By Yoon-Hang Kim, MD, MPH, DABMA
Depression is a common, chronic, and costly medical condition. The World Health Organization identified major depression as the fourth leading cause of worldwide disease in 1990, resulting in more disability than either ischemic heart disease or cerebrovascular disease.1 In the United States, depression’s impact on disability is comparable to that of heart disease.2 In addition, depression is associated with a heightened incidence of physical symptoms, such as pain and increased functional impairment.3 Furthermore, post-myocardial infarction depression is an independent risk factor for increased mortality.4
The effectiveness and side effects of selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) are well-documented. However, one of the potential side effects appears to be the possibility of increased suicide risk in select populations; this possibility currently is being investigated.5
The use of complementary and alternative medicine (CAM) for depression has been well documented by Kessler et al.6 Their findings suggest that CAM therapies are used more frequently than conventional therapies by people with self-defined anxiety attacks and people with severe depression. The efficacy of CAM modalities have been evaluated in a review by Jorm et al, which includes a brief section on acupuncture.7 The use of acupuncture within psychiatry has been described in a textbook by Flaws and Lake.8 Another text by Schnyer and Allen describes issues in conducting research on the use of acupuncture to treat depression.9
Mechanism of Action
Acupuncture is probably the most thoroughly researched modality in complementary and alternative medicine.10 It is widely believed that acupuncture stimulates 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.10
Endorphins are part of the mechanism for the acupuncture pathway. The discovery of naloxone, an endorphin antagonist, helped to elucidate the role of endorphins with acupuncture. Naloxone was shown to block acupuncture analgesia in human volunteers in a randomized, double-blind study.11 A subsequent study reproduced these results displaying a dose-response curve for naloxone, and found that increasing doses produced increasing blockade.12
More importantly for the treatment of depression, monoamines such as serotonin and norepinephrine appear to be involved in acupuncture. Microinjection of serotonin antagonists has been shown to block the effects of acupuncture.13 A similar study using microinjection of a norepinephrine antagonist has also been shown to block the effect of acupuncture.14 Sprott et al demonstrated the rise of serum serotonin during acupuncture treatments.15 Another recent study demonstrated characterization of serotonin receptor subtypes involved in modulation of electrical acupuncture.16
The monoamines’ involvement in the acupuncture pathway provides possible mechanisms by which acupuncture might be effective in treating monoamine-mediated conditions, including depression and anxiety. In addition, a recent study reported that acupuncture treatments result in increased nocturnal melatonin secretion, reducing both insomnia and anxiety.17
In 1975, Riederer et al conducted a human trial demonstrating that needling of specific acupuncture points results in changes in norepinephrine levels measured in blood and urine.18
In the 1980s, Han investigated the effects of electroacupuncture on serotonin and norepinephrine.19 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 electro-acupuncture; in contrast, the non-responding patients did not show significant changes in serum norepinephrine levels.20
In 1985, Luo et al conducted a clinical trial comparing the efficacy of acupuncture for treating depression vs. amitriptyline.21 The 47 patients were randomly assigned to two groups. One group received electric acupuncture at Bai Hui and Yintang acupuncture points for one hour per day, six days a week, for five weeks. The control group received amitriptyline. The results demonstrated that 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 of drug treatment.
Luo et al reported the results from a repeat trial with 241 patients in 1990. The results were similar to the earlier study: Acupuncture was found to be as effective as amitriptyline for treating depression and more effective for treating anxiety.22
In 1994, Yang et al reported the results of a clinical trial comparing the effects of acupuncture and amitriptyline.23 In contrast to the two previous studies by Luo et al where only two acupuncture points were utilized, Yang et al explored the use of traditional acupuncture taking into account the presenting traditional Chinese medicine diagnoses. The findings were similar to the earlier two trials conducted by Luo et al where acupuncture treatment was found to be 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 involving 33 female outpatients who met criteria for major depression and were assigned to one of three groups: acupuncture treatment specific for depression; a non-specific treatment using valid acupuncture points; and a no-treatment group of patients who were placed on a wait list.24 They reported that 64% of patients who received acupuncture treatments specific for depression showed full remission and improved significantly more than women in the non-specific treatment group. However, no statistical differences were shown between the depression-specific treatment group and the no-treatment group. The full-scale trial was recently completed and results should be soon available.
In 1999, Roscheke et al studied the effect of adding acupuncture to antidepressant medication. They assigned 70 inpatients to three groups: acupuncture plus antidepressant, sham acupuncture plus antidepressant, and antidepressant.25 The results showed that the addition of acupuncture resulted in a significantly better clinical response than antidepressants alone. However, there was no difference between the true acupuncture and sham acupuncture groups.
In 2000, Eich et al published results of a trial in which 43 subjects received either acupuncture or sham acupuncture for the treatment of depression.26 They concluded that acupuncture was significantly more effective than sham acupuncture after 10 treatments but not after five treatments.
The safety of acupuncture is well documented. Ernst and White conducted a systematic review to determine the incidence of adverse events associated with acupuncture.27 The most common adverse events were needle pain (1-45%) from treatments, tiredness (2-41%), and bleeding (0.03-38%). Feelings of faintness and syncope were uncommon, with an incidence of 0-0.3%. Pneumothorax was rare, occurring only twice in nearly a quarter of a million treatments.
A significant amount of information exists on the effectiveness of acupuncture for treating depression. The chain of evidence, from neurotransmitter involvement to clinical trials, supports biological plausibility and efficacy. Further studies comparing acupuncture to newer antidepressant agents are needed, however.
Depression is a prevalent medical problem with huge social, economical, and medical implications. Given the low risk of side effects, a trial of acupuncture can be considered a potentially useful option for some patients with depression, including those with mild-to-moderate anxiety/depression, patients experiencing significant adverse reactions to medications, and patients who have not yet achieved optimal benefit from conventional treatments.
Dr. Kim is consulting physician at the Institute for Health and Healing, California Pacific Medical Center, in San Francisco.
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