Prevalence and correlates of suicide attempt among Chinese individuals receiving methadone maintenance treatment for heroin dependence

To date, there have been very limited studies regarding the clinical epidemiology of attempted suicide in Chinese individuals with heroin-dependence. The objective of this study was to examine the prevalence and correlates of suicide attempt in Chinese individuals receiving methadone maintenance treatment for heroin dependence. Demographic, clinical, and psychosocial data of 603 methadone-maintained patients with heroin dependence were collected with a standardized self-administered questionnaire. The presence of suicide attempt and antisocial personality disorder was assessed by using a single question and the Mini-International Neuropsychiatric Interview 5.0. The one-month and lifetime prevalence rates of suicide attempt were 9.5% and 34.2%, respectively. In multivariable logistic regression, lifetime suicide attempt was significantly associated with female gender (OR = 2.81), being 20–39 years old (OR = 2.73), an education level of primary school or lower (OR = 2.07), poor economic status (OR = 3.06), injecting heroin before methadone maintenance treatment (OR = 2.92), depressive symptoms (OR = 3.46), anxiety symptoms (OR = 1.88), and antisocial personality disorder (OR = 2.85). Suicide attempt is very prevalent among Chinese individuals receiving methadone maintenance treatment for heroin dependence. Services for patients with heroin dependence in methadone maintenance treatment clinics in China should include psychosocial supports, periodic screening for suicide attempt and other suicidal behaviors and, when needed, psychiatric treatment and crisis intervention.

Persons who use heroin and other opioids are at greater risk for premature deaths, with suicide representing a substantial and important contributor to the overall excess mortality seen in opioid users [1][2][3] . For example, in Taiwan, the all-cause mortality and suicide death rates are over seven and 15 times higher in individuals who use heroin (IUH) than those in the general population, respectively 4,5 . It has been estimated that approximately 3-35% deaths among IUH could be ascribed to suicide 6 . Considering the "hidden" suicides among deaths of IUH certified as opioid overdose and accidents 4,[7][8][9] , the percentage of deaths by suicide among IUH would be higher than the above estimates.
IUH are also at elevated risk for other suicidal behaviors, including ideation, plan, and attempt 10,11 . Among all known risk factors for suicide, including these non-fatal suicidal behaviors, a prior attempted suicide is one of the most robust predictor of completed suicide [12][13][14][15] . Evidence also shows that some suicide-preventive measures aimed at individuals who previously attempted suicide are effective to reduce suicides 16,17 . Therefore, a better understanding on the clinical epidemiology of suicide attempt may help the early identification of IUH at elevated risk for suicide and would facilitate the development of preventive measures for suicide in this high-risk population.
Given the large number of persons with opioid dependence and serious consequences associated with opioid dependence, opioid dependence remains the largest contributor to the current global burden of disease caused The outcome of this study, suicide attempt, was measured with the question adapted from the National Comorbidity Survey 48 : "Have you ever attempted suicide?". If the patient endorsed it, he/she would be recorded as having lifetime suicide attempt. Patients with lifetime attempt would be further asked: "When was the last time?". If a response was affirmative for any time during the past month, the patient would be recorded as having one-month suicide attempt.
The survey investigators were six treating psychiatrists of patients in the three MMT clinics. They were arranged to interview patients with MINI and read out questions for subjects who had difficulty in completing the questionnaire.
Statistical analysis. Prevalence rates of lifetime and one-month suicide attempt were calculated.
Demographic, clinical, psychosocial, and personality characteristics of IHD with and without suicide attempt were described and compared by Chi-square test. Multivariable logistic regression model with the "Enter" method was used to identify factors significantly associated with suicide attempt. Suicide attempt was entered as the dependent variable, and all demographic, clinical, psychosocial, and personality factors were entered simultaneously as independent variables. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to quantify the associations between factors and suicide attempt. The statistical significance level was set at P ≤ 0.05 (two-sided). SPSS software version 15.0 package was used for analyses. ethics approval. All study procedures were conducted in accordance with the ethical standards of the 1975 Helsinki Declaration. Written informed consent was obtained from each participant and declarations of anonymity and confidentiality had been made before the start of data collection. The institutional reviewed board of Wuhan Mental Health Center approved the study protocol.

Results
At the time of the survey, there were a total of 743 patients receiving MMT in the three clinics. All these patients were assessed for eligibility and 652 were eligible for this study. No patients were excluded due to a current diagnosis of alcohol dependence. A final sample of 603 patients (92.5%) successfully completed the survey. The subject recruitment process is shown in Fig. 1.
In this sample of IHD from MMT clinics, 69.8% were men and the mean age was 38.1 years (range: 21-59, standard deviation [SD] = 7.0). Before admission to MMT, the main route of heroin use was injection (84.1%) and the average duration of heroin use was 10.8 years (SD = 8.7). At the time of the survey, these patients had taken methadone for a mean duration of 24.6 months (SD = 11.0) at an average dosage of 69.5 mg per day (mg/d) (SD = 29.6). Table 1 shows detailed demographic, clinical, psychosocial, and personality characteristics of our sample of IHD receiving MMT.
In multivariable logistic regression analyses (Table 2), one-month suicide attempt was significantly associated with female gender (OR   Table 1. Characteristics of Chinese individuals receiving methadone maintenance treatment (MMT) for heroin dependence and prevalence rates of attempted suicide by different characteristics. *"Non-married" includes never-married, remarried, cohabitating, separated/divorced, and widowed. **Continuous variables were dichotomized by a median split approach.

Discussion
To the best of our knowledge, this is the first large-scale study in China examining the prevalence and correlates of suicide attempt in IHD receiving MMT. We found 9.5% and 34.2% of the methadone-maintained IHD attempted suicide during the past month and their lifetime, respectively. The two prevalence figures indicate an extremely high prevalence of suicide attempt in Chinese IHD, because the lifetime prevalence, even the one-month prevalence of suicide attempt in IHD is much higher than the lifetime prevalence in the Chinese general population, which is estimated to be 0.8% only 49 . Compared to existing Chinese studies, the lifetime prevalence in our study is higher than that in the five studies with samples of IHD in mainland China (0.66-30.7%) [33][34][35][36][37] and one study with a sample of IHD in Taiwan (17.8%) 50 . Nevertheless, our lifetime prevalence estimate still falls within the upper end of the lifetime prevalence range reported by Western studies with samples of patients with opioid dependence 10,[20][21][22][23][24][25] . In addition, the one-month prevalence of attempted suicide in our sample is similar to that of IHD in Taiwan (10.9%) 50 , but higher than that of IUH in Australia (5.0%) 10 . These discrepancies could be attributed to differences in the assessment of suicide attempt (i.e., self-report vs. interview), treatment modality (i.e., MMT vs. inpatient), clinical settings (i.e., voluntary vs. compulsory detoxification institutions), type of opioid used (i.e., opioids vs. heroin), and patient characteristics (i.e., acute vs. prolonged withdrawal phase). Our data suggest that Chinese methadone-maintained IHD are at very high risk for suicide attempt. In our sample, 51.1% were not married, 47.4% were unemployed, 23.2% had poor financial status, 33.8% were depressed, 36.3% were anxious, 53.6% suffered from pain, and 55.9% felt lonely. Therefore, a considerable portion of the IHD are socially and economically disadvantaged and have psychological and physical health problems. In addition, owing to the lack of mental health professionals and social workers in MMT clinics in China, psychosocial problems often go under-recognized and under-treated 11,51 , which further exacerbates the mental health of www.nature.com/scientificreports www.nature.com/scientificreports/ IHD. Because of these prevailing risk factors for suicidal behaviors, a very high prevalence of suicide attempt in IHD of MMT clinics is not surprising.
Overall, our findings on demographic and psychosocial correlates of suicide attempt in IHD are similar to those of the general population 48,[52][53][54][55] . Because women have lower suicidal intent and use less lethal suicide methods than men, attempted suicides occur primarily among women 56,57 . This explains the higher prevalence of suicide attempt in female than in male IHD in our study. In general, compared to old age groups, attempted suicide in adolescents and young adults is characterized by greater attempt rate and higher attempt/completion ratio 58,59 . Accordingly, young IHD were more likely to survive due to attempted suicide but old IHD were more likely to die due to completed suicide. In this case, the old IHD may represent a special subgroup of IHD, who were less susceptible to suicide. In keeping with this possible survival bias, we found a higher rate of attempt in young than old age groups (20-39 vs. 40-59 years) in IHD. Because the two age-groups were born in different years, the age-group difference in rates of suicide attempt may also suggest the existence of a birth-cohort effect on the risk of attempted suicide among IHD. In addition, this study measured suicide attempt by a self-report question, so our measure of suicide attempt might be subject to recall bias. Due to age-related memory decline, the recall bias is likely to be more substantial in old than young age groups. The possible birth-cohort effect and recall bias may also explain the observed lower prevalence of suicide attempt in old than young IHD in this study. Because individuals with marital status of "other than married" may have inadequate spousal support to buffer against the negative effects of stressful life events 60 , non-married individuals receiving MMT may be more likely to attempt suicide when they have difficulties in daily life.
In this sample of IHD under MMT, we replicated the association between attempted suicide and a low socioeconomic status in the general population, as indicated by low levels of education and income 61 . Qualitative studies have shown that socioeconomically disadvantaged persons are more likely to experience negative life events across their life course, have negative emotions such as anger and shame, and hold a pessimistic attitude about future 62 . As a result of these, the significant relationships of suicide attempt with a low level of education and poor economic status in IHD is expected.
In line with prior studies with samples of patients with opioid dependence and community-adults 21,22,50,63-65 , we ascertained the elevated risk of attempted suicide in IHD with loneliness, depression and anxiety. Borderline personality disorder (BPD) is a commonly reported personality risk factor for attempted suicide in the literature 63,66 . However, because suicidal behaviors and self-harm are one of the diagnostic criteria for BPD, the cross-sectional BPD-attempt association is very likely to be spurious, as a result of the overlapping constructs between BPD and suicide attempt. Therefore, BPD was not assessed in the present study. We found that APD was significantly associated with an increased risk of suicide attempt in IUH, which is rarely reported in the literature. This association may be ascribed to the antisocial traits of IHD with APD such as impulsivity and aggression 67 , because a higher degree of aggression/impulsivity is a risk factor of attempted suicide in both opioid users and general population 24,68 .
Neither MMT duration nor dose of methadone was kept in the final multiple logistic regression model, despite their significant associations with lifetime suicide attempt in the univariate analyses. This finding may suggest that only providing MMT to IHD in MMT clinics may not be effective to reduce attempted suicides, because its effect can be easily masked or offset by other risk factors such as depression and anxiety. We found that patients who previously injected heroin and had a long duration of heroin use were at higher risk for attempted suicide. Evidence has shown that injecting drug users have very high prevalence of HIV, HCV, and HIV-HCV co-infection, and both HCV and HIV/AIDS has been linked to suicidal behaviors [69][70][71] . Duration of past heroin use can be viewed as a cumulative measure of past exposure to heroin, and long-term heroin use has been associated with more physical and mental health problems 72 . We speculate that the significant links between suicide attempt and injection heroin use and a long duration of heroin use might be due to these infectious diseases and deleterious health of injection users and long-term users.
This study has some limitations. First, detailed data on suicide attempt such as attempt methods, level of intention to die, total number of previous attempts, and age at first attempt were also important for suicide prevention, but we did not collect such data. Second, our sample of IHD was recruited from MMT clinics only, IHD of other settings, i.e., communities, compulsory detoxification centers, and hospitals, were not included, limiting the generalizability of our study findings. Third, due to the observational nature of this cross-sectional study, the causal relationships between suicide attempt and correlates could not be ascertained. Fourth, this study used self-rating scales to assess severities of depressive and anxiety symptoms. No clinical diagnostic interviews were conducted to ascertain the etiology of these symptoms, i.e., primary, secondary to physical illnesses, or induced by heroin dependence. This information is also important for the clinical implication of the study findings. Fifth, as we mentioned above, this study may be subject to recall bias due to the use of a self-report measure of suicide attempt. We may underestimate the prevalence of suicide attempt in this sample of IHD. Sixth, due to limitations in the study design, a secondary data analysis, some potentially important risk factors of attempted suicide such as medical illnesses, alcohol dependence, and psychotic symptoms, were not included in our analysis. It should be noted that, because China's clinical guideline for MMT does not recommend MMT for IHD with alcohol dependence 73 , no patients with alcohol dependence were identified in the three MMT clinics of our study. Recruiting patients from other clinical settings such as compulsory detoxification institutions and community-based rehabilitation centers for IHD would solve this issue. Finally, we ran the multivariable logistic regression twice to identify factors associated with suicide attempt but did not correct for multiple testing because the analysis was exploratory in nature. Findings of some correlates might be false positive. Longitudinal studies that assess detailed characteristics of suicide attempt, include more candidate risk factors such as alcohol dependence, and recruit samples of IHD from diverse clinical settings are warranted to address these issues.
In conclusion, suicide attempt is highly prevalent among Chinese IHD of MMT clinics, indicating the high risk of suicide in this patient population. There is an urgent need for the mental health professionals to identify (2019) 9:15859 | https://doi.org/10.1038/s41598-019-52440-x www.nature.com/scientificreports www.nature.com/scientificreports/ and address the epidemic of suicide attempt and other suicidal behaviors in MMT clinics in China. Among IHD, suicide attempt is associated with a range of demographic, psychosocial, and clinical factors. Given the strong predictive value of attempted on completed suicide, efforts to prevent or reduce suicides in MMT clinics may be effective to target on those who are females, are young, are not married, have a low socio-economic status (i.e., a low level of education, poor financial status), inject heroin before MMT, have a long duration of heroin use, feel lonely, have clinically significant depressive and anxiety symptoms, and have APD. Services for IHD in MMT clinics should include regular screenings for those at risk for attempted suicide and other suicidal behaviors, expanded psychosocial supports, and, when necessary, psychiatric assessment and treatment and crisis intervention.

Data availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.