374. Intranasal esketamine in treatment-resistant bipolar depression maintained on long-acting aripiprazole
The International Journal of Neuropsychopharmacology September 1, 2026 DOI: 10.1093/ijnp/pyag040.273 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Case series Case report Peer reviewed |
|---|---|
| Sample size | 4 |
| Population | Adults with bipolar disorder and treatment-resistant depression maintained on monthly long-acting injectable aripiprazole (ages 21-38) |
| Intervention | Intranasal esketamine |
| Dose | 84 mg |
| Topics | Depression Esketamine |
| Key findings | The authors report that four patients with bipolar depression maintained on monthly aripiprazole injections plus other antidepressants and mood stabilizers achieved complete remission of depressive symptoms after add-on intranasal esketamine at 84 mg. They suggest intranasal esketamine may have a role in treatment-resistant bipolar depression, while noting limited existing data. |
Abstract
Abstract Background Esketamine intranasal spray is FDA-approved for treatment-resistant depression (TRD), but it is not licensed for use in bipolar disorder due to the risk of antidepressants inducing manic or hypomanic episodes. To date, there is limited data on the use of intranasal esketamine in bipolar disorder, and no previous reports of using esketamine as an add-on treatment in patients with bipolar depression maintained on long-acting antipsychotic injections as a mood stabilizer. Aims & Objectives The efficacy and safety o esktamine with long-acting injectable antipsychotics in bipolar patients.
Method: We report on four cases of bipolar depression maintained on a monthly long-acting aripiprazole injection, who were prescribed intranasal esketamine, and experienced a remission in depressive symptoms.
Results: Case 1: A 30-year-old female with bipolar disorder was maintained on a monthly aripiprazole injection of 400 mg since June 2024 in combination with clomipramine 150mg, quetiapine 300mg, and lisdexamfetamine 30mg. She experienced depressive symptoms in 2020. She was initiated on intranasal esketamine, reaching a dose of 84 mg, and was maintained on it for October 2024, during which she experienced an improvement in depressive symptoms, achieving complete remission. Case 2: A 21-year-old female with bipolar disorder was maintained on a monthly aripiprazole injection 400 mg since February 2025 in combination with lithium 400 mg, lamotrigine 400mg, Zyprexa 10 mg, and bupropion 300mg. She experienced depressive symptoms since 2019. She was initiated on intranasal esketamine, reaching a dose of 84 mg, and has been maintained on it since September 2024, during which she experienced an improvement in depressive symptoms, achieving complete remission. Case 3: A 31-year-old male with bipolar disorder was maintained on a monthly aripiprazole injection of 400 mg since May 2024in combination with desvenlafaxine 150mg. He experienced depressive symptoms since 2013. He was initiated on intranasal esketamine, reaching a dose of 84 mg, and was maintained in October 2024, during which he experienced an improvement in depressive symptoms, achieving complete remission. Case 4: A 38-year-old female with bipolar disorder was maintained on a monthly aripiprazole injection of 400 mg since July 2025 in combination with escitalopram 20 mg, Wellbutrin 300 mg, and lithium 400 mg. He experienced depressive symptoms since 2004. He was initiated on intranasal esketamine, reaching a dose of 84 mg, and was maintained in September 2024, during which he experienced an improvement in depressive symptoms, achieving full remission Discussion & Conclusions These cases demonstrated that there may be a role for adding intranasal esketamine in treatment-resistant bipolar depression in patients already maintained on monthly aripiprazole injections in combination with other antidepressants and mood stabilizers.