Chinese medicine for major depressive disorder: clinical evidence, patients’ experience and expectations, and doctors’ perceptions

Background Major depressive disorder (MDD), also known as unipolar depression or simply referred to as depression, is characterised by a mood disorder that causes a persistent feeling of sadness and worthlessness and loss of interest in activities. Second-generation antidepressants such as selective serotonin reuptake inhibitors (SSRIs) are perceived as first-line pharmacological treatment. Non-pharmacological therapies such as psychotherapy are also commonly used. There are differing results of using these treatments and some with reported adverse events. The practice of Chinese medicine (CM) including Chinese herbal medicine (CHM) and acupuncture for depression is common. Such practice should be developed in parallel with the adoption of evidence-based medicine (EBM) considering the best available evidence, patients¿ values and clinical expertise. These elements have been systematically investigated in this project, to identify the gaps between evidence and practice, and to improve knowledge translation during clinical decision-making. Objectives The objectives of this study were to: 1. evaluate the evidence of CM for depression in the historical CM literature; 2. evaluate the current clinical trial evidence of CM for depression; 3. understand patients' experience and expectations of using CM for depression; and 4. understand doctors' perceptions of using CM for depression. Chinese herbal medicine and acupuncture in historical Chinese medicine literature The Encyclopedia of Chinese Medicine, a collection of over 1,000 historical CM books, was researched. The findings indicated that the most frequently used formulae and herb ingredients identified in the classical literature are still commonly used today and recommended in the contemporary CM clinical guidelines for depression, including the formulae Gan mai da zao tang and Gui pi tang and the herbs, fu ling, ren shen, bai zhu and dang gui. Acupuncture is commonly used in contemporary clinical practice for depression but was found to be only mentioned in a few classical citations. Acupuncture points used in this setting included PC7 Da ling-PC5 Jian shi, PC6 Nei guan, KI3 Zhao hai, and BL15 Xin shu. Chinese herbal medicine and acupuncture in clinical trials Modern clinical evidence was evaluated and synthesised through systematic reviews and meta-analyses of RCTs following the Cochrane Systematic Reviews of Interventions methods. The reviews were registered in PROSPERO. Quality of the evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Chinese herbal medicine Forty-six studies were identified that compared CHM to SSRIs and 32 studies that compared CHM plus SSRIs to SSRIs alone. CHM alone or given as integrative medicine with SSRIs reduced depression severity. The number of adverse events in the CHM groups was less than the SSRIs groups. However, the certainty of evidence is low, limited by bias in the included studies and heterogeneity. Acupuncture Forty-five RCTs including 30 studies were identified that compared acupuncture to SSRIs and 15 studies that compared acupuncture plus SSRIs to SSRIs alone. Meta-analysis results indicated that acupuncture treatment alone or in combination with SSRIs produced statistically significant reductions in depression severity with considerable heterogeneity. Fewer adverse events were observed among people treated with acupuncture compared to the SSRI groups. The certainty of evidence is very low to low. Results should be interpreted with caution due to the trials' risk of bias and heterogeneity. Acupuncture plus Chinese herbal medicine Six RCTs were identified that compared the effect of acupuncture plus CHM to SSRIs. Acupuncture plus CHM indicated positive effects on improving HRSD scores and appeared to be well-tolerated for patients with depression. However, there is insufficient evidence due to the small number of studies and sample sizes in these studies. Patients' experience and expectations of using Chinese medicine An anonymous, self-administered survey was conducted among 139 participants with depression to investigate their experience and expectations of using CM for depression. Thirty-four participants (50.0% of 68 responses) preferred to use integrative treatments. The majority of participants who used CM (31, 83.8% of 37 responses) rarely experienced adverse events and continued using CM (36, 97.3% of 37 responses). Patients expressed a desire/preference for their doctor to communicate with them regarding treatment types and options. About half of participants (80, 57.6% of 139 responses) were given adequate information about CM for depression. Participants also expressed an interest in knowing information on research evidence for CM, CM classical literature and case studies, but most of all were concerned to know the doctors' experience of using CM for depression. Doctors' perceptions of using Chinese medicine Based on thematic analysis driven by grounded theory, two rounds of semi-structured interviews involving 26 and 24 doctors were conducted. Doctors indicated that they treated patients with depression based on clinical training and experience, new knowledge and patient preferences. Participants acknowledged the potential benefits and safety of CM for mild to moderate depression but not severe depression. Gaps were identified in the evidence and limitations in applying research into practice. Participants attempted to integrate clinical expertise, evidence and patient preferences during clinical decision-making, but this was yet to be fully optimised or standardised in the practice. Conclusion Chinese medicine including CHM and acupuncture has been consistently used from pre-modern times to contemporary clinical practice. The systematic reviews conducted herein provided evidence showing benefits of CM for reducing depressive symptoms and severity, and that CM use was safe for people with depression. These results provide the scientific basis and guidance for using CHM and acupuncture for depression in clinical practice. However, due to risk of bias and methodological shortfalls, caution should be taken when interpreting and translating these findings into clinical practice or when forming clinical decisions. The survey of patients with depression revealed that they perceived CM to be beneficial and they chose to continue using CM mainly because of fewer side effects associated with its use. Overall, patients with depression preferred to use integrative medicine for their condition. They expected to communicate with doctors about the use of CM as well as knowing about doctors¿ experience. Understanding patients' experience and expectations can help doctors have better collaboration with patients when formulating treatment plans. Findings from the interviews understood doctors' perception of using CM for depression. Doctors acknowledged the potential benefits and safety of CM for depression based on evidence from classical and modern literature and summary information from patients' value. They acknowledged the benefit of integrative medicine for depression, which was also preferred by some patients. Doctors intended to update their practice and translate knowledge based on EBM. They perceived CM may be beneficial for patients with mild to moderate depression. This is helpful for implementing EBM into CM clinical practice for depression and contributes to future research.