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Efficacy of Acupuncture for Treating Depression
By Yoon-Hang "John" Kim, MD, MPH, DABMA, and Jeanne Bowers, Dr. Kim is the director of Georgia Integrative Medicine in Atlanta; and Ms. Bowers is completing a master's degree in psychology at West Georgia University. They report no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study.
Depression is a potentially life-threatening mood disorder. The World Health Organization identified major depression as the fourth leading cause of worldwide disease in 1990, causing more disability than either ischemic heart disease or cerebrovascular disease.1 In the United States, the impaired functioning associated with depression is comparable to the impairment associated with heart disease and exceeds that of several other medical conditions, including hypertension, diabetes, and arthritis.2
In a given year, 9.5% of the population, or 20.9 million American adults, suffer from a depressive illness.3 In addition to considerable pain and suffering that interfere with individual functioning, depression also affects those who care about the ill person, sometimes destroying family relationships and work dynamics. The annual economic cost of depressive illness is estimated to be $30-44 billion in the United States alone.2
Depression is also associated with heightened concern about physical symptoms, such as pain and increased functional impairment.4 Furthermore, post-myocardial infarction depression is an independent risk factor for increased mortality.5
A variety of medications are available to treat depression; the effectiveness of selective serotonin reuptake inhibitors and tricyclic antidepressants are well established. However, one potential side effect of these antidepressant therapies appears to be an increased risk of suicide in select populations.6
The popular use of complementary and alternative medicine (CAM) for depression has been well documented. In fact, research indicates that CAM therapies are used more than conventional therapies by people with self-defined anxiety attacks and people with severe depression.7
The efficacy of CAM modalities, including acupuncture, for psychiatric purposes has been reviewed by a number of researchers,8,9 and special attention has been given to describing the challenges associated with conducting research using acupuncture to treat depression.10
Mechanism of Action
Acupuncture is probably the most thoroughly researched modality in complementary and alternative medicine,11 and Paramore estimates that about one million people utilize acupuncture annually within the United States.12 It is widely believed that acupuncture initiates stimulation of small diameter nerves in muscles, sending impulses to the spinal cord, midbrain, and pituitary, and results in the release of neurotransmitters such as monoamines and endorphins.11
Endorphins play a part in the mechanistic pathway for acupuncture. The discovery of naloxone, an endorphin antagonist, helped elucidate the role of endorphins in acupuncture. Naloxone was shown to block acupuncture analgesia in human volunteers in a randomized, double-blind study.13 A subsequent study reproduced the same results, displaying a dose-response curve for naloxone and found that increasing doses produced increasing blockade.14
More importantly for the treatment of depression, in addition to endorphins, monoamines such as serotonin and norepinephrine have been shown to be involved in acupuncture. Microinjection of serotonin antagonists blocked the effects of acupuncture,15 and a similar study used microinjection of a norepinephrine antagonist to block acupuncture's effects.16 The rise of serum serotonin during acupuncture treatments has been demonstrated by Sprott et al.17 Another recent study characterized the serotonin receptor subtypes involved in modulation of electrical acupuncture.18
The monoamines' involvement in the acupuncture pathway provides possible mechanisms by which acupuncture is able to treat other monoamine-mediated conditions. A recent study documented that acupuncture treatments resulted in increased nocturnal melatonin secretion and reduced both insomnia and anxiety.19
In 1975, Riederer et al conducted a clinical trial demonstrating that needling of specific acupuncture points in subjects resulted in changes in norepinephrine levels measured in blood and urine.20 In the 1980s, Han investigated the effects of electroacupuncture on serotonin and norepinephrine, two neurotransmitters commonly implicated in depression and anxiety.21 The findings demonstrated that electroacupuncture accelerates the synthesis and release of serotonin and norepinephrine in the central nervous system. Furthermore, Fanqiang et al reported that plasma norepinephrine concentrations were significantly elevated in depressed patients who improved following a six-week course of electroacupuncture; whereas, the nonresponding patients did not show significant changes in serum norepinephrine levels.22
In 1985, Luo et al conducted a clinical trial comparing the efficacy of acupuncture vs. amitriptyline, a tricyclic antidepressant medication, for treating depression.23 The 47 patients were randomly assigned to two groups. One group received electric acupuncture at the Bai Hui and Yintang points for one hour per day, six days a week, for five weeks. The control group received amitriptyline. The results demonstrated that the electric acupuncture was as effective as amitriptyline for treating depression. In addition, electric acupuncture was found to be more effective for treating anxiety without the side effects often associated with drug treatment. In 1990, Luo et al reported the results from a repeat trial with 241 patients.24 The results were similar to the earlier study: Acupuncture was as effective as amitriptyline for treating depression and more effective for treating anxiety.
Yang et al also compared the effect of acupuncture vs. amitriptyline and reported the results in 1994.25 In contrast to the two previous studies conducted by Luo et al where only two acupuncture points were utilized, Yang et al explored the use of traditional acupuncture taking account of the presenting traditional Chinese medicine syndromes. Again, the findings were similar: Acupuncture treatment was as effective as amitriptyline for the treatment of depression and more effective for treating anxiety.
In 1998, Allen et al published results of a pilot trial consisting of 33 female outpatients who met the criteria for major depression.26 The patients were assigned to one of three groups: acupuncture treatment specific for depression; a nonspecific treatment using valid acupuncture points; and a no-treatment group consisting of wait-list. Sixty-four percent of patients who received acupuncture treatments specific for depression showed full remission, and improved significantly more than women in the nonspecific treatment group. However, no statistical differences were shown between the treatment group and the no-treatment group.
In a 1999 study, Roschke et al examined the effect of adding acupuncture to antidepressant medication. Seventy inpatients were divided into three groups: acupuncture plus antidepressant, sham acupuncture plus antidepressant, and antidepressant.27 The addition of acupuncture produced improvements over antidepressants alone. However, there was no difference between the true acupuncture and sham acupuncture group.
Eich et al published results of a trial in 2000 comparing acupuncture to sham acupuncture for the treatment of depression.28 They divided 43 patients into two groups: acupuncture and sham acupuncture. They concluded that acupuncture was significantly better than sham acupuncture after 10 treatments but not after five treatments.
In 2004, Manber et al reported findings of a randomized controlled trial comparing acupuncture vs. massage vs. sham acupuncture in pregnant patients with depression.29 Sixty-one pregnant women with major depressive disorder were divided into three groups: acupuncture, sham acupuncture, and massage. The results demonstrated that symptoms among the acupuncture group improved more than in the massage group (69% vs. 32%, respectively). However, there was no statistical difference between the acupuncture group and sham acupuncture group.
Quah-Smith et al published results in 2005 of a randomized controlled trial comparing laser acupuncture and sham laser acupuncture for the treatment of depression.30 Thirty patients were divided into two groups. Results showed that the laser acupuncture group improved significantly more than the sham laser acupuncture group (P = 0.007).
In 2006, Allen et al published the results of larger randomized controlled trial using same design as the earlier 1998 study.31 The results failed to document effect of acupuncture for treating depression. Allen et al employed an individualized protocol rather than using the Yin Tang and Bai Hui protocol developed in China.
Adverse Effects/Safety Trials
The safety of acupuncture is well documented. Ernst and White conducted a systematic review to determine the incidence of adverse events associated with acupuncture.32 The most common adverse events were needle pain, tiredness, and bleeding. Feelings of faintness and syncope were uncommon. Pneumothorax was rare, occurring only twice in nearly a quarter of a million treatments. However, the use of nonsterile needles may cause infections. One overview identified 126 documented cases of hepatitis associated with acupuncture.33
The chain of evidence, from the neurotransmitters research to clinical trials, supports the biological plausibility and efficacy of acupuncture for the treatment of depression.
Depression is a prevalent medical problem with huge social, economical, and medical implications. Given the low risk of acupuncture, a trial of acupuncture should be considered a potentially useful option for patients with depression.
1. Murray CJ, Lopez AD, eds. Global Burden of Disease: A Comprehensive Assessment of Mortality and Disability from Diseases, Injuries, and Risk Factors in 1990 and Projected to 2020 (The Global Burden of Disease and Injury). Cambridge, MA: Harvard University Press; 1996.
2. Wells KB, et al. The functioning and well-being of depressed patients: Results from the Medical Outcomes Study. JAMA 1989;262:914-919.
3. Regier DA, Robins LN, eds. Psychiatric Disorders in America, The Epidemiologic Catchment Area Study. New York: The Free Press; 1990.
4. Wells KB, et al. Psychiatric disorder and limitations in physical functioning in a sample of the Los Angeles general population. Am J Psychiatry 1988;145:712-717.
5. Ziegelstein RC. Depression in patients recovering from a myocardial infarction. JAMA 2001;286:1621-1627.
6. Jick H, et al. Antidepressants and the risk of suicidal behaviors. JAMA 2004;292:338-343.
7. Kessler RC, et al. The use of complementary and alternative therapies to treat anxiety and depression in the United States. Am J Psychiatry 2001;158:289-294.
8. Jorm AF, et al. Effectiveness of complementary and self-help treatments for depression. Med J Aust 2002;176(suppl):S84-S96.
9. Flaws B, Lake J. Chinese Medical Psychiatry: A Textbook and Clinical Manual. Boulder, CO: Blue Poppy Press; 2001.
10. Schnyer R, Allen J. Acupuncture in the Treatment of Depression: A Manual for Practice and Research. Edinborough: Churchill Livingstone; 2001.
11. Stux G, Pomeranz B. Acupuncture: Textbook and Atlas. Berlin: Springer-Verlag; 1987.
12. Paramore L. Use of alternative therapies: Estimates from the 1994 Robert Wood Johnson Foundation National Access to Care Survey. J Pain Symptom Manage 1997;13:83-89.
13. Mayer DJ, et al. Antagonism of acupuncture analgesia in man by the narcotic antagonist naloxone. Brain Res 1977;121:368-372.
14. Cheng RS, Pomeranz BH. Electroacupuncture analgesia is mediated by stereospecific opiate receptors and is reversed by antagonists of type I receptors. Life Sci 1980;26:631-638.
15. Han CS, et al. The role of central 5-hydroxytrypta-mine in acupuncture analgesia. Sci Sin 1979;22:91-104.
16. Han JS, et al. Neurochemical basis of acupuncture analgesia. Annu Rev Pharmacol Toxicol 1982;22:193-220.
17. Sprott H et al. Pain treatment of fibromyalgia by acupuncture. Rheumatol Int 1998;18:35-36.
18. Takagi J, Yonehara N. Serotonin receptor subtypes involved in modulation of electrical acupuncture. Jpn J Pharmacol 1998;78:511-514.
19. Spence DW, et al. Acupuncture increases nocturnal melatonin secretion and reduces insomnia and anxiety: A preliminary report. J Neuropsychiatry Clin Neurosci 2004;16:19-28.
20. Riederer P, et al. Manipulation of neurotransmitters by acupuncture (?) (A preliminary communication). J Neural Transm 1975;37:81-94.
21. Han JS. Electroacupuncture: An alternative to antidepressants for treating affective diseases? Int J Neuro-sci 1986;29:79-92.
22. Fanqiang M, et al. Plasma NE concentration and 24 hour urinary MHPG-Sov excretion changes after electro-acupuncture treatment in endogenous depression. World J Acupuncture Moxibustion 1994;4:45-52.
23. Luo H, et al. Electro-acupuncture vs. amitriptyline in the treatment of depressive states. J Tradit Chin Med 1985;5:3-8.
24. Luo H, et al. Electro-acupuncture vs. amitriptyline in the treatment of depressive psychosis. Int J Clin Acupuncture 1990;1:7-13.
25. Yang X, et al. Clinical observation on needling extrachannel points in treating mental depression. J Tradit Chin Med 1994;14:14-18.
26. Allen J, et al. The efficacy of acupuncture in the treatment of major depression in women. Psychol Sci 1998;9:397-401.
27. Roschke J, et al. The benefic from whole body acu-puncture in major depression. J Affect Disord 2000;57:73-81.
28. Eich H, et al. Acupuncture in patients with minor depressive episodes and generalized anxiety. Results of an experimental study. Fortschr Neurol Psychiatr 2000;68:137-144.
29. Manber R, et al. Acupuncture: A promising treatment for depression during pregnancy. J Affect Disord 2004;83:89-95.
30. Quah-Smith JI, et al. Laser acupuncture for mild to moderate depression in a primary care setting—a randomised controlled trial. Acupunct Med 2005;23:103-111.
31. Allen JJ, et al. Acupuncture for depression: A randomized controlled trial. J Clin Psychiatry 2006;67:1665-1673.
32. Ernst E, White A. Prospective studies of the safety of acupuncture: A systematic review. Am J Med 2001;110:481-485.
33. Rampes H, James R. Complications of acupuncture. Acupunct Med 1995;13:26-33.
Depression in Women
Women experience depression about twice as often as men.1 Many hormonal factors may contribute to the increased rate of depression in women, particularly such factors as menstrual cycle changes, pregnancy, miscarriage, postpartum period, premenopause, and menopause. Many women also face additional stresses such as responsibilities both at work and home, single parenthood, and caring for children and for aging parents.
A recent National Institute of Mental Health study showed that in the case of severe premenstrual syndrome (PMS), women with a preexisting vulnerability to PMS experienced relief from mood and physical symptoms when their sex hormones were suppressed. Shortly after the hormones were re-introduced, they again developed symptoms of PMS. Women without a history of PMS reported no effects of the hormonal manipulation.2,3
Many women are also particularly vulnerable after the birth of a baby. The hormonal and physical changes, as well as the added responsibility of a new life, can be factors that lead to postpartum depression in some women. While transient "blues" are common in new mothers, a full-blown depressive episode is not a normal occurrence and requires active intervention. Treatment by a sympathetic physician and the family's emotional support for the new mother are prime considerations in aiding her to recover her physical and mental well-being and her ability to care for and enjoy the infant.
1. Blehar MD, Oren DA. Gender differences in depression. Medscape Women's Health 1997;2:3. Revised from: Women's increased vulnerability to mood disorders: Integrating psychobiology and epidemiology. Depression 1995;3:3-12.
2. Rubinow DR, et al. Estrogen-serotonin interactions: Implications for affective regulation. Biological Psychiatry 1998;44:839-850.
3. Schmidt PJ, et al. Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome. JAMA 1998;338:209-216.
Reprinted from: National Institute of Mental Health. Available at: www.nimh.nih.gov/publicat/depression.cfm#ptdep1. Accessed June 6, 2007.