Understanding potential of illicit drug ketamine in treating depression

Advancing the understanding and treatment of psychiatric disorders is a principal goal of neuroscientists. As mental disorders are the leading cause of disabilities worldwide, it is concerning that there are few effective therapeutics on the market due to the lack of knowledge regarding pathophysiology. In particular, the main treatment for major depressive disorders are antidepressants, which target the monoaminergic system and include selective serotonin reuptake inhibitors (SSRIs). However, these drugs take six weeks on average before symptom relief and many individuals are unaffected by them.

Ketamine, a synthetic analogue of PCP, has recently taken the spotlight as a novel, fast-acting antidepressant. The benefits of ketamine include a one-time, low-dose IV infusion, where symptoms are alleviated within hours and which lasts for up to two weeks in patients with depression. Even more compelling is that this regimen affects patients with treatment-resistant depression, meaning those who do not respond to current antidepressants. These effects are especially important in helping individuals with depression who may be experiencing suicidal ideation because of ketamine's fast-acting nature and it is the only treatment effective for treatment resistant patients.

However, there are many downsides to the use of ketamine as an antidepressant, especially with long-term or repeated use. For example, ketamine is an illicit drug with high abuse potential, commonly known as the party drug "Special K." Therefore, close clinical monitoring of the use of this drug is necessary. In regards to neuroscience research in the past decade, it has been demonstrated that chronic, low-dose ketamine has been used to study learning and memory deficits in a rodent model of schizophrenia. The biochemical data from these animals reveal a change in a specific type of neuron in the brain that is important for network activity underlying normal cognitive functioning. This begs the question: Can ketamine work as an antidepressant without producing cognitive deficits associated long-term use?

In order to address this question, we need to understand the molecular mechanisms that ketamine is utilizing to produce these beneficial antidepressant effects. Although researchers do not know exactly how ketamine works, we know that it is in a different way than current antidepressants on the market. There is no clear answer yet, but researchers have produced some promising results. Using ketamine to deepen our understanding of depression will advance the field of neuroscience and ultimately lead to a more effective treatment for the disorder.

Source: American Association of Pharmaceutical Scientists (AAPS)


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