Omega-3 for Peri- and Postmenopausal Depression

The perimenopause is commonly defined as a time of hormonal fluctuation that typically occurs in women 40-55 years of age with changes in menstrual patterns (Soares et al. 2001; Cohen et al. 2003). Women are at a particularly high risk for depressive symptoms during the perimenopause, as demonstrated by epidemiological data that support a higher risk in perimenopause (15-18% prevalence rates) than premenopause (8-12%) (Bromberger et al., 2003). Women may be especially vulnerable to depressive symptoms during perimenopause due to declining levels of estrogen. Estrogen interacts with the neurotransmitter serotonin and its receptor expression, and may have antidepressant effects; estrogen monotherapy may alleviate depressive symptoms and has been associated with improved quality of life (Soares et al. 2001; Cohen et al., 2003). Of great practical clinical importance, hormone replacement therapy has become increasingly controversial in light of the findings of the Women's Health Initiative study (Roussouw et al.,2002). Soares et al. (2003) found that women with perimenopausal and postmenopausal depression responded well with treatment with citalopram alone and in combination with estrogen. Venlafaxine, mirtazapine, escitalopram, and duloxetine appear efficacious in open pilot studies for perimenopausal depression (Ladd et al., 2005, Joffe et al. 2001; Freeman et al., 2006; Joffe et al., 2007). However, antidepressant medications may be associated with significant side effects. Clinicians, researchers, and patients are now seeking alternative treatments for menopausal-related emotional and physical symptoms.

Investigators have demonstrated promising results with omega-3 fatty acids as a treatment intervention for MDD (Major Depressive Disorder). Overall, treatment data in MDD support a role for EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) in combination or EPA as the omega-3 fatty acid intervention. The majority of published trials that have utilized EPA and DHA in combination or EPA alone have demonstrated a significant benefit in MDD.

Omega-3 fatty acids (sometimes abbreviated n-3 fatty acids) are nutritional compounds with widely established health benefits. Omega-3 fatty acids are polyunsaturated fatty acids. The American Psychiatric Association's (APA) Committee on Research on Psychiatric Treatments conducted a meta-analysis of placebo-controlled treatment studies of MDD and bipolar depression and found a significant benefit for omega-3 fatty acids (Freeman et al., 2006).

Treatment with estrogen compounds, such as oral contraceptive pills or oral estrogen replacement therapy, has been shown to increase levels of DHA in women, theoretically from the upregulation of DHA synthesis from dietary precursors (Giltay et al., 2004). Increased EPA and DHA in plasma due to hormone replacement therapy have been proposed to account for its antidepressant effects (Sumino et al., 2003). Should decline in endogenous estrogen levels, therefore, lower the amount of omega-3 fatty acids available to the brain, supplementation in the perimenopause may be of particular importance.

Inclusion criteria

• Women age 40 and older in the peri- or postmenopausal period, as defined in Soules et al. 2001
• Meet criteria for Major Depressive Disorder on the MINI (Mini-International Neuropsychiatric Interview)
• Score of 18 or greater on MADRS (Montgomery-Asberg Depression Rating Scale) at screening visit
• Do not meet criteria for placebo response during placebo run-in phase; placebo response is defined as a > 50% decrease in MADRS from screening to end of placebo run-in phase
• Willing to receive treatment on an outpatient basis
• Presence of general good health

Exclusion criteria

• Currently pregnant, trying to conceive, or breastfeeding
• Treatment with an antidepressant medication currently or in the past 1 month
• Treatment with hormone replacement therapy currently or in the past 1 month
• Treatment with Omega-3 supplements currently or in the past 1 month
• Use of birth control pills currently or in the past 1 month
• Presence of suicidal ideation
• Meet criteria for current or within the past month for panic disorder, obsessive compulsive disorder (OCD), psychosis, mania or hypomania, as assessed by the MINI
• Diagnosis of treatment resistant Major Depressive Disorder, defined as patients who have been treated with two or more therapeutic courses of antidepressant medication without remission of symptoms for the current episode of depression, as assessed by the MINI
• Any medical condition that would make participation in the study unsafe, as determined by investigator
• Presence of a known allergy to fish or fish oil that would put participant at risk, as determined by a study investigator