Omega-3 fatty acids: Do ‘fish oils’ have a therapeutic role in psychiatry?
Analysis. For patients with unipolar depression who were treated with omega-3 fatty acids:
- the most promisingresults have been seen with adjunctive EPA
- safety and tolerability have been good across studies.
No positive monotherapy studies have been published. Studies are needed to confirm EPA’s efficacy in unipolar depression and to determine the most effective dosage.
Treating bipolar disorder
EPA and DHA have been studied in bipolar disorder (Table 2) because their actions in modulating signal transduction pathways resemble those of lithium and valproate.10,17 Biochemical studies also have shown decreased AA and DHA in erythrocyte membranes of manic patients compared with controls.18
- Stoll et al. 19 Thirty patients receiving usual treatment for bipolar disorder were randomly assigned to adjunctive omega-3 fatty acids (6.2 grams/d of EPA plus 3.4 grams/d of DHA) or placebo for 4 months. Results were promising; patients receiving the omega-3 fatty acids remained in remission significantly longer than the placebo group.
- Keck et al. 20,21 On the other hand, two more-recent studies were disappointing. Both were 4-month, randomized, controlled trials in which patients received adjunctive EPA, 6 grams/d, or placebo. One study enrolled 59 patients with acute bipolar depression;20 the other enrolled 62 patients with rapid-cycling bipolar disorder.21 EPA was well-tolerated, but both studies found little difference in effectiveness between EPA and placebo.
Table 2
Controlled trials of adjunctive omega-3 fatty acids in treating bipolar disorder
| Author, year of publication | Duration and dosages | Number of patients | Results |
|---|---|---|---|
| Stoll et al, 1999 19 | 4 months, maintenance therapy (6.2 grams/d of EPA and 3.4 grams/d of DHA) in patients with bipolar I or II disorder | 30 | Significantly longer remission in omega-3 fatty acid group compared with placebo group |
| Keck et al, 2003 20 | 4 months, 6 grams/d of EPA in patients with acute bipolar depression | 59 | No significant difference in mean change from baseline to endpoint between EPA and placebo groups |
| Keck et al, 2003 21 | 4 months, 6 grams/d of EPA in patients with rapid-cycling bipolar disorder | 62 | Little difference in mean change from baseline to endpoint between EPA and placebo groups |
| DHA: docosahexaenoic acid | |||
| EPA: eicosapentaenoic acid | |||
Analysis. Further studies are needed to determine omega-3 fatty acids’ usefulness in treating bipolar illness.
Treating schizophrenia
Essential fatty acid deficiency and resulting lipid membrane abnormalities have been hypothesized to play a role in schizophrenia onset.22 Moreover, epidemiologic data suggest an association between high fish consumption and positive outcomes in patients with schizophrenia.23
Open-label trials, adjunctive therapy
- Mellor et al. 24 Twenty patients receiving antipsychotics for schizophrenia were treated for 6 weeks with 10 grams/d of a fish oil formulation containing 1.7 grams of EPA and 1.1 grams of DHA (Table 3). Psychotic symptoms improved significantly and were correlated with increased omega-3 fatty acid levels in erythrocyte membranes. Tardive dyskinesia also improved significantly, as measured by Abnormal Involuntary Movement Scale (AIMS) scores.
- Arvindakshan et al. 25 Thirty-three patients receiving antipsychotics for schizophrenia were given omega-3 fatty acids (360 mg/d of EPA and 240 mg/d of DHA) plus antioxidants (800 IU vitamin E and 1,000 IU vitamin C) for 4 months. Symptom and quality-of-life measures improved significantly, and clinical improvement was retained after 4 months of supplement washout.
Table 3
Clinical trials of omega-3 fatty acids in treating schizophrenia
| Authors, year of publication | Duration and dosages | Number of patients | Results |
|---|---|---|---|
| Open-label trials, adjunctive therapy | |||
| Mellor et al, 1995 24 | 6 weeks, 10 grams/d of fish oil (1.7 grams EPA and 1.1 grams DHA) | 20 | Significant improvement on PANSS and AIMS scores from baseline to endpoint |
| Arvindakshan et al, 2003 25 | 4 months, 360 mg/d of EPA and 240 mg/d of DHA, plus antioxidants (1,000 IU of vitamin C and 800 IU of vitamin E) | 33 | Significant improvements on total BPRS, PANSS, and Henrich’s Quality of Life Scale scores; improvements sustained after 4 months of supplementation washout |
| Controlled trials, adjunctive therapy | |||
| Peet et al, 2001 26 | 3 months, 2 grams/d of EPA or DHA | 45 | Greater improvement in total PANSS scores with EPA compared with DHA and placebo; EPA more effective than DHA in treating positive symptoms |
| Fenton et al, 2001 27 | 16 weeks, 3 grams/d of ethyl-EPA in patients with schizophrenia or schizoaffective disorder | 87 | No difference between ethyl-EPA and placebo groups in positive or negative symptoms, cognition, mood, or EPS |
| Peet et al, 2002 28 | 12 weeks, 1, 2, or 4 grams/d of ethyl-EPA with typical and atypical antipsychotics, including clozapine | 115 | Significantly greater improvement in mean total PANSS scores in clozapine-treated patients taking ethyl-EPA, 2 grams/d, compared with placebo; no difference between ethyl-EPAand placebo in patients taking typical or atypical antipsychotics |
| Emsley et al, 2002 29 | 12 weeks, 3 grams/d of ethyl-EPA | 40 | Significantly greater reduction in total PANSS and EPS Rating Scale dyskinesia scores in ethyl-EPA group compared with placebo |
| Controlled trial, monotherapy | |||
| Peet et al, 2001 26 | 3 months, 2 grams/d of EPA | 26 | EPA-treated patients had significantly lower PANSS scores at endpoint, compared with placebo; significantly more patients on placebo required antipsychotics (12 of 12) than did those on EPA (8 of 14) |
| AIMS: Abnormal Involuntary Movement Scale | |||
| BPRS: Brief Psychiatric Rating Scale | |||
| DHA: docosahexaenoic acid | |||
| EPA: eicosapentaenoic acid | |||
| EPS: extrapyramidal symptoms | |||
| PANSS: Positive and Negative Syndrome Scale | |||
