Key points from the evidence

Key points from the evidence

The content of this evidence summary was up-to-date in September 2013. See summaries of product characteristics (SPCs), British national formulary (BNF), BNF for children (BNFc) or the MHRA or NICE websites for up-to-date information.


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.


  • Inconclusive evidence from 8 placebo-controlled RCTs in people with schizophrenia.

  • 4 RCTs show some statistically significant (but possibly minimal clinical) improvement in symptoms with omega-3 fatty acids.

  • 4 RCTs show no difference between omega-3 fatty acids and placebo.


  • Summary of product characteristics cautions around moderate increase in bleeding time and use in people with non-insulin dependent diabetes with aspirin-sensitive asthma.

  • Potential changes in weight and lipid metabolism.

Patient factors

  • Well-tolerated; mild gastrointestinal symptoms (dyspepsia, nausea, diarrhoea) may occur.

  • Number of capsules to take each day could be high.

Resource implications

  • Between £41 and £71 for 28 days' treatment based on 5 capsules per day of Omacor (or generic) or 10 capsules per day of Maxepa.

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 4th 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.

About this evidence summary

'Evidence summaries: unlicensed or off-label medicines' summarise the published evidence for selected unlicensed or off-label medicines that are considered to be of significance to the NHS, where there are no clinically appropriate licensed alternatives. The summaries provide information for clinicians and patients to inform their decision-making and support the construction and updating of local formularies.

The summaries support decision-making on the use of an unlicensed or off-label medicine for an individual patient, where there are good clinical reasons for its use, usually when there is no licensed medicine for the condition requiring treatment, or the licensed medicine is not appropriate for that individual.

The strengths and weaknesses of the relevant evidence are critically reviewed within this summary, but this summary is not NICE guidance.