Repeated intravenous infusions of esketamine in inpatients with bipolar depression: A retrospective real-world study

• IV esketamine may reduce depressive symptoms in bipolar depression. • Low response rates observed after two weeks in highly selected patients. • Treatment-emergent hypomania occurred in 15.4 % of patients. • No significant effect on self-rated suicidality after two weeks. • Randomized controlled trials needed to clarify esketamine's role. Ketamine shows promise for treating bipolar depression, particularly in severe cases. However, the optimal administration route and enantiomer (esketamine, arketamine, or racemic mixture) remain unclear. This case series presents data on intravenous (IV) esketamine in bipolar depression, addressing a gap in published literature. This retrospective chart review included adult inpatients with bipolar depression treated with multiple IV esketamine infusions. Outcomes were measured using the self-rated Montgomery Åsberg Depression Scale (MADRS-S) and clinician-rated improved Global Clinical Impression Scale-Severity Index (rCGI-S). Tolerability data were also collected. Thirteen patients received 4–6 IV esketamine infusions over two weeks. Statistically significant improvements were observed in MADRS-S total scores ( p = 0.002) and rCGI-S scores ( p < 0.001) but not in MADRS-S suicidal thoughts item ( p = 0.125). Infusions were generally well-tolerated, with treatment-emergent hypomania in two patients (15.4 %). The retrospective design without a control group limited effectiveness evaluation. Preliminary results of IV esketamine for bipolar depression are promising, but its role in treatment algorithms requires clarification. Randomized controlled studies are needed to investigate its effectiveness further.