Efficacy and tolerability of controlled-release and immediate-release paroxetine in the treatment of depression.

BACKGROUND

Antidepressant efficacy may be compromised by early discontinuation of treatment secondary to common, treatment-emergent side effects, including nausea, agitation, and somnolence. Paroxetine controlled-release (CR) was developed to improve general tolerability and, in particular, gastrointestinal tolerability.

OBJECTIVE

To determine the antidepressant efficacy and tolerability of paroxetine CR in adult patients 18 to 65 years of age with DSM-IV major depressive disorder.

METHOD

Paroxetine CR (25-62.5 mg/day; N = 212) and paroxetine immediate-release (IR; 20-50 mg/day; N = 217) were compared with placebo (N = 211) in the pooled dataset from 2 identical, double-blind, 12-week clinical trials.

RESULTS

Both paroxetine CR and paroxetine IR exhibited efficacy in major depressive disorder as assessed by the reduction in 17-item Hamilton Rating Scale for Depression total score compared with placebo. Moreover, depressed mood and psychic anxiety symptoms improved as early as treatment week 1 in the paroxetine CR group compared with the placebo group. After 6 weeks of treatment, response and remission rates were 41.5% and 20.5% for placebo, 52.8% and 29.6% for paroxetine IR, and 58.9% and 34.4% for paroxetine CR, respectively. After 12 weeks of treatment, response and remission rates were 61.2% and 44.0% for placebo, 72.9% and 52.5% for paroxetine IR, and 73.7% and 56.2% for paroxetine CR, respectively. Rates of nausea were significantly lower for paroxetine CR (14%) than for paroxetine IR (23%; p < or = .05) during week 1. Rates of dropout due to adverse events were comparable between paroxetine CR and placebo, while significantly (p = .0008) more patients treated with paroxetine IR withdrew from the study prematurely compared with those treated with placebo.

CONCLUSION

Paroxetine CR is an effective and well-tolerated antidepressant exhibiting symptomatic improvement as early as week 1. Paroxetine CR is associated with low rates of early-onset nausea and dropout rates due to adverse events comparable to those of placebo. The clinical improvement seen with paroxetine CR, coupled with its favorable adverse event profile, suggests a benefit for therapeutic outcome with paroxetine CR.