Differential effects of nefazodone and cognitive behavioral analysis system of psychotherapy on insomnia associated with chronic forms of major depression.
BACKGROUND
The antidepressant nefazodone and the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) were recently found to have significant, additive effects in a large multicenter study of chronic forms of major depression. As nefazodone-mediated blockade of serotonin-2 receptors may directly relieve insomnia associated with depression, we examined the more specific effects of CBASP and nefazodone, singly and in combination, on sleep disturbances.


METHODS
A total of 597 chronically depressed outpatients (DSM-III-R criteria) with at least 1 insomnia symptom were randomly assigned to 12 weeks of treatment with nefazodone (mean final dose = 466 mg/day), CBASP (mean = 16.0 sessions), or the combination (mean dose = 460 mg/day plus a mean of 16.2 CBASP sessions). Continuous and categorical insomnia outcomes, derived from standard clinician- and self-rated assessments, were compared.


RESULTS
Patients receiving nefazodone (either alone or in combination with CBASP) obtained significantly more rapid and greater ultimate improvement in insomnia ratings when compared with those treated with CBASP alone. This difference was maximal by the fourth week of therapy and sustained thereafter. Combined treatment did not result in markedly better insomnia scores than treatment with nefazodone alone on most measures, although patients receiving both CBASP and nefazodone were significantly more likely (p < .001) to achieve > or = 50% decrease in insomnia severity.


CONCLUSIONS
Despite comparable antidepressant efficacy, monotherapy with nefazodone or CBASP resulted in markedly different effects on the magnitude and temporal course of insomnia symptoms associated with chronic forms of major depression. Patients receiving the combination of psychotherapy and pharmacotherapy benefited from both the larger and more rapid improvements in insomnia associated with nefazodone therapy and the later-emerging effects of CBASP on the overall depressive syndrome.
Thase
Michael E
ME
Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, PA 15213-2593, USA. thaseme@msx.upmc.edu
Rush
A John
AJ
Manber
Rachel
R
Kornstein
Susan G
SG
Klein
Daniel N
DN
Markowitz
John C
JC
Ninan
Philip T
PT
Friedman
Edward S
ES
Dunner
David L
DL
Schatzberg
Alan F
AF
Borian
Frances E
FE
Trivedi
Madhukar H
MH
Keller
Martin B
MB
D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D002908:Chronic Disease; D015928:Cognitive Behavioral Therapy; D003131:Combined Modality Therapy; D003866:Depressive Disorder / Q000175:diagnosis / Q000523:psychology / Q000628:therapy*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D017063:Outcome Assessment, Health Care; D010555:Personality Inventory / Q000706:statistics & numerical data; D010879:Piperazines; D007319:Sleep Initiation and Maintenance Disorders / Q000175:diagnosis / Q000523:psychology / Q000628:therapy*; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*
D018687:Antidepressive Agents, Second-Generation; D010879:Piperazines; D014230:Triazoles; C051752:nefazodone