Efficacy of controlled-release paroxetine in the treatment of late-life depression.
BACKGROUND
Depression is the second most common neuropsychiatric disorder in older Americans, with significant clinical and public health costs. Despite advances in treatment, late-life depression remains a clinical challenge. Although the selective serotonin reuptake inhibitors (SSRIs) are the most common pharmacologic intervention for late-life depression, few placebo-controlled trials have assessed the efficacy of SSRIs for this condition.


METHODS
In this 12-week, multicenter, placebo-controlled, flexible-dose, double-blind, randomized trial, 319 elderly patients (mean age = 70 years) were treated with controlled-release paroxetine (paroxetine CR) up to 50 mg/day (N = 104), immediate-release paroxetine (paroxetine IR) up to 40 mg/day (N = 106), or placebo (N = 109). Patients met DSM-IV criteria for major depressive disorder and had a total score of 18 or more on the 17-item Hamilton Rating Scale for Depression (HAM-D). The primary efficacy measure was change from baseline to endpoint in HAM-D total score.


RESULTS
The primary efficacy analysis showed an adjusted difference between change from baseline in HAM-D score for paroxetine CR and placebo of -2.6 (95% confidence interval [CI] = -4.47 to -0.73, p = .007) at the week 12 last-observation-carried-forward (LOCF) endpoint. The adjusted difference between paroxetine IR and placebo was -2.8 (95% CI = -4.65 to -0.99, p = .003) at week 12. Paroxetine CR and IR were more effective than placebo, with mean +/- SD endpoint HAM-D total scores of 10.0 +/- 7.41 and 10.0 +/- 7.10, respectively, for the active treatments compared with 12.6 +/- 7.34 for placebo. Response, defined as a score of 1 or 2 on the Clinical Global Impressions-global improvement scale, was achieved by 72% of paroxetine CR patients (LOCF; p < .002 vs. placebo), 65% of paroxetine IR patients (p = .06 vs. placebo), and 52% of placebo patients. Remission, defined as a HAM-D total score < or = 7, was achieved by 43% of paroxetine CR patients (LOCF; p = .009 vs. placebo), 44% of paroxetine IR patients (p = .01 vs. placebo), and 26% of placebo patients. In a post hoc analysis, mean HAM-D improvement for paroxetine CR and paroxetine IR was greater than for placebo in both chronically depressed patients (duration > 2 years) and those with short-term (< or = 2 years) depression. Dropout rates due to adverse events were 12.5% for paroxetine CR, 16.0% for paroxetine IR, and 8.3% for placebo.


CONCLUSIONS
Paroxetine CR and paroxetine IR are effective and well tolerated treatments for major depressive disorder in elderly patients, including those with chronic depression.
Rapaport
Mark Hyman
MH
Department of Psychiatry, Cedars-Sinai Medical Center, David Geffen School of Medicine, University of California, Los Angeles, 8730 Alden Dr., Suite C301, Los Angeles, CA 90048, USA. mark.rapaport@cshs.org
Schneider
Lon S
LS
Dunner
David L
DL
Davies
John T
JT
Pitts
Cornelius D
CD
D000368:Aged; D000369:Aged, 80 and over; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage* / Q000009:adverse effects; D003692:Delayed-Action Preparations; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000008:administration & dosage* / Q000009:adverse effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects
D018687:Antidepressive Agents, Second-Generation; D003692:Delayed-Action Preparations; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors