Complimentary and Alternative Approaches to Perinatal Mental Illness Dena Whitesell, MD April 29, 2011

Importance of Treatment Therapeutic relationship Therapeutic relationship Traditional medications Traditional medications …but what about women who want a different approach, or for whom the traditional approach hasn’t worked?

Alternative Methods Omega-3 fatty acids Omega-3 fatty acids St. John’s wort St. John’s wort Acupuncture Acupuncture Massage Massage Light therapy Light therapy

Omega-3 fatty acids Best evidence of any alternative treatment Best evidence of any alternative treatment Two types well studied: Two types well studied: EPA– eicosapentaenoic acid EPA– eicosapentaenoic acid DHA—docosahexaenoic acid DHA—docosahexaenoic acid Meta-analyses show benefit of supplements over placebo as ADJUNCTIVE therapy for both unipolar and bipolar depression Meta-analyses show benefit of supplements over placebo as ADJUNCTIVE therapy for both unipolar and bipolar depression (Parket et al., 2006; Freeman et al, 2006; Su et al., 2006; Nemets et al., 2007)

Omega-3 fatty acids Depletion is common during pregnancy Depletion is common during pregnancy Selectively transferred to the fetus for brain and retinal development Selectively transferred to the fetus for brain and retinal development Intake of omega-3 fatty acids by pregnant and lactating women in US is only 20-60% of the recommended amounts Intake of omega-3 fatty acids by pregnant and lactating women in US is only 20-60% of the recommended amounts (Otto et al., 1997; Holman et al., 1991; Al et al., 1995; Hornstra et al., 1995, Min et al., 2000; Benisek et al., 2000)

Omega-3 fatty acids US FDA mercury advisories for pregnant women—2003 US FDA mercury advisories for pregnant women—2003 Avoid tilefish, swordfish, shark, king mackerel Avoid tilefish, swordfish, shark, king mackerel Limit other fish intake to 12 oz/week Limit other fish intake to 12 oz/week Main concern is CNS teratogenicity Main concern is CNS teratogenicity  Women hear “Don’t eat fish!” - We know fish intake in pregnant women has fallen significantly since this advisory has fallen significantly since this advisory - We also know higher fish intake during pregnancy has been associated with better infant cognitive function (Oken et al., 2005; Helland et al., 2003)

Omega-3 fatty acids Freeman, et al., Omega-3 fatty acids and supportive psychotherapy for perinatal depression: A randomized placebo-controlled study. Journal of Affective Disorders, n = 59, 8 week trial n = 59, 8 week trial Both pregnant and post-partum women Both pregnant and post-partum women Randomized to 1.9 g. of EPA/DHA or placebo Randomized to 1.9 g. of EPA/DHA or placebo All received manualized supportive psychotherapy All received manualized supportive psychotherapy Omega 3 fatty acids well tolerated Omega 3 fatty acids well tolerated BOTH groups had significant decrease in EPDS and HAM- D scores (p < ) but no significant difference between the groups BOTH groups had significant decrease in EPDS and HAM- D scores (p < ) but no significant difference between the groups

Omega-3 fatty acids Study Study design N Omega-3 dose LengthOutcome Freeman, et al., 2008 Double-blindPlacebo-controlled Pregnant and post-partum Supportive psychotherapy 59DHA/EPA 1.9 g 8 weeks No significant differences between omega-3 fatty acids and placebo Su, et al., 2008 Double-blindPlacebo-controlledPregnant36 DHA/EPA 3.6 g 8 weeks Significantly higher response and remission rates in omega-3 group Rees, et al., 2008 Double-blindPlacebo-controlled Pregnant and post-partum 26DHA/EPA (much higher EPA) 2.1 g 6 weeks No significant differences between omega-3 fatty acids and placebo

Omega-3 fatty acids Fish Oil Use in Pregnancy Didn’t Make Babies Smart Makrides et al., Effect of DHA Supplementation During Pregnancy on Maternal Depression and Neurodevelopment of Young Children. JAMA, Oct DHA supplementation during pregnancy - No clear cognitive benefit to babies - No evidence that DHA can reduce postpartum depression (maybe for women already at risk for it)

Omega-3 fatty acids Considerable evidence for use as an add-on to more traditional medications Considerable evidence for use as an add-on to more traditional medications Potentially beneficial as monotherapy in pregnancy/postpartum– maybe more so at higher doses, higher EPA: DHA ratios Potentially beneficial as monotherapy in pregnancy/postpartum– maybe more so at higher doses, higher EPA: DHA ratios May have cognitive benefit for baby (combination EPA/DHA) May have cognitive benefit for baby (combination EPA/DHA) Low risk! Low risk!

St. John’s wort Hypericum perforatum Hypericum perforatum Conflicting evidence for use in treatment of mild to moderate depression Conflicting evidence for use in treatment of mild to moderate depression N = 49, no increased rate of birth defects N = 49, no increased rate of birth defects N = 33, neonatal syndrome N = 33, neonatal syndrome Increased rates of colic, drowsiness, lethargy in exposed infants Increased rates of colic, drowsiness, lethargy in exposed infants Breastfeeding case reports Breastfeeding case reports Low levels in breastmilk Low levels in breastmilk Undetectable levels in infant plasma Undetectable levels in infant plasma (Lee et al., 2003; Klein et al., 2002; Klein et al., 2006 Dugoua et al., 2006)

St. John’s wort Animal studies: Animal studies: Increased uterine muscle tone, ? Implications Increased uterine muscle tone, ? Implications Increased rates of miscarriage Increased rates of miscarriage Overall: Overall: Potential risks, drug-drug interactions Potential risks, drug-drug interactions Natural does not mean better/safer– antidepressants have been much better studied Natural does not mean better/safer– antidepressants have been much better studied (Dugoua, et al., 2006; Moretti et al., 2009)

Acupuncture Mixed results as a treatment Mixed results as a treatment for depression in the general population Difficult to study because difficult to control Difficult to study because difficult to control

Acupuncture Studies by Manber et al., 2004 and 2010 Both studies had three groups: Both studies had three groups: acupuncture for depression acupuncture for depression “sham” acupuncture, needles in different places “sham” acupuncture, needles in different places massage therapy massage therapy 2004 study, n = study, n = 61 Acupuncture for depression response 69% Acupuncture for depression response 69% “sham” acupuncture response 47% “sham” acupuncture response 47% Massage response 32% Massage response 32% 2010 study, n = 150, more rigorous, defined response as > 50% reduction in HAM-D score 2010 study, n = 150, more rigorous, defined response as > 50% reduction in HAM-D score Acupuncture for depression response 63% Acupuncture for depression response 63% Massage response 50% Massage response 50% “sham” acupuncture response 37.5% “sham” acupuncture response 37.5%

Massage Therapy Very limited data in the literature specifically for mental health treatment Very limited data in the literature specifically for mental health treatment Depressive symptoms, when measured, often decrease in studies using massage for other indications Depressive symptoms, when measured, often decrease in studies using massage for other indications Meta-analysis of 17 studies showed significant improvement in depressive symptoms compared to control conditions Meta-analysis of 17 studies showed significant improvement in depressive symptoms compared to control conditions Studies vary regarding number of sessions Studies vary regarding number of sessions Studies vary in terms of controls, including no control, relaxation exercises, treatment as usual Studies vary in terms of controls, including no control, relaxation exercises, treatment as usual (Hou et al., 2010)

Massage Therapy Field et al., Journal of Bodywork and Movement Therapies Randomized study, n = Pregnant women with diagnosis of depression - Compared interpersonal therapy (group format) to interpersonal therapy plus massage - Depressive symptoms measured by Center for Epidemiological Studies Depression Scale (CES-D) - Women in massage group: - Had significantly greater improvements on depression AND anxiety measures - Had more study completers - Attended more sessions of the interpersonal therapy

Massage Therapy Massage Therapy Field et al., Infant Behavior and Development, Field et al., Infant Behavior and Development, Pregnant women with depression, n = 88 Pregnant women with depression, n = 88 Randomized to receive 2x week massage from Randomized to receive 2x week massage from partner (after training) vs. treatment as usual, partner (after training) vs. treatment as usual, weeks of pregnancy weeks of pregnancy - Massage group had: - Greater decrease in depression scores - Lower rates of low birth weight and prematurity - Infants had lower saliva cortisol levels - Infants scored higher on Brazelton Neonatal behavioral Assessment Scales

Massage Therapy Manber et al., Strong study: - Verified diagnosis of major depression, minimum HAM-D score - Blinded raters - Standardized Swedish massage - Response rate (> 50% reduction of HAM-D) = 50% - Remission rate (HAM-D < 7) 31% Unclear mechanism of action - Increased parasympathetic activity  decreased stress hormones, BP, HR - Increasing serotonin availability - Increasing oxytocin production

Light Therapy Has benefit in major Has benefit in major depressive disorder, both seasonal and both seasonal andnon-seasonal Risk of switching into hypomania or mania Risk of switching into hypomania or mania Very few, small, open trials for treatment of depression in therapy with light therapy Very few, small, open trials for treatment of depression in therapy with light therapy Though promising Though promising

Light Therapy Wirz-Justice et al., 2011 Randomized, double-blind, Randomized, double-blind, placebo-controlled study for pregnant women 7000 lux fluorescent bright white light 7000 lux fluorescent bright white light vs. 70 lux dim red light Depressive symptoms measured via Structured Interview Guide for the Hamilton Depression Rating Scale, with Atypical Depression Supplement Depressive symptoms measured via Structured Interview Guide for the Hamilton Depression Rating Scale, with Atypical Depression Supplement Response rates: Response rates: Bright light: 81% Bright light: 81% Placebo light 45% Placebo light 45%

Take Home Messages Continue antidepressants when you can Continue antidepressants when you can When you can’t, or the patient needs adjunctive therapy, consider: When you can’t, or the patient needs adjunctive therapy, consider: Omega-3 fatty acids Omega-3 fatty acids Acupuncture Acupuncture Massage therapy Massage therapy Light therapy Light therapy Have a “menu of reasonable options” for your patients Have a “menu of reasonable options” for your patients

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