Low Doses of Controlled-Release Paroxetine in the Treatment of Late-Life Depression: A Randomized, Placebo-Controlled Trial

Objective: To evaluate the efficacy and tolerability of low daily (loses of controlled-release (CR) paroxetine in patients with late-life depression. Method: This was a 10-week, multicenter, placebo-controlled, double-blind, fixed-dose trial randomly assigning patients >= 60 years old to daily doses of paroxetine CR 12.5 mg (N = 168), paroxetine CR 25 mg (N = 177), or placebo (N = 180). Patients had major depressive disorder (DSM-IV criteria) and 17-item Hamilton Rating Scale for Depression (HAM-D) total scores of 18. The primary efficacy variable was the chance from baseline to study endpoint in total HAM-D scores. The study was conducted from June 2003 to October 2004. Results: The drug/placebo difference in HAM-D change from baseline at study endpoint was -1.8 (95% CI = -3.41 to -0.19, p = .029) for paroxetine CR 12.5 mg, and -3.3 (95% CI = -4.84 to -1.68, p <.001) for paroxetine CR 25 mg. A significantly larger percentage of patients achieved remission (HAM-D total score : 7 at endpoint) with paroxetine CR 25 mg (41%). but not with 12.5 mg (31%), as compared with placebo (28%) (p = .008). Both doses of paroxetine CR also achieved statistical significance compared to placebo for the Clinical Global Impressions-Severity of Illness scale (p < .01) and the patient-rated measures of depression severity (p < .05) and quality of life (p <= .001). Both active treatments were generally well tolerated, with adverse event withdrawal rates of 6%, 8%, and 7% for paroxetine CR 12.5 mg, paroxetine CR 25 mg, and placebo, respectively. Conclusion: These data demonstrate that paroxetine CR 12.5 mg and 25 mg daily are efficacious and well tolerated in the treatment of major depressive disorder in patients ! 60 years of age, although effect sizes are relatively smaller with the 12.5 mg/day dose.