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Articles

Major Depressive Disorder Treatment Guidelines in China

Major Depressive Disorder Treatment Guidelines in China

Depression is a common illness in the Chinese population, but very few people with depression seek treatment or are properly diagnosed and treated when they do visit a medical professional. One potential result of this situation is that suicidality is higher than it might be if more people with depression received appropriate treatment. When patients do receive pharmacotherapy for depression, benzodiazepines and tricyclic antidepressants are overprescribed. The Chinese psychiatric establishment has published a sufficient guideline outlining treatment strategies for depressive disorders, but education for psychiatrists and general practitioners is needed.

(J Clin Psychiatry 2010;71[suppl E1]:e06)

From Shanghai Jiaotong University and Shanghai Mental Health Center, Shanghai, China.

This article is derived from the roundtable discussion “International Consensus Group on Depression,” which was held on September 1, 2009, in Tokyo, Japan, and supported by an educational grant from GlaxoSmithKline.

Dr Zhang has no personal affiliations or financial relationships with any commercial interest to disclose relative to this article.

Corresponding author: Mingyuan Zhang, MD, Shanghai Mental Health Center, 600 Wan Ping Nan Lu, Shanghai 200030, China (myzhang2006@gmail.com).

China houses roughly one-fifth of the world’s population, but an accurate picture of the prevalence of mental disorders in China has been slow to emerge. Depressive disorders have been reported to occur at a lower rate in China than in the West, but evidence1 suggests that depression is often denied and somatized among the Chinese, probably because of social stigmas associated with mental disorders. In the past, having depression was viewed as degrading, out of sync with traditional medicine, or even politically antagonistic. Those with depression were often given other diagnoses such as neurasthenia. Treatment of nonpsychotic mental illness was rare, and psychiatric services were not available in general practice settings. Increased Western influence after the end of the Mao Zedong era and education about psychiatry have contributed to a decrease in the stigmatization of depression in China since the 1980s, and recent studies have provided information about the prevalence of psychiatric conditions and the status of mental health care in the country.

For Clinical Use

  • Educate Chinese patients and their families about depression so that they are more likely to seek treatment.
  • Follow proper diagnostic criteria and current guidelines to decrease the number of cases of unrecognized and untreated depression.
  • Choose first-line medications appropriate to the depressive subtype and patient characteristics.

Prevalence of Depressive Disorders in China

Epidemiologic studies of depression in China performed in the past few years have found much higher rates of major depressive disorder (MDD) than were previously reported in the 1980s and 1990s, which were < 1% for both lifetime and current prevalence.1 Surveys2-6 of adult populations in some of China’s largest cities, using the Composite International Diagnostic Interview,7 found 12-month prevalence rates of MDD ranging from 1% to 3% and lifetime prevalence rates ranging from 2% to 5% (Table 1). Surveys8 of adults in 5 Chinese provinces, using the General Health Questionnaire9 and the Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Patient Edition (SCID-I/P),10 reported 1-month prevalence rates of 2% to 3% for MDD. However, these rates of MDD are still much lower than those in the United States, which are about 7% for 12-month prevalence and 16% for lifetime prevalence.11 Some have suggested that US culture tends to elevate depressive symptomatology to disorder status too readily, while Chinese culture still may minimize or somatize depressive disorder diagnoses to an extent.1

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Not only is depression more common among the Chinese than previously thought, but more than one-third of those with mood disorders may have severe impairment. Phillips and colleagues12 showed that nearly 40% of depressed patients in China have moderate-to-severe functional impairment due to their illness, when evaluated with the Global Assessment of Functioning scale.13 Lee et al14 reported that, according to the Sheehan Disability Scale,15 patients with MDD in China rated their disability level higher than did patients with chronic physical disorders including diabetes, asthma, arthritis, ulcer, back/neck pain, heart disease, chronic pain, and high blood pressure. Among the categories of impairment in work, home management, social life, and close relationships, MDD created greater dysfunction than each chronic physical disorder did except for diabetes with social life.

Psychiatric Resources in China

China’s mental health care resources have developed quickly during the previous 3 decades, but more growth is needed. The number of psychiatrists in clinical practice was about 1 per 100,000 people in 2005.16 The number of psychiatric inpatient beds was about 11 per 100,000 people. However, these resources are concentrated within the larger cities, a fact that has left the vast rural population with few avenues when seeking treatment for mental conditions. Most of the psychiatric services in China mainly serve patients suffering from psychotic disorders, although some general hospitals have begun offering mental health services for patients with common nonpsychotic mood disorders such as MDD. In 2005, 325 of the 436 general hospitals in Beijing (75%) answered a survey about mental health care, and 53% of these hospitals reported that they provided 1 or more types of mental health services.17

China’s Treatment Guidelines for Depression

The Chinese Guideline for Prevention and Treatment of Mental Disorders: Depressive Disorder18 was edited by the Chinese Society of Psychiatry and the National Center for Mental Health, China-CDC, and was completed in 2002 and formally published in 2007. The aims of treatment, as guided by the publication, are to achieve clinical remission and reduce suicide, to improve quality of life and reduce disability, and to prevent relapse.

Diagnostic Criteria

Diagnosis of depressive disorders is made using the Chinese Classification of Mental Disorders, Third Edition (CCMD-3),19 which was published in 2002. Wang et al20 diagnosed inpatients and outpatients with depression from 50 general hospitals in Beijing using both the CCMD-3 and the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV),21 and found a high concordance between the 2 sets of criteria.

Using the CCMD-3, diagnosis of a depressive episode requires that patients must experience for at least 2 weeks a depressed mood plus fulfill at least 4 of 9 additional criteria including, but not limited to, lack of energy or fatigue, sleep disturbances, and suicidality. The symptoms must impair social function or cause subjective distress and must not be caused by organic mental disorders or schizophrenia. Diagnostic criteria provide for specifying the type of depressive episode, such as psychotic depression, recurrent depression, dysthymia, or bipolar depression.

Treatment Algorithm

First-line treatment for MDD according to the Chinese guidelines19 is monotherapy with an appropriate antidepressant, such as a selective serotonin reuptake inhibitor (SSRI), serotonin-norepinephrine reuptake inhibitor (SNRI), or noradrenergic and specific serotonergic antidepressant (NaSSA), as shown in the guideline’s treatment algorithm (Figure 1). Treatment selection should take into account patients’ individual illness profiles, meaning that full psychiatric and medical histories and symptom severity must be considered. Assuming the chosen drug is effective and no significant complications arise, acute treatment should continue for 4 to 6 weeks. After remission from a first depressive episode, the continuation treatment phase typically lasts 4 to 6 months, with maintenance proceeding for an additional 4 to 6 months. If the depression is recurrent, maintenance therapy may continue for 2 or 3 years.

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If the patient cannot tolerate the first-line treatment or sufficient response is not achieved, dose optimization or switching to another first-line antidepressant are the suggested strategies.19 If the depression is still resistant to treatment, second-line strategies may be considered; these include switching to tricyclic antidepressants (TCAs) and augmenting antidepressant treatment with another antidepressant or a mood stabilizer. In the algorithm, TCAs are shown as a second-line treatment, but due to issues of cost and availability of novel antidepressants in China, TCAs are often employed as first-line agents. Electroconvulsive therapy (ECT) is reserved for cases still resistant after an adequate trial of an appropriate second-line treatment option. However, ECT may be prescribed as an immediate first-line treatment for patients with severe suicidality or stupor. Classical ECT and modified ECT are both available.

The Chinese guideline19 also makes recommendations specific to depressive subtypes (eg, agitated, psychotic, or atypical depression) and special populations such as the elderly, children, and patients with comorbid mental or physical disorders. Benzodiazepines may be used as adjunctive therapy in the short-term for cases of agitated depression, and antipsychotics are recommended as adjunctive medication for psychotic depression.

The Gap Between Standards of Care and Clinical Practice in China

Although in recent years the stigmatization of mental disorders has decreased, psychiatric resources have increased, and standards of care have improved, very few individuals suffering from mental disorders other than psychotic disorders receive treatment in China. Phillips and colleagues12 found that approximately 8% of people with mood disorders saw health care professionals for their illness, compared with around 72% of people with psychotic disorders. In fact, among those with mood disorders, moderate-to-severe impairment barely increased treatment-seeking compared with mild impairment (Figure 2).12 Patients with chronic physical conditions in metropolitan China were found to be 14 times more likely to receive treatment than patients with mental disorders, even though chronic physical disorders were associated with less impairment than mental disorders.14 This finding may reflect continued stigma and shortage of mental health resources.

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Even when patients see a physician, their depression may not be recognized. In the primary care setting, the rate of recognition of depressive disorders was found to be low. In 23 randomly selected general hospitals in Shenyang, China, Qin et al22 found that 11% of outpatients met diagnostic criteria for a depressive disorder, but only 4% of these patients were diagnosed and only 3% were treated with an antidepressant. More training of general practitioners to recognize and treat a variety of mental syndromes is needed. Antidepressant treatment in the mental health setting is superior to that in nonpsychiatric settings. A study23 of antidepressant treatment at 21 health facilities in China, Japan, Korea, Singapore, and Taiwan found that the prescription of newer antidepressants (ie, those that became available in 1990 or later) was significantly associated with treatment within a psychiatric hospital (P < .001). A survey of 1,383 patients with MDD from 46 psychiatric hospitals in 10 Chinese cities found that approximately 95% were receiving antidepressant pharmacotherapy, in accordance with the guidelines (T.M. Si, MD, unpublished data, 2009). The majority of patients (approximately 62%) were treated with SSRIs, while only about 17% were treated with TCAs. About 42% of patients were prescribed benzodiazepines, which may be too high. Psychiatrists in China routinely prescribe benzodiazepines in conjunction with antidepressants to avoid early activation syndrome and to prevent patients from discontinuing antidepressant treatment. This practice should be reevaluated to determine if, when, and for how long benzodiazepine therapy is appropriate for patients with depression.

Common Problems With the Treatment of Depression

China has a sufficient treatment guideline for depression in place, but Chinese physicians lack a systematic knowledge of depression and its treatment. Education about common psychiatric illnesses in medical school is suboptimal. Therefore, psychiatrists and general practitioners in China may look at the guideline and see that, in certain situations, switching antidepressants or augmenting with a second agent is recommended, but they are generally not well versed in the practical methods for instituting these steps. Education is needed concerning why, when, and how to switch or augment, and what drug to switch to or augment with. Physicians must become familiar with appropriate medications and dosages for subtypes of depression, depression with common comorbidities such as anxiety disorders and substance abuse, and depression in special populations. Education about the appropriate duration of antidepressant treatment also is needed.

Finally, improvements are needed in the way patients are managed after pharmacotherapy has been instituted. Many physicians in China are unaware of the importance of the therapeutic alliance in the treatment of depression. Training in the recognition, monitoring, and management of adverse events is required, and psychosocial interventions for patients and their families should be widely instituted.

Suggestions for Improvement

Publishing China’s guideline for the treatment of depression was the first step toward relieving the burden of depressive disorders. To close the gap between the standards of care and clinical practice, a systematic plan for education of physicians about the guidelines must be developed and implemented. The effectiveness of guideline implementation must also be assessed, and the guideline must be regularly updated. Additionally, a concise version of the guideline should be developed for general practitioners and other nonpsychiatric medical professionals to use. Training for general practitioners might differ from that given to psychiatric professionals.

The Chinese public would also benefit from general education about depression and other mental illnesses, which would help to reduce stigmatization of mental disorders in Chinese society. The media could be very helpful in increasing public awareness of the problem of depression. Some educational television programming promoting various interests already exists in China, and the same medium could be useful in disseminating information about mental health and the principles of the treatment guidelines.

Summary

Evidence shows that depressive disorders are common in the Chinese population and have been underreported in the past. Unfortunately, very few people with depression seek treatment, and opportunities to recognize and diagnose depression are often missed when patients do visit a medical professional. Psychiatric resources for patients with depression have increased but are mostly centralized in large cities, leaving a large portion of the population with few options for treatment. Of those patients receiving treatment for depression, many are prescribed appropriate antidepressants, but benzodiazepines may be overprescribed. Chinese psychiatrists have a sufficient guideline to instruct them in choosing treatment strategies for patients with depression, but education about the guideline is needed for physicians as well as the general public.

DISCUSSION

Professor Nutt: Do people in China visit healers other than those with formal medical training?

Dr Zhang: Very few people seek alternative treatments for depression such as herbal treatments or acupuncture. The reason is that, in most cases, particularly when the severity of depression is mild, no treatment is sought at all. Usually, only people with severe depression seek treatment in China, and those people generally visit a medical doctor.

Dr Higuchi: In your algorithm, TCAs are not explicitly recommended as a first-line treatment, but they are technically considered a first-line option. In Japan, TCAs are not considered a first-line option, primarily because of safety concerns. Why does China include TCAs as a first-line antidepressant in its guidelines?

Dr Zhang: This is mostly due to the cost of medications. The Chinese medical system is reforming and, for economic reasons, the government has a list of preferred drugs for which it will pay if a patient cannot afford medications. The list includes only 2 antidepressants, amitriptyline and doxepin.

Dr Terao: I hear that in China, young women have a particularly high risk of suicide, and I wonder if this is due to a high prevalence of depression in that population.

Dr Zhang: The suicide rate for young women, particularly in rural areas, is very high.24 Overall, the rate of suicide in women in China is 3 times greater than the rate in men, and the rate in rural areas is 3 times greater than that in urban areas. Rural women attempting suicide often impulsively ingest some sort of agricultural poison and are too far from any suitable treatment facility to receive the immediate attention needed to save them. However, these suicides may be less related to depression than suicides in other populations. A study25 comparing suicide rates and characteristics in men and women in both urban and rural areas found that young rural women had the lowest rate of mental illness (39%) among the groups. The majority (63%) of suicide victims did have mental illnesses, few (13%) of whom had received psychiatric treatment.

Professor Nutt: I have a question about dosing. Especially in the rural areas of China, people tend to have a small body size. Do you have smaller tablets with smaller amounts of the active ingredient than in Western countries?

Dr Zhang: I think that all the antidepressant doses are very similar to those in other countries. This problem may exacerbate the already present safety concerns associated with TCAs, which are used frequently in rural communities.

Drug Names: doxepin (Zonalon and others).

Disclosure of off-label usage: The author has determined that, to the best of his knowledge, no investigational information about pharmaceutical agents that is outside US Food and Drug Administration−approved labeling has been presented in this article.

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