5º semestre.part01 - artigo II - ezquizofrenia

5º semestre.part01 - artigo II - ezquizofrenia

(Parte 1 de 2)

Revista de Psiquiatria Clínica Print version ISSN 0101-6083

Rev. psiquiatr. clín. Vol. 37 No. 5 São Paulo 2010 http://dx.doi.org/10.1590/S0101-60832010000500007

Omega 3 fatty acids and treatment of schizophrenia Omega 3 fatty acid and schizophrenia treatment

Juliane Costa Silva ZemdegsI; Gustavo Duarte PimentelI; Margaret Rose PrielII

(I)Graduate program in Nutrition of the Universidade Federal de São Paulo (Unifesp) IIGraduate studies and research of Centro Universitário São Camilo

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CONTEXT:Schizophrenia is a psychiatric disorder and complex whose debilitating treatment is performed with antipsychotic medications. However, evidence suggests that dietary supplementation with Omega 3 fatty acids (n-3) can be beneficial in several psychiatric disorders. GOAL:Review the effectiveness of n-3 as an adjunct in the pharmacological treatment of schizophrenia. METHODS:A search was held in electronic databases Medline, Lilacs and SciELO. The search strategy also included the search in the tree. All randomized and controlled studies were included in this review, relevant regardless of the year of publication. RESULTS: So far, were disclosed six randomized, double-blind placebo controlled; five of them showed positive results in the improvement of symptoms of schizophrenia, indicating even superiority of fatty acid Eicosapentaenoic (EPA) compared to the fatty acid docosaexaenoico. In General, the consumption of 2 g/day of EPA in conjunction with the usual seems to reduce the medication hallucinogen symptoms of schizophrenia, particularly positive symptoms. CONCLUSION:Nutritional therapy with EPA proved useful as an adjunct in the treatment of schizophrenia.Therefore, it is suggested that schizophrenia patients are encouraged to consume healthy and balanced meals rich in EPA and, if the ideal amount is not affected by diet, supplementation may be beneficial.

Keywords:Schizophrenia, nutrition, Eicosapentaenoic Acid, fatty acid Omega 3, treatment.

BACKGROUND:Schizophrenia is a complex and debilitating psychiatric disorder, whose primary pharmacological intervention is the use of antipsychotics. There is, however, growing evidence that dietary supplementation with omega 3 fatty acids (n-3) may be beneficial in several psychiatric conditions. OBJECTIVE:To review the efficacy of n-3 as a treatment for schizophrenia. METHODS: Electronic searches of the following databases were performed: Medline, Lilacs and SciELO. The search strategy also included cited reference searching. All relevant randomized controlled trials were included in the review. RESULTS: To date, five out of six randomized, double-blind, placebo-controlled studies obtained and improvement in the symptoms of the psychosis. Besides, an advantage in the intake of fatty acid eicosapentaenoic (EPA) in relation to docosahexaenoic fatty acid was designated. Essentially, the intake of 2 g/day of EPA in addition to the standard medication was effective in decreasing the symptoms of schizophrenia. DISCUSSION: The nutritional therapy with EPA revealed to be useful the coadjutant in the treatment of schizophrenia. Therefore, we suggest that the schizophrenic patients should be encouraged to consume balanced and healthy meals rich in EPA and, if the ideal amount is not reached by the diet, the supplementation is likely to be beneficial.

Keywords: Schizophrenia, nutrition, eicosapentaeinoic acid, omega 3 fatty acid, treatment.

Introduction

After the fat, the central nervous system has the highest lipid content of the human body, and 35% of lipids of an adult brain are polyunsaturated fatty acids1-3.

Polyunsaturated fatty acids are involved in cell signaling, enzymatic regulation, synthesis of Eicosanoids, regulation of neuronal migration, determination of the synaptic plasticity and modulation of cytokines that have neuromodulatória activity and neurotransmitter4-10, so that possibly involved in the pathophysiology of some psychiatric disorders such as schizophrenia and depression11-13.

Despite the uncertain etiology of schizophrenia, evidence points to an abnormal metabolism of phospholipids, particularly on the composition of fatty acids of cell membranes14-19. In this context, studies have shown that schizophrenia patients have reduced levels of long chain fatty acids in membranes of red blood cells, probably because of excessive activity of phospholipase A2 20,21.

It is possible that dietary changes increase or relieve symptoms of schizophrenia. Accordingly, Christensen and Christensen22 found positive correlation between improvement of prognosis of schizophrenia and the low total fat and fats of animal sources – made up mostly by saturated fatty acids. Additionally, observed trend of positive relationship between the high consumption of fats from vegetables, fish and marine animals (rich in unsaturated fatty acids) and best outcome of psychosis. Corroborating this study, positive association between the consumption of red meat, dairy products and sugar and worse prognosis of schizophrenia was demonstrated and the low intake of Omega 3 fatty acid (n-3) Eicosapentaenoic (EPA) was associated with the presence of more severe symptoms of schizophrenia14.

Preliminary studies have reported an improvement of symptoms of schizophrenia after supplementation with n-3 as an adjunct therapy to antipsychotics23-26. Based on this perspective and in view of that, despite the pharmacological advancement occurred over recent decades, the extent of complete remission of these patients still constitutes a major challenge27, this work was intended to review randomized, double-blind and placebo-controlled who evaluated the effects of supplementation with n-3 as treatment of schizophrenia.

Methods

The bibliographic search was to search for articles published in the following electronic databases: Medline (National Library of Medicine), Lilacs (Latin American and Caribbean Health Sciences) and SciELO (Scientific Electronic Library Online).

The search strategy was the Boolean logic "and" for the following descriptors of health: diet, nutrition, Omega 3 fatty acid and the central nervous system, combined with the term schizophrenia. Language and publishing period have not been restricted. All clinical trials randomized, double-blind and placebo-controlled who used Omega 3 fatty acid for the treatment of schizophrenia patients were included in this analysis, regardless of gender, age and race of participants. Studies in which more than 30% of the participants did not continue the treatment were excluded from this review. For articles not available in national territory, the respective authors were contacted by e-mail in order to request the dispatch of articles in full.

Results Description of selected studies

The electronic search returned 13 clinical trials that evaluated the effects of supplementation with n-3 on symptoms of schizophrenia patients. Of these 13 articles, 7 were deleted because they were not randomized, double-blind and placebo-controlled.

Excluding patients who did not follow the treatment, the six articles included in this review randomizaram total 381 patients. In all studies, the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders) was the criterion for the diagnosis of schizophrenia and various scores were used to monitor the severity of the disease.

Fenton et al.28 also included patients with esquizoafetivas disorders. Emsley et al.29 not referred to the genus of the participants, while other studies included both genders (female and male) for analysis. The age of patients analyzed 15 and 65 years varied between, and the sample size ranged between 30 and 122 participants. All studies supplemented n-3 and compared with the placebo supplementation. The study of Peet et al.30 was the only one in which participants discontinued medication hallucinogen during n-3 supplementation or placebo.Fenton et al.28 compared different doses of ethyl-EPA with placebo.

N-3 supplementation in schizophrenia patients: clinical trials

The characteristics of randomized, double-blind and placebo-controlled achieved so far that have evaluated the effects of supplementation with n-3 in patients with schizophrenia are presented in table 1, while the characteristics of excluded studies are in table 2.

In 2001, Peet et al.30 conducted a double-blind randomized clinical trial with 45 patients receiving daily oil rich in fatty acid Eicosapentaenoic (EPA) – 2 g/day – or docosaexaenoico fatty acid-rich oil (DHA) – 2 g/day – or placebo for three months. The authors reported improvement in score PANSS (Positive and Negative Syndrome Scale) in the EPA Group, while the therapeutic response in the group treated with DHA did not differ from placebo. The effect of the EPA about the positive symptoms of the disease was superior to DHA by repeated measures analysis of variance and the percentage of improvement of symptoms.

Peet and Horrobin31 exploring the effects of supplementation of different doses of ethyl-EPA (1, 2 or 4 g/day) or placebo for 12 weeks in 115 patients of schizophrenia under medication hallucinogen. Patients who received 2 g/day of ethyl-EPA associated with treatment with clozapine 25% improvement presented in scale PANSS.However, a placebo effect was observed in patients under medication typical and atypical hallucinogen.

Fenton et al.28 randomizaram 87 patients with schizophrenia or under medication for disorders esquizoafetivas hallucinogen receive 3 g/day of ethyl-EPA or placebo for 16 weeks. According to the authors, the groups were homogeneous, even for the daily intake of n-3. No significant differences were observed in the PANSS scores on any of the times analyzed (1, 2, 4, 8, 12 or 16 weeks) and two adverse effects were reported in the EPA Group: upper respiratory tract infection and diarrhea. A secondary analysis of the data showed that patients treated with clozapine and ethyl-EPA showed significant improvement of symptoms.

Emsley et al.29 randomizaram 40 patients of schizophrenia to receive 3 g/day of ethyl-EPA or placebo for three months. The EPA has made significant improvement of group symptoms of the disease when compared to the placebo group after 3, 9 and 12 weeks of treatment. According to the authors, the dietary intake of n-3 before and during treatment did not differ between groups. At the end of 12 weeks of treatment, the Group ethyl-EPA has made improvement in scale and significant reduction in PANSS scores of Extrapyramidal Symptom Rating Scale (ESRS).

The efficacy of supplementation of 2 g/day of EPA as single treatment for schizophrenia has also been investigated in 26 patients by Peet et al.30. at the end of three months of double-blind clinical study, all patients of the placebo group, while the requested medication hallucinogen EPA Group presented significant improvement in scale PANSS positive symptoms, particularly for disease, and half of these patients are not needed to conventional treatment.

According to Berger et al.32, the chronicity of the disease and the use of established can accentuate or hallucinogen medication mask the effects of n-3. For this reason, these authors evaluated the effectiveness of 2 g/day supplementation of ethyl-EPA for 12 weeks in patients with a first episode of psychosis that had not received recent hallucinogen medication or who had been previously treated with atypical antipsychotics recently. Patients were subjected to a series of clinical rating scales (Table 1) after 3, 6, 9 and 12 weeks of treatment. The results suggest that the ethyl-EPA can accelerate the response to treatment and improve tolerance to medications antipsicóticas.

Discussion

The studies done to date are of major importance to clinical practice. However, some flaws in their methodologies may be mentioned: 1) variables that were not controlled; 2) bioavailability of ethyl-EPA; 3) changes observed on symptom scales were compared in relation to the basal score, i.e. the previous score to supplementation, and supplied in percentage of change; 4) small number of participants evaluated.

With respect to the variables that are not controlled, Horrobin37 believes the information of experimental procedures in term of consent may have induced patients to consume foods high in n-3 or fish oil supplements.Despite speculation, this has not been examined.

Additionally, the fact that some studies had not conducted an assessment of the dietary intake of patients constitutes a variable of contradiction to searches and alludes to the need for distinction between necessity and pharmacological dose supplementation, dietary n-3 for schizophrenia patients.

N-3 recommendations for healthy population are shown in table 3, from which it is possible to observe that the doses that have benefits in treating patients of schizophrenia are approximately four times greater than the recommended quantities for healthy adults. However, as a result of declining data intake of n-3 for humanity throughout the centuries39,40, it is assumed that it is possible that schizophrenia patients to obtain the optimal quantity n-3 through food, not implying, in principle, the need for supplementation.

On the bioavailability of n-3, it is important to remember that this fatty acid is not an isolated compound in its natural state, but part of larger, as the molecules naturally triacylglycerols and phospholipids. To obtain EPA or DHA capsules, these molecules need to be purified and stabilized the hydrolysed, ethyl-ester. This procedure results in a product that is more natural, and Yes, chemist whose bioavailability is lower than when the n-3 is provided in the form of phospholipids41.

Furthermore, the concept of response may present some problems as to its interpretation, because the use of the criterion of reduction percentage in relation to the basal score does not provide a precise information about how the patient is at the end of treatment in relation to symptoms42.

Despite the flaws and limitations discussed, it is surprising to find the level of statistical significance that has emerged considerably on a small group of participants. In addition, the diagnostic criteria adopted in these experimental tests for inclusion of patients was the DSM-IV, which tends to select patients with less favourable prognosis than more inclusive criteria43.

Although most of the studies assessed in this review has no reported adverse effects associated with supplementation with n-3, healthcare professionals should be aware of a possible increase in bleeding time, body weight and levels of total cholesterol and HDL-cholesterol44.

Conclusion

The compilation of experimental clinical studies highlighted the relationship between the EPA and the supplementation improves the symptoms of schizophrenia. Therefore, it is suggested that schizophrenia patients are encouraged to consume healthy and balanced meals rich in EPA and, if the ideal amount is not reached by the diet, it is possible that n-3 supplementation is beneficial. It is worth mentioning that, as with any form of treatment, nutritional therapy should be supervised and the doses adjusted where necessary to ensure that the benefits of treatment are met.

(Parte 1 de 2)

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