Current treatments for major depressive disorder and bipolar depression have major limitations with many patients do not responding to available antidepressant drugs. Even for those who do respond, it takes several weeks before symptoms improve.
Ketamine, an anesthetic, is one of several glutamatergic drugs affecting neurotransmitters in the central nervous system.
In patients with treatment-resistant major depressive disorder, ketamine produced initial reductions in depressive symptoms within two hours, with peak effects at 24 hours.
Several studies have reported "rapid, robust, and relatively sustained antidepressant response" to ketamine, injected intravenously at low, subanesthetic doses, the researchers said.
Ketamine and related drugs may represent a "paradigm shift" in the treatment of major depressive disorder and bipolar depression -- especially in patients who do not respond to other treatments, according to Carlos A. Zarate, from the National Institute of Mental Health, National Institutes of Health, in Maryland, US.
Another study led by Cristina Cusin, from Massachusetts General Hospital, showed that ketamine-induced changes in several brain areas involved in the development of depression.
Ketamine may exert its antidepressant effects by "acutely disabling the emotional resources required to perpetuate the symptoms of depression", as well as by increasing emotional blunting and increasing activity in reward processing.
The two studies on ketamine and other glutamatergic drugs for depression were published in the journal Harvard Review of Psychiatry.
Ketamine may also rapidly reduce suicidal thoughts. It has also produced rapid antidepressant effects in patients with treatment-resistant bipolar depression.
However, since the drug is FDA-approved only as an anesthetic, use of ketamine in depressive disorders is "off-label", unregulated, and not standardised.
"Efforts are underway to bring ketamine to market, standardise its use, and determine its real-world effectiveness," Zarate said.
Independent of how ketamine works or its ultimate role in clinical treatment, antidepressant response to glutamatergic drugs points to an exciting conclusion: "that rapid antidepressant effects are indeed achievable in humans".
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