How effective are antidepressants? That’s a question that many people with depression have asked — and research suggests that the answers aren’t simple.

It’s a question that’s relevant to millions. About one in 10 Americans takes an antidepressant, now the most commonly prescribed type of drug in the U.S., according to research published in 2009 in the Archives of General Psychiatry. Much of the surge has happened in the past two decades. From 1996 to 2005, the rate of antidepressant use rose from 5.84% to 10.12%.

But a report recently published in The Journal of the American Medical Association showed that the drugs work best for very severe cases of depression and have little or no benefit over placebo (inactive pills) in less serious cases.

That report isn’t the last word on the topic, but it got plenty of media attention. So much, in fact, that many psychiatrists became concerned that people would misunderstand the findings and possibly dismiss crucial treatment.

But the controversy also creates an opening to get a reality check about the popular drugs’ advantages and limitations, experts tell WebMD.

Here’s what those experts said — and the four questions they recommend you consider when deciding if an antidepressant is right for you.

1. Do you truly have depression?
2. Are you willing to stick with treatment long-term, including trying more than one drug?
3. Would counseling help your mild depression, either alone or combined with an antidepressant?
4. Do you have a good working relationship with your doctor?

Psychiatrists Dissect the Study

The report published in JAMA isn’t new research — it’s a pooled analysis of data from six previously published studies. And it only includes two types of antidepressants — selective serotonin reuptake inhibitors (SSRIs) and older drugs called tricyclics.

In light of those limits, experts interviewed for this story caution against reading too much into the findings.

“This is the kind of study that really gets misinterpreted by the general public. It’s always frustrating when that happens,” says Jennifer Payne, MD, assistant professor of psychiatry at Johns Hopkins School of Medicine and director of the Women’s Mood Disorders Center.

Some other psychiatrists agree. The report is “very limited,” says David Mischoulon, MD, PhD, associate professor of psychiatry at Harvard Medical School and director of research at Massachusetts General Hospital’s Depression and Clinical Research Program.

Best for Severe Cases?

Even before the JAMA study, psychiatrists have long known that antidepressants have a bigger effect in severe cases, Payne says. “The fact is that many different types of medications work better in people who are more severely affected than in people who are less severely affected,” she says.

For example, someone with very high cholesterol will experience a bigger drop in levels after taking a cholesterol drug than a person with mildly raised levels, she says.

“When we’re studying something like depression, if you’re more severe and you get better, you see a larger effect from that. So I don’t think it implies that antidepressants don’t help patients who are more mildly or moderately depressed,” Payne says.

Reality Check on Antidepressants

The JAMA study aside, it’s a fact that many people with depression don’t seek any treatment — whether it’s medication or therapy.

“There is still a tendency, unfortunately, to think that you can get over depression on your own — [that] it’s just a sign that you’re not trying hard enough, it’s a sign of weakness to be depressed — and people need to get past that,” says Andrew F. Leuchter, MD, a professor in the department of psychiatry and biobehavioral sciences at UCLA’s David Geffen School of Medicine.

Mischoulon is concerned that research, such as the JAMA findings, might further discourage people. “My concern was that it might lead certain people to think, ‘Oh, I shouldn’t take antidepressants,’ ” he says.

None of his patients has asked to stop their drugs, Mischoulon says. But “a lot of patients do ask, ‘What implications do these findings have, especially for my case?’ — which is perfectly understandable.”

Great Expectations

Make no mistake: For many people, antidepressants do work. In fact, they can be life-saving.

But Mischoulon also spoke frankly about the failure of antidepressants to live up to the high expectations of doctors and patients alike. He and the other two psychiatrists who spoke to WebMD have consulted for pharmaceutical companies that make antidepressants.

“Antidepressants may not be quite as effective as historically, we’ve believed, when we look at the overall response rate, especially compared to placebo,” he says.

In fact, antidepressants typically don’t approach the success rates shown in clinical trials, he says.

“We have known for many, many years that these antidepressants don’t have the kinds of response rates in the real world of practice that they have in those clinical trials that are funded by industry or by the government,” Mischoulon says.

He notes that in industry-funded studies, “patients are selected very carefully. For example, they don’t accept patients that have certain co-existing illnesses or other health problems or other factors that might rule them out,” Mischoulon says.

“That doesn’t reflect how practice works in the real world. In other words, if I have a patient coming to see me because they have depression, I’m not going to say, ‘Well sir, I’m not going to treat you because you also have diabetes.’ That’s not how we practice. The fact is, the more comorbidity [co-existing disease] there is, the less likely people are to get well when they’re depressed. Depression and medical illnesses and other psychiatric illnesses all interact with each other. For me to see these meta-analyses that show that antidepressants aren’t that fantastic, well, this is what I’ve been observing for years in my practice and so have most of my colleagues,” Mischoulon says.

“Even our best antidepressants work only about half the time,” Payne says. And the odds of success drop if the patient doesn’t respond to the first drug they try, Payne says.

Trial and Error

Antidepressant treatment can be tricky because scientists haven’t truly cracked the secrets of depression. Despite the widespread belief that depression stems from chemical imbalances in the brain, it’s only one theory.

“One of the hardest things in psychiatry in general, but particularly in mood disorders, we do not know what the broken part is. We don’t know what the pathophysiology of depression is. We have some guesses,” Payne says. “But we really don’t understand this well enough, and it’s likely that major depression really represents a group of illnesses, meaning that there several different ways, biologically, to get to what we call major depression.”

That leaves doctors with trial and error to find the right antidepressant.

“We can’t tell ahead of time if a particular class of medication is going to work better for this particular patient or not,” Payne says. “We are essentially doing an experiment. We’re going to try this medication, we’re going to see how you do. If that doesn’t work, we’ll try a different medication.”

Using an Antidepressant: 4 Questions to Ask

Despite the limitations of antidepressants, Mischoulon says, “It doesn’t make me less enthusiastic about antidepressants because I’ve always thought that I’ve had a fairly balanced and realistic picture of how these medications work in the world of practice. So in terms of making recommendations for my patients, I know that not everyone is going to do well on these medications. They have to be used carefully, and you have to select them carefully for each patient.”

For anyone considering treatment with antidepressants, here are four important questions.

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1. Do you truly have depression?

Seek a professional opinion to make sure you have “major depressive disorder,” Mischoulon says. “I tell people, ‘You have to get a diagnosis by a medical professional, preferably someone who is a psychiatrist or psychologist, somebody who understands the diagnostic criteria very well.’ “

Why? Because life crises can trigger symptoms that look a lot like depression, but don’t lend themselves to being treated with medication, he says. “For example, say a person loses their job. It may be normal for them to feel sad or blue about it for a while, particularly if they’re having trouble finding a new job, which in this economy is increasingly common.”

“It’s normal to feel sad or discouraged about these things, but that doesn’t necessarily mean that you have a psychiatric disorder,” he says. “Likewise, if there’s the death of a loved one, again, grieving is normal. It’s a human process, and grieving can sometimes be similar or overlap a little bit with symptoms of depression. So we shouldn’t necessarily assume that people who come in with these situational problems are the ones that need to be treated with medications.”

Psychotherapy or even professional coaching might be the best route for them, Mischoulon says. “A lot of these people with bereavement may get well on their own.”

But many are put on antidepressants too quickly, he says.

“Those people might be taking a medication that they don’t really need. Thus, they would be risking getting side effects, which many antidepressants have.” These effects include dizziness, drowsiness, and stomach upset, Leuchter says.

“Also, by giving everyone medications, we’re sending a message that it’s not normal to feel badly,” Mischoulon says. “To grieve when you lose a loved one — ‘that’s something that we can treat with a medication,’ and that’s not the case. There is a certain amount of normal suffering that is part of the human condition, and unfortunately, we live in a society that increasingly wants to be happy all the time and feels that if you’re not happy all the time, then something’s wrong,” Mischoulon says. “That’s just not the way it is.”

But in some cases, it’s tough to distinguish normal sadness from clinical depression.

“Sometimes it can be difficult,” Mischoulon says. “Sometimes grief can actually complicate into a major depression. A lot of people who lose their jobs, as a result of the stress of it, may actually develop a major depressive episode. One of the ways in which we make the distinction is that we look at the degree of impairment.”

For example, a grieving person might cut back on work and other responsibilities for a while and then gradually return to a normal routine.

But if the person misses a lot of time from work, stops leaving the house, stops engaging in activities, or feels suicidal, those are more serious signs of depression, Leuchter says.

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2. Are you willing to stick with treatment long-term, including trying more than one drug?

With antidepressants, patience matters. “I tell people, ‘You have to be willing to stick with treatment for the long-term to get the most benefit,” Mischoulon says. “Most antidepressants don’t work immediately. They can take several weeks to work. I tell people, don’t feel discouraged if you don’t start feeling better right away because most people don’t.”

Side effects deter many people from continuing, Leuchter says. “People need to work with their doctors to get past the first couple of weeks when side effects occur so that they stand a chance to get the benefits.”

Furthermore, Mischoulon says, “If they try a first antidepressant and it just doesn’t work or if it causes too many side effects, that doesn’t mean that it’s going to be this way with all antidepressants. People should be open to trying another one.”

In some cases, patients require a combination of drugs to control depression, Payne says.

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3. Would counseling help your mild depression, either alone or combined with an antidepressant?

Experts say that in cases of mild depression, psychotherapy often works just as effectively as antidepressants.

“I think it’s always been appropriate… to try other things like therapy, particularly with mild cases,” Payne says. “When you start getting into moderate cases, there really starts to be a big impact on someone’s life. But certainly for mild cases of depression, it’s totally appropriate to start with therapy.”

If people decide to use antidepressants, it’s still best to combine drugs with psychotherapy, Payne says. “When someone has had a depression, many parts of their lives are affected–their relationships, the way they think about things. You can have some leftover symptoms because you were thinking so negatively for a year. It’s hard to break that thought pattern. It’s not just about chemistry. That’s where therapy can really help people to rebuild their relationships, rebuild their lives.”

Exercise also improves depression, she says. “It’s abundantly clear that exercise is very helpful with mood, whether you have mild, moderate, or severe” depression.

Other measures that may help are things that relax you and promote a positive outlook, such as yoga, meditation, and acupuncture, Payne says. “All of those things can be very helpful in moving people away from the more negative thoughts that are associated with depression,” she says.

Seeking out pleasurable experiences also improves mood, she says. And it’s best to do that daily.

“If they really enjoy taking the dog for a walk, they need to be doing that every day,” Payne says. “They need to increase the number of positive experiences that they’re having on a daily basis.”

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4. Do you have a good working relationship with your doctor?

People often get information about antidepressants online or from TV commercials, Mischoulon says. Educating yourself is good, but it can also be confusing to evaluate all of the treatment options without the help of a mental health professional.

“I think for the layperson, it can be difficult to sort through all of this when they don’t have the training to think critically about these different choices that are out there,” Mischoulon says. “So the best thing is, sure, be an informed consumer, but work collaboratively with a doctor that you trust because the doctor has the training and expertise to give you the best advice.”