Abstract
Aims:
Alcohol-related disorders (ARDs) have become an increasing mental health and social challenge in China. Research from China may provide important clinical information for researchers and clinicians around the world. However, most of the Chinese research on ARDs has only been published in Chinese language journals. This article summarizes publications related to treatments for ARDs found in the Chinese literature.
Methods:
A descriptive study based on literature identified from searches of the China National Knowledge Infrastructure (1979–2012), Pubmed databases and hand-picked references with emphasis on traditional Chinese medicine (TCM).
Results:
More than 1500 Chinese language papers on treatment for ARDs were found and ~110 were selected. Many medications used in the Western countries (e.g. disulfiram and acamprosate) are not available in China, and no drugs have been officially approved for alcohol dependence. TCM approaches (including acupuncture, electroacupunture and herbals) have played a role in treatment for ARDs with some positive results. These unique methods are reviewed and the need for additional controlled studies is noted.
Conclusion:
Currently, very limited facilities, medications or programs are available for patients with ARDs in China, thus much improvement is needed in the field, including setting up intervention/treatment programs.
Alcohol-related disorders (ARDs) are an increasing health and social problem worldwide, including in China (Tang, 1998a, 1997b; Lee et al., 2009; Phillips et al., 2009; Zhou et al., 2011). Several recent studies have suggested a significant increase in alcohol consumption and alcohol-related health problems in China (Hao et al., 2005; Meng et al., 2008; Lee et al., 2009; Zhou et al., 2011).
The history of treatment for ARDs in China is relatively short. Treatments for individuals with ARDs were virtually non-existent before the 1990s, except for those who had severe psychotic symptoms or delirium tremens (DTs). The first inpatient addiction psychiatry unit was opened in Beijing in 1990 and several special clinics were opened afterwards. Currently, a few psychiatric hospitals in China have a specialized addiction unit to treat patients with alcohol-related psychotic disorders; most of these units are in major cities. A common scenario for patients with alcohol dependence who seek psychiatric treatment is that they have developed serious psychiatric symptoms, including hallucinations, delusions or have engaged in self-harm/or made a suicide attempt. Those who have severe alcohol intoxication or DTs are commonly seen in the emergency room (ER) and those who have other clinically significant alcohol-related medical problems (e.g. alcoholic liver diseases, pancreatitis, etc.) can be seen in other departments in general hospitals. Although very limited in scale and availability in China, the treatment modalities in China can be roughly classified as: (a) outpatient treatment, providing brief counseling and pharmacotherapy, including anti-depressants for comorbid depression/anxiety—currently there are only a few psychiatric hospitals have this special clinic; (b) inpatient treatment, providing short-term detoxification and intensive treatment for acute withdrawal symptoms—for those who are severely dependent and often have medical/psychotic conditions; and (c) ER: the most common cases treated in ERs in general hospitals are severe alcohol intoxication or DTs; patients with psychosis or suicidality are often seen in a psychiatric ER.
As China has the largest population internationally, the research from China may provide important clinical information for researchers and clinicians around the world. However, most of the research has only been published in Chinese language journals. We summarize here the publications related to treatments for ARDs in the Chinese literature: current treatments for ARDs in China, particularly pharmacotherapies and other non-psychological treatments, including traditional Chinese medicine (TCM) approaches. We chose to use ‘alcohol-related disorders’ instead of ‘alcohol dependence’ or ‘alcohol use disorders’, because the topics covered in the article are more broad and inclusive. We not only discuss alcohol use disorder (abuse and dependence) but also include alcohol-induced disorders (intoxication, withdrawal and DTs).
METHODS
The data for this review are based on the Chinese language literature identified from searches of the China National Knowledge Infrastructure (CNKI) (www.cnki.net) (1979–2012) and studies in Chinese populations identified from the Medline databases (up to 3 April 2012). The CNKI is the largest online Chinese language database. Considering the terms in the Chinese literature are somewhat inconsistent, the CNKI was searched for alcohol-related publications using the following search words: ‘alcohol dependence/alcohol abuse’ (jiujing yilai/jiujing lanyong) or ‘alcohol intoxication (poisoning)’ (jiu zhongdu/jiujing zhongdu/yichun zhongdu) plus ‘treatment’ (zhiliao or Liaofa) in the title. This search yielded 284 and 1241 journal papers, respectively (up to 3 April 2012). Approximately 110 publications were selected for this review, the selection criteria were: (a) comparative studies or representative studies on certain treatments; (b) clinical cases analysis with a larger sample (usually >50); (c) meta-analysis and (d) some pertinent review articles on the topics. The Medline databases were also searched using the words ‘alcohol dependence/abuse’, ‘alcoholism’, plus ‘Chinese’ or ‘China’ in the titles, which yielded 12 publications (up to 3 April 2012).
TREATMENTS FOR ARDS
Several treatments have been studied and are available for different stages of treatment for ARDs in China (Table 1). Here we describe them, in order, from acute intoxication, general withdrawal symptoms, DTs and relapse prevention. Before we go into more details for each treatment, a few general comments need to be made: (a) many published reports are case analysis or clinical observations involving a relatively small sample size, with only a few studies following a randomized controlled design; (b) none of the medications/treatments have been officially approved for alcohol dependence (except naloxone for acute alcohol intoxication); (c) some medications have been widely used in patients with alcohol-related mental disorders, such as antidepressants and antipsychotics. Given they are used for comorbid conditions, not for alcohol abuse/dependence per se, they will not be included in this article.
Table 1.
Treatments available for alcohol intoxication and alcohol dependence in China
| Stage | Treatment | References | Comments |
|---|---|---|---|
| Acute intoxication | Naloxone, Xingnaojing, kudzu extract meclofenoxate | Bai et al. (1998), Xue et al. (1998), Wang et al. (2007); Wei et al. (2007), Xue (2009), Yang et al. (2009), Ge et al. (2010), Lin and Liu (2010), Liu et al. (2010), Tang et al. (2010), Wang and Chang (2010), Huang (2011), Su (2011), Zhang (2011) | Lack of controlled studies in large samples |
| Withdrawal syndrome, including delirium tremens | Benzodiazepines, Valproate, Vitamin B1 | Tang (1998b), Xiao et al. (2001), Liang and Zhao (2007) | Similar to that used in other countries |
| Relapse prevention | Aversive therapy | Zhao and Zhuang (1990), Zhong and Tang (1996), Zhou et al. (2001), Song (2009) | Disulfiram is not available in China |
| Relapse prevention | Naltrexone topiramate | Huang et al. (2002), Yuan et al. (2009), Ma et al.(2011) | The studies on naltreaxone and topiramate were double-blind, placebo controlled, but sample sizes were relatively small (n < 100) |
| Relapse prevention | Acupuncture, electroacupunture, acupoint stimulation | Xie et al. (2004), Jin et al. (2006), Wang et al. (2008), Zhang and Sun (2010), Zhang et al. (2010) | Some positive findings, but lack of controlled studies |
On the other hand, as TCM has a different theory and classification system regarding ARDs and their treatments, sometimes it is difficult to categorize a specific TCM treatment. A recently published review article by Liu et al. (2011) provides an overview on this topic; however, the large body of literature on Xingnaojing (see below for details) was minimally discussed in that paper.
Treatment of Acute Intoxication
Alcohol intoxication has become more prevalent in China in the last years. Several studies showed that alcohol intoxication is among the top two types of intoxication seen in the ER (15–67.1% of all intoxication/overdose/poisoning ER cases) (Shan et al., 2007; Chen et al., 2008; Chen and Han, 2008).
Naloxone
Since the mid-1990s, naloxone has been widely used in the ER for patients with intoxication, overdose, poisoning and other patients who presented with altered mental status, including coma (Liu and Gao, 2005; Chen et al., 2008). Among other conditions, the use of naloxone in ERs for cases with alcohol intoxication has probably been most studied (Liu and Gao, 2005). A literature search in the CNKI databases between 1979 and 2012 yielded more than 700 journal publications in which titles included both ‘alcohol intoxication’ and ‘naloxone’ (assessed on 3 April 2012).
Naloxone has been used alone as well as combined with other treatments. When used alone, naloxone (0.8–2.8 mg i.v. drip) was found to favorably influence the state of consciousness in alcohol-intoxicated patients, as reported by numerous reports (Han and Yang, 2000; Liu, 2005; Qin, 2011; Su, 2011; Zhang, 2011). For example, Zhang (2011) reported the results in 120 cases with severe alcohol intoxication/poisoning, and found that the recovery time of consciousness and the length of ER stay in the naloxone group (83.5 ± 33.2 and 178.4 ± 63.7 min) were significantly shorter than the control group (184.9 ± 65.6 and 384.7 ± 61.4 min, both P < 0.01). Studies also found that the efficacy of naloxone seemed to be dose-dependent. For example, Su (2011) found that, compared with control group (routine management), and low-dose (1.0 mg/day) group, a higher dose naloxone (1.8 mg/day) was associated with a shorter recovery time of consciousness and a shorter time to return to baseline of vital signs. Since a longer time was required for naloxone to counteract benzodiazepine or alcohol intoxication compared with opiate overdose (Liu and Gao, 2005), the mechanism of action may be different from that implied in narcotic overdose. Some found that naloxone attenuated brain ischemia–reperfusion injuries and, the possible mechanism including its counter β-endophin activity and reducing the total calcium and free radicals (Wang et al., 2001).
Chinese herbs—Xingnaojing
Some Chinese herbs have also been used for treatment of alcohol intoxication. For example, one herbal injection, Xingnaojing, which includes extracts of muskiness, radix curcumae, Gardenia and borneol, has been repeatedly reported for the use in alcohol intoxication (Bai et al., 1998; Ge et al., 2010; Liu et al., 2010; Lin and Liu, 2010; Tang et al., 2010). As one of the commonly used herbal injections in neurological disorders, Xingnaojing was first used in the treatment of alcohol intoxication in the 1990s (Bai et al., 1998; Xue et al., 1998). Most reports have shown that a combination of naloxone with Xingnaojing hastened the recovery of respiratory and circulatory functions of intoxicated patients (Lin and Liu, 2010; Tang et al., 2010), even for those in a severe coma (Wang and Chang, 2010). In addition, patients who received combination therapy reported less symptoms of headache, dizziness, nausea, vomiting and palpitations compared with patients on naloxone alone (Lin and Liu, 2010). Of note, some of the published reports used a randomized design, but none of them were double-blind and placebo-controlled. In fact, this herbal injection might be one of the most commonly used one in the Chinese ERs for alcohol intoxication. A literature search found more than 160 journal papers published on Xingnaojing and alcohol intoxication in Chinese journals (accessed on 3 April 2012). One recent meta-analysis (Yang et al., 2009) also supports the combined treatment of naloxone and Xingnaojing is better than naloxone alone. So far, there have been few studies on the mechanism of Xingnaojing. The only two published reports suggested that its mechanism of action might be due to possible anti-oxidant effects. These findings were based on oxidant levels in rabbits (Bai et al., 1998) and mouse models (Wei et al., 2007) after Xingnaojing treatment.
Kudzu
The role of kudzu in alcohol intoxication has been studied. A literature search in the CNKI database showed that there are more than 80 papers on alcohol and kudzu (Pueraria lobata). Kudzu is a root that is used in TCM and its use dates back to an ancient Chinese text entitled Ben Cho Gang Mu (Li, 1590–1596 AD). Wang et al. (2007) wrote a comprehensive review on the role of kudzu extract-containing preparations in alcohol intoxication. Several studies have been focused on its role in alcohol intoxication. For example, Liu et al. (2002) reported that, for cases with alcohol intoxication, the effects of puerarin injection were comparable with that of naloxone (n = 90, P > 0.05) (Liu, 2002). Several other studies have reported similar findings, including one involving the combined use of vitamin C and puerarin (Ge, 2009) and one comparing its effect with a combination treatment of naloxone and Xingnaojing (Xue, 2009). In addition, some animal studies suggest that kudzu might help reduce cravings and hangover (Keung and Vallee, 1998; Carai et al., 2000). An additional study showed that the administration of extracts of P. lobata, as well as of the two major isoflavones present in P. lobata extracts such as daidzin and daidzein, reduced ethanol intake in Syrian Golden hamsters (Keung and Vallee, 1993). Puerarin represents the most concentrated isoflavonoid in kudzu although it is not as potent as daidzin. Interestingly, other animal studies suggest the potential utility of puerarin as an anti-craving agent, given its effects on alcohol intake in alcohol-preferring rats and monkeys (Overstreet et al., 2003; Rezvani et al., 2003).
In humans, the data present in the literature are controversial. One study in humans failed to show any benefit (Shebek and Rindone, 2000) of kudzu root extract on alcohol craving and abstinence in 38 patients with ARDs randomized to receive either kudzu root extract (1.2 g twice daily) or placebo. Lukas et al. (2005) performed a human laboratory study with heavy drinkers treated with either placebo or a kudzu extract for 7 days. After the 7-day period, subjects had the opportunity to drink their preferred brand of beer in a naturalistic laboratory setting. Kudzu treatment resulted in a significant reduction in the amount of beers consumed, increase in the number of sips and the time to consume each beer and a decrease in the volume of each sip. These changes occurred without significant effects on the urge to drink alcohol. The authors concluded that kudzu might be a useful adjunct in reducing alcohol intake although the exact mechanism by which kudzu suppresses ethanol intake remains to be clarified. A more recent human laboratory alcohol challenge study showed that kudzu extract did not alter participants’ subjective responses to the alcohol challenge or to alcohol’s effects on stance stability or vigilance/reaction time (Penetar et al., 2011). More studies are needed to examine the efficacy of kudzu in alcohol intoxication/alcohol dependence.
Other medications
Another potentially interesting drug is metadoxine, a drug formed by the salification of pyrrolidone carboxylic acid and pyridoxol, and approved in 17 countries for alcohol intoxication, based on its ability to facilitate the elimination of alcohol from blood and tissues (Addolorato et al., 2003; Vonghia et al., 2008). Metadoxine has been found to accelerate ethanol metabolism in both rats and humans (reviewed in Addolorato et al., 2003) and to be effective in alcohol intoxication (Shpilenya et al., 2002; Vonghia et al., 2008). Several studies also reported a beneficial effect of metadoxine in alcoholic liver disease (e.g. Caballeria et al., 1998), and preliminary evidence suggests a potential role of metadoxine to promote alcohol abstinence (Guerrini et al., 2006). Finally, a preliminary study has recently suggested the potential role of metadoxine as a unique treatment for both alcohol dependence itself and alcoholic liver disease (Leggio et al., 2011). Metadoxine, however, has not been studied in the treatment of alcohol intoxication in China, although there have been reports examining its efficacy in alcoholic liver disease (Mao et al., 2009).
The effects of meclofenoxate on alcohol intoxication have also been studied. A report involving 80 cases with alcohol intoxication in ER found that the effects of meclofenoxate (0.3 g, in 250 ml i.v. drip) were comparable with naloxone (1.2 mg in 250 ml i.v. drip) (Huang, 2011).
Treatment of alcohol withdrawal
Over 100 prescription drugs have been suggested as useful in the treatment of alcohol withdrawal syndrome, but very few studies have been conducted on their effectiveness (Tang, 1998a, 2002; Tang et al., 2002). Detoxification is a critical step for many alcoholic patients, and inadequate treatment could discourage patients from quitting drinking and may even lead to death. However, many professionals in China underestimate its importance or are reluctant to call it a treatment (Tang, 1997a).
Currently, benzodiazepines are the drug class of choice for managing withdrawal symptoms, including the longer-acting diazepam (Tang, 1998b), but some prefer oxazepam or lorazepam. Non-benzodiazepines have also been tested and used in China. For example, Zhen et al. (1997) reported a study comparing sodium valproate (0.6–2.4 g/day) and alprazolam (1.2–4.8 mg/day) for alcohol withdrawal syndrome and found that valproate was efficacious and well-tolerated. Another study, comparing valproate (800 mg/day) with diazepam (20 mg/day) in a group of patients with alcohol dependence, both tapering off within 1 week, also showed that valproate was effective in controlling alcohol withdrawal syndrome (Xiao et al., 2001).
Treatment of DTs
DTs is the most severe form of ethanol alcohol and is a medical emergency that requires prompt recognition and treatment (Tang, 1998a; Mayo-Smith et al., 2004), though it only occurs in a relatively small number of patients undergoing alcohol withdraw (Stern et al., 2010). Although little data are available in China about the prevalence of DTs in the general population and among alcoholic patients in communities, data from clinical samples showed that it is a rather common condition. According to an analysis of 1680 cases of alcohol dependence detected in an epidemiological study across seven regions in China in the mid-1990s, the prevalence of DTs in individuals with alcohol dependence was 8.3%. Consistent with reports in other countries, rates of DTs in hospitalized populations are higher than that in community samples or outpatients. Clinical data analysis of 851 psychiatric inpatients whose primary diagnoses were alcohol dependence or other alcohol-related mental disorders (Chi et al., 2004) showed that, at admission, while most cases had alcohol withdrawal syndrome (53.8%), alcoholic hallucinations (33.5%) and alcoholic delusion (25.1%), the rate of patients having DTs was not uncommon (14.7%), which was similar to that reported in the USA (Buchsbaum et al., 1992). Several other studies of hospitalized patients with alcohol dependence in China also found similar rates (18.9–21%) (Hu et al., 2006; Liu et al., 2007). In the report (Chi et al., 2004), they also found that comorbid infection, abnormality in liver tests and tachycardia at admission were associated with DTs. As reported by Yang et al. (2002), large-dose thiamine (100 mg i.v.) is essential in treatment of DT in patients with chronic alcohol dependence; in addition, benzodiazepines are also widely used in China to treat DTs.
The loading dose of diazepam strategy has also been tested in China, especially for patients with DTs. For example, Liang and Zhao (2007) reported a comparative study between diazepam and haloperidol in 60 patients with DTs. They administered diazepam i.v., 10–15 mg every 1–2 h until patients were mildly sedated. The same dose was maintained for 3 days, followed by switch to oral diazepam and tapering off after 1 week. The dose of haloperidol was 20–30 mg for the first 3 days (i.m.) and then switched to 10–15 mg/day and given orally. They found diazepam was superior to haloperidol in symptom reduction, tolerability and side effects. Of note, one case in the haloperidol group died during the trial (Liang and Zhao, 2007).
Relapse prevention: pharmacological and non-pharmacological approaches
Currently, only a few medications used in the West are available in China, and none of them has been approved for alcohol dependence. Here we review some medications that have been studied or used in China. In addition, we specifically review the role of traditional Chinese treatments (including herbals, acupuncture and acupoint stimulation) in relapse prevention.
Aversive therapy
Although it is available in many places in the world, disulfiram has never been available in mainland China. The only clinical observation on disulfiram was a case report of a Pakistani patient who was hospitalized in China (Zhang and Sun, 1992) and whose family brought the medication from abroad. Regardless, many Chinese clinicians have tried other drugs or herbal medicines that are supposed to induce disulfiram-like aversive reactions toward alcohol, especially for cases who have multiple relapses. The agents that have been tried for this purpose include furazolidone (Zhao and Zhuang, 1990; Zhong and Tang, 1996), apomorphine, among others (Song, 2009).
As with other behavior therapies, aversive therapy is a treatment based on learning theory. Long-term effects remain unknown. So far, there is only one small open-label study (Zhou et al., 2001) showing that, for patients who received furazolidone aversive therapy, the abstinence rate at 12 months after discharge was 73.3% (22 of 30). Except the expected disulfiram-like reaction, they study did not report other adverse drug reactions from long-term use of furazolidone.
Chinese herbal medicine
According to Chinese traditional medicine theory, excessive alcohol drinking can cause accumulation of ‘toxins’ in the body, with excessive heat and phlegm, leading to damages in qi and yin. Therefore, treatment should aim at detoxification, removing the excessive heat and phlegm (Yang et al., 2006). As part of natural medicine, many herbs have been used for alcohol dependence itself or its complications, especially liver problems (Xu et al., 2005). Some studies have also found that extract of kudzu roots can protect the gastric mucus membrane (Yang et al., 2006, also see discussion of kudzu above).
Naltrexone
Disulfiram, acamprosate, oral naltrexone (Pettinati et al., 2006) and the once-monthly injectable, extended-release naltrexone (Lee et al., 2010; see reviews by Garbutt, 2009; Edwards et al., 2011) are approved for treating alcohol dependence in several countries, but not in China. Nonetheless, there have been studies in China involving naltrexone and topiramate in the treatment of alcohol dependence.
Two published studies have examined naltrexone in China. A placebo-controlled trial in an outpatient setting (Huang et al., 2002) found that, compared with patients receiving placebo, patients receiving naltrexone (30 mg/day, a special formulation not available now) reported less craving (assessed using the 0–9 visual analogue scale based on Volpicelli et al., 1992) and had higher rates of abstinence at 4, 8 and 12 weeks. Yuan et al. (2009) in a double-blind, placebo-controlled trial, found that, compared with the placebo group, the naltrexone (50 mg/day) group had significantly lower craving scores at 10 and 12 weeks (all P < 0.05), alcohol consumption in the naltrexone group was lower than that of placebo group (P < 0.05) and the rate of abstinence in naltrexone group was significantly higher (P < 0.001). These findings are consistent with most of the naltrexone studies on alcohol dependence in USA, Europe and Australia (for review, see Anton, 2008; but see also, for example, Krystal et al., 2001), the sample size were relatively small (n = 45 and 68).
Topiramate
Topiramate has been shown in two large-scale, randomized, placebo-controlled, clinical trials to reduce heavy drinking and promote abstinence (Johnson et al., 2003, 2007). Ma et al. (2011) reported the first double-blind, placebo-controlled randomized clinical trial with low-dose topiramate to treat alcohol dependence in China. The trial enrolled 78 patients with alcohol dependence treated with either topiramate (50 mg/day) or placebo, with assessments at enrollment and after 2, 4, 8, 12 and 24 weeks of treatment. Outcomes measured were alcohol intake, craving, disability and general symptoms, including the AUDIT, Obsessive Compulsive Drinking Scale (OCDS) and Symptom Checklist-90 (SCL-90). At 24 weeks, patients taking topiramate had significantly lower scores on the OCDS (41.3 ± 1.2 vs. 51.3 ± 1.5, P < 0.05) and AUDIT (20.4 ± 4.6 vs. 27.3 ± 5.1, P < 0.05). Similarly, the overall rate of abstinence in the topiramate group (23 of 39) was significantly higher than in the placebo group (9 of 39, P = 0.001). Interestingly, compared with published reports from western populations, the dosage used in this study was substantially lower (Johnson et al., 2007; Olmsted and Kockler, 2008) (50 mg vs. up to 300 mg). The common side effects reported in the study of Ma et al. (2011) included mild dizziness, drowsiness, tiredness, burning, tingling, poor appetite and nausea. Overall side effects early in treatment (Weeks 2 and 8) were more common with topiramate than placebo (P < 0.05), but not different at 12 and 24 weeks of treatment, suggesting that most side effects improved as treatment continued (Ma et al., 2011).
Acupunture, electroacupunture and acupoint stimulation
As an ancient Chinese method to treat diseases and relieve pain, acupuncture has been studied in numerous disorders, including addictive disorders such as opiate addiction (Cui et al., 2008). Studies have shown that electroacupuncture (EA) is more effective than manual acupuncture (Ulett et al., 1998). Furthermore, electrical stimulation via skin patch electrodes is as effective as EA. However, its role in alcohol dependence treatment has been understudied. The available evidence from animal and clinical studies suggests that EA may be effective in reducing alcohol drinking and preventing relapse.
Based on alcohol-dependent animal (SD rats) models, Wang et al. (2008) found that both single or multiple EA at zusanli point (stomach-36) significantly reduced ethanol consumption and preference in ethanol-dependent rats compared with a control group.
In humans, at least a study showed that EA, when added to pharmacotherapy with an antidepressant (Zhang et al., 2010), was effective in ameliorating depression and anxiety in patients with alcohol dependence (measured by Hamilton rating scale for anxiety, Hamilton rating scale for depression and SCL-90). In addition, another study showed EA to be more effective than manual acupuncture in improving peripheral neuropathy in chronic alcoholic individuals (Zhang and Sun, 2010).
Xie et al. (2004) compared the efficacy of acupoint stimulation vs. alprazolam (1.2–2.4 mg/day) in alcohol dependence. Active treatments lasted for 4 weeks with follow-up at 12 weeks. The acupoints selected were hegu and shenmen, twice a week for the first 2 weeks and once a week for Weeks 3 and 4. Acupoint stimulation did better than alprazolam in terms of days of sobriety (69.7 ± 18.5 vs. 59.1 ± 18.6 days, P < 0.05) and rate of relapse (17/32 vs. 28/32, P < 0.01). Jin et al. (2006), emphasizing the aversive effect induced by acupoint stimulation, also showed this method to be effective in reducing relapse.
Other methods
Although without systematic data collection, some other methods have been used in China. For example, psychosurgery, once used for intractable schizophrenia and depression, has been used for alcoholic patients (Liu et al., 2009). Hemodialysis, a method in drug overdose treatment, has been reported (Wu et al., 2002) to be effective in 30 cases with alcohol dependence. Ultraviolet blood irradiation and oxygenation has also been claimed to be effective in alcohol dependence. These methods should be more vigorously studied before they can be considered for wide clinical use and possible approval, especially considering the risk of complications.
CURRENT CHALLENGE AND RECOMMENDED RESPONSES
In China, the level of awareness of ARDs is low and filled with myths. A recent survey (Sun et al., 2009) found that the public attitude toward individuals with alcohol abuse and dependence was negative, with many (73.4 and 65.9% for urban and rural residents, respectively) agreeing it would not be worthwhile to treat an alcoholic individual. The notion that alcohol dependence is a disease has not been widely accepted in China (Tang, 2000). A few with ARDs seek treatment. According to a survey in early 1990s (Shen and The Collaborative Group on Alcoholism, 1992) that interviewed 44,920 people between 15 and 65 years old, 97.2% of the positive cases detected in the survey had never received any kind of treatment. A study in Beijing, a more socioeconomically developed area in China, found a similar rate (Xiang et al., 2009), with only 2.4% of the subjects with alcohol dependence receiving treatment, and a mere 1.4% seeking treatment from mental health professionals. The reasons mentioned included low awareness of public and medical professionals, limited availability and limited accessibility of treatment (Tang et al., 2002; Xiang et al., 2009). Furthermore, most doctors in primary care and general hospitals spend little effort to screen ARDs and offer treatment, even though studies conducted in China have shown early intervention to be effective in both clinical (Li et al., 2006) and community samples (Liu et al., 2008; Li et al., 2010).
Additionally, alcohol-related problems have been largely neglected as a public health problem, although there have been public campaigns against cigarette smoking and illegal drug use.
In the past 10–20 years, health care and insurance in China have undergone dramatic changes, from a state-run system to a market-oriented one (Wagstaff et al., 2009), and from limited health care to a comprehensive universal health one by 2020 (Yip et al., 2012). Although a detailed description of historical changes and the details of currently evolving health care system are beyond the scope of this paper, here we list briefly a few highlights: (a) compared with medical/surgical disorders, psychiatric disorders are neglected by the health care system. Among psychiatric disorders, substance-related disorders are probably the most neglected ones, since negative attitudes toward individuals with substance use-related disorders are prevalent. (b) The socio-economic development in rural and urban areas is uneven and therefore there is a rural–urban disparity in health care coverage and services—most of mental health (including substance abuse) services are located in cities, especially in large and mid-sized cities. Psychiatric hospitals remain the major service providers to the mentally ill in China. (c) Though not covered by most health insurance plans, clinicians usually find a way around it by modifying the primary diagnosis of a substance use disorder to a substance-induced disorder (W. Hao., Personal communication). (d) Regarding medications, many of the medications mentioned in this article are available and on the list of National Essential Drugs. However, none of them have been officially approved for use for alcohol dependence.
Based on the above, we would like to suggest some measures to improve the treatment for ARDs in China:
First, a public awareness campaign is needed. It should be emphasized that ARDs are preventable and treatable disorders. Given that even medical professionals lack of awareness of alcohol-related problems, more educational efforts are clearly needed. This should start in medical school and residency training and include continued medical education for physicians in general hospitals as well as psychiatrists.
Second, specific interventional/treatment programs for ARDs should be created, with funds set aside by governments. Treating ARDs may lead to a decrease in total health care utilization, thus producing significant economic benefits. Although only a few studies have examined specifically the cost–benefit of psychosocial and pharmacological interventions for ARDs, especially for alcohol dependence, most of the available treatment options produce marked economic benefits, as recently reviewed by Popova et al. (2011). Experience from Australia (Cobiac et al., 2009), the USA (Zarkin et al., 2010) and other countries (Tariq et al., 2009; Moraes et al., 2010) show that alcohol treatments can lead to long-term social benefits, including reduced costs associated with health care, arrests, and motor vehicle accidents. One approach, Screening, Brief Intervention and Referral to Treatment (SBIRT), should be considered for China’s primary care service, evidence in other countries showing short-term improvements in individuals’ health (Substance Abuse and Mental Health Service Administration, 2011).
Third, it is necessary to conduct studies on the methods used in China using more rigorous study designs. As mentioned, many reports have limited value due to issues of randomization, lack of appropriate controls and/or a small sample size. In addition, since there is no officially approved medication (other than benzodiazepines for acute withdrawal), we propose that the State Drug Administration organize and fund some large-scale clinical trials to assess medications that are already widely used in the West (such as naltrexone, topiramate and acamprosate) as well as other novel medications under investigation. Some TCM approaches need to be carefully investigated before being considered for clinical use.
We recognize that alcohol treatment will only address a small proportion of alcohol-related harm. A more important step is to develop a comprehensive national alcohol policy, based on the experience of other countries and recommendations by World Health Organization (WHO, 2010). This can be achieved through measures aimed at controlling overall alcohol consumption (a population-based approach), and specific measures targeted toward risk behaviors (a high-risk approach). Advertisement restriction, alcohol taxation, setting a legal age for drinking and drinking driving counter-measures could all have a significant impact on alcohol-related problems (Anderson et al., 2009; Casswell and Thamarangsi, 2009).
CONCLUSIONS
Though treatments for ARDs in China are rapidly developing, there is room for improvement. Several unique treatment methods currently used in China deserve to be more rigorously studied. Above all, a more comprehensive alcohol policy needs to be developed, for example, setting up specific interventional/treatment programs such as SBIRT in primary care and general hospitals and developing a comprehensive national alcohol policy, based on the experience of other countries and recommendations by World Health Organization.
Acknowledgement —
The authors wish to thank Dannie Perdomo for her comments on a previous version of the manuscript. We also appreciate the expert comments from Dr Karen Drexler (Department of Psychiatry and Behavioral Sciences, Emory University and Atlanta VA Medical Center) on the manuscript.
Funding —
This work was supported by State Key Program of National Natural Science of China (grant no. 81130020) and National Key Basic Research and Development Program (grant no. 2009CB522007) to W.H.
REFERENCES
- Addolorato G, Ancona C, Capristo E et al. (2003) Metadoxine in the treatment of acute and chronic alcoholism: a review. Int J Immunopathol Pharmacol 16:207–14. [DOI] [PubMed] [Google Scholar]
- Anderson P, Chisholm D, Fuhr DC. (2009) Effectiveness and cost-effectiveness of policies and programmes to reduce the harm caused by alcohol. Lancet 373:2234–46. [DOI] [PubMed] [Google Scholar]
- Anton RF. (2008) Naltrexone for the management of alcohol dependence. N Engl J Med 359:715–21. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bai J, Zeng Q, Chai Z. (1998) Clinical and experimental study on treatment of acute alcohol intoxication with xiangnaojing injection. Zhongguo Zhong Xi Yi Jie He Za Zhi 18:607–9. [PubMed] [Google Scholar]
- Buchsbaum DG, Buchanan RG, Poses RM et al. (1992) Physician detection of drinking problems in patients attending a general medicine practice. J Gen Int Med 7:517–21. [DOI] [PubMed] [Google Scholar]
- Caballeria J, Pares A, Bru C et al. (1998) Metadoxine accelerates fatty liver recovery in alcoholic patients: results of a randomized double-blind, placebo-control trial. Spanish Group for the Study of Alcoholic Fatty Liver. J Hepatol 28:54–60. [DOI] [PubMed] [Google Scholar]
- Carai MA, Agabio R, Bombardelli E et al. (2000) Potential use of medicinal plants in the treatment of alcoholism. Fitoterapia 71 (Suppl 1):S38–42. [DOI] [PubMed] [Google Scholar]
- Casswell S, Thamarangsi T. (2009) Reducing harm from alcohol: call to action. Lancet 373:2247–57. [DOI] [PubMed] [Google Scholar]
- Chen J, Han JY. (2008) A retrospective analysis of acute intoxication cases in a general hospital. J Clin Emerg Call 8:324–6. [Google Scholar]
- Chen BA, Chen JY, Ling DM et al. (2008) Epidemiological analysis of 2658 intoxicated/poisoned patients. Chin J Crit Care Med 28:409–11. [Google Scholar]
- Chi Y, Guo S, Jiang ZN. (2004) Clinical features and outcome of 851 inpatients with alcoholism. Chin J Drug Depend 13:41–5. [Google Scholar]
- Cobiac L, Vos T, Doran C et al. (2009) Cost-effectiveness of interventions to prevent alcohol-related disease and injury in Australia. Addiction 104:1646–55. [DOI] [PubMed] [Google Scholar]
- Cui CL, Wu LZ, Luo F. (2008) Acupuncture for the treatment of drug addiction. Neurochem Res 33:2013–22. [DOI] [PubMed] [Google Scholar]
- Edwards S, Kenna GA, Swift RM et al. (2011) Current and promising pharmacotherapies, and novel research target areas in the treatment of alcohol dependence: a review. Curr Pharm Des 17:1323–32. [DOI] [PubMed] [Google Scholar]
- Garbutt JC. (2009) The state of pharmacotherapy for the treatment of alcohol dependence. J Subst Abuse Treat 36:S15–23. ; quiz S24–15. [PubMed] [Google Scholar]
- Ge XH. (2009) Comparison of naloxone, puerarin plus vitamine C in treatment of alcohol intoxication. Shandong Med J 42:567–9. [Google Scholar]
- Ge L, Zhang L, Wang BJ. (2010) Xingnaojing injection for acute alcohol intoxication: a clinical observation. J Emerg Tradit Chin Med 19:957–58. [Google Scholar]
- Guerrini I, Gentili C, Nelli G et al. (2006) A follow up study on the efficacy of metadoxine in the treatment of alcohol dependence. Subst Abuse Treat Prev Policy 1:35. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Han AL, Yang JP. (2000) Use of naloxone hydrochloride in medical emergencies. Chin J Hospital Pharmacy 20:154–5. [Google Scholar]
- Hao W, Chen H, Su Z. (2005) China: alcohol today. Addiction 100:737–41. [DOI] [PubMed] [Google Scholar]
- Hu XH, Liu XJ, Xu HM. (2006) Risk factors for delirium tremens in patients with alcoholism. Chin J Nerv Ment Dis 32:324–6. [Google Scholar]
- Huang CB. (2011) Meclofenoxate for alcohol intoxication: a clinical report. Med Innov China 8:55–7. [Google Scholar]
- Huang X, Huang XB, Peng HJ et al. (2002) A placebo-controlled trial of naltrexone for alcohol dependence in outpatients. Chin Ment Health J 16:302–5. [Google Scholar]
- Jin M, Li J, Yang YC. (2006) Evaluation of the clinical effect of electro-acupuncture aversion therapy of alcohol-dependence. Chin J Clin Rehab 5:24–8. [Google Scholar]
- Johnson BA, Ait-Daoud N, Bowden CL et al. (2003) Oral topiramate for treatment of alcohol dependence: a randomised controlled trial. Lancet 361:1677–85. [DOI] [PubMed] [Google Scholar]
- Johnson BA, Rosenthal N, Capece JA et al. (2007) Topiramate for treating alcohol dependence: a randomized controlled trial. J Am Med Assoc 298:1641–51. [DOI] [PubMed] [Google Scholar]
- Keung WM, Vallee BL. (1993) Daidzin and daidzein suppress free-choice ethanol intake by Syrian golden hamsters. Proc Natl Acad Sci USA 90:10008–12. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Keung WM, Vallee BL. (1998) Kudzu root: an ancient Chinese source of modern antidipsotropic agents. Phytochemistry 47:499–506. [DOI] [PubMed] [Google Scholar]
- Krystal JH, Cramer JA, Krol WF et al. (2001) Naltrexone in the treatment of alcohol dependence. N Engl J Med 345:1734–9. [DOI] [PubMed] [Google Scholar]
- Lee S, Guo WJ, Tsang A et al. (2009) Associations of cohort and socio-demographic correlates with transitions from alcohol use to disorders and remission in metropolitan China. Addiction 104:1313–23. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lee JD, Grossman E, DiRocco D et al. (2010) Extended-release naltrexone for treatment of alcohol dependence in primary care. J Subst Abuse Treat 39:14–21. [DOI] [PubMed] [Google Scholar]
- Leggio L, Kenna GA, Ferrulli A et al. (2011) Preliminary findings on the use of metadoxine for the treatment of alcohol dependence and alcoholic liver disease. Hum Psychopharmacol 26:554–9. [DOI] [PubMed] [Google Scholar]
- Li Z, Arthur D, Wu XJ et al. (2006) The effect of a brief intervention for problem drinkers in a Beijing general hospital: a randomized controlled trial. Chin J Nurs 41:585–8. [Google Scholar]
- Li YZ, Liu Z, Li HJ et al. (2010) Study of Early Intervention in Hazardous and Harmful Drinkers. Chin J Health Psychol 18:397–400. [Google Scholar]
- Liang XF, Zhao GX. (2007) A comparative study of modified diazepam loading therapy in the treatment of delirium tremens. J Clin Psychiatry (China) 17:385–6. [Google Scholar]
- Liu ZH. (2002) Use of puerarin injection for alcohol intoxication in 90 cases. Clin Focus 17:150–1. [Google Scholar]
- Liu Y. (2005) Naloxone for severe alcohol intoxication: an analysis of 148 cases. J Modern Med Health 22:1181–2. [Google Scholar]
- Liu YQ, Gao YL. (2005) Updates on clinical use of naloxone. Chin J New Drugs 14:403–7. [Google Scholar]
- Liu XF, Wang XG, Zhao XY. (2007) A clinical analysis of 88 patients with delirium tremens. Chin J Civil Med 19:774–5. [Google Scholar]
- Liu QW, Luo Y, Yan CR et al. (2008) Early intervention of problem drinking in community. Chin J People’s Health 24:2003–4. [Google Scholar]
- Liu QH, Zhang JW, Huang X et al. (2009) Stereotactic Nucleus Accumbens Lesion-based Treatment of Mental Illness. Chin Mod Doctors 5:56–8. [Google Scholar]
- Liu JC, Zhang N, Zhao CH. (2010) Xingnaojing combined with naloxone in alcohol intoxication: analysis of 67 cases. Chin Community Doctors 10:45–6. [Google Scholar]
- Liu Q, Lawrence AJ, Liang JH. (2011) Traditional Chinese medicine for treatment of alcoholism: from ancient to modern. Am J Chin Med 39:1–3. [DOI] [PubMed] [Google Scholar]
- Lin SH, Liu Q. (2010) Naloxone combined with Xingnaojing for treatment of acute alcohol intoxication. J Chongqing Med Univ 35:1077–81. [Google Scholar]
- Lukas SE, Penetar D, Berko J et al. (2005) An extract of the Chinese herbal root kudzu reduces alcohol drinking by heavy drinkers in a naturalistic setting. Alcohol Clin Exp Res 29:756–62. [DOI] [PubMed] [Google Scholar]
- Ma JH, Li YZ, Liu Z et al. (2011) Topiramate for alcohol depdendence: a double-blind, placebo-controlled study. Chin J Health Psychol 19:156–8. [Google Scholar]
- Mao YM, Zeng MD, Li YM et al. (2009) Capsule metadoxine in the treatment of alcoholic liver disease: a randomized, double-blind, placebo-controlled, multicenter study. Zhonghua Gan Zang Bing Za Zhi 17:213–6. [PubMed] [Google Scholar]
- Mayo-Smith MF, Beecher LH, Fischer TL et al. (2004) Management of alcohol withdrawal delirium. An evidence-based practice guideline. Arch Intern Med 164:1405–12. [DOI] [PubMed] [Google Scholar]
- Meng G, Liu TQ, He DR et al. (2008) Alcoholism and drinking culture. Med Philos 29:45–7. [Google Scholar]
- Moraes E, Campos GM, Figlie NB et al. (2010) Cost-effectiveness of home visits in the outpatient treatment of patients with alcohol dependence. Eur Addict Res 16:69–77. [DOI] [PubMed] [Google Scholar]
- Olmsted CL, Kockler DR. (2008) Topiramate for alcohol dependence. Ann Pharmacother 42:1475–80. [DOI] [PubMed] [Google Scholar]
- Overstreet DH, Keung WM, Rezvani AH et al. (2003) Herbal remedies for alcoholism: promises and possible pitfalls. Alcohol Clin Exp Res 27:177–85. [DOI] [PubMed] [Google Scholar]
- Penetar DM, Maclean RR, McNeil JF et al. (2011) Kudzu extract treatment does not increase the intoxicating effects of acute alcohol in human volunteers. Alcohol Clin Exp Res 35:726–34. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pettinati HM, O’Brien CP, Rabinowitz AR et al. (2006) The status of naltrexone in the treatment of alcohol dependence: specific effects on heavy drinking. J Clin Psychopharmacol 26:610–25. [DOI] [PubMed] [Google Scholar]
- Phillips MR, Zhang J, Shi Q et al. (2009) Prevalence, treatment, and associated disability of mental disorders in four provinces in China during 2001–05: an epidemiological survey. Lancet 373:2041–53. [DOI] [PubMed] [Google Scholar]
- Popova S, Mohapatra S, Patra J et al. (2011) A literature review of cost-benefit analyses for the treatment of alcohol dependence. Int J Environ Res Public Health 8:3351–64. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Qin HJ. (2011) Effects of nalaxone in alcohol poisoning in ER. Zhejiang J Clin Med 13:1109–11. [Google Scholar]
- Rezvani AH, Overstreet DH, Perfumi M et al. (2003) Plant derivatives in the treatment of alcohol dependency. Pharmacol Biochem Behav 75:593–606. [DOI] [PubMed] [Google Scholar]
- Shan HW, Lin ZF, Zhao L et al. (2007) An epidemiological analysis of cases with acute intoxication in a gerneral hospital. Med J Chin PLA 46:734–6. [Google Scholar]
- Shebek J, Rindone JP. (2000) A pilot study exploring the effect of kudzu root on the drinking habits of patients with chronic alcoholism. J Altern Complement Med 6:45–8. [DOI] [PubMed] [Google Scholar]
- Shen YC, The collaborative group on Alcoholism. (1992) Epidemiological survery on alcohol dependence in populations of four occupations in nine cities of China: I: Methodology and prevalence. Chin Ment Health J 6:112–5. [Google Scholar]
- Shpilenya LS, Muzychenko AP, Gasbarrini G et al. (2002) Metadoxine in acute alcohol intoxication: a double-blind, randomized, placebo-controlled study. Alcohol Clin Exp Res 26:340–6. [PubMed] [Google Scholar]
- Song YX. (2009) Comparison of apomorphine and furazolidone in treatment of alcoholism. J Qiqhar Med Coll 36:322–4. [Google Scholar]
- Stern TA, Gross AF, Stern TW et al. (2010) Current approaches to the recognition and treatment of alcohol withdrawal and delirium tremens: ‘old wine in new bottles’ or ‘new wine in old bottles’. Prim Care Companion J Clin Psychiatry 12. PCC.10r00991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Su ZJ. (2011) Effects of different doses of naloxone on alcohol intoxication. China Mod Med 18:61–2. [Google Scholar]
- Substance Abuse and Mental Health Service Administration (2011) White paper on screening, brief intervention and referral to treatment (SBIRT) in behavioral healthcare. In: (eds). Rockville, MD: Substance Abuse and Mental Health Service Administration, DHHS. [Google Scholar]
- Sun XH, Li XY, Phillips MR. (2009) A cross-sectional survey of the awareness of common mental disorders among urban and rural residents in Northern China. Chin Ment Health J 23:729–33. [Google Scholar]
- Tang YL. (1997a) Alcohol abuse and alcoholism. In Jiang ZN (ed). Clinical Aspects and Treatment of Drug Addiction. Beijing, China: People’s Health Publishing House, 162–241. [Google Scholar]
- Tang YL. (1997b) Alcohol intoxication and withdrawal syndrome: clinical meanifestations and management. Chin J Pract Med 17:689–91. [Google Scholar]
- Tang YL. (1998a) Neurobiological mechanism of alcoholism and treatment progress. Chin J Drug Depend 7:198–201. [Google Scholar]
- Tang YL. (1998b) Pharmacotherapy for alcoholism: current status and progresses. Chin J New Drugs 7:280–4. [Google Scholar]
- Tang YL. (2000) Medicalization of deviance—disease concepts of alcoholism and drug addiction. Chin J Drug Depend 9:303–5. [Google Scholar]
- Tang YL. (2002) Alcohol and alcohol dependence. In Jiang ZN (ed). Contemporary Psychiatry, 2nd edn. Beijing, China: Science Press, 245–65. [Google Scholar]
- Tang YL, Li Q, Zhu Y. (2002) Alcoholism and Treatments, 1st edn. Beijing: Science Press. [Google Scholar]
- Tang YF, Pan XM, Zhan YX. (2010) Xingnaojing combined with naloxone in alcohol intoxication. Chin Mod Doctors 48:134–5. [Google Scholar]
- Tariq L, van den Berg M, Hoogenveen RT et al. (2009) Cost-effectiveness of an opportunistic screening programme and brief intervention for excessive alcohol use in primary care. PLoS ONE 4:e5696. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ulett GA, Han S, Han JS. (1998) Electroacupuncture: mechanisms and clinical application. Biol Psychiatry 44:129–38. [DOI] [PubMed] [Google Scholar]
- Volpicelli JR, Alterman AI, Hayashida M et al. (1992) Naltrexone in the treatment of alcohol dependence. Arch Gen Psychiatry 49:876–80. [DOI] [PubMed] [Google Scholar]
- Vonghia L, Leggio L, Ferrulli A et al. (2008) Acute alcohol intoxication. Eur J Intern Med 19:561–7. [DOI] [PubMed] [Google Scholar]
- Wagstaff A, Yip W, Lindelow M et al. (2009) China’s health system and its reform: a review of recent studies. Health Econ 18 (Suppl 2):S7–23. [DOI] [PubMed] [Google Scholar]
- Wang JN, Chang JF. (2010) Xingnaojing combined with naloxone in alcohol intoxication: analysis of 67 cases. Chin Pract Med 5:151–2. [Google Scholar]
- Wang T, Chen L, Wen L. (2001) Effects of naloxone on neuronal damage in ischemia-reperfusion in the brain. Chin J Crit Care Med 21:196–8. [Google Scholar]
- Wang Y, Zhou JY, Zhou SW. (2007) Role of kudzu extract-containing preparation in alcohol intoxication. Chin Pharm 18:1424–6. [Google Scholar]
- Wang YH, Yu JL, Huang JS et al. (2008) Effects of low frequency electroacupuncture at Zusanli on ethanol taking behavior in ethanol dependent rats. Chin Ment Health J 22:157–63. [Google Scholar]
- Wei YX, Song J, Li XH et al. (2007) Effects and mechanism of Xingnaojing combined with naloxone in alcohol intoxication. J Med Theory Pract 20:871–2. [Google Scholar]
- WHO. (2010) Global Strategy to Reduce the Harmful Use of Alcohol, Vol. 1. Geneva, Switzerland: World Health Organization, 44. [Google Scholar]
- Wu J, Qiu ZH, He M. (2002) Effects of hemodialysis for alcoholism in 30 cases. Ningxia Med J 24:760–1. [Google Scholar]
- Xiang YT, Ma X, Lu JY et al. (2009) Alcohol-related disorders in Beijing, China: prevalence, socio-demographic correlates, and unmet need for treatment. Alcohol Clin Exp Res 33:1111–8. [DOI] [PubMed] [Google Scholar]
- Xiao LQ, Laiang T, Li AM et al. (2001) Valproate and diazepam in alcohol withdrawal: a clinical comparative study. Shandong Arch Psychiatry 14:235–6. [Google Scholar]
- Xie CG, Chen GL, Pan YF et al. (2004) The efficacy of acupoint stimulation for alcoholism: a perspective, controlled study. Chin J Behav Med Sci 13:307–8. [Google Scholar]
- Xu BJ, Zheng YN, Sung CK. (2005) Natural medicines for alcoholism treatment: a review. Drug Alcohol Rev 24:525–36. [DOI] [PubMed] [Google Scholar]
- Xue B, Zeng Q, Cai XJ. (1998) Xingnaojing, a Chinese herbal injection add on in treatment of alcohol intoxication. J Med Theory Pract 11:159–60. [Google Scholar]
- Xue WA. (2009) A comparative study Kudzu extract and naloxone combined with Xingnaojing in 216 cases of severe alcohol intoxication. Hebei Med J 31:525–36. [Google Scholar]
- Yang JS, Xuan GZ, Jin HG. (2002) Treatmet of delirium tremens: Outcome and related factors. Chin J Drug Abuse Prevent Treat 8:24–7. [Google Scholar]
- Yang MX, Yu WT, Xu HZ et al. (2006) Effect of mucal protection in mice with acute alcohol intoxication. Chin J TCM Pharmacy 21:341–3. [Google Scholar]
- Yang YH, Ding R, Liu F et al. (2009) Xingnaojing in the Treatment of Acute Alcohol Intoxication: A Systematic Review. Chin J EvidBased Med 9:957–63. [Google Scholar]
- Yip WC, Hsiao WC, Chen W et al. (2012) Early appraisal of China’s huge and complex health-care reforms. Lancet 379:833–42. [DOI] [PubMed] [Google Scholar]
- Yuan W, Wu XW, Lu HY et al. (2009) Naltrexone for alcohol dependence: a double-blind, placebo-controlled study. Chin J Drug Depend 18:325–9. [Google Scholar]
- Zarkin GA, Bray JW, Aldridge A et al. (2010) The effect of alcohol treatment on social costs of alcohol dependence: results from the COMBINE study. Med Care 48:396–401. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zhang ZT. (2011) Naloxonew for severe alcohol intoxication: an analysis of 120 cases. Med Innov China 8:166–8. [Google Scholar]
- Zhang DR, Sun XF. (1992) A case report of disulfiram in alcohol dependence. Chin Ment Health J 16:87. [Google Scholar]
- Zhang CX, Sun YZ. (2010) Clinical observation of electroacupuncture for peripheral neuropathy in chronic alcoholics. J Clin Acupunct Moxibustion 26:376–7. [Google Scholar]
- Zhang YH, Zhang RG, Chen YC et al. (2010) Effect of electroacupunture on mood disorders in patients with alcoholism. Med J Chin People Health 5:75–8. [Google Scholar]
- Zhao CY, Zhuang BX. (1990) Furazolidone used as aversive therapy for alcohol dependence. Chin Ment Health J 14:45–8. [Google Scholar]
- Zhen XZ, Zhou YP, Yang YZ et al. (1997) Sodium valproate and alprazolam for alcohol withdrawal syndrome: a double-blind study. Sichuan Ment Health 10:41–2. [Google Scholar]
- Zhong Y, Tang HY. (1996) Comparison of apomorphine and furazolidone in treatment of alcoholism. Chin Ment Health J 10:145–7. [Google Scholar]
- Zhou HL, Zhou CL, Zhou RL et al. (2001) The long term follow-up result of aversion therapy combined with brain metabolism promoting drugs for alcohol-dependence. Chin J Behav Med Sci 10:120–2. [Google Scholar]
- Zhou L, Conner KR, Caine ED et al. (2011) Epidemiology of alcohol use in rural men in two provinces of china. J Stud Alcohol Drugs 72:333–40. [DOI] [PMC free article] [PubMed] [Google Scholar]
