While [Ketamine] has been used as an anesthetic for decades, small studies at prestigious medical centers like Yale, Mount Sinai and the National Institute of Mental Health suggest it can relieve depression in many people who are not helped by widely used conventional antidepressants like Prozac or Lexapro. And the depression seems to melt away within hours, rather than the weeks typically required for a conventional antidepressant. Pharmaceutical companies hope to [develop] drugs that work like ketamine but without the side effects, which are often described as out-of-body experiences. Some doctors and patients are not waiting for the pharmaceutical industry. Because ketamine has long been approved for anesthesia, doctors are allowed to use it off-label to treat depression. There is clearly a need for new drugs. "Almost half of depressed patients are not being treated adequately by existing drugs," said Dr. Sheldon H. Preskorn, a professor of psychiatry at the University of Kansas School of Medicine-Wichita. That, he said, is because virtually all the antidepressants used in the last 60 years work essentially the same way. Ketamine would represent a new mechanism of action. "Synaptic connections that help us to cope seem to grow back," said Dr. John H. Krystal, chairman of psychiatry at Yale and a pioneer in the study of ketamine for depression.