Heart rate deceleration (HRD) as a low cost scalable indicator of target engagement during SAINT for treatment resistant depression (TRD)

Introduction and objectives: The impact of multiple subcutaneous (s.c.) esketamine injections on the blood pressure (BP) and heart rate (HR) of patients with unipolar and bipolar treatment-resistant depression (TRD) is poorly understood. This study aimed to assess the cardiovascular safety of multiple s.c. doses of esketamine in patients with TRD. Methods: Seventy TRD patients received 394 weekly s.c. esketamine injections in conjunction with oral antidepressant therapy for up to six weeks. Weekly esketamine doses were 0.5, 0.75 or 1.0 mg/kg according to each patient’s response to treatment. Participants were monitored before each treatment and every 15 minutes thereafter for 120 minutes. We assessed systolic blood pressure (SBP), diastolic blood pressure (DBP), and HR measurements for the entire treatment course. Results: BP increased after the first s.c. esketamine injection, reaching maximum mean SBP/DBP levels of 4.87/5.54 mmHg within 30–45 minutes. At the end of monitoring, 120 minutes post dose, vital signs returned to pretreatment levels. We did not detect significant differences in BP between doses of 0.5, 0.75, and 1 mg/kg esketamine. Mean HR did not differ significantly between doses or before and after s.c. esketamine injection. Conclusions: The BP changes observed with repeated s.c. esketamine injections were mild and well tolerated for doses up to 1 mg/kg. The s.c. route is a simple and safe method of esketamine administration, even for patients with clinical comorbidities, including obesity, hypertension, diabetes, and dyslipidemia. However, 14/70 patients experienced treatment-emergent transient hypertension (SBP >180 mmHg and/or a DBP >110 mmHg). Therefore, we strongly recommend monitoring BP for 90 minutes after esketamine dosing. Since s.c. esketamine is cheap, requires less frequent dosing (once a week), and is a simpler procedure compared to intravenous infusions, it might have an impact on public health.

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17.1 Target Engagement With Brain Energy Metabolism: Studies of Creatine for Adolescent Female Patients With Treatment-Resistant Depression

Journal of the American Academy of Child & Adolescent Psychiatry ◽

10.1016/j.jaac.2016.07.756 ◽

2016 ◽

Vol 55 (10) ◽

pp. S283

Author(s):

Douglas G. Kondo

Keyword(s):

Energy Metabolism ◽

Brain Energy Metabolism ◽

Adolescent Female ◽

Treatment Resistant Depression ◽

Target Engagement ◽

Treatment Resistant ◽

Female Patients ◽

Resistant Depression ◽

Brain Energy

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Somatic Comorbidities and Cardiovascular Safety in Ketamine Use for Treatment-Resistant Depression

Medicina ◽

10.3390/medicina57030274 ◽

2021 ◽

Vol 57 (3) ◽

pp. 274

Author(s):

Joanna Szarmach ◽

Wiesław Jerzy Cubała ◽

Adam Włodarczyk ◽

Maria Gałuszko-Węgielnik

Keyword(s):

Diabetes Mellitus ◽

Blood Pressure ◽

Heart Rate ◽

Small Sample ◽

Tolerability Profile ◽

Acute Administration ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Somatic Comorbidities ◽

Resistant Depression

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. Materials 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.

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