Dennis Hartman, a 47-year-old former business executive for an Illinois gaming company, described the diagnosis he had been given as “major depression disorder with severity of the extreme, social phobia and generalized anxiety disorder,” something he had lived with for more than 30 years. He had tried Prozac-like drugs, an earlier generation of antidepressants, tranquilizers, mood stabilizers, supplements, meditation and psychotherapy. Nothing helped.

Last year he set a date and made a plan for how he would take his own life. He had given himself some time to get his affairs in order to cause as little distress as possible to his family. One night last fall before the date he had mentally set for himself, Hartman was up at 3 A.M., distraught and unable to sleep. Milling about the Web, he came upon an article about ketamine, an anesthetic and hallucinogenic club drug that is being intensively researched because of growing evidence that it can rapidly relieve major depression. He read about a study underway at the National Institutes of Health that was enrolling patients. He called the next day and was quickly accepted.

“I received a single infusion as part of that study,” Hartman says, “and I achieved 100 percent remission—a complete relief of all symptoms, which for me was dysphoria, anhedonia, extreme anxiety, cognitive impairment, very severe physical fatigue—I felt normal and healthy and happy within three or four hours after the infusion.”

The study protocol only allowed for one infusion—and the dramatic transformation began to gradually wear off beginning three weeks later. During that time Hartman, still at NIH as researchers conducted brain imaging and other studies, began a determined search of the Internet for a physician who might be willing to provide more ketamine, despite cautions conveyed by researchers that the drug was still experimental and had never been approved by the U.S. Food and Drug Administration for depression.

Hartman didn’t have far to look. Grassroots ketamine prescribing is on the upswing (read part 1), as physicians channel some of the same DIY-sentiment behind the medical marijuana movement, even while drug companies try to figure out ways to create a new class of antidepressant derived from ketamine's chemical makeup. Ketamine itself holds little interest to pharma outfits because of its generic status. A raft of studies has shown that the compound can provide rapid reversal of symptoms for patients who have not responded to psychotherapy or the standard line of antidepressants.

Drugmakers have begun trials of ketaminelike pharmaceuticals. Some physicians, though, have decided that desperate patients simply can’t wait years for completion of clinical trials and regulatory approval. Prescribing a drug for a use other than the one for which it was approved—in other words, off the label—does not break any laws. That has given psychiatrists and anesthesiologists in the U.S. the latitude to begin prescribing ketamine from their offices or to set up small specialty clinics for dispensing the drug.

After he left the study Hartman went first to a physician in San Diego and later ended up at New York Ketamine Infusions in New York City where he received six treatments, at $525 apiece, which again achieved relief of the depression symptoms. Clinics like the one Hartman went to take their message to customers with direct, very direct, advertising. A drug company can get saddled with fines reaching into the megamillions if its sales reps promote a drug off-label. Nothing, however, stops a physician who prescribes off-label from buying an ad. Plugging ketamine resembles a cross between highway billboards trumpeting physicians offering Botox and drug company direct-to-consumer ads. The New York Ketamine Infusions Web site has a link titled: “Is Ketamine Right for me?” On the home page, the phrase “Dramatic Improvements in Mood within Hours flashes on the screen. A Massachusetts clinic offers a “revolutionary and promising new treatment” from a Dr. Ablow [first name omitted], identified on the site as “America’s most well-known psychiatrist.”

Acknowledging the amateurish marketing tone, Hartman says he will be “first in line” when the FDA approves a ketaminelike drug for depression, but for the moment the clinics are essential for him to deal with the profound anguish that has beset him his entire adult life. “When I’m talking to friends and family and people who have not heard my story, I try to make it an easy, brief metaphor,” he says. “I'm the guy in a burning car who is unconscious and there is somebody who could rescue me, and they have to smash out the window with a hammer or ax, and the people who are discouraging ketamine use are the ones who are saying: ‘Don’t hit that window because you might hit Dennis and you might hurt him.’ But if you don’t break the window with the ketamine ax, I’m going to die a horrible death. That’s how I view things.”

Physicians are treating more and more patients like Hartman. A Santa Barbara physician, Robert Early, had been interested for years in finding alternatives to electroconvulsive therapy for patients who didn’t respond or were petrified of the side effects. When a pivotal study on ketamine and depression was published in 2006, Early, then at Baylor College of Medicine in Houston, saw an opportunity and started doing the procedure within six months. There and in Santa Barbara, Early has administered the therapy to some 125 patients—having prescribed it more than 700 times to that group.

An Arizona entrepreneur may have the most ambitious vision for supplying ketamine: Gerald Gaines started a company last year called Depression Recovery Centers with a single clinic in Scottsdale. As the name suggests, Gaines wants to make a brand out of walk-in clinics for depression, perhaps expanding nationwide, making them as common as suburban kidney dialysis centers.

A Harvard MBA who was instrumental in the launch of Sprint PCS, Gaines has suffered from lifelong manic-depressive episodes—and has numerous family members who have also wrestled with depression. Gaines became involved with the medical marijuana business, with the hope that some of the multitude of compounds that can be isolated from the plant’s leaves might be extracted to help with mania. He still donates money for this line of research but has given up for the moment on the idea that a pot-derived depression drug will arrive anytime soon.

Instead, he became intrigued with research on ketamine, which led to his opening the Scottsdale clinic. So far, the clinic has treated 30 patients under the care of an anesthesiologist and a psychologist. Most patients require more than one infusion, and the clinic has delivered in excess of 200 infusions since it opened. (The clinic posted “Tiffany’s Transformation Day” on Vimeo about one patient’s before-and-after experience.) Gaines himself is a customer. “I’ve been symptomatic for 45 years and have had two or three depressions every year, except for the last year, when I’ve had none,” he says. “I’ve had five treatments in last 12 months, and that’s the typical pattern of what we’re seeing for bipolar disorder.”

The cost of each infusion, at $750, is not covered by insurance. “Our target market very unfortunately—anybody who knows me knows I don’t feel good about this—is the top 10 percent of family income individuals,” Gaines says. A course of treatment typically costs $4,000 and can range up to $15,000—and may need to be repeated as the effects wear off.

Absent large-scale clinical trials, ketamine for depression will remain a form of drug development based on testimonial and anecdote. Drugs in the pipeline at major pharmaceutical companies may help fill in some of the blanks, but the first one may not arrive before 2017 and questions linger about whether these rejigged versions of ketamine will be any better than what is currently available from off-label clinics.

Read about the plans of Johnson & Johnson and other large pharma companies to cook up ketamine-derived blockbusters.