Pharmacodynamic Interactions Between Ketamine and Psychiatric Medications Used in the Treatment of Depression:A Systematic Review

Background The use of ketamine for depression has increased rapidly in the past decades. Ketamine is often prescribed as an add-on to other drugs used in psychiatric patients, but clear information on drug-drug interactions is lacking. With this review, we aim to provide an overview of the pharmacodynamic interactions between ketamine and mood stabilizers, benzodiazepines, monoamine oxidase-inhibitors, antipsychotics, and psychostimulants. Methods MEDLINE and Web of Science were searched. Results Twenty-four studies were included. For lithium, no significant interactions with ketamine were reported. Two out of 5 studies on lamotrigine indicated that the effects of ketamine were attenuated. Benzodiazepines were repeatedly shown to reduce the duration of ketamine's antidepressant effect. For the monoamine oxidase-inhibitor tranylcypromine, case reports showed no relevant changes in vital signs during concurrent S-ketamine use. One paper indicated an interaction between ketamine and haloperidol, 2 other studies did not. Four papers investigated risperidone, including 3 neuroimaging studies showing an attenuating effect of risperidone on ketamine-induced brain perfusion changes. Clozapine significantly blunted ketamine-induced positive symptoms in patients with schizophrenia but not in healthy participants. One paper reported no effect of olanzapine on ketamine's acute psychotomimetic effects. Conclusion Current literature shows that benzodiazepines and probably lamotrigine reduce ketamine's treatment outcome, which should be taken into account when considering ketamine treatment. There is evidence for an interaction between ketamine and clozapine, haloperidol, and risperidone. Due to small sample sizes, different subject groups and various outcome parameters, the evidence is of low quality. More studies are needed to provide insight into pharmacodynamic interactions with ketamine

Correction to:Oral esketamine for treatment-resistant depression: rationale and design of a randomized controlled trial

After publication of our article [1] we were notified that Figure 1 was wrongly presented

Oral esketamine for treatment-resistant depression:rationale and design of a randomized controlled trial

BACKGROUND: There is an urgent need to develop additional treatment strategies for patients with treatment-resistant depression (TRD). The rapid but short-lived antidepressant effects of intravenous (IV) ketamine as a racemic mixture have been shown repeatedly in this population, but there is still a paucity of data on the efficacy and safety of (a) different routes of administration, and (b) ketamine's enantiomers esketamine and arketamine. Given practical advantages of oral over IV administration and pharmacodynamic arguments for better antidepressant efficacy of esketamine over arketamine, we designed a study to investigate repeated administration of oral esketamine in patients with TRD. METHODS: This study features a triple-blind randomized placebo-controlled trial (RCT) comparing daily oral esketamine versus placebo as add-on to regular antidepressant medications for a period of 6 weeks, succeeded by a follow-up of 4 weeks. The methods support examination of the efficacy, safety, tolerability, mechanisms of action, and economic impact of oral esketamine in patients with TRD. DISCUSSION: This is the first RCT investigating repeated oral esketamine administration in patients with TRD. If shown to be effective and tolerated, oral esketamine administration poses important advantages over IV administration. TRIAL REGISTRATION: Dutch Trial Register, NTR6161. Registered 21 October 2016

Ketamine as an anesthetic, analgesic and anti-depressant

ACHTERGROND Therapieresistentie komt voor bij ongeveer 30% van de patiënten met een depressie. Er is dan ook grote behoefte aan nieuwe behandelmogelijkheden. Ketamine, oorspronkelijk ontwikkeld als anestheticum, wordt onderzocht en incidenteel reeds toegepast bij patiënten met een therapieresistente depressieve stoornis. DOEL Kritische beschouwing over het huidige gebruik van ketamine als antidepressivum. METHODE Literatuuronderzoek. RESULTATEN Een kortdurend antidepressief effect van ketamine is aangetoond. Veel minder is bekend over het in stand houden van dit effect, de potentiële risico’s van herhaalde toediening, en de effectiefste toedieningsmethoden en behandelschema’s. CONCLUSIE Aanvullend onderzoek naar ketamine als antidepressivum blijft noodzakelijk. Eventuele (offlabel-) behandeling dient in de tussentijd alleen onder voorbehoud van zorgvuldige patiëntselectie en strikte monitoring te worden toegepast.BACKGROUND Treatment-resistance occurs in about 30% of patients with depression. Therefore, there is an urgent need to identify new treatment strategies. Ketamine, originally developed as an anesthetic, is studied and applied as treatment for patients with treatment-resistant depression. AIM A critical review of the current use of ketamine as an antidepressant. METHOD Literature study. RESULTS Ketamine is a proven effective acute antidepressant. However, limited information is available about maintenance of effect of ketamine, potential risks of repeated administration, and different routes of administration and treatment schedules. CONCLUSION Additional research on ketamine as an antidepressant is needed. Meanwhile, (off-label) treatment should only be applied after careful patient selection and under close monitoring.</p

Search for composite and exotic fermions at LEP 2

A search for unstable heavy fermions with the DELPHI detector at LEP is reported. Sequential and non-canonical leptons, as well as excited leptons and quarks, are considered. The data analysed correspond to an integrated luminosity of about 48 pb^{-1} at an e^+e^- centre-of-mass energy of 183 GeV and about 20 pb^{-1} equally shared between the centre-of-mass energies of 172 GeV and 161 GeV. The search for pair-produced new leptons establishes 95% confidence level mass limits in the region between 70 GeV/c^2 and 90 GeV/c^2, depending on the channel. The search for singly produced excited leptons and quarks establishes upper limits on the ratio of the coupling of the excited fermio