Drug Companies Push Japan
To Change View of Depression

Once-Taboo Illness Gets New Face
As TV Star Speaks About Disease

By Peter Landers
The Wall Street Journal, October 9, 2002

In April 1996, a producer at Japan's biggest television broadcaster stumbled across a paperback copy of "Listening to Prozac" in a Tokyo store. By that time, the antidepressant was a household name in America, and the book had become a best-selling study of how medicine can affect the mind.

But the Prozac revolution had barely created a ripple in Japan. Producer Kenichiro Takiguchi persuaded his bosses to air a 50-minute prime-time special portraying depression as a treatable disease rather than a character flaw. Millions watched, and more than 2,000 viewers called in afterward to thank the network.

It was the beginning of an extraordinary transformation in Japan. Once, says Mr. Takiguchi, "no one would say, 'I have a psychiatric illness.' ... It was a really shameful disease." Today, thanks in part to Mr. Takiguchi's show and the marketing efforts of several giant pharmaceutical companies, many Japanese doctors have embraced the new model of depression, and there are two fast-selling Prozac-type drugs on the market -- although the country still has to wait another two years for Prozac itself.

Japan's experience in some ways mirrors that of many other industrialized nations outside the U.S., which still accounts for three-quarters of the world's $16 billion antidepressant market. But Japan's attitude toward mental illness also offers an insight into the country's culture. As the nation plunged into deep economic slump in the late 1990s, widespread bankruptcies and layoffs contributed to an increasing divorce rate and a suicide rate that is now double that of the U.S. Yet through the end of the decade, Japanese psychiatrists continued to focus almost exclusively on psychosis and depression severe enough to require hospitalization. In such extreme cases, they administered older forms of antidepressants, known as tricyclics, which have more side effects than the newer, Prozac-class drugs. Sufferers of milder forms of depression typically neither sought nor received treatment, either through psychotherapy or medication.

Eli Lilly & Co., the inventor of Prozac, didn't even try to market it in Japan during the 1990s, thinking the sales would be too small because "people's attitude toward depression was very negative," says a spokeswoman.

Other Japanese barriers also slowed the entry of antidepressants. For instance, until recently, Japan barred drug makers from using results from foreign studies in new-drug applications. So when one Japanese pharmaceutical company, Meiji Seika Co., wanted to market an antidepressant in the late 1980s, it had to start from scratch, even redoing animal tests. When Meiji sought to get the drug approved for obsessive-compulsive disorder, which is medically related to depression, it found Japan didn't have any standard test for measuring the disorder. So it had to write its own based on a translation of the U.S. standard.

Meiji's drug, which it sells under the name Luvox, was finally approved by Japanese regulators in 1999 -- making it the first Prozac-class drug available in Japan. But the real challenge was getting the drug accepted by the Japanese public. Meiji and the two other companies that share rights to sell the drug in Japan -- the drug's inventor, Solvay SA of Belgium, and a larger Japanese company, Fujisawa Pharmaceutical Co. -- set about effecting nothing less than a sweeping cultural change.

One crucial step: altering the language people use to discuss depression. The Japanese word for clinical depression, utsu-byo, had unpleasant associations with severe psychiatric illness. So Meiji and its partners began using the phrase kokoro no kaze, which loosely translated means "the soul catching a cold." The message: If you take pills to fix a stuffy nose in wintertime, why not do the same for depression? Norikazu Terao, who directed marketing for Meiji and its partner companies, says he would constantly trot out the kokoro no kaze line to explain to Japanese reporters why the taboo surrounding the disease should be lifted. (The origin of the phrase isn't clear, but Mr. Takiguchi's TV program had remarked that Americans took Prozac as if it were cold medicine.)

Ichiro Kitasato, Meiji's president, read "Listening to Prozac" and required all senior pharmaceutical managers to do the same. But that was tough: The book, which was written by psychiatrist Peter Kramer and published in the U.S. in 1993, has yet to be translated into Japanese. So they split up the work, each reading a chapter and reporting its main message to the others, recalls Katsuyoshi Ogawa, head of product management. Dr. Kitasato, the scion of a well-known Japanese medical family, recalls that he jumped at the chance to market the drug when Solvay was looking in the late '80s to bring it to Japan. "People in the company said there are too few patients in Japan," he says. "But I looked at the U.S. and Europe... and thought this is sure to be a big market."

The marketing drive accelerated in December 2000, when GlaxoSmithKline PLC became the first Western company to get approval on its own for another Prozac-class antidepressant, Paxil. These antidepressants, known as selective serotonin reuptake inhibitors, or SSRIs, work by improving the flow in the brain of serotonin, a chemical thought to help control mood. Glaxo helped form and underwrote a committee of psychiatrists and depression patients, which in turn signed up a top Japanese advertising agency to create a fancy Web site called utu-net.com.

The site, which doesn't mention Glaxo's sponsorship, features articles about depression, all with the underlying message that drugs can help. It includes a testimonial from former TV talk-show host Hiroshi Ogawa, who tells how depression nearly led him to commit suicide in 1992 before older antidepression drugs helped him to recover. A Glaxo spokesman says the site keeps quiet about its backer because it wants to focus attention on awareness of depression rather than on a specific company or medication.

Declining Suicides

The number of suicides in Japan each year -- which hit a peak of 33,048 in 1999 -- declined 3.3% in 2000 and another 2.9% in 2001, the first full two years that SSRIs were available. However, the rate remains very high compared with earlier years, and many factors can contribute to suicide, so it's too early to tell whether the new drugs contributed to the reduction.

Japanese sales of GlaxoSmithKline's Paxil reached ¥12 billion ($96.5 million) in 2001, its first full year on the market, and the figure is on track to rise this year. By comparison, U.S. sales of the drug last year were $1.8 billion. Japanese sales of Luvox and Depromel -- the name under which the drug is sold by Meiji's marketing partner, Fujisawa -- totaled ¥14.5 billion last year. (In May Solvay removed Luvox from the U.S. market, where it had been approved to treat obsessive-compulsive disorder, after the Food and Drug Administration cited problems with documents filed by Solvay to the FDA. The company, which has been the drug's U.S. marketer, says Luvox is safe and expects it to be back on the market next year. The generic form of the drug, fluvoxamine, is still sold in the U.S.)

Other drug companies have also ramped up their efforts in Japan. Pfizer Inc. had started trials of its blockbuster Zoloft in Japan in the early '90s, but its crucial large-scale human trial failed to use strict enough standards when picking patients, says Kenneth Wolski, who oversaw the trial as head of development for Pfizer's Japan subsidiary until he left the company in 1996. The company's new-drug application, which has been pending with Japanese regulators since 1998, hasn't been approved. A Pfizer spokesman blamed the low awareness of depression in Japan at the time, and "different standards in clinical-trial design." Two months ago, Pfizer announced a new clinical trial of Zoloft at 20 sites across Japan.

And Prozac -- which had world-wide sales of $1.99 billion and U.S. sales of $1.53 billion last year -- is finally coming to Japan. Andrew Macarenas, head of Lilly's Japan operations, says it should be on the market by 2004 -- some 17 years after it first went on sale in the U.S. The company is preparing the way by paying for the activities of a committee of Japanese doctors that promotes awareness of depression. The committee holds seminars for doctors and operates a Web site. "A number of things are happening to take mental health out of the cupboard" in Japan, says Mr. Macarenas. "It's not a taboo anymore."

The message from drug companies has fit well with Japan's medical culture. Japanese doctors are accustomed to loading up patients with medication, and are permitted to sell drugs directly to patients, often at a significant profit. Meiji and Glaxo have conducted hundreds of seminars about depression for general practitioners and psychiatrists across Japan, and the companies say interest is strong.

Atsushi Satomura, a psychiatrist in the Tokyo suburb of Fujimi, says he gets most of his information about treatment regimens from "lectures sponsored by drug companies." He says he is "constantly" visited by drug salespeople.

Image Change

Some psychiatrists have begun changing their image to reach out to less severely ill patients. Traditionally, Japanese psychiatrists worked in either general hospitals or psychiatric hospitals, known as seishin byoin -- a term that suggests buildings surrounded by barbed wire and patients in a drugged stupor. Recently, hundreds of psychiatrists have opened stand-alone offices designed to serve the general public, dubbing such places mentaru kurinikku -- a more benign term that derives from the Japanese pronunciation of "mental clinic."

"People with mild depression or panic disorder don't want to go to a psychiatric hospital," says Dr. Satomura, who worked for many years in large hospitals but last year opened a solo practice called the Fujimi Mental Clinic. Dr. Satomura says it's become easier recently to diagnose many of his patients because they often have heard about depression from books and the popular media, and describe their symptoms clearly. He says 70% of his patients are women; they often complain that they've lost all energy to do household tasks such as cooking and cleaning.

Unlike in the U.S., where a wide variety of psychologists, clinical social workers and other practitioners can receive a state license, the Japanese government doesn't officially recognize nonphysicians in the mental-health field. The national health-insurance system covers visits to a psychiatrist as well as psychiatric drugs and hospitalization, but it doesn't pay psychiatrists any more for an hour-long psychotherapy session than it does for a quick visit to get a prescription refilled. Many U.S. specialists believe the drugs work best in combination with psychotherapy, also known as talk therapy. But in Japan, many people -- including some psychiatrists who administer the drugs -- dismiss Western-style psychotherapy as alien to Japanese culture.

Recently, a few private bodies have begun licensing so-called counselors to provide such therapy. Some big Japanese companies, worried about potential lawsuits from families of suicide victims, have started programs such as mental-health hotlines to give troubled employees easier access to psychiatrists and counselors. And some reformers are pushing for the government to provide insurance coverage for counseling, but these changes are still in their infancy.

In Japan, "there's no tradition of paying money to visit a counselor," says Kentaro Kawakami, head of the Japan Counseling Association, a licensing body for counselors. Still, it's a far cry from a decade ago. Hiroko Mizushima, who was a medical student specializing in psychiatry at prestigious Keio University in the early 1990s, says, "We weren't taught anything about how depression is increasing or how it's the disease of the modern age." Instead, the traditional Japanese view prevailed, that depression was just a figment of the imagination that could be solved with konjo, or willpower.

"There's been a big jump in progress," says Shuko Fujiomi, a 40-year-old who has struggled with depression. "Recently it's become something you can say more lightly." Ms. Fujiomi has publicly discussed her depression, including on a TV show this year. Her career, creating books of cartoons for adults -- a popular Japanese art form -- has flourished, and she has even written one called "Let's Go to a Psychiatrist!" Ms. Fujiomi says many of her friends in the entertainment world are open about their depression, but -- much as in the U.S. -- employees of big companies are more reticent. "They're worried they'll be fired," she says.