Minocycline and/or Omega-3 Fatty Acids Added to Treatment as Usual for At Risk Mental States

Primary hypothesis is that the persons with ARMS who are prescribed minocycline and / or Omega-3 fatty acids will have reduced transition rates to psychosis over a one year follow up period (from baseline) compared with Treatment-As-Usual (TAU). The transition rates will be lowest in the group receiving minocycline and Omega-3 fatty acids in combination.

Secondary objective is to determine that the Persons with ARMS who are prescribed minocycline and / or Omega-3fatty acids in combination will have greatest symptom reduction compared with TAU.

This study will be a six-month intervention of minocycline and/or Omega-3 fatty acids added to TAU in patients with ARMS, using a randomised, placebo-controlled, double-blind factorial design.The study will be a four-arm trial: one arm will receive minocycline with TAU; the second arm will receive Omega-3 fatty acids with TAU; the third arm will receive both minocycline and Omega-3 fatty acids with TAU; the fourth arm will receive placebo with TAU.

Inclusion criteria

• Male and female help seeking individuals aged between 16-35 years.
• Meets at least one of the criteria for ARMS (see CAARMS Operationalized Intake Criteria section below).
• Assessed as competent to provide informed consent.

Exclusion criteria

• History ofpreviously experiencing a psychotic illness (treated or untreated).
• IQ < 70 and/or history of learning disability.
• Any pre-existing inflammatory conditions e.g. rheumatoid arthritis.
• Organic brain disease e.g. epilepsy.
• treatment with an antipsychotic or mood-stabilising agent.
• Prior history of intolerance or serious side effects (hepatotoxicity, photosensitivity, blood dyscrasias) to any of the tetracyclines or Omega-3 fatty acids.
• Concomitant penicillin therapy or concomitant anticoagulant therapy.
• Active substance abuse (except nicotine or caffeine) or dependence within the last three months, according to DSM-V criteria.
• Treatment with warfarin or lamotrigine.
• Current or previous treatment with tetracycline antibiotics or Omega-3 fatty acids in the preceding three months before study entry.
• Current treatment with any anti-inflammatory medication.
• Treatment with electroconvulsive therapy within the 12 weeks preceding the study.
• Active expression of suicidal ideation (CAARMS item 7.3 severity score 6) or current aggression/dangerous behaviour (CAARMS item 5.4 severity score 6). 14. Relevant current or past hematologic, hepatic, renal, neurological or other medical disorder that in the opinion of the principal investigator may interfere with the study.

• Pregnant or breastfeeding females.