Introduction Ketamine exhibits antidepressant properties in treatment-resistant depression (TRD) with some concern over its cardiovascular safety and tolerability issues. This paper reports on the cardiovascular safety in short-term intravenous ketamine treatment in TRD inpatients with major depressive disorder (MDD) and bipolar disorder (BP). Materials and Methods The observational study population comprises 35 MDD and 14 BP subjects treated with intravenous ketamine. Results Blood pressure (RR) and heart rate (HR) values returned to baseline within 1.5-hours post infusion with no sequelae for all study subjects. Six time points were analyzed for each infusion: 0’, 15’, 30’, 45’, 60’ and 90’ for RR and HR. After the infusion significant peaks in systolic (p = 0.004) and diastolic (p = 0.038) RR were seen. In concomitant medication with selective serotonin reuptake inhibitors (SSRIs), higher RR peaks (p = 0.020; p = 0.048) were seen as compared to other subjects. The decrease in HR was greater (p = 0.02) in the absence of concomitant medication with mood stabilizers as compared to subjects receiving mood stabilizing medication accompanied by the observation of a greater decrease in diastolic RR among those taking mood stabilizers (p = 0.009). Limitations The study may be underpowered due to the small sample size. The observations apply to an inhomogeneous TRD population in a single-site, pilot study, with no blinding and are limited to the acute administration. Conclusion The study demonstrates good safety and tolerability profile of intravenous ketamine as add-on intervention to current psychotropic medication in TRD, regardless of the MDD or BP type of mood disorders. The abatement of elevated RR and BP scores was observed in time with no sequelae nor harm. Still, cardiovascular risks appear to be more pronounced in subjects with comorbid arterial hypertension and diabetes mellitus.

Background and Objectives: There is evidence for ketamine efficacy in treatment-resistant depression (TRD). Several safety and tolerability concerns arise that some psychotropic agents may provide blood pressure or/and heart rate alterations. The aim of this study is to review blood pressure measurements in course of the treatment with ketamine on treatment refractory inpatients with somatic comorbidities in the course of MDD and BP. Methods and Methods: The study population of 49 patients comprised MDD and BP subjects treated with ketamine registered in the naturalistic observational protocol of treatment-resistant mood disorders (NCT04226963). Results: The conducted analysis showed that among people suffering from hypertension there is a higher increase in systolic blood pressure (RR) after infusion 2 (p = 0.004) than among people who do not suffer from hypertension. Patients with hypertension have a higher increase in diastolic RR compared to those not suffering from hypertension (p = 0,038). Among the subjects with diabetes mellitus, significant differences occurred for infusions 2 (p = 0.020), 7 (p = 0.020), and 8 (p = 0.035) for heart rate (HR), compared to subjects without diabetes mellitus. A higher increase in diastolic RR was noted in the group of subjects suffering from diabetes mellitus (p = 0.010) compared to those who did not. In the hyperlipidemic patients studied, a significantly greater decrease in HR after infusion 5 (p = 0.031) and systolic RR after infusion 4 (p = 0.036) was noted compared to nonpatients. People after a stroke had significantly higher increases in diastolic RR after infusions 4 (p = 0.021) and 6 (p = 0.001) than those who did not have a stroke. Patients suffering from epilepsy had a significantly greater decrease in systolic RR after the 8th infusion (p = 0.017) compared to those without epilepsy. Limitations: The study may be underpowered due to the small sample size. The observations apply to inhomogeneous TRD population in a single-site with no blinding and are limited to the acute administration. Conclusions: This study supports evidence for good safety and tolerability profile for short-term IV ketamine use in TRD treatment. However, risk mitigation measures are to be considered in patients with metabolic and cardiovascular comorbidities.

There is evidence for ketamine use in treatment-resistant depression (TRD). Several safety and tolerability concerns arise regarding adverse drug reactions and specific subpopulations. This paper aims to investigate the relationship between dissociative and psychometric measures in course of intravenous ketamine treatment in TRD inpatients with major depressive disorder and bipolar disorder.This study result represents safety data in a population of 49 inpatients with major depressive disorder and bipolar disorder subjects receiving eight 0.5 mg/kg of ketamine intravenous infusions, with a duration of 40 min each, as an add-on treatment to standard-of-care pharmacotherapy, registered in the naturalistic observational protocol of the tertiary reference unit for mood disorders (NCT04226963). The safety psychometrics assessed dissociation and psychomimetic symptomatology with the Clinician-Administered Dissociative States Scale (CADSS) the Brief Psychiatric Rating Scale (BPRS).The significant differences in CADSS scores between measurements in course of the treatment were observed (P = .003). No significant differences between BPRS measurements were made after infusions. In each case, both BPRS and CADSS values dropped to the "absent" level within 1 hour from the infusion. Neither CADSS nor BPRS scores were associated with the treatment outcome.The study demonstrates a good safety profile of intravenous ketamine as an add-on intervention to current psychotropic medication in TRD. The abatement of dissociation was observed in time with no sequelae nor harm. The study provides no support for the association between dissociation and treatment outcome.This study may be underpowered due to the small sample size. The protocol was defined as a study on acute depressive symptomatology without blinding.

Background: There is evidence supporting the use of ketamine in treatment-resistant depression (TRD). However, there are some safety and tolerability concerns associated with ketamine. This study aimed to investigate ketamine’s safety and tolerability to the central nervous system and to assess the relationship between dissociative symptomology and psychometric outcomes during and after intravenous ketamine treatment concurrent with treatment by varying psychotropic medications in treatment-refractory inpatients with major depressive disorder (MDD) and bipolar disorder (BP). Methods: A total of 49 patients with MDD and BP were included in this study. The subjects were administered ketamine and were assessed for changes using an observational protocol. Results: No antidepressants were associated with psychomimetic symptomatology except for citalopram ( p = 0.019). Patients treated with citalopram showed a higher intensity of psychomimetic symptomatology. The use of classic mood-stabilizers was significantly associated with an increase in psychomimetic symptomatology according to the Brief Psychiatric Rating Scale (BPRS; lamotrigine p = 0.009, valproate p = 0.048, lithium p = 0.012). No sequelae were observed. Conclusions: Despite the limitations that this study may be underpowered due to the small sample size, the sample consisted of a heterogeneous TRD population in a single site, and there no blinding of who underwent only acute ketamine administration, our observations indicate ketamine use requires close safety and tolerability monitoring with regards to psychomimetic and dissociative symptoms in TRD-BP and careful management for MDD patients. ClinicalTrials.gov identifier: NCT04226963

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