Depression, an unmet health need in Africa: Understanding the promise of ketamine.

In Africa, there is currently a paucity of data on the epidemiology of depression, its treatment and management. The prevalence of depression is severely underestimated, with unique circumstances and societal risk factors associated with depression and its public awareness. Treating and managing depression is confounded by an inaccessibility to efficient and low-cost treatments for patients with depression. The aetiology of depression is multifactorial, with various theories implicating multiple neuronal networks. Despite this, the treatment of depression is one-dimensional focussing on outdated theories of depression and mainly targeting dysfunctional neurotransmitter pathways. Hence, it is not surprising that there is a significant increase in the prevalence of patients suffering from treatment resistant depression (TRD), with a large portion of patients deriving little clinical benefit from these traditional anti-depressant therapies. This highlights the need for more effective treatment strategies for depression, especially applicable to resource limited environments such as Africa, where there is little investment in public healthcare resources towards managing mental health disorders. The clinical potential of using ketamine in managing depression has received considerable attention in the past two decades, with the FDA approving esketamine for the management of TRD in 2019. This widespread attention has significantly increased ketamine's appeal as a novel antidepressant. Consequently, many ketamine infusion clinics have been established in Africa. However, there is little regulation or guidance for ketamine infusions. Furthermore, while esketamine is expensive and hence inaccessible to a large portion of the African population, racemic ketamine is significantly cheaper and has demonstrated clinical potential. However, there is currently a limited understanding of the neurological mechanisms of action of racemic ketamine in treating and managing depression, especially in a diverse African population. Therefore, this review aims to provide an African context of depression and the therapeutic potential of ketamine by highlighting aspects of its molecular mechanism of action.