Prescription for obesity

When she was 12, Jena Graves could still wear the thin Hollister shirts fashionable among girls her age. Her slender figure on a 5-foot-2 frame was a daily presence on the softball field.

Then the Napa native started feeling short of breath. When softballs hit her body, they left giant, dark bruises. And she was gaining a little weight. The diagnosis came in 2008: lupus.

Graves was given a daily prescription of prednisone, a corticosteroid that mostly kept the chronic autoimmune disorder under control. But it had unintended side effects. Over five years, Graves's weight ballooned from around 120 to 272 pounds.

Prednisone "just tells you to eat, and you want to eat," said Graves, now 19. "There is nothing in your mind thinking, 'Hmm, maybe I shouldn't be eating this.' "

What Graves didn't know was that prednisone belongs to a class of medications known as obesogenic drugs. They are designed to treat a diverse range of ailments, such as lupus, diabetes and depression, but, in ways still not fully understood, can also increase a person's appetite or make them more likely to retain fat, contributing to a small to severe weight gain.

Whatever form they take, obesogenic drugs are an unwitting contributor to the U.S. obesity epidemic in part because they are so common, medical experts say. One example is antidepressants, which grew in use nearly 400 percent from 1988 to 2008, according to the Centers for Disease Control and Prevention.

"All these medications are absolutely wonderful when they work in the right patients," said John Morton, director of bariatric surgery at Stanford Hospital and Clinics, who performed a gastric bypass surgery on Graves in June that helped curb her weight gain. "But we've got to figure out if it's appropriate or not to blanket America with prednisone and other obesity-generating drugs that are creating problems."

Graves isn't the only patient who has paid the price for being on one prescription too many, he said.

"I can't tell you how many patients come in to see me who've been on medications for years," he said. He asks: "Why are you on this medication? 'I don't know.' Has someone followed up? 'No. I just get my prescription refilled.' "

Graves' struggles

From the seventh grade onward, Graves was put on a laundry list of medications, including prednisone, prescribed by a UCSF physician at a high daily dose of 80 milligrams.

She tried to satisfy her newly emerged appetite with junk food, but never felt quite full.

"Mostly I would ask my mom for it," she said, "but when she was gone to work, I would just stand at the fridge and eat, because that's what it does to you."

Prednisone - a corticosteroid most commonly used to treat lupus - mimics the effects of hormones the body produces in the adrenal glands, according to the Mayo Clinic. When prescribed in doses that exceed the body's usual levels, prednisone suppresses both inflamed body tissues and the immune system, thus controlling conditions such as lupus, in which the body's immune system mistakenly attacks its own tissues.

But prednisone, like other corticosteroids, also prevents carbohydrates from being absorbed. Instead, they are converted into fat, which the body retains along with water.

The side effect is well documented in medical research, but Graves said she didn't figure it out until she was well into the regimen.

"No one told us that was the big side effect," she said.

Her mother, Mindy Graves, a surgical scrub technician, worried about how the drugs were changing her daughter but decided to trust the doctors. "I just wanted her to be better," she said. "I figured, 'These people know what they're doing.' "

Diabetes diagnosis

Prednisone wasn't the only drug Jena Graves took, nor was lupus the only disease she had.

Doctors soon determined that she also had developed Type 2 diabetes, the most common form of the disease. The condition may have been triggered by high blood sugar in her body, another side effect of prednisone.

So Graves took metformin, a pill that helps regulate blood glucose levels. Metformin has been shown to promote modest weight loss, though Graves is not sure what effect it had on her. She was not put on insulin treatments, which are known to cause weight gain.

Insulin, an injection medication taken by many of the nearly 26 million diabetics in the United States, allows glucose to enter the body's cells from a patient's bloodstream. Glucose levels in the blood drop - the desired effect - but if the patient doesn't exercise enough or eats too much, unneeded glucose will remain in the cells, leading to fat buildup.

A United Kingdom study of 2,520 diabetics from 1977 to 1997 showed that diabetics who were treated with insulin gained an average of 14 pounds over a decade.

Patients who are obese often aren't that way because they lack self-control, but because they may have inherited their parents' body mass index or risk of Type 2 diabetes, said Alison Reed, a pediatric endocrinologist at California Pacific Medical Center in San Francisco.

Metformin and other oral medications can be useful alternatives to insulin, but if the weight gain is not life threatening, and insulin ultimately helps patients get a handle on their disease, the therapy shouldn't be thrown out the window, she said.

The dilemma is that more than 80 percent of people with Type 2 diabetes are overweight to begin with and would benefit from lifestyle changes such as healthier eating and exercise. Giving them medication that can increase their weight even more can impede that goal.

"It's really difficult because I think they can get down about their weight and feel depressed about it," Reed said. "That impairs their ability to really make those healthy lifestyle changes, because they feel bad."

Psychological toll

Watching her weight more than double took a psychological toll on Graves.

"I basically slept all the time," she recalled. "That's when I started gaining weight and basically got depressed because I couldn't play softball anymore and depressed because of my weight."

After she was diagnosed with lupus, Graves withdrew from seventh grade at Redwood Middle School in Napa. She took classes in the hospital and last year earned her diploma from Vintage High School, another public school in town, walking across the stage for graduation.

But she no longer found it easy to socialize and make friends.

"I just felt like people were judging me every time they saw me and didn't want to hang out with me and stuff," Graves said. "I stayed at home most of the time and was antisocial."

Mental anguish is common among patients who are caught off guard by weight gain caused by prescribed drugs, physicians said. Sometimes the result is clinical depression, though that wasn't the case with Graves.

If depression leads to a loss of appetite and lost weight, antidepressants can help patients rediscover their desire for food. But antidepressants can also trick their brains into thinking they're hungrier than they are, or sap their energy so they feel less active.

These days, the more popular antidepressants, known as selective serotonin reuptake inhibitors, are not likely to cause people to gain weight if they are used for six months or less. But one of them, paroxetine, also known as Paxil, raises the risk of weight gain. In a 2000 study, a quarter of subjects on the drug gained significant weight over six months, compared with about 4 percent who took sertraline and 7 percent on fluoxetine.

Weight gain from antidepressants usually isn't life threatening, so it is important to think carefully before quitting, said Laura Davies, a child, adolescent and adult psychiatrist at California Pacific Medical Center.

"Antidepressants aren't perfect, but is your life overall better than it was before? So often the answer is yes," she said.

"It sucks to be 25 pounds heavier, but (if) you're getting out of bed - that's a really good thing," Davies added. "Yeah, it's not good to be 25 pounds overweight, but at least you're involved in life and at least you can tackle the 25 pounds."

The right balance

The key, medical experts said, is for patients and physicians alike to re-evaluate a medication after a certain amount of time - six months to a year, for example - to determine if it is doing more harm than good. There might be an alternative that doesn't cause big weight gain.

Finding the right balance between what a patient needs and wants in a successful treatment can be tricky, said Patrick Finley, a clinical pharmacy professor at UCSF.

"There's definitely people on medications who don't need to be on medications," he said. "But I think there are more people not receiving medications that would benefit from them."

Around 2009, Graves and her mother, seeking a second opinion, left UCSF for Stanford. Doctors there immediately lowered Graves's dose of prednisone. Eventually, they threw out most of her 25 other medications, declaring them unnecessary.

Prednisone had slowly depleted the calcium from Graves's bones, fracturing her back. In June, Morton, the surgeon, performed a gastric bypass surgery that allows food to bypass her stomach, advance more quickly through her body and make her feel fuller in smaller amounts.

Graves is now healthy, happy and active. She is no longer on prednisone. Instead, another drug called azathioprine keeps her immune system - and her lupus - under control. Her diabetes is in remission.

Someday she wants to raise show cattle on a ranch of her own. She's off to a good start: She was just named grand champion for a heifer she entered in the Napa Town and Country Fair.

And she is on her way back to her normal weight, losing 40 pounds since the surgery. Recently, her mother recounted, Graves bought a pair of jeans online and turned to her proudly.

"Mom," she told her, "I can actually fit in teen sizes."