Ethyl-eicosapentaenoic acid in first-episode psychosis: a randomized, placebo-controlled trial.
OBJECTIVE
To investigate if ethyl-eicosapentaenoic acid (E-EPA) augmentation improves antipsychotic efficacy and tolerability in first-episode psychosis (FEP).


METHODS
We performed a 12-week, randomized, double-blind, placebo-controlled trial of 2-g E-EPA augmentation in 80 FEP patients. Sixty-nine patients were eligible for analysis; a post hoc analysis was computed for a subgroup of nonaffective FEP patients (N = 53). The first participant was included in November 2000 and the last participant completed the trial in August 2003. Primary outcome measures were symptom change scores and time to first response, while tolerability measures and cumulative antipsychotic dose were secondary outcome measures.


RESULTS
Analysis of covariance controlling for baseline symptoms found no significant mean difference between E-EPA and placebo at week 12 for symptom change scores. Cox regression analysis revealed a significant treatment by diagnosis interaction (p = .024) for time to first response favoring E-EPA in nonaffective psychosis. Post hoc analysis for cumulative response rates further confirmed a higher response rate at week 6 (42.9% [15/35] vs. 17.6% [6/34] for all participants, p = .036; 54.2% [13/24] vs. 17.2% [5/29] for the nonaffective psychosis subset, p = .008); however, the difference at week 12 was no longer significant. Analysis of secondary outcome measures revealed that E-EPA-augmented participants needed 20% less antipsychotic medication between weeks 4 through 6 (p = .03), had less extrapyramidal side effects in the initial 9 weeks (p < .05 for all participants and for all timepoints), and reported less constipation (p = .011) and fewer sexual side effects (p = .016) than those treated with antipsychotic medication alone.


CONCLUSIONS
The findings suggest that E-EPA may accelerate treatment response and improve the tolerability of antipsychotic medications. However, it was not possible to demonstrate a sustained symptomatic benefit of E-EPA in early psychosis, possibly due to a ceiling effect, since a high proportion of first-episode patients already achieve symptomatic remission with antipsychotic medication alone. Further controlled trials in nonaffective early psychosis seem warranted.


BACKGROUND
Australian Clinical Trials Registry identifier 12605000267651 (http://actr.org.au).
Berger
Gregor E
GE
ORYGEN Research Centre (incorporating the Early Psychosis Prevention and Intervention Centre [EPPIC]), University of Melbourne, Australia. bergerg@mac.com
Proffitt
Tina-Marie
TM
McConchie
Mirabel
M
Yuen
HokPan
H
Wood
Stephen J
SJ
Amminger
G Paul
GP
Brewer
Warrick
W
McGorry
Patrick D
PD
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D015118:Eicosapentaenoic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D011618:Psychotic Disorders / Q000188:drug therapy*; D012720:Severity of Illness Index; D016896:Treatment Outcome
D014150:Antipsychotic Agents; C035276:eicosapentaenoic acid ethyl ester; D015118:Eicosapentaenoic Acid