What is the role of Latuda (lurasidone) in targeting hypomanic or manic episodes in bipolar disorder?

Lurasidone (Latuda) Is Not Indicated for Hypomanic or Manic Episodes in Bipolar Disorder

Lurasidone (Latuda) is not indicated for the treatment of hypomanic or manic episodes in bipolar disorder and should not be used for this purpose. 1, 2, 3

Approved Indications for Lurasidone in Bipolar Disorder

• Lurasidone is FDA-approved specifically for the treatment of bipolar depression, not for manic or hypomanic episodes 4, 5
• The mechanism of action of lurasidone in bipolar depression is unclear but likely involves dopamine D2 and serotonin 5-HT2A receptor antagonism 3
• Clinical trials have demonstrated lurasidone's efficacy in treating depressive episodes in bipolar I disorder, but not in treating manic or hypomanic states 4, 5

First-Line Treatments for Manic/Hypomanic Episodes

• For acute mania/mixed episodes, the American Academy of Child and Adolescent Psychiatry recommends lithium, valproate, or atypical antipsychotics such as aripiprazole, olanzapine, risperidone, quetiapine, and ziprasidone 1, 2
• Combination therapy with lithium or valproate plus an atypical antipsychotic is considered for severe manic presentations 1
• Lithium is FDA-approved for both acute mania and maintenance therapy in patients age 12 and older 1

Clinical Evidence for Lurasidone in Mixed Features

• A post-hoc analysis of clinical trials showed that lurasidone was effective in treating bipolar depression with mixed (subsyndromal hypomanic) features 4
• However, this evidence only supports lurasidone's use in predominantly depressive episodes with some hypomanic symptoms, not for primary hypomanic or manic episodes 4
• The study defined mixed features as patients with bipolar depression who had a Young Mania Rating Scale (YMRS) score ≥4 but ≤12 (still below the threshold for hypomania) 4

Pharmacological Properties of Lurasidone

• Lurasidone is an antagonist with high affinity binding at dopamine D2 receptors and serotonin 5-HT2A and 5-HT7 receptors 3
• It also has partial agonist activity at serotonin 5-HT1A receptors, which may contribute to its antidepressant effects 3, 5
• These pharmacological properties make lurasidone suitable for bipolar depression but not specifically targeted for treating manic symptoms 5, 6

Safety Considerations

• Using medications outside their approved indications may lead to suboptimal outcomes and unnecessary side effects 1, 3
• Common side effects of lurasidone include akathisia, extrapyramidal symptoms, and somnolence 7, 8
• Lurasidone has a favorable metabolic profile compared to other atypical antipsychotics, with minimal weight gain and metabolic disturbances 5, 7

Clinical Implications and Recommendations

• For patients experiencing hypomanic or manic episodes, clinicians should select from FDA-approved treatments such as lithium, valproate, or atypical antipsychotics specifically approved for mania 1, 2
• If a patient with bipolar disorder is currently stable on lurasidone for depression management and develops hypomanic or manic symptoms, consider adding or switching to a mood stabilizer or antipsychotic approved for mania 1
• For patients with bipolar depression who have some subsyndromal hypomanic symptoms (mixed features), lurasidone may be appropriate 4

Common Pitfalls to Avoid

• Using medications outside their FDA-approved indications without strong evidence can lead to treatment failure and unnecessary side effects 1, 3
• Misdiagnosing bipolar depression with some mixed features as a full hypomanic or manic episode could lead to inappropriate treatment selection 4
• Inadequate treatment of manic episodes with medications not proven effective for mania can lead to prolonged episodes and poorer outcomes 1