Schizophrenia: omega-3 fatty acid medicines

Summary

The randomised controlled trial (RCT) evidence for using omega-3 fatty acid medicines in people with schizophrenia is limited and the results are not consistent.

Regulatory status: off-label.

Key points

There are numerous products on the UK market that contain omega-3 fatty acids. Amongst them there are 14 that have a current licence as a medicinal product. The majority of the oral formulations are indicated for use as adjuvant treatment in secondary prevention of myocardial infarction and for treatment of hypertriglyceridaemia when dietary measures are not sufficient.

Three other products with UK marketing authorisation contain named unsaturated fatty acids that belong to the group of omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid).

None is licensed for schizophrenia, so use of these products is off-label. Using omega-3 fatty acids to treat schizophrenia has been studied in 8 relevant RCTs, 7 of which were analysed in a Cochrane systematic review (Irving et al. 2006, updated 2009). However, the evidence was limited because the RCTs were small (30–122 people in each trial), short term (up to 16 weeks), and often reported selective or incomplete data.

All 8 RCTs recruited people with schizophrenia diagnosed using Diagnostic and Statistical Manual of Mental Disorders 4^th edition (DSM-IV), and most of the RCTs added omega-3 fatty acids to existing antipsychotic drug treatment in people with chronic schizophrenia.

The results from the RCTs were not consistent. Of the 8 RCTs, 4 reported some statistically significant improvement in symptoms, favouring omega-3 fatty acids compared with placebo (Peet et al. 2001a, Peet et al. 2001b, Peet and Horrobin 2002 and Emsley et al. 2002). These changes in scores on rating scales may represent 'minimally improved' on the Clinical Global Impression (CGI) scale (Levine et al. 2008, Leucht et al. 2006); however, this remains a subject of debate (Irving et al. 2006). The remaining 4 found no difference between omega-3 fatty acids and placebo (Fenton et al. 2001, Emsley et al. 2006, Berger et al. 2007 and Manteghiy et al. 2008).

Safety data from the short-term RCTs suggested that omega-3 fatty acids were well tolerated. One study suggested a possible link with diarrhoea (Fenton et al. 2001) and another with possible increases in bleeding time and weight gain (Emsley et al. 2008), which are consistent with summaries of product characteristics.

The Cochrane systematic review concluded that the overall RCT evidence was not conclusive, and that the use of omega-3 fatty acids for people with schizophrenia remains experimental.