Escitalopram Bests Duloxetine For Severe Major Depression


CHICAGO — Severely depressed patients who fail to respond to 2 weeks of escitalopram at 10 mg/day typically do better with uptitration to 20 mg/day for 8 weeks than with a switch to 8 weeks of duloxetine at 60 mg/day, according to a multicenter double-blind randomized clinical trial.

The advantage of escitalopram (Lexapro) over duloxetine (Cymbalta) in terms of reduction in Montgomery-Asberg Depression Rating Scale (MADRS) scores was evident at week 1, Dr. Gregory M. Asnis said at the American Psychiatric Association's Institute on Psychiatric Services.

“Prior to switching nonresponders to escitalopram to another antidepressant, clinicians should consider increasing the dose to 20 mg/day—perhaps another 8 weeks,” said Dr. Asnis, professor of psychiatry and behavioral sciences at Montefiore Medical Center, New York.

The study involved 571 adults with severe major depressive disorder as defined by a baseline MADRS of 30 or more. They had a mean 11.6-year history of major depression, with an 11-month duration of their current episode. They were placed on escitalopram at 10 mg/day for 2 weeks. Of those who completed this 2-week single-blind lead-in phase, 90% were judged nonresponders, meaning they experienced less than a 50% improvement in MADRS scores. Then, 474 nonresponders were randomized double-blind to 8 weeks of treatment with escitalopram at 20 mg/day or duloxetine at 60 mg/day.

The primary study end point—time to premature treatment discontinuation—was closely similar in the two groups. The premature discontinuation rate was 20.5% in the escitalopram arm and 21.2% with duloxetine, indicating treatment equivalence from a safety and tolerability standpoint.

However, from a mean baseline MADRS score of 34.7, the escitalopram group showed a greater than 20-point average drop during 8 weeks of double-blind therapy—significantly greater than the reduction with duloxetine.

Moreover, more than half of the escitalopram group achieved remission as defined by a MADRS total score of 10 or less, significantly greater than the 40% rate with duloxetine.

These findings are in line with the results of previous studies indicating escitalopram is at least as effective as is duloxetine for the acute treatment of major depressive disorder, Dr. Asnis said. He cited a 194-patient, double-blind, 24-week Scottish study (Curr. Med. Res. Opin. 2007;23:1605–14) and a 278-patient, double-blind, 8-week U.S. trial (Clin. Drug Investig. 2007;27:481–92). In both studies significantly more patients dropped out of the duloxetine arm because of side effects, unlike in the trial presented by Dr. Asnis, where 5.7% in the escitalopram arm and 5.3% in the duloxetine arm withdrew because of adverse events.

The rates and types of side effects were generally similar in the two treatment groups in the trial presented by Dr. Asnis. Dry mouth was more common with duloxetine (10.2% vs. 5.7%), as were constipation (8.6% vs. 4.4%) and insomnia (8.6% vs. 3.9%).

The trial was supported by Forest Laboratories. Dr. Asnis disclosed that he serves as a consultant to Forest, Jazz Pharmaceuticals, and Sanofi-Aventis.

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