Acupuncture for Depression in Pregnancy

Abstract & Commentary

By Judith L. Balk, MD. Dr. Balk is Associate Professor, Magee-Women's Hospital, University of Pittsburgh; she reports no financial relationship to this field of study.

Synopsis: Although depression is a serious condition that needs to be treated, many women are reluctant to take antidepressant medications during pregnancy. Depression during pregnancy tends to be underdiagnosed and undertreated. This study aims to evaluate the efficacy of acupuncture for depression during pregnancy, using a three-arm randomized trial. The three arms are acupuncture specific for depression, acupuncture not specific for depression, and massage. Treatment expectation was assessed for both subjects and practitioners. The treating acupuncturists were blind to assignment group, with the individualized acupuncture protocols being assigned to them by more senior acupuncturists. Acupuncture specific to depression significantly decreased depression severity, and it had a significantly greater response rate compared to the control groups.

Source: Manber R, et al. Acupuncture for depression during pregnancy: A randomized controlled trial. Obstet Gynecol 2010;115:511-520.

To assess the efficacy of acupuncture to treat depression in pregnant women, these researchers randomized 151 pregnant women who met criteria for major depressive disorder to receive either the active treatment (acupuncture specific for depression) or one of two control interventions (acupuncture not specific for depression, or massage). Subjects received a total of 12 sessions over 8 weeks. Senior acupuncturists evaluated the subjects and created treatment plans, and junior acupuncturists carried out the treatment plans without knowledge of group assignment. The primary outcome variable was the Hamilton Rating Scale for Depression (HRSD), administered by study staff masked to treatment group. Subjects who received acupuncture specific for depression had a greater rate of decrease in symptom severity (P < 0.05) compared to the other two groups. They also had a significantly greater response rate (63%) compared to the control groups combined as one group (44.3%) and to the acupuncture control group alone (37.5%). The control groups did not differ significantly from each other. The acupuncture protocol studied appears to be on par with standard depression treatments with respect to symptom reduction and response rate. Acupuncture could be a viable treatment option for depression during pregnancy.

Commentar

Acupuncture is thought to be helpful in treating depression in nonpregnant subjects.1 Basic science research may indicate the mechanisms involved. Neurotransmitters are thought to play a role in depression.2 Many antidepressants affect the monoamine systems, such as the serotonergic and norepinephrine (NE) systems. The goal of treatment with antidepressant agents is to correct abnormalities in the serotonergic and NE systems, although it is likely the therapeutic action is mediated by postreceptor intracellular targets. Physiological methods of activating the endogenous monoamine system in the CNS could potentially treat depression.3 Acupuncture is one method of accelerating the synthesis and release of serotonin and NE in the CNS. Acupuncture also releases opioid peptides and gamma-aminobutyric acid, both of which may be related to depression and mania.3 Medications, such as selective serotonin reuptake inhibitors and selective norepinephrine uptake inhibitors, improve depression via modulation of neurotransmitters.

During pregnancy, the use of antidepressant medications is controversial. Recently, the American Psychiatric Association in combination with the American College of Obstetricians and Gynecologists reviewed the management of depression during pregnancy.4 The report noted that both depressive symptoms and antidepressant exposure are associated with fetal growth changes and shorter gestations. Because most studies evaluating antidepressant risks did not control for the possible effects of the depression, it is difficult to definitively assign the effects from the antidepressant medications vs. the effects of depression. Symptoms such as neonatal irritability and neurobehavioral changes are linked with both maternal depression and antidepressant treatment. Some fetal malformations are associated with first trimester antidepressant exposure, although clear patterns do not exist. Late gestational use of selective serotonin reuptake inhibitor antidepressants is associated with transitory neonatal signs known as "poor neonatal adaptation," such as tachypnea and hypoglycemia, and a low risk for persistent pulmonary hypertension in the newborn. Thus, due to the concerns regarding both depressive symptomatology and antidepressant medications, effective alternatives to medications for use in pregnancy would be beneficial.

Human studies suggest that acupuncture is beneficial for the treatment of depression. However, randomized, prospective, controlled trials of acupuncture for depression are rare. One RCT evaluated electroacupuncture vs. amitriptyline in 241 patients with "depressive psychosis." To be included, patients needed scores 3 20 on the HRSD. The acupuncture group received a placebo capsule and acupuncture daily for 60 minutes per day. The amitriptyline group received daily amitriptyline, with an average dose of 161 mg per day. Both groups significantly lowered their HRSD from baseline; no differences occurred between the groups. The authors suggested that the effectiveness of the two modalities is similar.

Inpatient depression was studied by Luo et al.5 In a randomized, double-blind, placebo-controlled study in 29 inpatients, patients received either electroacupuncture + placebo, amitriptyline, or electroacupuncture + amitriptyline for 6 weeks. Therapeutic efficacy and side effects were evaluated. Based on the results of this small study demonstrating that electroacupuncture was equally efficacious as amitriptyline, a larger, multicenter study was then conducted by the same authors. Patients were randomized to one of two groups: electroacupuncture + placebo or amitriptyline. No difference existed between groups for therapeutic efficacy overall. However, acupuncture was more effective for anxiety somatization and cognitive process disturbance of depressed patients. Side effects of acupuncture were significantly less than that of amitriptyline. Although this study is controlled, a placebo effect for acupuncture still might exist.

Findings from the Current Study

This study enrolled 150 pregnant women who met DSM-IV criteria for major depressive disorder. Women were randomized to receive either acupuncture specific for depression, acupuncture not specific for depression, or massage. The interventions occurred twice weekly for 4 weeks, followed by weekly sessions for 4 weeks. The control groups were comprised of the acupuncture not specific for depression and the massage interventions. The primary analysis was an intention-to-treat analysis of all 150 randomized subjects. Those in the group receiving acupuncture specific for depression experienced a significantly greater reduction in HRSD scores than the participants in the combined control groups. Response rates were significantly higher for the group receiving acupuncture specific for depression than for the combined control groups. The control groups did not differ from each other in their effects. Remission rates were not significantly different between the groups. Expectation of the participants and acupuncturists was also measured. The participants' expectation did not differ between the two acupuncture groups, but the acupuncturists' expectations were lower for the group receiving acupuncture not specific for depression compared to acupuncture specific for depression. This lower expectation was taken into account via statistical analysis, and the difference in provider expectation did not account for the improved efficacy in the true treatment group. Ten unexpected/adverse events occurred, including premature delivery, pregnancy loss, congenital defects, and hospitalization for various causes. All events were considered to be unrelated to treatment. Side effects were minor, and included transient discomfort and bleeding at the needle site.

This study has a few limitations and many strengths. One is the lack of generalizability given the healthy, educated, and predominantly Caucasian population. The approach used, where the treating acupuncturist did not do the assessment, is not what is done in standard care; however, most acupuncture studies do not mimic usual care.

Although the treating acupuncturist did not do the assessment, this study mimics usual care in that the acupuncture treatments were individualized, rather than formulaic, a study strength. The use of two control groups helps to delineate whether effects are from the acupuncture relative to massage, and from the true acupuncture relative to acupuncture not specific for depression. This study had a low dropout rate, and it did not differ by treatment group. The careful assessment of expectation among subjects and providers is also a strength, as it points to whether expectation of positive outcome plays a role in the effectiveness of the outcome.

Although acupuncture was not directly compared to a medication control group, the response rates seen from acupuncture specific for depression are similar to the rates from standard antidepressant medication trials. Importantly, there were not adverse events due to the acupuncture, and side effects were minor. While more research is necessary to make a definitive statement, this study suggests that an individualized acupuncture protocol specific for depression in a healthy pregnant woman could be a viable treatment option.

References

1. Gibbons R, et al. Some conceptual and statistical issues in analysis of longitudinal psychiatric data. Application to the NIMH treatment of Depression Collaborative Research Program dataset. Arch Gen Psychiatry 1993;50:739-750.

2. Duman R, et al. A molecular and cellular theory of depression. Arch Gen Psychiatry 1997;54:597-606.

3. Han J. Electroacupuncture: An alternative to antidepressants for treating affective disease? Int J Neurosci 1986;29:79-92.

4. Yonkers K, et al. The management of depression during pregnancy: A report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists. Obstet Gynecol 2009;114:703-713.

5. Luo H, et al. Electro-acupuncture vs. amitriptyline in the treatment of depressive states. J Tradit Chin Med 1985;5:3-8.