Ketamine has been a glimmer of hope for decades for those battling treatment resistant depression, whose symptoms have failed to abate after conventional antidepressants. A single infusion of the drug at a sub-psychiatric dose has been known to alleviate severely debilitating symptoms within hours on some patients, an outcome that leaves researchers and clinicians puzzled. But, there had been no reliable early predictor that the positive effects would endure. A recent study from Texas A&M University has identified an electrophysiological signature that may predict persistent benefitthe study was conducted mainly in elderly women with long-standing treatment resistant depression.
The study evaluated U.S. veterans over 55 years old. From a tightly controlled ketamine infusion, researchers followed up with neurons at three time points: 1 hour, 24 hours, and 7 days. Through measurements of the degree of informational sharing and integration among various brain areas, researchers observed several changes during the week. The most crucial occurred at 24 hours. Relative to 7 day responders, 7 day non-responders experienced greater increases in high-order brain interactions, defined as higher order multiregional information exchange.
Another reason this finding is important: standard antidepressants usually require many weeks to produce benefit, and many patients don’t respond even then. Ketamine acts through a different mechanismon the glutamate system, not serotonin. Previously, clinicians could only sit back and wait, watching for improvement. Detecting this new signal may provide an early indicatorbiomarkerthat suggests the patient is improving before you can actually see it. An early indicator might be mostly helpful for older people, who suffer from higher rates of treatment-refractory depression and often have some complicated medical background to account for.
As noted in Translational Psychiatry the group did not conclude the brain signal was the complete account of ketamine’s action but rather one “more piece of a larger puzzle”. Brain activity continued to change throughout the week, implying that the drug initiates a cascade rather than all at once. The enhancement of information sharing twenty-four hours might have been a brief period of increased plasticity in which the brain is more capable of establishing healthier thoughts and emotional states and those patients, whose brains maximized utilization of this window, felt better a week later.
The team at Texas A&M’s Naresh K. Vashisht College of Medicine would like to what can be learned from all of this. If this same signal is seen in larger groups, the ability to more precisely determine exactly when and who needs additional help would be benefited. It may even urge researchers to find different methods of achieving this increase in sharing of information all across the brain, with and without the same dissociative effects that sometimes occur with ketamine.
The simplest of the practical promises is the straightforward one for patients and families living with refractory depression. Treatment options are very personalized, and ketamine is not for every patient.
