A randomised double-blind placebo-controlled pilot study of minocycline and/or Omega-3                                                                                             fatty acids added to  treatment as usual for At Risk Mental States (NAYAB)

The At Risk Mental State (ARMS) describes individuals at high risk of developing schizophrenia or psychosis. The use of antipsychotics in this population is not supported because most individuals with ARMS are unlikely to develop psychosis. Anti-inflammatory treatments and polyunsaturated fatty acids (PUFAs) may have some beneficial effects in the treatment of ARMS. There have been no controlled clinical trials that have investigated the use of minocycline for ARMS and no trials involving PUFAs in combination with other proposed treatments. There is a need to find effective, tolerable and inexpensive interventions for ARMS that are available both in high and low and middle-income countries.

A six-month intervention study of minocycline and/or Omega-3 fatty acids added to treatment as usual (TAU) in patients with ARMS is being conducted in Pakistan using a randomised, placebo-controlled, double-blind factorial design. Consenting participants are being recruited from community, general practitioner clinics and psychiatric units. We will determine whether the addition of minocycline and/or Omega-3 fatty acids to TAU attenuates rate of transition from ARMS to first-episode psychosis and improves symptoms and/or level of functioning in ARMS. We will also investigate whether any candidate risk factors such as negative symptoms, influence treatment response in the ARMS group. The primary efficacy end-point is conversion to psychotic disorder at 12 months post study entry. Analysis will be by intention-to-treat, using analysis-of variance, chi-squared tests and adjusted odds ratios to assess between-group differences. Regression analyses will be used to analyse potential between-group differences in time-to-onset of psychosis. Institutional review board approval has been obtained from the ethics committee of the Karachi Medical and Dental College, Pakistan. Trial outcomes will be reported in peer-reviewed journals, conferences and local newspapers for a general audience.