The antidepressant effect and safety of non-intranasal esketamine: A systematic review

Abstract

Background: The introduction of esketamine into the field of psychiatry comes on the heels of excitement from studies on racemic ketamine. While the intranasal route has been the most studied to date, other modes of administration of esketamine may also be of interest in the management of depression. Aims: To systematically review the literature on non-intranasal esketamine for depression in terms of its antidepressant effect and safety. Methods: We searched PubMed, Embase, the Cochrane Library, and Google Scholar from inception up to February 2021. Search terms included a combination of Medical Subject Headings and text words indicative of esketamine and depression. We selected both controlled and uncontrolled studies examining non-intranasal esketamine for the treatment of depression. Results: We identified four randomized controlled trials (RCTs) on intravenous esketamine and 15 open-label studies on intravenous ( n = 80), subcutaneous ( n = 73), and oral ( n = 5) esketamine. We found intravenous, subcutaneous, and possibly oral administration of esketamine to be effective in reducing depressive symptoms in most patients with major depressive disorder, bipolar depression, and (severe) treatment-resistant depression. Clinical response to repeated administration of esketamine persisted over the course of treatment. Esketamine was well tolerated by most patients, but open-label data indicate marked psychotomimetic symptoms in exceptional cases. The overall quality of the controlled studies was considered high, the overall quality of the uncontrolled studies low to moderate. Conclusions: Intravenous, subcutaneous, and possibly oral esketamine may offer an effective and safe addition to the depression treatment armamentarium. However, as most included studies lacked a control group and had small sample sizes, the quality of our results is limited. Different types and formulations of ketamine remain to be compared directly.

Oral esketamine in patients with treatment-resistant depression: a double-blind, randomized, placebo-controlled trial with open-label extension

“…Preliminary clinical data, however, indicate that esketamine may be at least as effective in reducing depressive symptoms as racemic ketamine. 32 The suggestion that dosing of esketamine was too low to obtain a clinical antidepressant effect in the RCT, is supported by the data from our open-label treatment program. At 0.5 to 3.0 mg/kg oral esketamine administered twice a week over six weeks, HDRS17 scores decreased on average 5.9 points, which is considered clinically meaningful.…”

Increasing the bioavailability of oral esketamine by a single dose of cobicistat: A case study

“…Oral administration of esketamine is less costly, and it is not associated with adverse effects specific for the intranasal treatment, such as postnasal drip or intranasal irritation. 5,6 In this study we explored whether oral esketamine can be an effective, safe, and tolerable alternative for intranasal esketamine, in collaboration with a patient with TRD treated with intranasal esketamine. This patient experienced a relapse of depressive symptoms when the frequency of intranasal esketamine Because oral esketamine has a relatively low bioavailability, it results in a different ratio between esketamine and its primary metabolite noresketamine.…”

“…Esketamine can also be administered orally as an off‐label treatment. Oral administration of esketamine is less costly, and it is not associated with adverse effects specific for the intranasal treatment, such as postnasal drip or intranasal irritation 5,6 …”

The Efficacy and Safety of Remimazolam Besylate Combined with Esketamine for Outpatient Colonoscopy: A Prospective, Randomized, Controlled Clinical Trial

“…Advantages of esketamine include its ability to maintain spontaneous breathing and its sympathomimetic properties. 15 Previous work has concluded that esketamine is a more attractive sedative adjunct to propofol compared with opioids. 16 Remimazolam combined with esketamine reduced the incidence of severe hypoxemia during gastrointestinal endoscopy in obese patients compared with propofol combined with esketamine.…”