The practical, ethical and longer-term efficacy arguments remain unresolved. Hypothetically could a suicidal patient be administered ketamine against their wishes either, in the UK, under the Mental Health Act where their life was in danger from a mental illness, or under the Mental Capacity Act where they lacked the ability to make decisions about their care? The future of ketamine: prototype

for a new class of antidepressant? The longer-term role of ketamine in the management of depression is unclear. Optimal dosing and longer-term data on relapse prevention Inhibitors,research,lifescience,medical and tolerability are lacking. Although most studies administered ketamine at a dose of 0.5 mg/kg in a saline drip over about 40 minutes, this was not the only schedule, with for example a bolus Inhibitors,research,lifescience,medical administration of 0.2 mg/kg over 1–2 minutes. Most studies utilized participants with treatment-resistant MDDs: on the one hand this adds to the clinical appeal of a therapy that works on those who have failed to respond to standard treatment; on the other hand it leaves open the question of the effects of ketamine on mild, CI-1040 manufacturer moderate or treatment-naïve depressive disorders. There is no current consensus whether those who are treatment

refractory and fail to respond to traditional antidepressants have a neurobiologically distinct form of the illness. All studies have methodologically Inhibitors,research,lifescience,medical appropriate inclusion and exclusion criteria that nevertheless might hinder the wider generalizability of the data. Whilst used in some individuals with bipolar depression it is not clear if the side effects would differ in those who Inhibitors,research,lifescience,medical had previous psychotic episodes as part of their BPAD. Ketamine is well established as a psychotomimetic: occurrences Inhibitors,research,lifescience,medical of psychotic symptoms were not common in the trials, but these were short-term studies

in controlled environments, and excluded those with psychotic illnesses and histories of drug dependency. The potential for harm and the broader use of this drug has not been satisfactorily answered, and MRI data on longer-term illicit use of the drug has shown it can cause very cortical atrophy [Wang et al. 2013]. The very strong efficacy data but the practical administration and side-effect problems may terminally limit the use of ketamine in general psychiatric practice, although undoubtedly larger longer follow-up RCTs are needed. Ketamine data have provided new neurobiological evidence to both support aspects of the monoaminergic hypothesis of depression, and also offering novel insights into this illness. There are current trials on selective NMDA receptor subunit 2B (NR2B) antagonists such as Ro 25-6981 to see whether they can elicit the therapeutic responses seen with ketamine without the major potential problems of psychosis and dependency [Maeng et al. 2008; Preskorn et al. 2008].