Targeting inflammation in depression: Ketamine as an anti-inflammatory antidepressant in psychiatric emergency

Major depressive disorder (MDD) is a common psychiatric disorder with multifactorial aetiology and complex pathophysiology. Despite availability of various pharmacological and non-pharmacological therapeutic strategies, treatment resistant depression (TRD) remains a significant challenge with specific concern for those patients with severe depressive symptoms in particular suicidal ideations who require immediate and effective intervention. Inflammation has been widely studied for its association with MDD and treatment response. Ketamine known as a dissociative anaesthetic has a novel rapid-acting antidepressant effect at lower doses. Anti-inflammatory actions of ketamine appear to play a role in mechanisms underlying its antidepressant effects. Considering the rapid antidepressant action of ketamine, this review provides a brief overview of antidepressant properties of ketamine as well as its effects on peripheral and central inflammation to better understand the mechanisms underlying the therapeutic action of ketamine as an anti-inflammatory antidepressant target in psychiatric emergency. Development of effective medications, which act rapidly with dual effect on both inflammation and MDD would be of a significant clinical importance for a successful and personalised treatment of inflammatory-induced TRD and suicidal thoughts and behaviour. •Anti-inflammatory actions of ketamine play a role in mechanisms underlying its antidepressant effects.•Ketamine’s dual effect on inflammation and depression is particularly important in treatment of inflammatory-induced TRD and suicidal patients.•Ketamine affects CNS receptors and pathways, neurotransmitter systems, synaptogenesis, and inflammatory responses.•Ketamine remains a promising target for treatment of TRD and suicidal thoughts.