Outcomes/Effectiveness Research

Newer class of antidepressants is similar in effectiveness, but side effects differ

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 the Agency for Healthcare Research and Quality (AHRQ). The findings, based on a review of nearly 300 published studies of second-generation antidepressants, show that about 6 in 10 adult patients get some relief from the drugs. The same proportion also experience at least one side effect, ranging from nausea to sexual dysfunction.

Patients who don't respond to one of these 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) can cause intolerable side effects and carry high risks.

The authors of the new Comparative Effectiveness Review analyzed the benefits and risks of a dozen second-generation antidepressants: bupropion, citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, trazodone, and venlafaxine. Many of these drugs are 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 their 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.

The report, Comparative Effectiveness of Second-Generation Antidepressants in the Pharmacologic Treatment of Adult Depression, from AHRQ's Effective Health Care program, can be found at http://effectivehealthcare.ahrq.gov.

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