• PANSS Total (weeks 0, 8, 16)
  

• PANSS Subscales Negative, Positive, General Psychopathology (weeks 0, 8, 16)
  
• GLOBAL ASSESSMENT OF FUNCTIONING– Split Version (S-GAF)Symptom Scale, Function Scale (weeks 0, 8, 16)
  
• WONCA-COOP FUNCTIONAL HEALTH ASSESSMENT CHARTS - 5 scales (weeks 0, 8, 16)
  
• NIACIN SKIN FLUSH TEST - 2 concentrations of niacin (weeks 0, 8, 16)
  
• THE UKU SIDE EFFECT RATING SCALE (USERS) - Sum of scores, patients with side effects (weeks 0,4,8,12,16)
  
• SERIOUS ADVERSE EVENTS (weeks 0,4,8,12,16)
  
• CONCOMITANT ANTIPSYCHOTIC MEDICATION - Defined Daily Doses (weeks 0,4,8,12,16)
  
• NEUROPSYCHOLOGICAL ASSESSMENT (weeks 0,16):
  
• Kimura Recurring Recognition Figures Test
  
• Hopkins Verbal Learning Test.
  
• Continuous Performance Test
  
• Hopkins Verbal Learning Test
  
• Paced Auditory Serial Addition Test
  
• Stroop Test
  
• Digit Span
  
• The Letter – Number Task
  
• Semantic and Category Fluency
  
• GENERAL MEDICAL EXAMINATION (weeks 0,16):
  
• Weight
  
• Blood pressure - systolic, diastolic
  
• Heart rate
  
• ORDINARY BIOCHEMICAL ANALYSES (Serum, blood)(weeks 0,16):
  
• Albumin
  
• Urate
  
• Glucose
  
• Cholesterol
  
• Triglycerides
  
• SPECIAL BIOCHEMICAL ANALYSES (Serum, blood)
  
• Fatty acids in red blood cells (DGLA, AA, EPA, DHA, total omega-3 PUFA, total omega-6 PUFA)
  
• Alpha-tocopherol adjusted for [triglycerides]+[cholesterol].
  
• Total antioxidant status
  
• Malondialdehyde
  
• F2-isoprostane (8-epiPGF2-alpha)
  
• Cytosolic PLA2 group IV in red blood cells(ELISA method)
  
• Gene expression of mRNA for PLA2 groups IVa and VIa in monocytes.
  

Objective:

Study the effect of adding Ethyl-EPA and/or Vitamins E + C to antipsychotic drugs in younger patients with schizophrenia and related psychoses.

Methods and material:

• Design: Multicentre, randomized, double-blind, placebo-controlled, fixed dose, 2x2 factorial, add-on clinical trial.

• Sample:

  • Patients with schizophrenia, schizoaffective disorder or schizophreniform disorder (DSM-IV); aged 18-40 years; less than 15 years since first psychotic symptoms;admitted to a psychiatric department within the previous 21 days before screening; speaks fluently a Scandinavian language;treated with antipsychotics; written informed consent;no known allergy to trial agents;no substance dependence (DSM-IV);no warfarin currently or anamnestic indicators of impaired haemostasis. Planned: 200 patients. Actually included: 99 intent-to-treat patients.
  • Healthy controls: aged 18-40 years;no mental disorder (DSM-IV). Included: 20 persons.
• Clinical assessments: Positive and Negative Syndrome Scale (PANSS) (main outcome variable). Self-report questionnaire. Adverse effects (UKURS). Neurocognitive assessment battery. Niacin skin flush test. General medical assessment.
• Blood samples: RBC fatty acids, S-α-tocopherol, F2-isoprostane (kits), monocyte mRNA Phospholipase A22 (PLA2) Gr4a and 6a (RT-PCR method), RBC Gr4a PLA2 concentration (ELISA technique), a range of other biochemical tests.
• Experimental treatment over 16 weeks: Ethyl-EPA 2 g/d or Placebo EPA and Vitamin E 364 mg/d + Vitamin C 1000 mg/d or Placebo Antioxidants
• Statistics: Linear Mixed Model for longitudinal analyses of effects; other uni- and multivariate methods (all SPSS 12.0).

Inclusion Criteria:

• Patients with schizophrenia, schizophreniform disorder or schizoaffective disorder (DSM-IV)
• Admitted to a psychiatric hospital/department within the previous twenty-one days before screening
• Less than fifteen years, in retrospect, since first psychotic symptoms (DSM-IV 295, criteria A,1-4)
• Age 18-40 years
• Speaks fluently a Scandinavian language
• A written informed consent must be obtained before any trial-related activities

Exclusion Criteria:

• A diagnosis of substance dependence (DSM-IV)
• Known allergy to study medication
• Currently taking warfarin or having anamnestic indicators of impaired haemostasis (profuse bleeding, except epistaxis)