From the Guidelines
SSRIs are not recommended as monotherapy in patients with bipolar disorder because they can trigger manic episodes or rapid cycling between mood states. When a person with bipolar disorder takes an SSRI without a mood stabilizer, the antidepressant effect can push them from depression into mania or hypomania, worsening their overall illness course, as noted in the practice parameter for the assessment and treatment of children and adolescents with bipolar disorder 1. This risk is particularly high in bipolar I disorder. The use of SSRIs in bipolar disorder is further complicated by the potential for destabilizing the patient’s mood or inciting a manic episode, which may represent the unmasking of the disorder or disinhibition secondary to the agent 1.
Key Considerations
- If antidepressant treatment is necessary for bipolar depression, SSRIs should only be used in conjunction with mood stabilizers such as lithium, valproate, or atypical antipsychotics like quetiapine or lurasidone.
- Even with mood stabilizer coverage, SSRI treatment should be time-limited (typically 8-12 weeks) and discontinued after the depressive episode resolves to minimize long-term risks.
- First-line treatments for bipolar depression should focus on mood stabilizers with antidepressant properties or approved antipsychotics rather than traditional antidepressants, due to the fundamental neurochemical imbalances in bipolar disorder that differ from those in unipolar depression.
- Clinicians should be aware of the concerns regarding the efficacy and safety (including suicidality) of antidepressants in youths, as highlighted in the study by Vitiello and Swedo (2004), referenced in 1.
Treatment Approach
- The combination of olanzapine and fluoxetine is approved for bipolar depression in adults, but this should not imply that SSRIs are safe or effective as monotherapy in bipolar disorder 1.
- Mood stabilizers and antipsychotic agents are commonly used for early-onset bipolar disorder in clinical settings, although none of the agents has been well studied in juveniles, emphasizing the need for cautious and evidence-based treatment decisions 1.
From the Research
Reasons for Not Recommending SSRIs in Patients with Bipolar Disorder
- SSRIs can induce mania in patients with bipolar disorder, especially those with a personal or family history of hypomania or mania 2
- The risk of treatment-emergent mania with SSRIs is not trivial, particularly among patients at risk for bipolar disorder 2
- SSRIs are not recommended as monotherapies for the treatment of bipolar depression, and their use can lead to incorrect treatment and poor outcomes 3
- Other treatments, such as olanzapine/fluoxetine combination, quetiapine, and lurasidone, have been approved for the treatment of bipolar depression and have similar efficacy profiles, but differ in terms of tolerability 3
Alternative Treatment Options
- Olanzapine + fluoxetine, olanzapine, quetiapine, lurasidone, valproate, and lithium are recommended for the treatment of bipolar depression 4, 3
- Valproate may be more effective as an antimanic rather than prophylactic agent, and may be a better choice in patients with many previous affective episodes/hospitalizations and psychiatric comorbidities 5
- Lithium may be effective in treating acute mania, and its efficacy is maximized when used to prevent both manic and depressive episodes 5
Important Considerations
- Individualizing treatment decisions requires consideration of the different potential adverse events that are more likely to occur with each medication 3
- The metric of the likelihood to be helped or harmed (LHH) can illustrate the tradeoffs inherent in selecting medications 3
- Valproate has been found to be superior to placebo in preventing new illness episodes, and its protective effects are similar to those of lithium and antipsychotics 6