Looking at the World Through Paxil-Colored Glasses

Michael Jenike, a professor of psychiatry at Harvard and director of the Obsessive-Compulsive Disorder Institute at McLean Hospital in Belmont, Mass., says SSRIs are "more likely to cause weight gain than any other class of antidepressants," and, on that score, "Paxil is by far the worst."

Brain scientists cannot fully explain what causes the weight gain, much as they cannot fully explain why the SSRIs work to ease depression, OCD and other mental illnesses. They are attempting to piece together the answers. According to Sheldon Preskorn, chair of the department of psychiatry at the University of Kansas School of Medicine, SSRIs were the first class of psychotropic drugs to target a specific molecular site in the brain, reducing the chances of unwanted effects on neighboring sites. Preskorn describes the working of the SSRIs with a complicated, clinical precision I shave to the basics here: Serotonin, the brain chemical most closely associated with both depression and OCD, flows through the synapse between neurons and back again to communicate chemical messages. Paxil and other SSRIs specifically target the uptake neurons to slow the reuptake of the serotonin, so that it lingers in the synapse. This appears to help patients with depression and OCD, although scientists are not sure why. At one point it was thought that such patients produce less serotonin, but scientists now say that appears not to be true.

Scientists have a similarly sketchy understanding of how Paxil and other SSRIs cause weight gain. Serotonin is associated with mechanisms affecting sleep, appetite, balance, sensory interpretation and the reproductive system; scientists believe serotonin may be implicated in disorders of these functions. Just why is unclear: Some people lose weight on SSRIs, some gain, others stay the same.

I was one of the unlucky ones. By 2004, I had to accept myself for who I was: a middle-aged woman with a thickened middle and an eating disorder. I ate healthy things -- grapes, pineapple, cherries or unsalted almonds -- but by the bowlful, and slice after slice of whole grain bread.

I also ate cookies. Three were never enough, and 10 were never too many. One night, as I stood in my kitchen staring down a bag of Milanos, I realized that it might as well have been a pack of cigarettes or a bottle of scotch. When I opened my refrigerator, I was in the thrall of something. I ran into a former therapist who hadn't seen me in years. "But you never had issues with food!" she said, genuinely astonished at the sight of me.

In the fall, I went to a gym to try a personal trainer and got shocked into reality. "I'm sorry, but I can't let you exercise," she said after taking my blood pressure, which was 150/96 -- too high by gym rules to use the facilities.

Six months later, I finally got up the courage to see my internist for cholesterol tests. He called me back with dismal news. My total cholesterol was 268. I needed Lipitor and exercise, or else. Ramsey prescribed the anti-seizure medication Topamax, which causes weight loss for many patients in the first few months.

In early June of this year, I spent a week alone at a yoga retreat in the Berkshires to kick-start a new regime. I rose at dawn every day for yoga and ate from a strict vegetarian buffet. I followed that with a week at the beach, where I walked for miles and swam every day in the surf. By July, I was 12 1/2 pounds lighter, my skirts were sliding off my hips, my blood pressure was normal, and my cholesterol levels were improving.

But I can't cue the fireworks yet. I now have two very potent chemical agents at work in my brain. Topamax is not without its downside. It makes me sleepy and thirsty, and, after several months, my balance is suffering. I can no longer hold a standing yoga pose without toppling. My excessive appetite is coming back, despite my best intentions, although for now the weight is staying off.

These days, I find myself beset by questions no one can answer for sure: Can I take Paxil forever? Must I take Topamax as well? If I regain weight and must switch drugs, will I have trouble going off Paxil? Of all the SSRIs, Paxil has the shortest half-life, which means that it is metabolized and washes out of the system the fastest. Stopping, even gradually, can shock the nervous system and bring difficult side effects. Even if I can switch without incident, will another drug work as well? Preskorn assures me that, thanks to the Human Genome Project, there are exquisitely precise pharmaceuticals to come. But will they come in time for me?

I'm keenly aware that the normalcy I enjoy now may be borrowed. No one knows if long-term use of Paxil will damage my body, and I worry that the drug's beneficial effect on my brain chemistry will diminish over time. I assume that OCD is napping in me somewhere. Even now, when I am overextended, or overly tired, there is a slight insistence in the

cadence of my brain. Much of the time, though, I am as steady as a pioneer. I believe I can face whatever is coming because I have endured all of what has gone before.

I remind myself frequently of a trip I took, alone, to Paris, for a glorious week in fall 2003. I woke up every morning in a tiny borrowed apartment in a North African section of the city and spent the day as I pleased, being, as the French say, a flaneur -- wandering the city at will. I ducked into used-book shops, boutiques and galleries. I spoke to strangers and once joked with some cops. I visited graves at Pere Lachaise, sat in the sun at Place des Vosges and ate couscous near an African market on le boulevard de Menilmontant.

One evening I took the Metro to my friends' place near l'avenue Georges V. It was my birthday, and they were taking me to dinner. The Metro stop near their apartment was Tour Eiffel, and, as I walked up the steps to the street, the Eiffel Tower was the first thing I saw, looming in the dusky sky like an enormous mechanical giraffe. As soon as my shoes touched the pavement, the entire tower lit up in tiny white lights. I stood there for a moment frozen in delight and, like a child, I decided that it was all for me -- for my birthday, for my trip, for my friendships and for my freedom. The last, alone, would have been more than enough.

Mimi Harrison is a Washington writer.