, 3, 4.

• Hypomania and mania have been reported in patients being treated with antidepressants.
• It is recommended to adequately screen patients for bipolar disorder before initiating treatment with an antidepressant. Given the information available, it is recommended to exercise caution when prescribing antidepressants to patients with bipolar type II disorder, and to consider the potential risk of inducing a hypomanic or manic episode.

From the Research

Risk of Hypomania in Bipolar Type II Disorder

The risk of hypomania in a patient with bipolar type II disorder taking an antidepressant (AD) only is a significant concern. According to 5, switches to hypomania or mania occurred in 27% of all patients, with 11% experiencing hypomanic episodes.

Factors Influencing the Risk of Hypomania

Several factors can influence the risk of hypomania in patients with bipolar type II disorder, including:

• The use of antidepressants, which can increase the risk of switching to hypomania or mania 5
• The presence of a hyperthymic temperament, which is associated with a greater risk of mood switches 5
• The type of antidepressant used, with selective serotonin reuptake inhibitors (SSRIs) potentially increasing the risk of switching 5

Treatment Considerations

When treating patients with bipolar type II disorder, it is essential to consider the potential risks and benefits of different treatments. According to 6, naturalistic studies have found antidepressants to be as effective as in unipolar depression, but a recent large controlled study found antidepressants to be no more effective than placebo. Additionally, results from naturalistic studies and clinical observations suggest that antidepressants may worsen concurrent intradepression hypomanic symptoms.

Alternative Treatment Options

Alternative treatment options, such as mood stabilizers, may be more effective in preventing relapse of mood episodes. According to 7, lithium and lamotrigine may have efficacy in preventing relapse of mood episodes, and hypomania will likely respond to monotherapy with antimanic agents.

Key Points

Key points to consider when treating patients with bipolar type II disorder include:

• The potential risks of antidepressant-induced hypomania or mania
• The importance of careful diagnosis and monitoring
• The potential benefits of alternative treatment options, such as mood stabilizers
• The need for individualized treatment plans that take into account the patient's specific needs and risk factors 6, 8, 7, 5, 9