Xenon Inhalation Therapy for Major Depressive Disorder and Bipolar Disorder

Major depressive disorder (MDD) occurs in up to 17% of the population, is associated with profound dysfunction and, according to the WHO Global Burden of Disease Study, is estimated to become the second leading cause of disability worldwide by 2020. While antidepressants have proven efficacy, they usually take weeks to work and then only about a third of patients reach remission.

Beyond the traditional monoaminergic approaches, recent advances in understanding the pathophysiology of MDD have focused on the dysregulation of glutamate and associated neuronal glutaminergic associated excitotoxicity. Xenon is a potent antiglutaminergic agent that has been used as an anesthetic with minimal side effects, has neuroprotective effects consistent with antidepressants, and has the potential to be a novel antidepressant drug.

Although mania or hypomania are the defining characteristics of bipolar disorder, throughout the course of the illness depressive symptoms are more common than manic symptoms. People with bipolar disorder spend a substantial proportion of time with syndromal or subsyndromal depressive symptoms. The risk of suicide is greatly elevated during depressive episodes. Approximately 17% of people with bipolar I disorder and 24% with bipolar II disorder attempt suicide during the course of their illness. Annually around 0.4% of people with bipolar disorder will die by suicide, which is vastly greater than the international population average of 0.017%.

Pharmacological treatments are commonly used during episodes of mania and bipolar depression. Over time these episodes, particularly depression, tend to become more frequent and as repeated episodes are associated with increased functional impairment, effective treatment is a priority. The treatment of bipolar depression is quite challenging. Treatments used during acute episodes include antidepressants, some antipsychotic drugs such as quetiapine, the anticonvulsant drug lamotrigine and lithium. Response to these agents both acutely and during maintenance treatment is often partial. There are concerns about the potential for switching into mania and more frequent cycling mood with antidepressant treatment.

Only a handful of treatments are approved for bipolar depression and have been shown to be superior to placebo (lurasidone, valproate, quetiapine, the combination of fluoxetine and olanzapine, olanzapine alone, and lamotrigine), however atypical antipsychotics carry significant burden of side effects in particular metabolic.