Sept. 19, 2005 – Does it matter which antidepressant you take?

No, if fighting depression is all you care about. Yes, if you worry about particular side effects, how often you have to take pills, or if cost is an issue.

The findings come from a pooled analysis of studies comparing one new-generation antidepressant to another by Richard A. Hansen, PhD, and colleagues at the University of North Carolina, Chapel Hill.

“Not all antidepressant drugs work for every person. We found about 40% of patients do not respond,” Hansen tells WebMD. “But with regard to comparing the number of people who respond to one versus the number who respond to another, there really aren’t significant differences. For the most part, what we know is that they have a relatively equal likelihood of responding to each agent on a first try.”

That leaves three things that are different about the drugs: their side effects, how often one must take them, and how much they cost.

“The big message is the side effect profile, and understanding how individual patients prefer different side effects,” Hansen says. “We were able to identify the side effects that are more common for some drugs than others. So being able to match a patient and their preferences for anticipated side effects could improve prescribing and eventual drug-therapy outcomes.”

Hansen and colleagues report their findings in the Sept. 20 issue of Annals of Internal Medicine.

Symptom Improvement vs. Remission

Emory University psychiatry professor Philip T Ninan, MD, takes issue with the methods used in the Hansen study. He says that just because antidepressant drugs don’t show any differences when all patients are considered as a whole doesn’t mean there aren’t differences in how the drugs work in specific subgroups of patients.

Ninan says neither depressed people nor their doctors care about a drug’s efficacy — defined by Hansen and most clinical trials as a 50% decrease in depressive symptoms. What matters to patients, Ninan says, is a drug’s effectiveness — its ability to put a person’s depression into remission.

“Would you find a difference among these drugs if you looked at remission? That is an important question,” Ninan tells WebMD. “Many of these studies don’t report remission rates, so the data are not available.”

Ninan does feel that all of the drugs have similar efficacy. For him, as for Hansen and other experts consulted by WebMD, differences in side effects are the main question.

“If a generic patient comes in, it doesn’t matter which they take,” he says. “I would weigh a patient’s gender, age, menopausal status, degree of symptoms, suicidality, concern with side effects — these are all issues I would take into consideration when choosing an antidepressant. Efficacy is not the primary issue. That is equivalent.”

Side Effects Determine Choice

Mark Zimmerman, MD, associate professor of psychiatry and human behavior at Brown University, has studied why psychiatrists prescribe different antidepressants. He says that the reasons don’t always match up with clinical trial findings.

He says that psychiatrists look at other problems patients may have besides depression — particularly anxiety, reported by at least half of people with clinical depression — specific patient symptoms, and specific side effects.

“So someone who presents with poor appetite with weight loss and insomnia may be prescribed Remeron because it tends to have the side effects of increased weight and works against fatigue,” Zimmerman tells WebMD. “Someone with retarded psychomotor function tends to be prescribed drugs that have restlessness as a side effect. But there is no evidence that this is an effective way of treating individual patients.”

Mark I. Levy, MD, a psychiatrist in private practice and assistant clinical professor of psychiatry at the University of California, San Francisco, says prescribing antidepressants is an art — an art based on understanding side effects.

“For example, if an antidepressant is causing sexual inhibition or gastrointestinal symptoms, then it is often worth switching to Wellbutrin because it has the least sexual side effects and no GI side effects,” Levy tells WebMD. “Sometimes sedating antidepressants like Paxil are preferred when depression-driven anxiety is interfering with sleep.”

Zimmerman makes patient preferences an explicit part of the decision.

“When I am prescribing a first antidepressant treatment, I give patients a chart I have developed that lists the most common side effects and lists the relative frequency of those side effects for the different medications,” he says. “We engage in a dialogue as to which medication makes the most sense for them. Some want to gain weight; some don’t care about sex dysfunction. There are clearly individual differences.”

And these differences in how well patients tolerate various side effects make a huge difference in whether patients take, and respond to, their medicine.

“Most patients do have very clear preferences,” Zimmerman says. “They say, ‘You think I am depressed now? Wait until I gain 10 pounds!’ or, ‘My sex life is the only good thing going on for me.’ The most common concerns are sexual function and weight gain. It’s not the old paternalistic I-prescribe-you-take style, but more of a collaborative approach.”