In 2001, a major study funded by the manufacturer of the antidepressant paroxetine (Paxil) found that the drug was safe and effective for adolescents suffering from depression. Since that time, doctors have written millions of prescriptions for depressed teens to take this drug.
Now: A re-analysis of that study conducted by an independent research group has come to a strikingly different conclusion: Paroxetine was not helpful in treating depression in teens and, in fact, increased their risk for suicide.
How could such a disparity exist in the interpretation of the evidence—and what does it mean for people of all ages who may be taking an antidepressant?
To find out, Bottom Line/Health spoke with Erick Turner, MD, a psychiatrist who has extensively studied scientific reporting methods within the psychiatric literature.
How can an independent analysis of the drug manufacturer’s research come to such a different conclusion from the earlier findings? One problem that affects the findings is a way that the data is interpreted if someone drops out of the study. It could be that 20% to 30% of patients don’t make it to the end of the study, and there are various methods for handling that. One method—a misleading one—is to analyze data only from patients who make it to the end of the study. That way, you wind up with a skewed sample because people may have dropped out because the drug wasn’t working for them or they were experiencing side effects. If those people are excluded from the overall analysis, then it makes the drug look more effective for depressed patients than it actually is, which makes the drug look better to doctors.
Also, regarding the issue of suicidal thinking and behavior, it’s all about the coding. Suppose there’s a patient who was angry one moment, crying the next and then thinking about jumping off a building. If the researchers code that as “emotional lability” (the opposite of “emotional stability”), but don’t code the suicidal behavior, then it gets brushed aside and doesn’t get counted the way it should. Coding differences of this sort led to different findings in the new report. This basic level of research can be subjective, so different parties can arrive at different conclusions.
Should adults who take Paxil or another antidepressant now be concerned about the safety and effectiveness of these drugs? This is just one study among many. The totality of the evidence may tell a different story. The real message with this new study is this—if an independent party gets access to the raw data at the granular level, they can reach very different conclusions and it can depend on whether the researcher has a vested interest in the study’s results.
In general, then, how effective and safe are antidepressants for depression? You can’t count on these drugs to be a magic bullet. You may have an excellent response, or you may not. You’ll likely need some persistence—you might need to try a second or third type of antidepressant or consider a combination of drugs. You can also start treatment with psychotherapy and consider medication later.
And in terms of safety, the FDA has found that the risk regarding suicidal tendencies seems to decrease with age. The risk is highest with people under age 18 and somewhat less among those ages 18 to 25. For people 25 and older, the risk seems to be neutral—the drugs are even protective after age 65.
What are the possible side effects of antidepressants? Selective serotonin reuptake inhibitors (SSRIs), which include not only paroxetine but also fluoxetine (Prozac), citalopram (Celexa), escitalopram (Lexapro) and sertraline (Zoloft), are the ones most commonly prescribed, and they’re usually pretty well tolerated. But one common side effect is sexual dysfunction. For some patients, that makes these drugs a no-go…for other patients, it’s a nonissue.
Other types of antidepressants have different side effects. For example, mirtazapine (Remeron) tends to be sedating, which can be good for people who have trouble sleeping, but the potential downside is that it can cause increased appetite and weight gain. However, weight gain can be a welcome side effect for patients who aren’t eating enough.
The dosage of an antidepressant should be gradually increased. With Zoloft, for instance, the FDA-recommended dosage for depression ranges from 50 mg to 200 mg once daily. I generally start people at 25 mg daily and continue that for a week or two…then go to 50 mg daily for a week or two…then 75 mg and then 100 mg. After a few months, the patient might need to go up to 150 mg or to the 200-mg maximum daily dose. It depends on the balance between therapeutic benefits and side effects.
Tapering off antidepressants should be done gradually, as well. If you run out of pills or stop suddenly, you could have discontinuation syndrome with side effects including nausea, dizziness and feeling teary and emotionally unstable.
So you should consult your doctor—an internist or a mental-health practitioner—whenever starting or going off antidepressants.
In general, when do the benefits of antidepressants outweigh the risks? A number of studies have shown that you get more bang for your buck in terms of effectiveness when the depression is more severe. So if a person is severely depressed—if he/she can’t get out of bed or has suicidal thinking—then it’s certainly worth pulling out all the stops to help that person.
You and your doctor should be sure to review your progress after six to 12 months of treatment. It’s important to remember not to stop treatment once you begin to feel better. And never stop taking antidepressants without first consulting your doctor.
But if you have mild depression, you’re less likely to see a substantial benefit from taking an antidepressant. You might consider other ways to treat your depression—decreasing isolation, getting more exercise and seeking psychotherapy.
A recent study found that light therapy—sitting in front of a light box daily—helped ease depression symptoms. But check with your doctor first before considering light therapy, especially if you have bipolar disorder or certain other health conditions. Your doctor can guide you on the optimal amount of time to use a light box.
