Depression in Parkinson's disease: A double-blind, randomized, placebo-controlled pilot study of omega-3 fatty-acid supplementation

Abstract

Background

Effect of fish oil supplementation in parkinsonian patients with depression measured by Montgomery–Asberg Rating Scale (MADRS), the Clinical Global Impressions Scale (CGI) and Beck Depression Inventory (BECK).

Method

Double-blind, placebo-controlled study analyzed depression in 31 patients with Parkinson's Disease and Major Depression (DSM-IV). The patients were double-blind separated in 2 groups that received fish oil (containing omega-3 fatty acids) or mineral oil capsules for 3 months; each group was separated in 2 new groups: one taking antidepressant medication and another one not taking it.

Results

29 patients completed the 12-week trial, 58% were female and the mean age was 64.4 years old. Patients supplemented with fish oil showed a significant decrease in MADRS and CGI-Depression scores, and there was no difference among groups in BDI. 14 patients (42%) met criteria for ≥ 50% reduction in MADRS score, 7 patients (22%) met criteria for remission (final MADRS total score ≤ 12), and 2 patients (6%) discontinued supplementation of fish oil. HPLC analysis of fatty-acid profile showed increase of omega-3 fatty acid in the erythrocyte membrane of patients taking fish oil.

Conclusion

These results reveal that PD patients taking fish oil, with or without antidepressants, presented improvement in depressive symptoms and indicate that the intake of omega-3 can be used with an antidepressant effect or as adjuvant therapy with some other medication. This is a first pilot study with parkinsonian patients and omega-3 supplementation and requires replication in a larger sample.

Introduction

Parkinson's disease (PD) is a neurodegenerative illness, one of the most frequent neurological conditions whose cause remains unknown (Teive and Meneses, 2003) and its prevalence is of 200 cases for each 100,000 habitants. This condition causes various motor and non-motor symptoms (Mercury et al., 2007). The most common non-motor symptom affecting the patients with PD is depression, with estimates of depressive symptoms in 40–56% of PD patients (Nuyen et al., 2006, Wichowicz et al., 2006), constituting one of the major health problems in elderly (Malamakis et al., 2002). Depression in PD is associated to a deficiency of dopamine, which causes motor difficulties, and, in lesser extension, of noradrenalin and serotonin (Anand and Charney, 2000).

In a considerable number of cases, depression appeared before the manifestation of Parkinson's classic symptoms, even previous to any evidence of motor incapacity, and a recent study observed that people diagnosed with depression are three times more disposed to develop PD (Mercury et al., 2007, Tolosa et al., 2007, Ziemssen and Reichmann, 2007).

The Docosahexaenoic acid (DHA, 22:6 n−3) and the Eicosapentaenoic acid (EPA, 20:5 n−3) from omega-3, one important family of polyunsaturated fatty acids (PUFA), are essential and can be obtained mostly from fish and marine derivates. The presence of these PUFA in cellular membranes is important to maintain the properties of the lipid bilayer (Farooqui et al., 2000, Youdim et al., 2000).

Since DHA and other PUFAs are widely involved with neural function and cerebral structure, it has been suggested a relation between alterations in the lipid profile of the diet and the manifestation of depression (Logan, 2004, Moriguchi et al., 2000). The hypothesis that fatty-acid levels in the organism can be involved with the expression of depression and mood disorders has been supported by epidemiological studies that associated fish consumption and prevalence of the illness (Freeman, 2000, Morris et al., 2005, Tanskanen et al., 2001). In countries like Japan, Korea and Chile, where there is a large fish and marine derivatives consumption, the depression index is consider lower when compared to the majority of occidental countries with smaller consumption of these foods (Hibbeln, 1998, Timonen et al., 2004).

Polyunsaturated fatty acids have been regarded as effective in the treatment of some psychiatric pathologies, and it was verified the association of reduced fractions of omega-3 PUFAs in erythrocyte membranes of depressive patients (Assies et al., 2004, Malamakis et al., 2002, Peet and Horrobin, 2002, Su et al., 2003).

Finally, some studies evaluated the antidepressant potential of fish oil supplementation or its constituents (DHA and/or EPA). These studies show contradictory results, with positive (De Vriese et al., 2003, Lin and Su, 2007, Nemets et al., 2002, Su et al., 2003) and negative results (Marangell et al., 2003, Silvers et al., 2005), which may be due to methodological differences and the use of DHA or EPA. These results suggest that omega-3 PUFAs supplementation could be involved in antidepressant clinical effects, one way or another.

Among the studies involving the development of neurodegenerative illnesses and fatty acids interaction, little has been seen concerning PD. A study from De Lau et al. (2005) analyzing profile of alimentary consumption in elderly associates high ingestion of PUFAs in the diet to a reduced risk of developing PD. Samadi et al. (2006) showed that DHA reduces or delay the development of levodopa-induced dyskinesias in parkinsonian-treated monkeys. Julien et al. (2000) suggested that changes in brain fatty acids relative concentrations are associated with levodopa treatment in PD patients and in non-human primate model of Parkinsonism.

Searching new forms of treatment consists in offering ways to overcome Parkinson's symptoms in a better way and in contributing to individual proper aptitude to support, accept and adapt to a new reality. So, the aim of this work was to study the effect of alimentary supplementation with fish oil, rich in omega-3 PUFAs, over depression symptoms in parkinsonian patients with major depression.