Effects of subcutaneous esketamine on blood pressure and heart rate in treatment-resistant depression

Abstract

<jats:sec><jats:title>Introduction and objectives:</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Conclusions:</jats:title><jats:p> 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 &gt;180 mmHg and/or a DBP &gt;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. </jats:p></jats:sec>

Oral S-ketamine effective after deep brain stimulation in severe treatment-resistant depression and extensive comorbidities

“…Safety and tolerability of oral S-ketamine as add-on to standard antidepressants has been previously described in a case series by Paslakis et al 13 S-ketamine augmentation via other routes of administration has also been studied in combination with regular antidepressants and antipsychotics. [13][14][15] However, to the best of our knowledge, this is the first paper reporting on S-ketamine administration in a patient with DBS implants. Given the enormous burden of TRD for patients, we believe trials with (S-)ketamine treatment in patients with extensive comorbidities are both needed and justified, if outcomes are thoroughly monitored over time.…”

Repeated subcutaneous esketamine for treatment-resistant depression: Impact of the degree of treatment resistance and anxiety comorbidity

“…The TRANSFORM-3 Study reported that treatment-emergent adverse events were transient and ultimately safe in several assessments, such as hematology and serum chemistry, urinalysis, physical examination, electrocardiogram, suicidal ideation, dissociation symptoms and cognition (Ochs-Ross et al, 2020). We have described the cardiovascular safety of repeated SC esketamine elsewhere (Del Sant et al, 2020).…”

“…Patients were monitored for at least 2 hours after each esketamine dose to manage possible side-effects, taking into account the risk of sedation and dissociation, as well as to carefully assess heart rate, blood pressure and digital pulse oximetry every 15 minutes (cf. Del Sant et al, 2020).…”

“…The S isomer, esketamine, appears to be a more potent NMDA receptor antagonist than its enantiomer R-ketamine (Andrade, 2017a; Muller et al, 2016; Yang et al, 2015). Compared to its racemic mixture, esketamine has a similar cardiovascular safety profile (Del Sant et al, 2020) and non-inferior antidepressant effect (Correia-Melo et al, 2020). Ketamine has been tested in several routes of administration; moreover, intravenous (IV) infusions are the most extensively researched (Berman et al, 2000; Coyle and Laws, 2015; Murrough et al, 2013).…”

Subcutaneous Ketamine in Depression: A Systematic Review

“…Of the selected articles, two were randomized clinical trials (17,18) five were case-reports (21,22) and five were retrospective studies (20,(26)(27)(28)(29) (see Table 2). From the retrospective studies, four of them (26)(27)(28)(29) were from the intervention in the same group of patients and, thus, will be presented together in Tables 2, 3.…”