Escitalopram Should Not Be Given to Patients with Bipolar 2 Disorder
Escitalopram (Lexapro) is contraindicated in patients with bipolar 2 disorder due to the significant risk of precipitating a mixed/manic episode. 1 This recommendation is based on strong evidence from FDA labeling and clinical guidelines.
Risks of SSRIs in Bipolar Disorder
Risk of Mood Switching
- The FDA label for escitalopram explicitly warns that in patients with bipolar disorder, treating a depressive episode with escitalopram or another antidepressant may precipitate a mixed/manic episode 1
- In placebo-controlled trials, activation of mania/hypomania was reported in 0.1% of patients treated with escitalopram 1
- Treatment with SSRIs should be avoided in patients with a history of bipolar depression due to the risk of mania 2
- Case reports have documented that escitalopram can induce treatment-emergent mania/hypomania in a dose-related manner 3
Screening Requirements
- Prior to initiating treatment with escitalopram, patients must be screened for any personal or family history of bipolar disorder, mania, or hypomania 1
- This screening requirement further emphasizes the risk of using escitalopram in known bipolar disorder patients
Recommended Treatment Approaches for Bipolar 2 Depression
First-Line Medications
First-line therapy for bipolar depression includes:
- Mood stabilizers (lithium)
- Anticonvulsants (valproate, lamotrigine)
- Atypical antipsychotics (quetiapine, lurasidone, cariprazine) 4
Lamotrigine is particularly effective for depressive episodes in bipolar disorder and has minimal sexual and metabolic side effects 5
Treatment Algorithm
Initial treatment: Start with a mood stabilizer monotherapy
- Lithium (target serum levels 0.6-1.2 mEq/L)
- Lamotrigine (start at 25 mg/day and titrate slowly to 200 mg/day)
- Valproate (750-1500 mg/day)
If inadequate response: Consider combination therapy
- Lithium + valproate
- Lithium/valproate + lamotrigine
- Lithium/valproate + aripiprazole 5
For treatment-resistant cases: Consider adding an atypical antipsychotic with antidepressant properties
Special Considerations
Limited Role of Antidepressants
- Antidepressants are not recommended as monotherapy in bipolar disorder 4
- If an antidepressant must be used (in treatment-resistant cases), it should always be combined with a mood stabilizer to minimize switch risk
Monitoring Requirements
- Regular monitoring for signs of hypomania/mania is essential in bipolar patients
- Symptoms to watch for include:
- Decreased need for sleep
- Increased energy
- Racing thoughts
- Pressured speech
- Grandiosity
- Impulsive behavior 5
Research Evidence on Antidepressants in Bipolar 2
While some limited research suggests that certain antidepressants might be used in bipolar II depression with careful monitoring, these studies are small and the risk remains significant:
- A small open trial of adjunctive escitalopram in bipolar depression reported that 4 out of 20 patients (20%) experienced manic switch or hypomanic symptoms 6
- A study of fluoxetine monotherapy in bipolar II depression reported a low manic switch rate, but this was a small sample with limited follow-up 7
- A comparison of venlafaxine versus lithium found no significant difference in treatment-emergent hypomanic episodes, but the study was not specifically powered to detect these differences 8
Despite these limited positive findings, the strong warnings in FDA labeling and clinical guidelines outweigh these small studies, particularly when considering the priority of morbidity, mortality, and quality of life outcomes.
Conclusion
The evidence strongly supports avoiding escitalopram in patients with bipolar 2 disorder. The risk of precipitating a manic/hypomanic episode outweighs potential benefits, especially when safer and more effective alternatives are available. Treatment should focus on mood stabilizers, anticonvulsants, and certain atypical antipsychotics that have demonstrated efficacy for bipolar depression without the same risk of mood switching.