On May 12, 2008, an earthquake measuring 8.0 on the Richter scale hit Sichuan Province in southwestern China. According to the official data, more than 69,200 people were confirmed dead, more than 374,600 were seriously injured [
Posttraumatic stress disorder (PTSD) is a significant public health problem [
Selective serotonin reuptake inhibitors are the usual first level pharmacological treatment for PTSD [
For centuries, traditional Chinese medicine (TCM) has been widely used in China and some other Asian countries for psychological disorders, and many classic herbal formulas have been used to treat such maladies [
Ingredients of
No. | Chinese name | Pharmaceutical name | Proportion, % |
---|---|---|---|
(1) | Chai-Hu | 4.5 | |
(2) | Dang-Gui | 4.5 | |
(3) | Fu-Ling | 15.2 | |
(4) | Chao Bai-Zhu | 4.5 | |
(5) | Chao Bai-Shao | 7.6 | |
(6) | Bo-He | 3.0 | |
(7) | Zhi Gan-Cao | 3.0 | |
(8) | Huang-Lian | 1.5 | |
(9) | Fa Ban-Xia | 7.6 | |
(10) | Chen-Pi | 4.5 | |
(11) | Duan Long-Gu | 15.0 | |
(12) | Duan Mu-Li | 15.0 | |
(13) | Zhi Da-Huang | 6.1 | |
(14) | Shi-Changpu | 7.6 |
Patients were enrolled into this study five months after the 2008 Sichuan earthquake, between October 2008 and January 2009, through a community-based epidemiological survey of four settlements of a severely affected city, Dujiangyan. In the enrollment survey, the relationship between exposure to the earthquake and PTSD was assessed. Preliminary screening was performed in the communities by our researchers according to the DSM III for PTSD, Chinese version [
Flow chart of the study sample.
Written informed consent was obtained from all patients before participation. Patients were free to withdraw from the study at any time. Clinical diagnoses, physicals, and laboratory examinations were mainly conducted in the outpatient clinic at the Air Force Sanatorium in the city of Dujiangyan by our psychologist and other investigators. The research staff collected patients’ weekly feedback on their medical conditions and delivered the XTJYF or placebo through in-house visits. The trial protocol was approved by the Ethics Committee of Shanghai Changzheng Hospital and the Air Force Sanatorium in Dujiangyan.
A sociodemographic inventory and a medical history were taken, and a routine physical and laboratory examination (i.e., blood pressure, ECG, clinical chemistry and hematology tests, and urinalysis) was performed by the investigators as a baseline for future toxicology screening.
Eligible patients were randomized to either XTJYF treatment or placebo control. Random numbers were generated by computer software; treatment codes were held by the chief investigator, who was isolated from patients and outcome data. The chief investigator was also responsible for distributing the XTJYF and placebo with the assistance of our research staff. Patients, research staff, and data entry clerks were blinded to treatment group assignment. Treatment compliance was assessed by package count and observation by the research staff. Treatment codes were disclosed after the entire study was completed.
All patients received 12 g packages of granulated XTJYF or placebo twice a day for eight weeks [
Each patient completed the SCL-90-R questionnaires twice, at baseline prior to randomization and in the eighth week after the randomization, that is, at the end of this clinical trial. The SCL-90-R is a questionnaire for self-reporting psychological distress. It is widely used in patients suffering from mental diseases and for psychological evaluation of healthy individuals. The instrument is well accepted for its good internal consistency, dimensional structure, reliability, and validity [
The SCL-90-R consists of 90 symptoms of distress. Patients were instructed to indicate the degree to which they had been troubled by each symptom during the preceding week by ranking the symptom from 0 to 4, with 0 being “not at all” and 4 being “extremely.” The statements were classified into nine dimensions, or factors (F), that reflect various types of psychopathology: (F1) somatization, (F2) obsessive-compulsive behavior, (F3) interpersonal sensitivity, (F4) depression, (F5) anxiety, (F6) hostility, (F7) phobic anxiety, (F8) paranoid ideation, and (F9) psychoticism. Three supplementary global indices reflect the degree of symptomatology. The global severity index (GSI) registers the average depth of impairment based on the severity recorded for each symptom; the positive symptom total index (PST) indicates the total number of symptoms experienced; the Positive Symptom Distress Index (PSDI) reflects the level of distress by correlating the reported symptoms [
During the trial, patients were closely monitored for adverse events (AEs) and worsening of symptoms. The time of onset of any observed or spontaneously reported AE, its duration and severity, any action taken, and the outcome were recorded.
The original formula,
All herbal substances used in this trial are listed with the Pharmacopoeia Commission of China, 2005, and are accepted as suitable for human consumption when administered within standard dosage levels. None of these herbs is a controlled substance or an endangered species. Raw herbs were purchased from the Lei Yun Shang Pharmaceutical Company (Shanghai, China). The herbs were extracted with water, and the resulting granules were packaged by the Chinese Drug Preparation Department of Shanghai Changzheng Hospital. Levels of heavy metals and microbial and pesticide residues were carefully assessed, and all fell well within the normal range [
The placebo granules, purchased from Jiangsu Tianjiang Pharmaceutical Company, Ltd., were designed to resemble the XTJYF granules in taste, smell, and appearance. The placebo was composed of dextrin, sunset yellow fcf, and a sweetener; the proportion was 1200 : 1 : 7. After being tested on five independent volunteers, the placebo was deemed indistinguishable from XTJYF. XTJYF and the placebo were dispensed in identical opaque packages.
Quantitative data was summarized using mean, standard deviation (SD), or 95% confidence interval (95% CI). Qualitative data was described using proportion, as percentages. Baseline characteristics of the two groups were compared using the two-sided chi-square test or
Since this was a randomized, blind clinical trial, the statistical analyses for treatment effect evaluation of the primary and secondary outcomes are relatively straightforward. Baseline-to-end-point score changes in the three global SCL-90-R indices and rates of response in the GSI were computed as the primary endpoints. For defining rate of response, patients with a reduction of at least 30% from the baseline GSI score were classified as “much improved”; at least 50%, as “very much improved.” Subanalyses of the baseline-to-end-point score changes of the nine SCL factors and sleep quality score (the average of the scores of the three SCl-90-R items on sleep quality) were secondary endpoints. Statistical analysis on both primary and secondary outcomes was done using intention-to-treat analysis (ITT) with statistical software SPSS. Missing values in the SCL-90-R questionnaire for the patients who withdrew from the study before the eighth week were imputed using the last-observation-carried-forward method. For primary outcomes, effect sizes (for three global indices) and number needed to treat (NNT, for rate of response in the GSI), as well as the
A total of 3478 individuals were screened, of whom 820 passed the preliminary screening and 245 were finally enrolled into the study; 575 were excluded. Of these, 372 were lost to follow-up or refused enrollment; 178 did not meet the inclusion criteria; 25 met the exclusion criteria. Enrolled patients were randomly assigned to XTJYF (
Table
Baseline characteristics, earthquake-affected PTSD patient treatment groups.
Variable | XTJYF | Placebo | |
---|---|---|---|
Sex, | |||
Female | 88 (71.5) | 86 (70.5) | 0.89 |
Male | 35 (28.5) | 36 (29.5) | |
Age, mean (SD) | 51.2 (15.0) | 51.0 (16.0) | 0.93 |
Marital status, | |||
Married or living together | 99 (80.5) | 96 (78.7) | 0.75 |
Others (unmarried, divorced, etc.) | 24 (19.5) | 26 (21.3) | |
Education, | |||
Primary school or less | 51 (41.5) | 53 (43.4) | 0.80 |
More than primary school | 72 (58.5) | 69 (56.6) | |
Occupation, | |||
Farmer or unemployed | 89 (72.4) | 86 (70.5) | 0.78 |
Other employment or retired | 34 (27.6) | 24 (19.5) | |
Clinical PTSD symptom data, | |||
Uncontrollable recall of earthquake experiences | 81 (65.9) | 85 (69.7) | 0.59 |
Repeated nightmares of earthquake | 53 (43.1) | 54 (44.3) | 0.90 |
Repeated hallucinations | 46 (37.4) | 38 (31.1) | 0.35 |
Heart racing, sweating, pallor when viewing earthquake ruins or victims | 91 (74.0) | 82 (67.2) | 0.26 |
Poor sleep | 87 (70.7) | 86 (70.5) | 1.00 |
Tense or easily agitated | 97 (78.9) | 92 (75.4) | 0.55 |
Lack of concentration | 60 (48.8) | 50 (41.0) | 0.25 |
Panic | 52 (42.3) | 45 (36.9) | 0.43 |
Avoids recalling anything related to the earthquake | 73 (59.3) | 73 (59.8) | 1.00 |
Avoids activities related to earthquake | 56 (45.5) | 55 (45.1) | 1.00 |
Avoids contact with others, indifferent to relatives | 54 (43.9) | 45 (36.9) | 0.30 |
Loss of interest and motivation | 51 (41.5) | 55 (45.1) | 0.61 |
Selectively forgetful | 67 (54.5) | 62 (50.8) | 0.61 |
Loss of hope for the future | 34 (27.6) | 39 (32.0) | 0.49 |
Lost relatives in the earthquake, | 7 (5.7) | 11 (9.0) | 0.34 |
Baseline outcome measures from SCL-90-R, mean (SD) | |||
Global severity index | 1.14 (0.61) | 1.12 (0.60) | 0.78 |
Positive symptom total index | 48.4 (20.0) | 48.8 (18.8) | 0.87 |
Positive symptom distress index | 2.14 (0.97) | 2.00 (0.52) | 0.18 |
Table
SCL-90-R Factor scores, Chinese and American norms compared to earthquake-affected PTSD patients at baseline.
Sample | Norm, China | Norm, USA● | PTSD, Sichuan |
SCL-90-R | |||
Mean (95% CI) | Mean (95% CI) | Mean (95% CI) | |
Somatization | 0.37 (0.34–0.40) | 0.36 (0.33–0.39) | 1.20 (1.11–1.29)* |
Obsessive-compulsive behavior | 0.62 (0.59–0.65) | 0.39 (0.36–0.42) | 1.38 (1.29–1.47)* |
Interpersonal sensitivity | 0.65 (0.62–0.68) | 0.29 (0.27–0.31) | 0.93 (0.84–1.02)* |
Depression | 0.50 (0.47–0.53) | 0.36 (0.33–0.39) | 1.29 (1.18–1.39)* |
Anxiety | 0.39 (0.37–0.41) | 0.30 (0.28–0.32) | 1.25 (1.15–1.34)* |
Hostility | 0.46 (0.43–0.49) | 0.30 (0.27–0.33) | 1.12 (1.02–1.23)* |
Phobic anxiety | 0.23 (0.21–0.25) | 0.13 (0.11–0.15) | 0.93 (0.83–1.03)* |
Paranoid ideation | 0.43 (0.40–0.46) | 0.34 (0.31–0.37) | 0.74 (0.65–0.83)* |
Psychoticism | 0.29 (0.27–0.31) | 0.14 (0.12–0.16) | 0.77 (0.69–0.85)* |
Global severity index | 0.31 (0.29–0.33) | 1.13 (1.05–1.20) | |
Positive symptom total index | 24.9 (24.0–25.9) | 19.3 (18.3–20.3) | 48.6 (46.2–51.1)* |
Positive symptom distress index | 1.32 (1.29–1.35) | 2.07 (1.97–2.17)∆ |
Table
XTJYF treatment effect on primary and secondary outcomes.(1)
SCL-90-R factor | XTJYF ( | Placebo ( | Effect size(2) | |
Mean (95% CI) | Mean (95% CI) | |||
Global severity index | 0.30 (0.24–0.37) | 0.15 (0.09–0.21) | ||
Positive symptom total index | 6.66 (4.58–8.73) | 3.52 (1.62–5.41) | 0.284 | |
Positive symptom distress index | 0.38 (0.30–0.45) | 0.19 (0.12–0.26) | ||
Somatization | 0.34 (0.25–0.43) | 0.16 (0.08–0.24) | ||
Obsessive-compulsive behavior | 0.28 (0.20–0.36) | 0.15 (0.07–0.24) | 0.270 | |
Interpersonal sensitivity | 0.27 (0.19–0.35) | 0.16 (0.08–0.24) | 0.241 | 0.061 |
Depression | 0.35 (0.27–0.44) | 0.16 (0.08–0.24) | ||
Anxiety | 0.40 (0.29–0.50) | 0.12 (0.04–0.21) | ||
Hostility | 0.31 (0.21–0.40) | 0.15 (0.06–0.24) | ||
Phobic anxiety | 0.23 (0.14–0.32) | 0.13 (0.05–0.21) | 0.211 | 0.101 |
Paranoid ideation | 0.16 (0.08–0.24) | 0.12 (0.04–0.21) | 0.070 | 0.586 |
Psychoticism | 0.19 (0.11–0.26) | 0.15 (0.08–0.23) | 0.077 | 0.548 |
Sleep quality | 0.76 (0.58–0.94) | 0.33 (0.19–0.47) |
(1)Statistical analysis was done using intent-to-treat analysis (ITT) with SPSS. (2)Cohen’s d effect size measure, in which an effect size of 0.2 to 0.3 is considered a “small” effect, around 0.5, a “medium” effect, and 0.8 to infinity, a “large” effect, is used here. (3)The
Treatment response rates of XTJYF versus placebo. Patients with a score reduction of at least 30% from the baseline SCL-90-R GSI score were classified as “much improved,” and 50%, as “very much improved.” *XTJYF versus placebo,
The second part of Table
Overall, XTJYF was well tolerated. Compliance rate, 83% for the XTJYF and 81% for the placebo group, was reasonably high. Six in the XTJYF and five in the control group withdrew due to adverse effects, so reported AEs were similar in the two groups. The most frequently reported AEs were nausea (14.6% versus 9.0%;
In the present study, we compared our data to the Chinese norm calculated by Jin et al. [
Hypothesizing that it would improve poor GPS in earthquake-related PTSD, we investigated a Chinese herbal formula, XTJYF, modified from a classic formula,
These findings suggest that XTJYF may globally improve GPS in earthquake-related PTSD patients, specifically in somatization, obsessive-compulsive behavior, depression, anxiety, and hostility. In addition, the formula may improve the sleep quality of the patients and appears to be safe. Although a few subjects reported gastrointestinal complaints such as nausea and diarrhea during treatment, these were probably due to the poor diet available after the earthquake; these symptoms were also frequently reported in the placebo control group. Our findings are consistent with those of our previous study on XTJYF for cancer patients with depression [
The results are meaningful because all five of the psychological disorders mentioned above are associated with high levels of functional and psychosocial disability in chronic PTSD patients [
The psychological mechanisms of action of
Several limitations to this study should be noted. First, our trial lacked a long follow-up assessment. This was largely due to the difficulties in following up this particular population, which consisted of earthquake survivors living in shelters with no specific address. In the patient recruitment stage, more than 45% (372 of 820) of those preliminarily screened for PTSD were lost to follow-up. Secondly, we did not include a questionnaire measuring specific PTSD core symptoms, mainly because of the low level of education in this mountain population. In our patient population, 43% had an elementary education or less and found it difficult to complete a single 90-question SCL-90-R questionnaire. However, although we did not include a specific questionnaire such as the Clinician-Administered PTSD Scale [
Despite the limitations, our findings provide preliminary support for the use of TCM in treating GPS in earthquake survivors with PTSD. TCM has been used extensively in China to treat people suffering from various diseases after disasters, for it is readily available, reasonably cheap, effective, and safe. Because of their wide usage, the production of TCM herbal products is quick and cost effective in China. Traditional Chinese herbal medicine may provide an adjuvant therapy that is safe, effective, and timely for affected populations in natural disasters such as earthquakes.
X.-Z. Meng and F. Wu made equal contributions.
XTJYF is a modified formula of a classic Chinese herbal formula,
The work was supported by a Modernization of Chinese Medicine Grant supported by the Shanghai Committee of Science and Technology (no. 08DZ1973900) and a Key Grant from the China National Science and Technology Foundation (no. 2008ZXJ09004-021). The authors acknowledge the assistance of the Air Force Sanatorium in Dujiangyan for the use of their research assistants and study facilities. This project could not have been completed without the ongoing support of the Psychology Department of the Second Military Medical University. Particular thanks are given to the psychologists Wei-Zhi Liu, Wen Dong, and Jun-Ling Wang and to all the patients who contributed their time to this study. They would like to thank Dr. Lyn Lowry of the Center for Integrative Medicine, University of Maryland School of Medicine, for her editorial support.