Comparison of racemic ketamine andS-ketamine in treatment-resistant major depression: Report of two cases

Abstract

Recent studies with intravenous infusion of the NMDA receptor antagonist ketamine showed robust and rapid antidepressant effects within hours after treatment. Ketamine is a racemic mixture consisting of two enantiomers, R- and S-ketamine. In contrast to ketamine, S-ketamine is reported to be less prone to psychomimetic side effects, such as derealisation and hallucinations. In this report we describe the effect of ketamine and S-ketamine infusion therapy, respectively, in two patients with treatment-resistant major depression. Severity of depression was rated using the Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI). While one patient did not respond to either treatment, in the other patient intravenous administration of ketamine as well as S-ketamine showed an antidepressant effect as assessed by a decrease in HAMD-21 and BDI at days 1 and 3 after infusion which faded until day 6. Both patients experienced psychomimetic side effects during ketamine infusion which were absent during treatment with S-ketamine. We conclude that S-ketamine might exert similar antidepressant effects as ketamine in drug-resistant depression but may be better tolerated by the patients.

Ketamine and suicidal ideation in depression: Jumping the gun?

“…In juvenile mice exposed to neonatal dexamethasone, single dose of R-ketamine showed rapid-onset and long-lasting antidepressant effects compared to S-ketamine [54]. Despite the lack of direct evidence, the results of this preclinical study, which is in line with a clinical case report [55], tempts us to speculate that R-isoform may contribute to the rapid and long-standing antidepressant effects, while the S-isoform may mediate the psychotomimetic effects. Schematic depiction of effects of ketamine in rodent brain published in the recent past.…”

“…Chronic thoughts of death were obliterated in one patient who received ketamine for treatment-resistant depression [87]. A number of other case reports indicated the beneficial effects of ketamine on patients with suicidal behaviour/ideation: at the dose level of 0.5 mg/kg (infused intravenously over 50 min) in treatment-resistant depression with alcohol and benzodiazepine dependence [88]; at a higher dose of 1.5 mg/kg (administered intramuscularly) in severe major depression [89]; at the dose level 0.5 mg/kg (infused intravenously over 50 min) administered twice, 34 days apart in treatmentresistant depression [90]; at the dose level of 0.5 mg/kg (infused intravenously over 50 min), administered 6 times in treatmentresistant depression [91]; ketamine and S-ketamine at the dose level of 0.5 and 0.25 mg/kg respectively (infused intravenously over 50 min) infused one week apart in one treatment-resistant major depression patient [55]; S-ketamine at the dose level of 0.5 mg/kg (infused intravenously over 40 min) in major depression with melancholic symptoms [92]; at the dose level of 0.5 mg/kg (infused intravenously over 40 min) for major depression with comorbid post-traumatic stress disorder [93]; at the dose level of 0.5 mg/kg (oral) in 2 patients with treatment-resistant depression [94] and at a dose level of 50 mg/kg over a day (5 intranasal 15 min apart) in a treatment-resistant depression patient [95]. Further, the risk of suicide was one of the reasons that warranted ketamine treatment (0.5 mg/kg infused intravenously over 40 min) in a patient who suffered severe chronic post-traumatic stress disorder (PTSD) and depression due to combat trauma [96].…”

Ketamine and other potential glutamate antidepressants

“…Of the remaining trials, a single blind study observed the effect of ketamine when used as part of an anaesthetic in patients with MDD undergoing orthopaedic surgery (Kudoh et al, 2002). The remaining studies were either open label (Correll and Futter, 2006;Machado-Vieira et al, 2009b;Phelps et al, 2009;Salvadore et al, 2009;aan het Rot et al, 2010;Paslakis et al, 2010;Okamoto et al, 2010;Salvadore et al, 2010;Ibrahim et al, 2011Ibrahim et al, , 2012bSalvadore et al, 2012;Carlson et al, 2013;Duncan et al, 2013a;Murrough et al, 2013b;Rasmussen et al, 2013) or crossover studies (Paul et al, 2009;Valentine et al, 2011). Mathew et al (2010) used open label i.v.…”

“…ketamine have been carried out (Paul et al, 2009;Machado-Vieira et al, 2009b;Mathew et al, 2010;Paslakis et al, 2010;Denk et al, 2011;Ibrahim et al, 2012b;Duncan et al, 2013a;Segmiller et al, 2013;Sos et al, 2013). One study investigated the effect of lamotrigine on ketamine response in treatment resistant MDD.…”

“…Two open-label case studies investigated the S-isomer of ketamine which has a higher affinity than the R-isomer for the phencyclidine site of the NMDA receptor site (Paul et al, 2009, Paslakis et al, 2010. S-ketamine has a 4 fold greater anaesthetic potency and higher frequency of psychotomimetic side effects in humans (Kohrs and Durieux, 1998).…”