Can Lurasidone Induce Mania?
Yes, lurasidone can induce mania or hypomania, though this occurs in less than 1% of patients according to FDA data, and the risk appears comparable to placebo in controlled trials. 1
Evidence from FDA Drug Label
The FDA label explicitly warns that "antidepressant treatment can increase the risk of developing a manic or hypomanic episode, particularly in patients with bipolar disorder," and advises clinicians to "monitor patients for the emergence of such episodes." 1 However, in both adult bipolar depression monotherapy and adjunctive therapy studies (with lithium or valproate), less than 1% of subjects in both the lurasidone and placebo groups developed manic or hypomanic episodes. 1
Case Report Evidence
Despite the low incidence in clinical trials, a documented case exists of lurasidone-induced manic switch in a male adolescent with bipolar I depression. 2 In this case:
- The patient was already on sodium valproate and olanzapine when lurasidone was added 2
- Five days after adding lurasidone, the patient became manic with psychotic features 2
- After discontinuing lurasidone, he required electroconvulsive therapy for stabilization and was switched to lithium-quetiapine combination 2
- This case highlights the potential risk in adolescents with bipolar depression 2
Clinical Context and Risk Assessment
When Lurasidone is Used Appropriately
Lurasidone is FDA-approved specifically for bipolar I depression, both as monotherapy and adjunctive to lithium or valproate. 1, 3, 4 The mechanism of action likely involves serotonin 7 receptor antagonism, which may explain its antidepressant effects. 3
Risk Mitigation Strategy
The American Academy of Child and Adolescent Psychiatry explicitly recommends against antidepressant monotherapy in bipolar disorder due to risk of mood destabilization, mania induction, and rapid cycling. 5 While lurasidone is an atypical antipsychotic rather than a traditional antidepressant, it is used to treat bipolar depression and carries the same FDA warning about activation of mania/hypomania. 1
When prescribing lurasidone for bipolar depression:
- Always combine with a mood stabilizer (lithium or valproate) rather than using as monotherapy in high-risk patients 5, 4
- Monitor closely for emergence of manic or hypomanic symptoms, particularly in the first few weeks 1
- Be especially vigilant in adolescents, where the single documented case occurred 2
- Discontinue lurasidone immediately if manic symptoms emerge 2
Comparison to Other Atypical Antipsychotics
The risk of treatment-emergent mania with lurasidone appears lower than with traditional antidepressants but is still present. 1 Other atypical antipsychotics approved for acute mania (aripiprazole, olanzapine, risperidone, quetiapine, ziprasidone) are used to treat mania rather than induce it. 5, 6
Common Pitfall to Avoid
Never assume that because lurasidone is an atypical antipsychotic it cannot trigger mania. 1, 2 The FDA boxed warning and documented case report demonstrate this risk is real, even if uncommon. The adolescent case is particularly instructive because the patient was already on two mood-stabilizing medications (valproate and olanzapine) when the manic switch occurred. 2