In a second trial, which featured design and titration schedule identical to that of the first study, 481 patients were randomized to vilazodone or placebo.10 At week 8, the vilazodone-treated patients had significantly greater improvement in MADRS, HAM-D-17, HAM-A, CGI-S, and CGI-I score compared with the placebo group (P <.05). Approximately 14% more patients in the vilazodone group were MADRS responders compared with placebo (44% vs 30%, P =.002). Remission rates were not statistically different between patients taking vilazodone vs placebo (27% vs 20% respectively).10 Demonstrating a statistically significant difference between a 27% vs 20% remission rate would require a much larger number of patients than were included in this study.
Table 2
Efficacy of vilazodone in phase III clinical trials
| Trial | Drug response rate | Placebo response rate | Drug-specific response rate* | NNT† | Average reduction in MADRS change (drug minus placebo) (mean) | Average reduction in HAM-D change (drug minus placebo) (mean) |
|---|---|---|---|---|---|---|
| Rickels et al9 | 40% | 28% | 12% | 100/12=8 | 12.9 to 9.6 (3.3) | 10.4 to 8.6 (1.8) |
| Khan et al10 | 44% | 30% | 14% | 100/14=7 | 13.3 to 10.8 (2.5) | 10.7 to 9.1 (1.6) |
| HAM-D: Hamilton Rating Scale for Depression; MADRS: Montgomery-Åsburg Depression Rating Scale; NNT: number needed to treat *Difference in response rate between the drug and placebo groups. This rate is what the drug added to the treatment effects seen as a result of time and clinical management provided in the trial †The number of patients who need to be treated to benefit (ie, achieve response) one additional patient compared with placebo Source: Reference 11. Table reproduced with permission from Sheldon H. Preskorn, MD | ||||||
Tolerability
Vilazodone’s safety was evaluated in 2, 177 patients (age 18 to 70) diagnosed with MDD who participated in clinical studies, including the two 8-week, randomized, doubleblind, placebo-controlled studies (N=891) and a 52-week, open-label study of 599 patients.12 Overall, 7.1% of patients who received vilazodone discontinued treatment because of an adverse reaction, compared with 3.2% of placebo-treated patients in the double-blind studies.3 Diarrhea, nausea, and headache were the most commonly reported adverse events; the incidence of headache was similar to that in the placebo group (13.2% vs 14.2%).10 These adverse events are consistent with serotonin agonism, mild to moderate intensity, and occurred mainly during the first week of treatment.3
Doses up to 80 mg/d have not been associated with clinically significant changes in ECG parameters or laboratory parameters in serum chemistry hematology and urine analysis.9,10 The drug had no effect on weight as measured by mean change from baseline.9,10
In one 8-week trial, there were no substantial differences between vilazodone and placebo in Arizona Sexual Experience Scale (ASEX) scores at treatment end for either sex.9 ASEX is a 5-item scale used to assess sexual dysfunction; a score >18 indicates clinically significant sexual dysfunction. At baseline, mean ASEX scores among men were 15.8 in the placebo group and 16.5 in the vilazodone group. Among women, the mean ASEX score was 21.2 in both groups.9 Overall sexual function for men and women was similar for vilazodone and placebo, as measured by the Changes in Sexual Function Questionnaire.10 The most commonly reported sexual adverse effect was decreased libido.10
Contraindications
Vilazodone is contraindicated for concomitant use with monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping or starting an MAOI. Vilazodone is contraindicated in patients taking strong CYP3A4 inhibitors (eg, ketoconazole) because of increased vilazodone concentrations and resulting concentration-dependent adverse effects.3 Concomitant administration of strong CYP3A4 inducers (eg, rifampin) might result in a reduction in vilazodone levels leading to lack or loss of efficacy.13
As with other antidepressants, vilazodone carries a black-box warning about increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants for MDD and other psychiatric disorders.3 Vilazodone showed evidence of developmental toxicity in rats, but was not teratogenic in rats or rabbits. There are no adequate, well-controlled studies of vilazodone in pregnant women and no human data regarding vilazodone concentrations in breast milk.3 Women taking vilazodone are advised to breastfeed only if the potential benefits outweigh the risks. Vilazodone is not recommended for use in pediatric patients.3
Similar to other antidepressants, vilazodone labeling carries warnings about serotonin syndrome, seizures, abnormal bleeding, activation of mania/hypomania, and hyponatremia.4
Dosing
Vilazodone is available as 10 mg, 20 mg, and 40 mg tablets. The recommended target dose for vilazodone is 40 mg/d, with a starting dose of 10 mg/d for 7 days, followed by 20 mg/d for 7 days, then 40 mg/d.3 The drug should be taken with food, but unlike other psychotropics, the manufacturer does not recommended a specific calorie amount.3 Dose tapering is recommended when the drug is discontinued.3