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Omega-3 for Peri- and Postmenopausal Depression

Omega-3 for Peri- and Postmenopausal Depression

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00825994
Acronym
O3Meno
Enrollment
31
Registered
2009-01-21
Start date
2008-11-30
Completion date
2009-06-30
Last updated
2014-08-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Depression

Keywords

menopause, perimenopause, postmenopause, depression, mood, sleep, hot flashes

Brief summary

The purpose of this study is to determine if an eight-week intervention with omega-3 fatty acids significantly reduces depressive symptoms in symptomatic peri- and postmenopausal women. We hypothesize that an eight-week trial with omega-3 fatty acids promotes significant improvement in depression symptoms in peri- and postmenopausal women.

Detailed description

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.

Interventions

DRUGOmega-3 Fatty Acids

2 g omega-3 fatty acids (docosahexaenoic acid \[DHA\] + eicosapentaenoic acid \[EPA\]), PO \[by mouth\], qd \[every day\]

Sponsors

GlaxoSmithKline
CollaboratorINDUSTRY
Massachusetts General Hospital
Lead SponsorOTHER

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
FEMALE
Age
40 Years to No maximum
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
Change in MADRS Score8 weeksThe instrument used to measure mood at each visit was the Montgomery-Åsberg Depression Rating Scale (MADRS). The MADRS is a widely used 10-item clinician-rated scale that describes the severity of depressive symptoms (range 0-60, higher score indicates greater symptom burden).

Secondary

MeasureTime frameDescription
Change in Hot Flash Daily Interference Scale (HFRDIS)8 weeksVasomotor symptoms (hot flashes) were tracked by using a self-report Hot Flash Related Daily Interference Scale (HFRDIS). The HFRDIS is a 10-item self-report questionnaire in which subjects rate the degree to which hot flashes interfere with daily activities and quality-of-life during the prior week. Each item is rated on a scale from 0 (does not interfere) to 10 (completely interferes) for a total score range of 0-100 (higher score indicates greater symptom burden/interference).

Countries

United States

Participant flow

Pre-assignment details

Of the 31 participants who consented at V1, 7 were ineligible at this visit. The remaining 24 were given a 1-week single-blind placebo lead-in. Women who met criteria for placebo response, defined as a \>= 50% decrease in MADRS (Montgomery-Asberg Depression Rating Scale) from screening to end of the run-in phase, were excluded from the study.

Participants by arm

ArmCount
Omega-3
omega-3 fatty acids, 2g qd (2 x 1 gram tablets), PO
24
Total24

Withdrawals & dropouts

PeriodReasonFG000
Overall StudyLost to Follow-up1
Overall StudyPlacebo Responder at V21
Overall StudyProtocol Violation1
Overall StudyWithdrawal by Subject2

Baseline characteristics

CharacteristicOmega-3
Age, Categorical
<=18 years
0 Participants
Age, Categorical
>=65 years
0 Participants
Age, Categorical
Between 18 and 65 years
24 Participants
Age, Continuous52.5 years
STANDARD_DEVIATION 4.9
Education
Attended graduate school
5 participants
Education
Attended some college
11 participants
Education
College graduate
5 participants
Education
High school diploma or GED
2 participants
Education
Unknown
1 participants
Employment Status
Disabled
1 participants
Employment Status
Full-time
12 participants
Employment Status
Homemaker
2 participants
Employment Status
Other
1 participants
Employment Status
Part-time
3 participants
Employment Status
Retired
1 participants
Employment Status
Student
1 participants
Employment Status
Unemployed
3 participants
Ethnicity (NIH/OMB)
Hispanic or Latino
2 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
21 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
1 Participants
History of previous major depressive episode
No
15 participants
History of previous major depressive episode
No answer
1 participants
History of previous major depressive episode
Yes
8 participants
Marital Status
Married/living with partner
8 participants
Marital Status
Single (never married)
6 participants
Marital Status
Widowed/divorced
10 participants
Menopause Status
Naturally Postmenopausal
13 participants
Menopause Status
Perimenopausal
9 participants
Menopause Status
Surgically Postmenopausal
2 participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
Race (NIH/OMB)
Asian
1 Participants
Race (NIH/OMB)
Black or African American
5 Participants
Race (NIH/OMB)
More than one race
0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
Race (NIH/OMB)
Unknown or Not Reported
2 Participants
Race (NIH/OMB)
White
16 Participants
Region of Enrollment
United States
24 participants
Sex: Female, Male
Female
24 Participants
Sex: Female, Male
Male
0 Participants

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
— / —
other
Total, other adverse events
3 / 24
serious
Total, serious adverse events
0 / 24

Outcome results

Primary

Change in MADRS Score

The instrument used to measure mood at each visit was the Montgomery-Åsberg Depression Rating Scale (MADRS). The MADRS is a widely used 10-item clinician-rated scale that describes the severity of depressive symptoms (range 0-60, higher score indicates greater symptom burden).

Time frame: 8 weeks

Population: Of 31 women who consented to participate per protocol 24 were eligible. Of these 24 eligible participants, three women withdrew and one was a placebo responder. 20 women started omega-3 fatty acid treatment and 19 completed the study.

ArmMeasureValue (MEAN)Dispersion
Omega-3 Fatty AcidsChange in MADRS Score12.0 units on a scaleStandard Deviation 8.3
Secondary

Change in Hot Flash Daily Interference Scale (HFRDIS)

Vasomotor symptoms (hot flashes) were tracked by using a self-report Hot Flash Related Daily Interference Scale (HFRDIS). The HFRDIS is a 10-item self-report questionnaire in which subjects rate the degree to which hot flashes interfere with daily activities and quality-of-life during the prior week. Each item is rated on a scale from 0 (does not interfere) to 10 (completely interferes) for a total score range of 0-100 (higher score indicates greater symptom burden/interference).

Time frame: 8 weeks

Population: Of 31 women who consented to participate per protocol 24 were eligible. Of these 24 eligible participants, three women withdrew and one was a placebo responder. 20 women started omega-3 fatty acid treatment and 19 completed the study. Of these 20, 15 women had hot flashes at baseline and could be included in the hot flash analysis.

ArmMeasureValue (MEAN)Dispersion
Omega-3 Fatty AcidsChange in Hot Flash Daily Interference Scale (HFRDIS)18.5 units on a scaleStandard Deviation 27.8

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026