Repeated IV ketamine infusions were associated with real-world improved psychosocial functional impairments as well as improved depressive and anxiety symptoms among adults with treatment-resistant bipolar disorder, according to study findings published in Bipolar Disorders.

Researchers sought to characterize real-world efficacy of repeated ketamine infusions for treatment-resistant bipolar depression assessing symptoms of depression, anxiety, suicidality, and functioning.

They conducted an observational study ( Identifier: NCT04209296) in a community clinic in Mississauga, Ontario (Canadian Rapid Treatment Centre of Excellence; Braxia Health). The study included 66 adult patients at least 18 years of age (mean 45.7±13.4 years; 59.1% women) with treatment-resistant bipolar I (n=28)/II (n=35) depression who received 4 sub-anesthetic doses of IV ketamine (0.5-0.75 mg/kg) over 2 weeks (mean number of psychotropics at infusion, 1.40; 34 patients received a dose increase). There were 3 patients unstratified due to medical record lack of clarity.

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Researchers found clinically and statistically significant antidepressant effects measured by the Quick Inventory for Depression Symptomatology-Self Report-16 (QIDS-SR16) (mean QIDS-SR16 reduction, 6.08±1.39; P <.0001) with additional reductions following each subsequent infusion. They noted significant reductions of anxiety (Generalized Anxiety Disorder-7 [GAD-7]) and suicidal thoughts (QIDS-SR16-Suicide Item) and functional improvements on the Sheehan Disability Scale (all P <.0001).

Significantly, they found the response rate (QIDS-SR16 total score decrease ≥50% from baseline) was 35% after 4 infusions. There were 46% of patients who improved by at least 25%. They noted the remission rate (QIDS-SR16 total score ≤5) was 20%. There were 7 patients excluded from this analysis due to the absence of scores. Researchers noted a significant main effect of bipolar disorder (BD)I vs BDII subgroups on QIDS-SR16 scores, though this effect was lost when controlling for baseline depression severity.

Sub-analysis of suicidality showed a significant decrease over time with treatment among those patients (n=33) with high QIDS-SR16 suicidality item scores.

Treatment-emergent hypomania was noted in 3 patients. There were no cases of psychosis or mania. Drowsiness (29%), dizziness (28%), blurred vision (27%), and confusion (27%) were the most frequently reported adverse events.

Anxiety sub-analysis showed no significant main effect of BDI vs BDII on GAD-7 scores (P >.05). Researchers noted a significant main effect of infusion for the SDS-SOCIAL score from baseline to posttreatment assessment (P <.001), and sub-analysis showed no significant main effect of BDI vs BDII on SDS-SOCIAL scores (P >.05).

Significant study limitations include the observational nature, lack of control group, significant amounts of missing data, selection bias, expectancy bias, and unaccounted-for ketamine treatment on top of various psychotropic medications already used by patients.

Researchers concluded “Repeated infusions of IV ketamine were associated with improving depressive and anxiety symptoms, as well as psychosocial functional impairments in a well-characterized cohort of adults with treatment-resistant bipolar disorder.” They added “Real-world effectiveness of IV ketamine for bipolar depression was observed.”


Fancy F, Rodrigues NB, Di Vincenzo JD, et al. Real-world effectiveness of repeated ketamine infusions for treatment-resistant bipolar depressionBipolar Disord. Published online December 14, 2022. doi:10.1111/bdi.13284

This article originally appeared on Psychiatry Advisor