Integrative Therapies for Depression: Redefining Models for Assessment, Treatment and Prevention PDF

Foreword

Depression is one of the most serious and costly health problems facing the world today and is the leading cause of death and disability from adolescence through middle age. Approximately 15% of adults will experience severe depressed mood during their lifetimes, and approximately 15% will eventually commit suicide. Depression is the second most costly disorder in the United States, with an estimated annual cost of $80 to $130 billion.¹ Antidepressants are the third most commonly prescribed medications to Americans and the most commonly prescribed medications to Americans between the ages of 18 and 44.² In spite of widespread prescribing of antidepressants in developed world regions, the majority of depressed persons in North America and Western Europe do not receive adequate treatment for their symptoms with conventional prescription antidepressants.3 This is probably the result of poor screening by mental health–care providers, underreporting by patients, and disagreement over uniform criteria for measuring response, remission, relapse, and recurrence of major depressive disorder.^4,5 There is considerable controversy over the efficacy of antidepressants in general as evidenced by the fact that among individuals who are correctly diagnosed and appropriately treated with antidepressants following American Psychiatric Association guidelines, between 40% and 70% do not respond to treatment or respond only partially,6,7 while roughly half of patients who achieve full remission following treatment for severe depressed mood relapse within 2 years even when continuing on antidepressants.^5,8

Individuals who do not respond or respond only partially to antidepressants have been labeled “treatment refractory.” Because the average difference in drug–placebo response in randomized controlled trials of antidepressants is only 10%, a study on antidepressants in so-called “treatmentrefractory” patients, which could potentially yield significant findings, would have to enroll at least 1600 patients.⁹ To date neither the pharmaceutical industry nor the National Institutes of Mental Health (NIMH) has funded the large studies needed to evaluate the effectiveness of conventionally used pharmaceutical antidepressants in current widespread use to treat severe depressed mood. One side of the debate contends that the majority of drug industry–sponsored studies on antidepressants have failed to demonstrate significant response differences between antidepressants and placebos,^6,10 while the other side maintains that meta-analyses purporting to show no benefits of antidepressants are methodologically flawed or ideologically biased, and that rigorous analysis of findings shows that antidepressants are indeed more effective than placebos.¹¹ The outcome of the debate over antidepressant efficacy will probably take many more years to resolve and will ultimately rest on expert consensus over complex methodological problems involved in research designs and systematic reviews. The limitations of available conventional treatments of depression suggest that contemporary biomedical models do not adequately explain the causes of major depressive disorder and other mood disorders.

Available antidepressants are limited by adverse effects that reduce adherence, including cognitive impairment, sexual dysfunction, nausea, weight gain, and cardiovascular effects. Other unresolved issues affecting available antidepressants include unfavorable outcomes with long-term use, “paradoxical” depression-inducing effects, antidepressant-induced switching in bipolar disorder, the development of tolerance to beneficial “mood-elevating” effects, reduced efficacy when an antidepressant that was previously effective is tried for recurring depressed mood, and so-called “discontinuation syndromes” when antidepressants are abruptly stopped.

The high cost of many newer antidepressants is a serious obstacle to care for a significant percentage of depressed individuals, especially the elderly and patients on fixed incomes, who cannot afford to use a recommended antidepressant. In response to the high cost of antidepressants, it has been argued that the cost-effectiveness of many older, less expensive antidepressants and expensive recently introduced drugs is roughly equivalent.¹² In addition to general problems related to the limited efficacy of antidepressants, many depressed patients fail to improve with conventional treatment for several reasons:

• Brief medication visits covered by insurance may preclude adequate assessment and treatment planning.

• Single-drug treatments are often used at inappropriate doses resulting in poor response or high rates of adverse effects, resulting in early discontinuation before a therapeutic regimen has been tried.

• Combining two or more drugs when treating resistant depression frequently leads to a higher incidence of adverse effects, medication nonadherence, and treatment failure.

• When psychiatrists treat patients complaining of depressed mood, psychotherapy is often underutilized or not provided, resulting in diminished treatment response.

• Conventional psychiatric care stresses management of severe depressed mood with relatively less emphasis on maintenance and prevention strategies.

In the context of serious unresolved concerns about the efficacy, safety, tolerability, and affordability of conventional pharmaceutical antidepressants, select alternative treatment modalities of depressed mood are being validated by the findings of placebo-controlled studies, and in some cases systematic reviews of studies. Examples of empirically validated nonpharmaceutical treatments of depressed mood reviewed in this book include select natural products including the herbals St. John’s Wort, saffron, and golden root; the vitamin folic acid; a methyl donor called SAMe; the amino acid 5-HTP; omega-3 essential fatty acids; and the pro-hormone DHEA. Select natural products including St. John’s Wort, SAMe, 5-HTP, EPA (an omega-3 fatty acid), and acetyl-Lcarnitine have been evaluated for their antidepressant efficacy alone or as adjuvants to prescription antidepressants. Accumulating research findings confirm that combining antidepressants with these natural products accelerates the rate of treatment response with few or no safety issues, and improved outcomes. As the authors of this unique volume point out, numerous large, well-designed studies have validated the safety and antidepressant efficacy of SAMe alone and in combination with antidepressants. Folate and vitamin B12 are required cofactors for the synthesis of SAMe, and should be taken together with SAMe for optimal results. It has been established that severely depressed persons found to have low serum folate levels are significantly less likely to respond to antidepressants; therefore, all severely depressed persons should be encouraged to take folate in a form that ensures optimal bioavailability in the brain. Depressed mood also responds to oral doses of the amino acid 5-hydroxy-tryptophan (5-HTP), the immediate precursor of serotonin, taken alone or as an adjuvant to antidepressants. 5-HTP crosses the blood-brain barrier more readily than a related molecule, L-tryptophan, and is converted to serotonin. Similar to a combined regimen of SAMe and an antidepressant, 5-HTP and antidepressants potentiate each other, resulting in a more complete and more rapid response. An important benefit of augmenting an antidepressant with a natural product is the achievement of equivalent response rates at reduced antidepressant dosages resulting in fewer adverse effects and improved medication adherence. Other nonpharmaceutical treatments of mood disorders reviewed in this book that may be safely combined with pharmaceutical antidepressants include exercise, diet, bright light exposure, and mind-body approaches. Other effective nonpharmaceutical treatments of depressed mood include exercise, mind-body therapies such as Yoga, Tai Chi, and Qigong, acupuncture, and bright-light exposure.

Dozens of expert contributing authors of Integrative Therapies for Depression have made an unprecedented contribution to the rapidly growing field of integrative mental health care. Through concise reviews of over 3000 published studies discussing cutting-edge research in neurobiology, nutrition, hormonal dysfunction, environmental stresses, and pharmacological and genetic factors in the pathogenesis of mood disorders, this book challenges the current limited biomedical approaches to the assessment of mood disorders. The book summarizes important emerging theories and research findings on the range of nonpharmaceutical therapies used to treat mood disorders, including vitamins, botanicals and other natural products, exercise, bright light, mind-body practices, and spiritual approaches. Three chapters discussing rational evidence-based approaches to integrative management of mood disorders in pregnant women, adolescents, and the elderly make this textbook unique. This text fills an enormous gap in the conventional model of therapeutics for mood disorders and should be required reading for psychiatrists, psychologists, family therapists, and all clinicians who devote their days to caring for individuals afflicted with melancholia.

James Lake, MD

International Network of Integrative Mental Health