Complementary and Alternative Medicine

From Mood and Anxiety Disorders, sponsored by Current Psychiatry and the American Academy of Clinical Psychiatrists

Educational Objectives

The goal of this program is to improve patient health through safe and appropriate use of complementary and alterna­tive medicine (CAM). After hearing and assimilating this program, the clinician will be better able to:

1.   Cite forms of CAM supported by high-quality clinical evidence.

2.   Recommend forms of CAM that have been shown to be effective in improving psychiatric symptoms.

3.   Identify patients most likely to benefit from additional intake of omega-3 fatty acids.

4.   Recognize potential consequences of herbal medications unique to elderly patients.

5.   Avoid potential toxicities and interactions associated with popular herbal medications.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the plan­ning committee to disclose relevant financial relationships within the past 12 months that might create any personal con­flicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the following has been disclosed: Dr. Freeman has received research support from Eli Lilly, Forest Laboratories, and GlaxoSmithKline, and a medical editing stipend from DSM Nutritional Products. Dr. Grossberg has received research support from Bristol-Myers Squibb, Elan Corporation, For­est Laboratories, Novartis, Pfizer, and Wyeth, and is a consultant for Forest Laboratories, Medivation, and Novartis. The planning committee reported nothing to disclose.

What the Psychopharmacologist Needs to Know

Marlene P. Freeman, MD, Lecturer, Department of Psychiatry, Harvard Medical School, and Faculty, Perina­tal and Reproductive Psychiatry Program, Center for Women's Mental Health, Massachusetts General Hospital, Boston

Background on complementary and alternative medicine (CAM): definition  —  diverse group of medical and health care systems, practices, and products not currently integrated with conventional medicine; complementary medicine typically used in addition to mainstream medicine; alternative medicine replaces mainstream medicine; integrative medicine  —  term preferred by speaker; combines best of mainstream treatment with best of CAM and holistic or collaborative approach to patient; statistics  —  used by 40% of adults in United States; use among chil­dren common; discussing CAM  —  critical; prevents patients from wasting money, delaying proper psychiatric care, or using unsafe treatments; popular forms of CAM  —natural nonvitamin or nonmineral products (eg, omega-3 fatty acids [FAs]); breathing exercises; meditation; psychiatry  —major depressive disorder (MDD) most common indi­cation for which CAM used; use of CAM often undisclosed; internet  —  often promotes CAM; however, accuracy of information varies; motivations  —  patients often feel empowered by self-diagnosis and treatment, but self-care may cause patients to forgo thorough evaluation and assessment of treatment options

Evidence: few CAM treatments studied in high-quality trials; many forms of CAM difficult to compare with placebo (eg, exercise, acupuncture); many treatments intended for holistic use in cultural context (rather than stand-alone use); American Psychiatric Association (APA) CAM Task Force  —intended to produce clinically relevant documen­tation for psychiatrists; focused on selected treatments for MDD

Omega-3 fatty acids: most common CAM treatment; studies evaluated efficacy of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish and seafood sources (not as well studied as a-linolenic acid from flaxseed and plant sources); meta-analysis  —  showed benefit over placebo for unipolar and bipolar depression; however, studies had substantial heterogeneity (eg, in design, FAs used) and small sample sizes; most studies assessed FAs as add-on therapy (eg, for patients with MDD receiving pharmacotherapy but showing no response); chemistry  —  saturated fats do not include double bonds; polyunsaturated fats contain multiple double bonds; number after omega (eg, omega-3) indicates placement of double bonds; metabolism  —  required dosage of FAs varies based on patient’s diet; omega-3 FAs and omega-6 FAs compete for necessary enzymes; in United States, diets contain ex­cessive quantities of omega-6 FAs; however, omega-3 FA typically insufficient; omega-3 FAs produce anti-inflam­matory metabolic cascades, while omega-6 FAs may promote inflammation; ratio of omega-3 FAs to omega-6 FAs indicates potential benefit of treatment with omega 3-FAs; evidence  —studied over many years; known for cardio­vascular benefits (particularly, reductions in triglyceride levels)

American Heart Association's (AHA) OFA recommendations: all adults should consume fish ³2 times per week; patients with coronary heart disease should ingest 1 g of EPA plus DHA daily (possibly 2-4 g if triglycerides ele­vated); doses ³3 g daily require physician’s supervision (due to additive anticoagulant effects when combined with other medications; high doses may increase bleeding time); however, no cases of bleeding with concomitant use found in literature (despite use of £10 g daily in patients receiving heparin or warfarin [Coumadin] after open-heart surgery)

Efficacy: all studies with positive outcomes assessed EPA plus DHA or EPA alone; studies of DHA alone have failed to show benefit over placebo; most commercial products include EPA and DHA

APA recommendations: AHA guidelines endorsed due to high comorbidity between psychiatric disorders and risk factors for cardiovascular disease (CVD; eg, obesity, lack of exercise, smoking); many psychiatric medi­cations also increase risk factors for CVD (eg, by causing weight gain, glucose changes, metabolic syndrome); guidelines  —  adults should consume fish ³2 times per week; patients with mood, impulse control, or psychotic dis­orders should consume 1 to 9 g of EPA plus DHA daily

Speaker's recommendations: most studies with positive outcomes used 1 to 3 g daily; studies of larger dosages have failed to show advantages; large dosages may interfere with compliance; have patients carefully study labels of FA products or bring in bottles to assess true dosing; most patients should start with 1 to 2 g daily (for general cardio­vascular or psychiatric benefits [particularly for depression])

St. John’s wort: common herbal remedy; trials show mixed or negative results; Shelton study  —  patients randomized to St. John’s wort or placebo for 8 wk; no difference in outcomes found; Hypericum study  —  both St. John’s wort and sertraline found inferior to placebo; efficacy  —  best results seen with mild to moderate depression; drug interactions  —  common and varied; decrease efficacy of oral contraceptives (OCs)

S-adenosyl-L-methionine (SAMe): occurs naturally in humans; acts as methyl donor; studies  —  typically assessed SAMe as monotherapy for MDD; most studies compared SAMe to tricyclic antidepressants (SAMe showed supe­rior tolerability); small short-duration studies consistently show benefits; meta-analysis  —  supported further re­search on SAMe in depression; dosing  —  oral formulation available; wide range of dosages studied; most benefits appeared soon after start of treatment (10-day separation from placebo); issues  —  typically costly and not covered by insurance; instances of mania reported in patients with bipolar depression (true of all antidepressants and St. John's wort)

Folate: low levels associated with poor response to antidepressants and higher rates of depression; treatment studies limited; fluoxetine study  —  supplementation with levels of folate commonly found in multivitamins improved re­sponse to fluoxetine (particularly in women) and reduced side effects; relationship to SAMe  —  involved in conver­sion of folate to L-methylfolate; has implications for neurotransmitter production and mood; recommendations  —not useful as monotherapy for depression; low risk; multivitamins with folate recommended for women of repro­ductive age due to known protection against birth defects (particularly neural tube defects); pregnancy  —  use dur­ing pregnancy not found to prevent postpartum depression

Bright light therapy: well studied; patients living in areas with sunny climates may still require light therapy (eg, due to lack of time spent outdoors); most positive study results seen with seasonal unipolar depression; associated with risk for mania (eg, in patients with underlying bipolar disorder); may benefit patients with nonseasonal MDD (particularly if patients refuse antidepressants); bright white light (full spectrum) at dosages of 10,000 LUX used in most studies

Acupuncture: studies have mixed results; research often unavailable in English language; Asian studies often use nonstandard diagnostic criteria; providing controls often difficult; some studies compare acupuncture for intended condition to untargeted acupuncture or to acupuncture with false or hollow needles (single-blind); wait-list control often ineffective (lack of full treatment experience may affect results); massage also used as control; Obstetrics & Gynecology study  —  150 women with verified MDD randomized to receive depression-specific acupuncture, con­trol acupuncture, or massage; depression-specific acupuncture showed superior response rates; however, massage group also showed response

Exercise: difficult to study due to lack of appropriate control conditions and low recruitment rates; adherence to or compliance with prescribed exercise often varies; results may be affected by differences between individual and group exercise, attention from trainers, and accuracy of home exercise diaries; dosing  —in studies, patients often randomized to exercise sessions of specific frequency or length; efficacy  —  studies support role in treatment of de­pression; however, role remains unclear due to varied usage; in general, patients should exercise if capable; speaker recommends authoritative prescription of exercise  

Herb-Drug Interactions

George T. Grossberg, MD, Professor, Department of Neurology and Psychiatry, St. Louis University School of Medicine, St. Louis, MO

Older adults: side effects most often seen in elderly; start at low doses; escalate dosages slowly; lowest available doses of new agents may be far too high for patients ³85 yr of age (due to lack of geriatric studies); never start 2 new drugs simultaneously; avoid fixed combinations (problem component may be difficult to isolate)

Background on herbal treatments: regularly used by >60 million patients (with significant proportion >75 yr of age); in United States, dietary supplements may be sold without proof of safety or efficacy if product not intended to diagnose, treat, cure, or prevent any disease

Care issues: patients often fail to report use of herbs and do not view herbs as medications; physicians often neglect to specifically ask patients about herb and supplement use; speaker recommends verifying supplement use with reliable informant (in case patient forgetful or cognitively impaired); information about psychiatric and nonpsy­chiatric medications critical; case  —  76-yr-old man underwent extensive testing due to onset of microscopic hema­turia; patient had started taking memory supplement with gingko biloba, but failed to inform physician; after discontinuing supplement use, patient had normal urinalysis

Garlic: most purchased supplement in United States; German commission findings  —  possibly useful for hyperten­sion, elevated cholesterol, and atherosclerosis; side effects  —decreased platelet aggregation; high doses may in­crease bleeding (particularly in combination with antiplatelet therapies), lower blood pressure (particularly with antihypertensives), and reduce efficacy of antiretroviral agents

Echinacea: second most purchased supplement; may heighten immune response (evidence limited); side effects  —hepatotoxic effects at doses of >3000 mg daily (particularly if combined with acetaminophen)

Saw palmetto: third most purchased supplement; primarily used by older men with prostatic hypertrophy; derived from berries of dwarf palm trees; German commission findings  —  possibly useful for enlarged prostate due to be­nign prostatic hypertrophy and for bladder irritation (in men and women); side effects  —  decreased platelet aggre­gation and increased bleeding time (particularly in combination with aspirin, ibuprofen, or other agents capable of affecting platelet aggregation or adhesiveness); decreased absorption of oral iron supplements (human body typi­cally incapable of absorbing >300 mg daily)

Gingko biloba: increasingly utilized despite increasing number of controlled studies with negative outcomes; not found to delay or prevent Alzheimer disease (AD); ineffective at delaying progression from mild cognitive impair­ment to AD; fails to slow progression and improve cognition in patients with AD; speaker advises against use in all patients; German commission findings  —  possible benefits for organic brain dysfunction, claudication, and vertigo or tinnitus (possibly due to increased blood flow to inner ear); side effects  —  bleeding diathesis (particularly at higher doses; eg, blood in urine, stomach, stool); high doses may cause seizures in patients taking anticonvulsants, or when used in combination with bupropion

Soy: increasingly utilized as natural source of plant-based estrogens for women in menopause; American Congress of Obstetrics and Gynecology recommendation  —  consuming soy may counteract symptoms of menopause; side effects  —decreased absorption of thyroid supplements; increased thyrotropin; decreased parathyroid hormone; large doses possibly capable of accelerating growth of estrogen-dependent tumors (data inconclusive)

Cranberry: recommended by speaker for older patients; contains flavonoid; available in pills; discourages bacterial growth by acidifying urine and decreases bacterial adherence to uroepithelial cells; useful in older adults (particu­larly women) with recurrent bladder or urinary tract infections; side effects  —  inhibits cytochrome P₄₅₀ (CYP)-2c9 (metabolizes warfarin); high doses may therefore interfere with optimization of international normalized ratio (INR) in patients taking warfarin

Ginseng: ginsenosides  —  active ingredients; have antioxidant and anti-inflammatory effects; antioxidant effects may protect against neuronal death; side effects  —  increased risk for bleeding (particularly in patients taking anticoagu­lants); hypoglycemia (particularly in diabetic patients; dangerous in elderly); monoamine oxidase inhibitors inter­act with certain forms of ginseng (cause irritability, anxiety, and headaches); unwanted pregnancies due to decreased efficacy of OCs; laboratory value abnormalities (eg, fasting blood glucose, hemoglobin A_1c, INR, digi­talis levels)

Black cohosh: increasingly utilized as alternative treatment for menopausal symptoms; side effects  —  induction of first trimester labor in sensitive individuals; augmentation of antihypertensive medications (eg, hydrochlorothia­zide) and angiotensin-converting enzyme inhibitors (eg, lisinopril); decreased absorption of many substances (eg, oral iron); emerging evidence of accelerated growth of estrogen-dependent tumors

St. John’s wort: extensively studied; German commission findings  —  possibly useful for depressed mood, anxiety, and skin inflammation or burns (when used topically); recent controlled studies  —  found effective for low-grade depression due to mild mood-elevating effects; side effects  —affects blood levels of many commonly prescribed medications (eg, warfarin, statins, digitalis, OCs); induction of CYP₄₅₀ 3a4 system; serotonin syndrome (when com­bined with prescribed antidepressants); increased bleeding; hypoglycemia; increased photosensitivity; delirium (when combined with loperamide); mania and psychosis in susceptible patients

Milk thistle: German commission findings  —  possibly useful for dyspepsia and gallbladder symptoms; side effects  —relatively safe (no significant interactions with commonly prescribed medications); diarrhea (rare)

Acknowledgments

Drs. Freeman and Grossberg were recorded at Mood and Anxiety Disorders, held April 8-10, 2010, in Chicago, IL, and sponsored by Current Psychiatry and the American Academy of Clinical Psychiatrists. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.

Suggested Reading

Colalto C: Herbal interactions on absorption of drugs: Mechanisms of action and clinical risk assessment. Pharmacol Res 62:207, 2010; Deligiannidis KM, Freeman MP: Complementary and alternative medicine for the treatment of depressive dis­orders in women. Psychiatr Clin North Am 33:441, 2010; Freeman MP et al: Complementary and alternative medicine for major depressive disorder. J Clin Psychiatry 71:682, 2010; Freeman MP: Complementary and alternative medicine for peri­natal depression. J Affect Disord 112:1, 2009; Freeman MP: Nutrition and psychiatry. Am J Psychiatry 167:244, 2010; Free­man MP: Omega-3 fatty acids in major depressive disorder. J Clin Psychiatry 70 Suppl 5:7-11, 2009; Grossberg GT, Fox B: The Essential Herb-Drug-Vitamin Interaction Guide: The Safe Way to Use Medications and Supplements Together. New York: Broadway Books, 2007; Moyad MA: Under-hyped and over-hyped drug-dietary supplement interactions and issues. Urol Nurs 30:85, 2010; Ngo N et al: The warfarin-cranberry juice interaction revisited: A systematic in vitro-in vivo evaluation. J Exp Pharmacol 2010:83, 2010; Pocobelli G et al: Total mortality risk in relation to use of less-common dietary supplements. Am J Clin Nutr 91:1791, 2010; Shord SS et al: Drug-botanical interactions. Integr Cancer Ther 8:208, 2009.