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Antidepressants Similar in Effectiveness, But Side Effects Differ

January 27, 2007

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Today's most commonly prescribed antidepressants are similar in effectiveness to each other but differ when it comes to possible side effects, according to an analysis released by HHS' Agency for Healthcare Research and Quality.

The findings, based on a review of nearly 300 published studies of second-generation antidepressants, show that about six in 10 adult patients get some relief from the drugs. About six in 10 also experience at least one side effect, ranging from nausea to sexual dysfunction.

Patients who don't respond to one of the drugs often try another medication within the same class. About one in four of those patients recover, according to the review. Overall, current evidence on the drugs is insufficient for clinicians to predict which medications will work best for individual patients.

Second-generation antidepressants, which include selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), are often prescribed because first-generation antidepressants (such as tricyclic antidepressants, or TCAs) can cause intolerable side effects and carry high risks.

"Second-generation antidepressants provide hope for many of the millions of Americans who struggle with depression," said AHRQ Director Carolyn M. Clancy, MD. "But often trying to find the right drug is trial and error, and in many cases relief is temporary or comes with serious side effects. It's clear we need more evidence to help patients and their doctors make the best choices."

Authors of the new Comparative Effectiveness Review analyzed the benefits and risks of a dozen second-generation antidepressants: bupropion (sold as Wellbutrin), citalopram (Celexa), duloxetine (Cymbalta), escitalopram (Lexapro), fluoxetine (Prozac), fluvoxamine (formerly sold as Luvox), mirtazapine (Remeron), nefazodone (formerly Serzone), paroxetine (Paxil), sertraline (Zoloft), trazodone (formerly Desyrel), and venlafaxine (Effexor).

Many of these drugs are also sold in generic form.

The analysis, which examined only adult use of second-generation antidepressants, drew on 293 published studies. Of those, 187 were judged to be of good or fair quality. The analysis compared the drugs' benefits and risks in the treatment of major depressive disorder, dysthymia (a chronic, less-severe form of depression), and subsyndromal depression (an acute mood disorder that is less severe than major depression).

Each of the disorders can be disabling. Major depressive disorder affects more than 16 percent of U.S. adults at least once during a lifetime, the review noted. In 2000, the economic burden of depressive disorders was estimated to be $83.1 billion. More than 30 percent of these costs are for direct medical expenses, such as doctors' fees, hospital bills and medications.

The new analysis, produced by AHRQ's Effective Health Care program, was completed by the Agency's RTI International-University of North Carolina Evidence-based Practice Center. Evidence reviewed by the authors suggests:

• In general, the various second-generation antidepressants have similar rates of effectiveness. In controlled studies, about 38 percent of patients saw no improvement and 54 percent had only partial improvement.

• According to the National Institute of Mental Health's Sequenced Treatment Alternative to Relieve Depression (STAR-D) trial, a substantial number (between about 25 percent and 33 percent) of patients will improve with the addition or substitution of a different drug.

• On average, 61 percent of patients taking second-generation antidepressants experience at least one side effect. The most common are nausea and vomiting, constipation, diarrhea, dizziness, headache and sleeplessness.

• Venlafaxine, an SNRI, is associated with a higher incidence of nausea and vomiting than SSRIs. That drug is also more likely than SSRIs to be discontinued due to adverse events.

• Sertraline is more likely to cause diarrhea than bupropion, citalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, or venlafaxine. Mirtazapine leads to higher weight gains than fluoxetine, paroxetine, venlafaxine, or trazodone. Trazodone is associated with higher rates of sleeplessness than bupropion, fluoxetine, mirtazapine, paroxetine, or venlafaxine.

• Paroxetine and venlafaxine have the highest rates of discontinuation. Fluoxetine has the lowest.

• Second-generation antidepressants work at different rates. Seven studies funded by the maker of mirtazapine showed that the drug works faster than citalopram, fluoxetine, paroxetine, or sertraline.

• Bupropion is less likely to cause sexual dysfunction than fluoxetine, paroxetine, or sertaline. Paroxetine has higher rates of sexual dysfunction than fluoxetine, fluvoxamine, nefazodone, or sertraline.

"As with all medications, second-generation antidepressants should be used after careful consideration of benefits and risks," Dr. Clancy said. "It's up to clinicians and patients to work closely together so the best possible results are achieved."

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