Smaller Dose of Vilazodone Safe and Effective for Major Depressive Disorder

A lower dosage of the antidepressant vilazodone (brand name: Vibryd) seems to show few significant differences in either efficacy or adverse effects compared with the current approved dosage on the market, according to a recent clinical trial.

The surprising results were presented in New York City on May 5 at the 2014 annual meeting of the American Psychiatric Association, by Carl Gommoll, MS, the senior director of clinical development psychiatry at Forest Research Institute, a subsidiary of the drug’s manufacturer, Forest Laboratories Inc.

The randomized, placebo-controlled, double-blind trial, which lasted 10 weeks and ended late last year, was unusually large, enrolling nearly 1,150 participants. About 280 patients each were given either a 40 mg dose of vilazodone (the currently approved dosage), or 20 mg. Another 281 participants were given a placebo, and the final group was given the SSRI antidepressant citalopram (brand name: Celexa).

As Gommoll explained, the post-market trial had been required by the US Food and Drug Administration in January 2011 when it approved vilazodone 40 mg for the treatment of major depressive disorder in adults.

Originally, during phase II clinical trials of the drug, Commell said, both the 20 mg and 40 mg formulations were tested, but neither seemed to be effective. However, “there were hints that they would work,” he said. Accordingly, researchers decided to press ahead in trials with the stronger, presumably more effective dosage.

Indeed, a 40 mg formulation did show effectiveness in phase III trials, and it was ultimately approved. But the FDA also sent the company back to reconsider the lower dosage.

Typically, in such situations, if a lower dosage is as effective or almost as effective as a higher dosage, it exhibits fewer adverse effects and thus becomes the preferred starting dosage.

In the case of vilazodone, however, the recent trial generally showed no significant differences between the two dosages, in terms of either efficacy or safety, according to Gommell.

Certainly, both dosages had similarly significant benefits when compared to placebo, using MADRS and CGI-S scores. For instance, patients who were treated with the 20 mg formulation had a MADRS score of -2.57, while patients who received the 40 mg version came in at -2.82. In the case of CGI-S scores, the lower dosage was associated with a reduction of -0.35, while the level for 40 mg was -0.33.

The biggest contrasts emerged in analyzing a few of the drug’s reported adverse events. Nineteen people on vilazodone 40 mg reported vomiting, compared with 11 at the lower dose, and there were similar rates of somnolence reported (18 people and 11, respectively). However, further confusing the results, it was the lower dosage that produced higher rates of dry mouth (22 people vs. 19) and insomnia (19 and 16).

Despite the similar, if not confusing, results, Gommoll said that he expected that the lower dosage would ultimately become the standard dosage for vilazodone.

“Since the diagnosis is so heterogeneous,” he said, “patients respond differently. But this trial gives practitioners more choices, and choices are good.”

He added that he expected the manufacturer to file an NDA with the FDA for the 20 mg formulation by June.