Brainstorming : Smoking addiction. Obesity. Compulsive shopping. Experts keep finding new uses for antidepressants. But critics say such treatments are getting ahead of the research.

John Dodd had tried to quit smoking for 19 years. Classes, private counseling, the nicotine patch, hypnosis--nothing worked to end his three-pack-a-day habit.

Dodd was so addicted that he quit his job as an engineer at General Dynamics when his building went smoke-free and his colleagues became annoyed with his penchant for holding outdoor meetings.

Even with emphysema, asthma and three bypass surgeries to treat arteriosclerosis in his right leg, the 55-year-old Ontario man could not free himself from the “intolerable” craving.

Told that his leg would have to be amputated if he did not stop smoking and improve his health overall, Dodd happened upon a smoking cessation clinic in 1993 at the Veterans Affairs hospital where he was recovering from bypass surgery. Unbeknown to him, researchers there were undertaking a revolutionary study to determine if the antidepressant Wellbutrin could help heavily addicted smokers quit.

“Within 48 hours of taking the medication, I was still having attacks of wanting to smoke, but for the first time, I had the feeling that I might be able to ride out the demon--that I might not go crazy,” says Dodd, who was treated at the Pettis Veterans Medical Center in Loma Linda. “The drug gave me a glimmer of hope. And I just kept going.”

He hasn’t smoked in 14 months and has seen both his physical health--and his outlook on life--improve dramatically while taking a low dose of Wellbutrin.

Antidepressants are clearly no longer just for the treatment of depression.

While the U.S. Food and Drug Administration has approved only a few antidepressants for disorders other than depression--Prozac has been given the go-ahead for obsessive-compulsive disorder--use of the medications for other conditions is multiplying while dozens of formal studies are under way.

Smoking addiction, obesity, autism, compulsive shopping, attention deficit disorder, obsessive hair-pulling, compulsive gambling, alcoholism, chronic fatigue syndrome, premature ejaculation, premenstrual syndrome, irritability and headache pain are also among the conditions for which antidepressants are being tested or enthusiastically embraced.

So ripe is this bulging research vein that at a meeting on new drug research slated for later this spring, researchers plan to present studies on the new antidepressant Effexor and its effects on cancer pain, premenstrual syndrome, attention deficit disorder, multiple sclerosis, panic disorder and social phobias, says a representative for Wyeth-Ayerst, the maker of Effexor.

Much of the research is centered on the newer class of selective serotonin reuptake inhibitors--or SSRIs--which includes Prozac. But even older antidepressants are being tried for other uses.

“It’s clear that antidepressants--the SSRIs and even the older, tricyclic antidepressants--have a much broader efficacy than just for depression,” says Dr. Steven M. Paul, vice president for central nervous system research at Eli Lilly, the makers of Prozac. “There is a lot of controlled, clinical research going on. . . . And when these research reports come out, I think physicians won’t want to withhold the drugs for these other purposes.”

Few mental health experts would disagree that Prozac and its chemical cousins Paxil, Zoloft and Effexor have benefited millions of people whose lives had been wrecked by crippling depression. About 17% of Americans suffer depression at some point during their lives, according to the American Medical Assn., but more than half are never treated.

The newer antidepressants, however, have made treatment easier because they are free of many of the harsh side effects, such as heart problems and memory loss, common to the previous generation of antidepressants. Moreover, they are safer and tend to be nonaddictive.

But while studies may yield evidence that antidepressants are effective for a wide range of serious conditions, detractors say there is still a dearth of hard proof, and they criticize their use for “conditions” that do not even rate mention in medical manuals.

“The prescriptions for Prozac, in particular, have increased dramatically, and the uses of it have been broadened considerably to a whole host of non-clinically diagnosable problems, such things as feelings of inadequacy, lack of self-confidence and social inhibitions,” says Russell Newman, executive director for practice at the American Psychological Assn.

“We at the APA have no problem with the use of medications that have been demonstrated to be useful. The concern is when drugs become used for some sort of performance or production enhancement. That begins to move us in the direction of: ‘Who is to say anyone can’t take Prozac to be more productive or energetic?’ It’s this unbridled use of medications that is of concern.”

But most critics concede that even when used inappropriately, the new breed of antidepressants appears to present little, if any, physical danger to the user.

Rather, they say, the threat lies more in their use as a substitute for traditional therapy or other solutions that might deal more directly with the person’s problems.

Because their side effects are clearly not life-threatening, the new drugs are a convenient “quick fix” for people who may need long-term psychotherapy, agrees New York psychologist Roger P. Greenberg, a critic of the widespread use of Prozac.

The SSRIs have no significant effects on the major organs, and studies show no harm from long-term use. The typical side effects experienced by some people include nausea, insomnia and the jitters.

Newman says one only has to look at a recent trend among veterinarians of giving Prozac to antisocial dogs to see that the traditionally tight restraints on psychotropic medications have been snapped.

“That, in and of itself, suggests the direction we’re moving in,” he says.

Misbehaving mutts aside, others see no problem with the liberal use of antidepressants if they are thought to be helpful.

“This only gets out of hand if you are forcing people to take things they don’t want to take,” says Dr. Donald Black, a professor of psychiatry at the University of Iowa. “If these medications have wonderful effects, I personally don’t see anything wrong with it. If they are relieving unhappiness or inappropriate behavior, what is wrong with that?”

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So sweeping is the drugs’ potential that some psychiatrists dislike referring to the SSRIs as “antidepressants.”

“That gives you a false idea of what these medications are about,” says Dr. Joel Yager, a professor of psychiatry at UCLA. “They are complex drugs that affect brain serotonin. They could just as easily be called anti-compulsivity, anti-obsession or anti-irritability drugs. It’s clear all of those psychological characteristics are impacted by SSRIs.”

No one is saying that compulsive shopping, premenstrual syndrome, depression and smoking addiction are similar conditions in either cause or treatment. But many disorders such as these appear to involve the neurotransmitters serotonin, and, possibly, dopamine and norepinephrine.

The SSRIs and related compounds increase serotonin, dopamine and norepinephrine. Sufficient quantities of these chemicals must be available between nerve cells to transmit brain messages affecting emotional expression. For example, serotonin is thought to regulate a number of central nervous system functions such as mood and appetite for food and sex.

But in some people, studies show that serotonin is rapidly reabsorbed by the sending cell instead of being suspended in the synapse and eventually binding with the receiving cell. The SSRI drugs halt the reuptake of serotonin.

“If you know the action of the drug, you can make good deductive reasoning on how the new agent might work,” says Dr. Robert Gerner, a psychiatrist and expert in psychopharmacology at the West Los Angeles Veterans Affairs Medical Center.

For example, the highly successful treatment of obsessive-compulsive disorder with SSRIs has led to an explosion of research on their use for other types of “compulsive” behaviors.

“There are many other obsessive disorders, like nail biting, hair-pulling, binge eating; compulsive behaviors that are criminalized, such as sexual perversions and exhibitionism, shoplifting, stalkings. There are many ways that obsessions can manifest themselves,” Gerner says.

At the University of Iowa, Black has completed a small study giving fluvoxamine to compulsive shoppers. Fluvoxamine is marketed under the name Luvox and is approved in the United States only for treating obsessive-compulsive disorder. But it is widely used as an antidepressant in other countries.

Black gave eight women fluvoxamine for eight weeks and then stopped the treatment. The women received no other counseling or therapy.

“Every single person responded,” Black says. “They told me they noticed fewer spontaneous thoughts and fantasies about shopping and spending. They spent less time shopping and spent less money. They were better able to resist their impulses.”

Similarly, UCLA’s Yager has used Prozac to help women with anorexia nervosa who also exercise compulsively. According to a recent study, women who had restored their weight while hospitalized and then began taking Prozac were much more likely to maintain their weight one year later, he says.

“I had one patient who exercised compulsively; she did the stair-climber hours a day. Two months after starting Prozac, the entire syndrome evaporated. She has put on weight and has been fine,” he says.

Prozac may soon be approved for bulimia. And while many doctors who treat eating disorders are also prescribing the SSRIs, “This needs to be studied in a much more systematic way now,” Yager says.

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More research is clearly needed to show which antidepressants work best for particular disorders.

For example, researchers have long suspected that heavily addicted smokers might also suffer from depression, but previous studies on the older classes of antidepressants showed little effect.

In a study directed by Dr. Linda Hyder Ferry at the Pettis Memorial Veterans Administration Medical Center in Loma Linda, heavily addicted male smokers who received Wellbutrin in addition to smoking cessation and behavior modification classes had a much higher rate of smoking cessation: 59% compared to 20% in men who received the placebo. Wellbutrin influences dopamine and norepinephrine in the brain.

A later study of 200 people showed that the medication was effective in smoking cessation even when the subjects were not depressed. The smokers receiving the drug still had almost double the quit rate--40% compared to 24%--as smokers receiving a placebo.

“We may be on the way toward a non-nicotine method to quit smoking,” says Ferry, chief of preventive medicine at Pettis. “I’m hoping (Wellbutrin) is the first one.”

The drug may work because it mimics the same sensations as nicotine and can be used to wean smokers without the disturbing withdrawal symptoms that sabotage many smokers.

Wellbutrin, Ferry says, “is the only antidepressant not to let dopamine come crashing down on people when they stop smoking. People tell me, ‘The craving isn’t totally gone, but I can handle it now. I can deal with it.’ ”

Prozac, meanwhile, is being used in some weight-loss programs because it seems to relieve the irritability and melancholy that dieters often experience. The drug may also act as an appetite suppressant.

Marti Lakin, 45, of West Los Angeles, had battled her weight for decades before she tried a diet and exercise program that utilized Prozac and an appetite suppressant called fenfluramine. She has lost 80 pounds.

“I can’t say enough for the Prozac. It doesn’t make me feel euphoric, but there is a feeling of self-loathing that comes from years of being chronically obese and society’s pressure. The Prozac keeps me from the severity of these feelings,” she says.

It’s not clear why Prozac is effective in obesity patients. It might improve mood, suppress appetite or both, says Dr. Morton Maxwell, director of the University Obesity Center at UCLA, where Lakin is treated. But, he notes:

“I started this program 19 years ago. All we had for a very long time was a low-calorie diet. Patients would lose a lot of weight and come back because they gained all or part of it back. With these drugs, I’m hearing things like, ‘For the first time in my life, I feel like a thin person. I don’t feel compelled to eat.’ ”

Nevertheless, Maxwell advises caution when using Prozac for obesity. The drug is prescribed as part of a strict regimen that includes another drug for appetite suppression, dieting, exercise, behavior modification and group therapy.

“Prozac is not the answer,” he says. “For one thing, these drugs don’t work very well by themselves. They have to be combined with behavioral changes, low-calorie diets and exercise. In the future, I think we’ll have a different category of (weight loss) drugs that work on metabolism. But the SSRIs are the best we have right now.”

Antidepressants have also been used in the arsenal of therapies to treat premenstrual syndrome and chronic fatigue syndrome. But, according to both patients and doctors, they are not a panacea.

Jody, a 36-year-old Pasadena woman who asked not to be fully identified, has struggled with chronic fatigue syndrome for 13 years. The cause of chronic fatigue syndrome is unknown but it often involves persistent flu-like symptoms. She tried Prozac at her doctor’s suggestion but gave up on it after a few months.

“I was doing better for a while on Prozac, but I think I overdid it,” she says. “It may improve your mood, but eventually you may run out of energy. I don’t think the serotonin drugs are the answer (for chronic fatigue), because the problem is also immunological.”

But the most questionable uses of Prozac, Zoloft and Paxil are as confidence builders, energy boosters or to “fix” irksome personality traits. Former world-class runner Alberto Salazar ignited this debate last year when he said that Prozac had helped him regain a competitive edge after a long period of feeling listless and tired.

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Yager, of UCLA, says he has no qualms with the use of SSRIs to smooth over troublesome personality characteristics, even when a clinical disorder is not apparent.

“It you are a snappy person, you don’t make friends so easily, and that can be a problem,” he says. “For some people, these SSRIs make a big impact on personality. . . . I had one patient tell me, ‘My husband says I had better never go off this drug.’ ”

But this is where opinions among health experts begin to diverge.

“Where do you draw the line between an actual disorder or a personality characteristic?” asks Newman, of the APA. He compares the use of Prozac for confidence or performance boosters as similar to the deadly trend of steroid use among weightlifters and other athletes.

“An athlete takes steroids for an enhanced performance only to precipitate other athletes taking steroids to enhance their performance as well,” he says.

Newman and others say another disturbing trend is the use of SSRIs to treat conditions that traditionally benefit from psychotherapy. For example, someone with a mild form of depression may receive a prescription for antidepressants much more quickly these days.

Since medications usually cost less than weekly psychotherapy, which, according to one study, usually lasts about 58 weeks, “reviewers for insurance companies are directing . . . psychologists to refer their patients for (medications) in lieu of psychotherapy,” Newman says.

He suggests that professional medical societies establish tighter guidelines for when antidepressants should be dispensed.

But Gerner, of the West Los Angeles Veterans Affairs Medical Center, notes that years ago, medications were denied for the treatment of schizophrenia, manic depression and depression because of fears of overuse. That strategy was clearly misguided.

“I don’t know who should control these drugs. To control them is to deny people the experience of growth,” he says. “To me, it’s not an alternative to say, ‘We shouldn’t use medications for this; we should use psychotherapy.’ Psychotherapy costs thousands and thousands of dollars a year. And a prescription costs a few hundred.”

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Other critics of the Prozac explosion simply fear the medication will not live up to its hype.

In a study published last fall, psychologist Greenberg analyzed 13 previous studies on Prozac and concluded that although the drug has far fewer side effects, Prozac was no more effective than the older tricyclic antidepressants.

“We concluded that the facts were more uncertain than the public has been led to believe,” says Greenberg, of the State University of New York-Health Sciences Center in Syracuse.

“People have latched on to it as if it’s something magical and that it will make a difference without any effort; that they won’t have to make any other changes in their lives. I think that illusion has been harmful to people who aren’t exploring psychotherapy.”

Greenberg urges doctors to avoid prescribing the SSRIs for various conditions until research clearly shows the treatment is effective.

“People are reaching to some degree,” he says. “They are trying all these things on a variety of different conditions for which the research literature hasn’t caught up. Of course, the pharmaceutical companies are happy to underwrite a lot of this research. But I don’t think there is basis for the wild enthusiasm, and it may ignore data that already suggests (SSRIs) aren’t as effective.”

Gerner, however, foresees few restraints on the widening use of antidepressants. Exactly 100 years ago, he says, Sigmund Freud suggested in a paper that scientific explanations would eventually be found to describe the way people feel and act. Of course, Freud lacked the tools to discover neurotransmitters and focused on psychoanalysis to delve into mysteries of depression, anxiety and psychosis.

But, Gerner notes: “Freud thought all behavior was biological.”