Randomized, placebo-controlled trial of nefazodone maintenance treatment in preventing recurrence in chronic depression.
BACKGROUND
Maintenance treatment to prevent recurrences is recommended for chronic forms of major depressive disorder (MDD), but few studies have examined maintenance efficacy of antidepressants with chronic MDD. This randomized, placebo-controlled study of the efficacy and safety of nefazodone in preventing recurrence was conducted for patients with chronic MDD.


METHODS
A total of 165 outpatients with chronic, nonpsychotic MDD, MDD plus dysthymic disorder ("double-depression"), or recurrent MDD with incomplete inter-episode recovery, who achieved and maintained a clinical response during acute and continuation treatment with either nefazodone alone or nefazodone combined with psychotherapy, were randomized to 52 weeks of double-blind nefazodone (maximum dose 600 mg/day) or placebo. The occurrence of major depressive episodes during maintenance treatment was assessed with the 24-item Hamilton Rating Scale for Depression, a DSM-IV MDD checklist, and a blinded review of symptom exacerbations by a consensus committee of research clinicians.


RESULTS
Application of a competing-risk model that estimated the conditional probability of recurrence among those patients remaining on active therapy revealed a significant (p =.043) difference between nefazodone (n = 76) and placebo (n = 74) when the latter part of the 1-year maintenance period was emphasized. At the end of 1 year, the conditional probability of recurrence was 30.3% for nefazodone-treated patients, compared with 47.5% for placebo-treated patients. Prior concomitant psychotherapy during acute/continuation treatment, although enhancing the initial response, was not associated with lower recurrence rates. Discontinuations due to adverse events were relatively low for both nefazodone (5.3%) and placebo (4.8%). Somnolence was significantly greater among the patients taking active medication (15.4%), compared with placebo (4.6%).


CONCLUSIONS
Nefazodone is well-tolerated and is an effective maintenance therapy for chronic forms of MDD.
Gelenberg
Alan J
AJ
Department of Psychiatry, Health Sciences Center, University of Arizona, PO Box 245002, Tucson, AZ 85724-5002, USA.
Trivedi
Madhukar H
MH
Rush
A John
AJ
Thase
Michael E
ME
Howland
Robert
R
Klein
Daniel N
DN
Kornstein
Susan G
SG
Dunner
David L
DL
Markowitz
John C
JC
Hirschfeld
Robert M A
RM
Keitner
Gabor I
GI
Zajecka
John
J
Kocsis
James H
JH
Russell
James M
JM
Miller
Ivan
I
Manber
Rachel
R
Arnow
Bruce
B
Rothbaum
Barbara
B
Munsaka
Melvin
M
Banks
Phillip
P
Borian
Frances E
FE
Keller
Martin B
MB
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000627:therapeutic use*; D002908:Chronic Disease; D003131:Combined Modality Therapy; D018592:Cross-Over Studies; D003865:Major Depressive Disorder / Q000517:prevention & control / Q000628:therapy*; D004311:Double-Blind Method; D004608:Eligibility Determination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines; D011613:Psychotherapy / Q000379:methods*; D012008:Recurrence; D013375:Substance Withdrawal Syndrome / Q000453:epidemiology / Q000209:etiology; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*
D018687:Antidepressive Agents, Second-Generation; D010879:Piperazines; D014230:Triazoles; C051752:nefazodone