Omega-3 fatty acids in first-episode schizophrenia - a randomized controlled study of efficacy and relapse prevention (OFFER): rationale, design, and methods.
BACKGROUND
Polyunsaturated fatty acid (PUFA) metabolism abnormalities have been long implicated in the etiology of schizophrenia. Although several randomized clinical trials have been carried out to assess the efficacy of omega-3 PUFA as add-on therapy in reducing psychopathology in populations of chronic patients with schizophrenia, only a few concern first-episode schizophrenia. The majority of these studies used a 12-week intervention based on ethyl-eicosapentaenoic acid (ethyl-EPA), however, with conflicting results. An intervention based on docosahexaenoic acid plus EPA has not been used in first-episode schizophrenia studies so far. No add-on supplementation studies have been carried out in medicated first-episode schizophrenia patients to assess the efficacy of omega-3 PUFA in preventing relapses.


METHODS
A randomized placebo-controlled one-center trial will be used to compare the efficacy of 26-week intervention, composed of either 1320 mg/day of EPA and 880 mg/day of DHA, or olive oil placebo with regard to symptom severity and relapse rate in first-episode schizophrenia patients. Eighty-two patients (aged 16-35) will be recruited for the study. Eligible patients will be randomly allocated to one of two intervention arms: an active arm or a placebo arm (olive oil). The primary outcome measure of the clinical evaluation is schizophrenia symptom severity measured by the Positive and Negative Syndrome Scale (PANSS). Other outcomes include depressive symptoms, patient functioning and the level of insight. Correlates of change measured during the study will include structural brain changes, oxidative stress and defense, as well as neuroplasticity indicators. Metabolic syndrome components will also be assessed throughout the study.


CONCLUSIONS
By comparing 26-week administration of EPA + DHA or (placebo) olive oil as add-on therapy in reducing symptom severity and one-year relapse rate in patients with first episode schizophrenia, it is intended to provide new insights into the efficacy of omega-3 PUFA and correlates of change, and contribute to the improvement of mental health care for individuals suffering from schizophrenia.


BACKGROUND
This study has been registered at Clinical Trials.gov with the following number: NCT02210962 .
Department of Affective and Psychotic Disorders, Medical University of Lodz, ul. Czechoslowacka 8/10, 92-216, Lodz, Poland. tomasz.pawelczyk@umed.lodz.pl.
Tomasz
T
Pawełczyk
Central Teaching Hospital, Medical University of Lodz, ul. Pomorska 251, 92-213, Lodz, Poland. martagrancow@gmail.com.
Marta
M
Grancow
Department of Affective and Psychotic Disorders, Medical University of Lodz, ul. Czechoslowacka 8/10, 92-216, Lodz, Poland. magdalena.kotlicka-antczak@umed.lodz.pl.
Magdalena
M
Kotlicka-Antczak
Department of Nutrition Hygiene and Epidemiology, Medical University of Lodz, ul. Jaracza 63, 90-251, Lodz, Poland. elzbieta.trafalska@umed.lodz.pl.
Elżbieta
E
Trafalska
Scanlab Medical Diagnostics, ul. Przedzalniana 66, 90-338, Lodz, Poland. piotr.gebski@umed.lodz.pl.
Piotr
P
Gębski
Department of Medical Biochemistry, Medical University of Lodz, ul. Czechoslowacka 8/10, 92-216, Lodz, Poland. janusz.szemraj@umed.lodz.pl.
Janusz
J
Szemraj
Clinical Psychology Resident in the Department of Affective and Psychotic Disorders, Medical University of Lodz, Lodz, Poland. nzurner@gmail.com.
Natalia
N
Żurner
Department of Affective and Psychotic Disorders, Medical University of Lodz, ul. Czechoslowacka 8/10, 92-216, Lodz, Poland. agnieszka.pawelczyk@umed.lodz.pl.
Agnieszka
A
Pawełczyk
D000293:Adolescent; D000328:Adult; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000008:administration & dosage*; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005231:Fatty Acids, Unsaturated / Q000627:therapeutic use; D005260:Female; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage; D008297:Male; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy; D055502:Secondary Prevention; D016896:Treatment Outcome
D005231:Fatty Acids, Unsaturated; D000960:Hypolipidemic Agents; D004281:Docosahexaenoic Acids; C035276:eicosapentaenoic acid ethyl ester; D015118:Eicosapentaenoic Acid