Ketamine, an anaesthetic agent often misused as a recreational ‘party drug’, may help treat severe depression by producing a response within hours rather than weeks, scientists say. Ketamine and related drugs may represent a “paradigm shift” in the treatment of major depressive disorder (MDD) and bipolar depression – especially in patients who do not respond to other treatments, according to a research review by Carlos A Zarate, and colleagues from the US National Institute of Mental Health. Current treatments for MDD and bipolar depression have major limitations. Many patients with severe depressive symptoms don’t respond to available antidepressant drugs. Even for those who do respond, it may take several weeks before symptoms improve. Ketamine, an anaesthetic, is one of several glutamatergic drugs affecting neurotransmitters in the central nervous system.
Over the past decade, several studies have reported “rapid, robust, and relatively sustained antidepressant response” to ketamine, injected intravenously at low, subanaesthetic doses. Scientists reviewed research on ketamine and other glutamatergic drugs for depression. Ketamine, by far the best-studied of these medications, is notable for its very rapid antidepressant effects. In patients with treatment-resistant MDD, ketamine has produced initial reductions in depressive symptoms within two hours, with peak effects at 24 hours. Ketamine may also rapidly reduce suicidal thoughts. Combined with other medications, ketamine has also produced rapid antidepressant effects in patients with treatment-resistant bipolar depression.
Prompted by these studies, some doctors are already using ketamine in patients with severe or treatment-resistant depression. However, since it is approved only as an anaesthetic, use of ketamine in depressive disorders is “off-label,” unregulated, and not standardised. Many questions remain about its short- and long-term side effects and potential for abuse. “Efforts are underway to bring ketamine to market, standardise its use, and determine its real-world effectiveness,” said Zarate.
Researchers from Massachusetts General Hospital in the US reviewed neuroimaging studies evaluating ketamine’s effects in the brain. The studies show ketamine-induced changes in several brain areas involved in the development of depression. Ketamine may exert its antidepressant effects by disabling the emotional resources required to perpetuate the symptoms of depression, as well as by increasing emotional blunting and increasing activity in reward processing researchers said.