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Meta-Analysis
. 2006 Jul 19;2006(3):CD001257.
doi: 10.1002/14651858.CD001257.pub2.

Polyunsaturated fatty acid supplementation for schizophrenia

Affiliations
Meta-Analysis

Polyunsaturated fatty acid supplementation for schizophrenia

C B Joy et al. Cochrane Database Syst Rev. .

Abstract

Background: Limited evidence supports a hypothesis suggesting that schizophrenic symptoms may be the result of altered neuronal membrane structure and metabolism. The structure and metabolism is dependent on blood plasma levels of certain essential fatty acids and their metabolites.

Objectives: To review the effects of polyunsaturated fatty acids for people with schizophrenia.

Search strategy: We have updated the initial searches of 1998 and 2002 (Cochrane Schizophrenia Group's Register, July 2005), and where necessary, we contacted authors and relevant pharmaceutical companies.

Selection criteria: We included all randomised clinical trials of polyunsaturated fatty acid treatment for schizophrenia.

Data collection and analysis: Working independently, we selected studies for quality assessment and extracted relevant data. We analysed on an intention-to-treat basis. Where possible and appropriate we calculated the Relative Risk (RR) and their 95% confidence intervals (CI) and estimated the number needed to treat (NNT). For continuous data we calculated weighted mean differences (WMD) and their 95% confidence intervals. We also inspected the data for heterogeneity.

Main results: When any dose omega-3 (E-EPA or EPA) is compared with placebo, small short trials suggest that the need for neuroleptics appears to be reduced for people allocated omega-3 supplementation (n=30, 1 RCT, RR 0.73 CI 0.54 to 1.00) and mental state may improve (n=30, 1 RCT, RR not gaining 25% change in PANSS scores 0.54 CI 0.30 to 0.96, NNT3 CI 2-29). There are no differences in the number of people leaving the study early (n=271, 4 RCTs, RR 0.91 CI 0.36 to 2.33). There are few data on the comparison of any dose omega-6 (GLA) with placebo. For movement disorder outcomes, the only small study we found does not show any difference for average short-term endpoint AIMS score (n=16, 1 RCT, MD 1.30 CI -1.96 to 4.56). When any dose omega 3 (E-EPA or EPA) is compared with any dose omega-3 (DHA) there is no clear difference for mental state outcome of not gaining 25% change in PANSS scores (n=31, 1 RCT, RR 0.66 CI 0.39 to 1.11). When different doses of omega-3 (E-EPA) are compared with placebo there are no differences in measures of global and mental state between the studies. For the outcome of 'experiencing at least one adverse effect' no differences between groups are found for any dose (1g/day E-EPA vs placebo n=63 1 RCT, RR 0.97 CI 0.60 to 1.56; 2g/day E-EPA vs placebo n=63 1 RCT, RR 0.67 CI 0.37 to 1.20; 4g/day E-EPA vs placebo n=58, 1 RCT, RR 1.15 CI 0.72 to 1.82).

Authors' conclusions: Two updates of this review have resulted in more included studies but relatively little useful additional data. The results remain inconclusive. The new trials all compare the omega-3 polyunsaturated fatty acids, in particular eicosapentaenoic acid and its ester, ethyl-eicosapentaenoic acid. The use of omega-3 polyunsaturated fatty acids for schizophrenia still remains experimental and this review highlights the need for large well designed, conducted and reported studies.

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Conflict of interest statement

None known.

Figures

1
1
Methodological quality graph: review authors' judgments about each methodological quality item presented as percentages across all included studies.
2
2
Methodological quality summary: review authors' judgments about each methodological quality item for each included study.
1.1
1.1. Analysis
Comparison 1 ANY DOSE OMEGA‐3 (E‐EPA or EPA ) versus PLACEBO, Outcome 1 Global state: 1. Needing standard neuroleptics by end of trial (short term).
1.2
1.2. Analysis
Comparison 1 ANY DOSE OMEGA‐3 (E‐EPA or EPA ) versus PLACEBO, Outcome 2 Global state: 2. Average scale score by end of trial (CGI, medium term, high=poor).
1.4
1.4. Analysis
Comparison 1 ANY DOSE OMEGA‐3 (E‐EPA or EPA ) versus PLACEBO, Outcome 4 Global state: 4. Not achieving symptomatic response by 12 weeks ‐ all participants.
1.5
1.5. Analysis
Comparison 1 ANY DOSE OMEGA‐3 (E‐EPA or EPA ) versus PLACEBO, Outcome 5 Global state: 5. Not achieving symptomatic response by 12 weeks ‐ nonaffective participants.
1.6
1.6. Analysis
Comparison 1 ANY DOSE OMEGA‐3 (E‐EPA or EPA ) versus PLACEBO, Outcome 6 Mental state: 1. Not improved by end of trial (<25% improvement on PANSS scale, short term).
1.7
1.7. Analysis
Comparison 1 ANY DOSE OMEGA‐3 (E‐EPA or EPA ) versus PLACEBO, Outcome 7 Mental state: 2. Average scale score by end of trial (PANSS, high=poor).
1.10
1.10. Analysis
Comparison 1 ANY DOSE OMEGA‐3 (E‐EPA or EPA ) versus PLACEBO, Outcome 10 Adverse events: Average time to first tardive dyskinesia response.
1.11
1.11. Analysis
Comparison 1 ANY DOSE OMEGA‐3 (E‐EPA or EPA ) versus PLACEBO, Outcome 11 Leaving the study early.
2.1
2.1. Analysis
Comparison 2 ANY DOSE OMEGA‐6 (GLA) versus PLACEBO, Outcome 1 Tardive dyskinesia: Average scale score by end of trial (AIMS, short term, high=poor).
2.2
2.2. Analysis
Comparison 2 ANY DOSE OMEGA‐6 (GLA) versus PLACEBO, Outcome 2 Leaving the study early (short term).
3.1
3.1. Analysis
Comparison 3 ANY DOSE OMEGA‐3 (EPA or E‐EPA) versus ANY DOSE OMEGA‐3 (DHA), Outcome 1 Mental state: 1. Not improved by end of trial (<25% improvement on PANSS scale, short term).
3.2
3.2. Analysis
Comparison 3 ANY DOSE OMEGA‐3 (EPA or E‐EPA) versus ANY DOSE OMEGA‐3 (DHA), Outcome 2 Mental state: 2. Percentage change in scale score by end of trial (PANSS, short term, high=good).
3.3
3.3. Analysis
Comparison 3 ANY DOSE OMEGA‐3 (EPA or E‐EPA) versus ANY DOSE OMEGA‐3 (DHA), Outcome 3 Leaving the study early (short term).
4.1
4.1. Analysis
Comparison 4 SPECIFIC DOSES OF E‐EPA versus PLACEBO, Outcome 1 Global state: Average scale score by end of trial (CGI, medium term, high=poor).
4.2
4.2. Analysis
Comparison 4 SPECIFIC DOSES OF E‐EPA versus PLACEBO, Outcome 2 Mental state: 1. Average scale score by end of trial (PANSS, medium term, high=poor).
4.4
4.4. Analysis
Comparison 4 SPECIFIC DOSES OF E‐EPA versus PLACEBO, Outcome 4 Adverse events: General 1. Experiencing at least one adverse effect (short term).
4.5
4.5. Analysis
Comparison 4 SPECIFIC DOSES OF E‐EPA versus PLACEBO, Outcome 5 Adverse events: Specific 1a. Gastrointestinal (diarrhoea).
4.6
4.6. Analysis
Comparison 4 SPECIFIC DOSES OF E‐EPA versus PLACEBO, Outcome 6 Adverse events: Specific 1b. Gastrointestinal (nausea, short term).
4.7
4.7. Analysis
Comparison 4 SPECIFIC DOSES OF E‐EPA versus PLACEBO, Outcome 7 Adverse events: Specific 2. Liver and biliary tract (short term).
4.8
4.8. Analysis
Comparison 4 SPECIFIC DOSES OF E‐EPA versus PLACEBO, Outcome 8 Adverse events: Specific 4. Metabolic and nutritional (short term).
4.9
4.9. Analysis
Comparison 4 SPECIFIC DOSES OF E‐EPA versus PLACEBO, Outcome 9 Adverse events: Specific 5. Musculoskeletal (short term).
4.10
4.10. Analysis
Comparison 4 SPECIFIC DOSES OF E‐EPA versus PLACEBO, Outcome 10 Adverse events: Specific 6. Psychiatric (short term).
4.11
4.11. Analysis
Comparison 4 SPECIFIC DOSES OF E‐EPA versus PLACEBO, Outcome 11 Adverse events: Specific 7. Reproductive (short term).
4.12
4.12. Analysis
Comparison 4 SPECIFIC DOSES OF E‐EPA versus PLACEBO, Outcome 12 Adverse events: Specific 8. Infections and respiratory system.
4.13
4.13. Analysis
Comparison 4 SPECIFIC DOSES OF E‐EPA versus PLACEBO, Outcome 13 Adverse events: Specific 9. Skin (short term).
4.14
4.14. Analysis
Comparison 4 SPECIFIC DOSES OF E‐EPA versus PLACEBO, Outcome 14 Adverse events: Specific 10. Urinary (short term).
4.15
4.15. Analysis
Comparison 4 SPECIFIC DOSES OF E‐EPA versus PLACEBO, Outcome 15 Adverse events: Specific 11. Vision (short term).
4.16
4.16. Analysis
Comparison 4 SPECIFIC DOSES OF E‐EPA versus PLACEBO, Outcome 16 Adverse events: Specific 12. Other (short term).
4.17
4.17. Analysis
Comparison 4 SPECIFIC DOSES OF E‐EPA versus PLACEBO, Outcome 17 Leaving the study early.

Update of

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MeSH terms