<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.2 20190208//EN" "http://jats.nlm.nih.gov/publishing/1.2/JATS-journalpublishing1.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="other" dtd-version="1.2" xml:lang="en">
    <front>
        <journal-meta>
            <journal-id journal-id-type="pmc">F1000Research</journal-id>
            <journal-title-group>
                <journal-title>F1000Research</journal-title>
            </journal-title-group>
            <issn pub-type="epub">2046-1402</issn>
            <publisher>
                <publisher-name>F1000 Research Limited</publisher-name>
                <publisher-loc>London, UK</publisher-loc>
            </publisher>
        </journal-meta>
        <article-meta>
            <article-id pub-id-type="doi">10.12688/f1000research.163621.2</article-id>
            <article-categories>
                <subj-group subj-group-type="heading">
                    <subject>Opinion Article</subject>
                </subj-group>
                <subj-group>
                    <subject>Articles</subject>
                </subj-group>
            </article-categories>
            <title-group>
                <article-title>Chinese Medicine as First-Line Treatment for Subthreshold Mental Disorders in Primary Care: Opportunities and Challenges</article-title>
                <fn-group content-type="pub-status">
                    <fn>
                        <p>[version 2; peer review: 2 approved, 1 approved with reservations]</p>
                    </fn>
                </fn-group>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Tang</surname>
                        <given-names>Hiu To</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <uri content-type="orcid">https://orcid.org/0009-0004-8519-172X</uri>
                    <xref ref-type="aff" rid="a1">1</xref>
                    <xref ref-type="aff" rid="a2">2</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Luo</surname>
                        <given-names>Jingyuan</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a1">1</xref>
                    <xref ref-type="aff" rid="a2">2</xref>
                    <xref ref-type="aff" rid="a3">3</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Wong</surname>
                        <given-names>Hoi Ki</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a1">1</xref>
                    <xref ref-type="aff" rid="a2">2</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Yeung</surname>
                        <given-names>Albert</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a4">4</xref>
                </contrib>
                <contrib contrib-type="author" corresp="yes">
                    <name>
                        <surname>Yu</surname>
                        <given-names>Danny J.</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <uri content-type="orcid">https://orcid.org/0000-0002-1811-3682</uri>
                    <xref ref-type="corresp" rid="c1">a</xref>
                    <xref ref-type="aff" rid="a1">1</xref>
                    <xref ref-type="aff" rid="a2">2</xref>
                </contrib>
                <contrib contrib-type="author" corresp="yes">
                    <name>
                        <surname>Bian</surname>
                        <given-names>Zhaoxiang</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="corresp" rid="c2">b</xref>
                    <xref ref-type="aff" rid="a1">1</xref>
                    <xref ref-type="aff" rid="a2">2</xref>
                    <xref ref-type="aff" rid="a3">3</xref>
                    <xref ref-type="aff" rid="a5">5</xref>
                </contrib>
                <aff id="a1">
                    <label>1</label>Vincent V.C. Woo Chinese Medicine Clinical Research Institute, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China</aff>
                <aff id="a2">
                    <label>2</label>School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China</aff>
                <aff id="a3">
                    <label>3</label>Centre for Chinese Herbal Medicine Drug Development Limited, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China</aff>
                <aff id="a4">
                    <label>4</label>Depression Clinical and Research Program, Massachusetts General Hospital, Boston, USA</aff>
                <aff id="a5">
                    <label>5</label>The Chinese Medicine Hospital of Hong Kong, Hong Kong SAR, China</aff>
            </contrib-group>
            <author-notes>
                <corresp id="c1">
                    <label>a</label>
                    <email xlink:href="mailto:dannyu@hkbu.edu.hk">dannyu@hkbu.edu.hk</email>
                </corresp>
                <corresp id="c2">
                    <label>b</label>
                    <email xlink:href="mailto:bzxiang@hkbu.edu.hk">bzxiang@hkbu.edu.hk</email>
                </corresp>
                <fn fn-type="conflict">
                    <p>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>9</day>
                <month>10</month>
                <year>2025</year>
            </pub-date>
            <pub-date pub-type="collection">
                <year>2025</year>
            </pub-date>
            <volume>14</volume>
            <elocation-id>475</elocation-id>
            <history>
                <date date-type="accepted">
                    <day>7</day>
                    <month>10</month>
                    <year>2025</year>
                </date>
            </history>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2025 Tang HT et al.</copyright-statement>
                <copyright-year>2025</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <self-uri content-type="pdf" xlink:href="https://f1000research.com/articles/14-475/pdf"/>
            <abstract>
                <p>Subthreshold mental disorders (SMDs), characterized by clusters of psychiatric symptoms that do not meet the criteria for a formal diagnosis yet are sufficiently severe to impair daily functioning. SMDs exhibit a high prevalence and an elevated risk of progression to diagnosed disorders and impose a substantial socioeconomic burden. Despite their significant impact, SMDs often go overlooked and untreated due to a global shortage of mental health professionals and stigmatization associated with conventional psychological and psychiatric treatments. This perspective advocates the integration of Chinese medicine (CM) as a first-line treatment for SMDs, focusing specifically on primary care settings in regions with established CM infrastructure and high public acceptance. Emerging evidence has shown that CM treatments, including acupuncture, herbal medicine, and other modalities, can be effective in managing various mental disorders. Systematic reviews have shown that herbal medicine not only has fewer side effects compared to psychotropic medications but also reduces adverse effects when used as adjunctive therapy. The potential benefits of using CM include mitigating the shortage of mental health professionals by supplementing primary care, preventing the exacerbation of SMDs, and offering a less stigmatized, cost-effective option that could improve help-seeking behaviors. However, challenges such as lack of recognition, insufficient collaboration between CM and mental health specialists, and differing theoretical frameworks hinder its integration into primary care in the mental health care field. Addressing these challenges will require public education, robust research evidence, policy changes, and the development of collaborative frameworks. This study highlights the need for greater recognition and integration of CM as a viable first-line treatment for the management of SMDs within primary care settings.</p>
            </abstract>
            <kwd-group kwd-group-type="author">
                <kwd>Chinese medicine</kwd>
                <kwd>Subthreshold mental disorders</kwd>
                <kwd>Primary care</kwd>
            </kwd-group>
            <funding-group>
                <award-group id="fund-1">
                    <funding-source>Start-up Grant 2023/24 (SG), Hong Kong Baptist University, Hong Kong SAR, China</funding-source>
                </award-group>
                <award-group id="fund-2">
                    <funding-source>Vincent and Lily Woo Foundation</funding-source>
                </award-group>
                <award-group id="fund-3">
                    <funding-source>Health@InnoHK Initiative Fund</funding-source>
                    <award-id>ITCRC/IHK/4/7</award-id>
                </award-group>
                <funding-statement>This study is supported by Health@InnoHK Initiative Fund (ITC RC/IHK/4/7) of the Hong Kong SAR, China; Vincent and Lily Woo Foundation; and Start-up Grant 2023/24 (SG), Hong Kong Baptist University, Hong Kong SAR, China.</funding-statement>
                <funding-statement>
                    <italic>The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</italic>
                </funding-statement>
            </funding-group>
        </article-meta>
        <notes>
            <sec sec-type="version-changes">
                <label>Revised</label>
                <title>Amendments from Version 1</title>
                <p>In our revised manuscript, we have revised our argument for integrating Chinese Medicine (CM) by narrowing our scope from a broad global recommendation to a targeted proposal focused on East Asian regions, specifically mainland China and Hong Kong. This strategic shift grounds our proposal in areas with existing CM infrastructure, high public acceptance, and a robust professional workforce, making our case for integration more feasible and context-specific. To bolster this focused approach, we substantially developed the economic considerations, now including examples of existing public funding mechanisms and a direct cost-effectiveness comparison that highlights acupuncture's financial advantages over standard counseling. Furthermore, we clarified the practical details of implementation by comparing the superior scalability of acupuncture against the workforce limitations of psychotherapy and specifying the use of established, evidence-based herbal formulas to ensure safety and standardization. Through these revisions, which also include minor edits for readability and statistical clarity, we have transformed our article into a more pragmatic, well-supported, and compelling case for CM integration within specific, well-suited healthcare systems.</p>
            </sec>
        </notes>
    </front>
    <body>
        <p>

            <def-list>
                <title>Abbreviations</title>
                <def-item>
                    <term id="G1">APA</term>
                    <def>
                        <p>American Psychological Association</p>
                    </def>
                </def-item>
                <def-item>
                    <term id="G2">CBT</term>
                    <def>
                        <p>Cognitive Behavioral Therapy</p>
                    </def>
                </def-item>
                <def-item>
                    <term id="G3">CHM</term>
                    <def>
                        <p>Chinese herbal medicine</p>
                    </def>
                </def-item>
                <def-item>
                    <term id="G4">CI</term>
                    <def>
                        <p>Confidence interval</p>
                    </def>
                </def-item>
                <def-item>
                    <term id="G5">CM</term>
                    <def>
                        <p>Chinese Medicine</p>
                    </def>
                </def-item>
                <def-item>
                    <term id="G6">DSM</term>
                    <def>
                        <p>Diagnostic and Statistical Manual of Mental Disorders</p>
                    </def>
                </def-item>
                <def-item>
                    <term id="G7">HDRS</term>
                    <def>
                        <p>Hamilton Depression Rating Scale</p>
                    </def>
                </def-item>
                <def-item>
                    <term id="G8">NICE</term>
                    <def>
                        <p>National Institute for Health and Care Excellence</p>
                    </def>
                </def-item>
                <def-item>
                    <term id="G9">OR</term>
                    <def>
                        <p>Odds ratio</p>
                    </def>
                </def-item>
                <def-item>
                    <term id="G10">RAR</term>
                    <def>
                        <p>Rate ratio</p>
                    </def>
                </def-item>
                <def-item>
                    <term id="G11">RCT</term>
                    <def>
                        <p>Randomized controlled trial</p>
                    </def>
                </def-item>
                <def-item>
                    <term id="G12">SMD</term>
                    <def>
                        <p>Standardized mean difference</p>
                    </def>
                </def-item>
                <def-item>
                    <term id="G13">SMDs</term>
                    <def>
                        <p>Subthreshold mental disorders
</p>
                    </def>
                </def-item>
            </def-list>
</p>
        <sec id="sec1" sec-type="intro">
            <title>1. Introduction</title>
            <p>Subthreshold mental disorders (SMDs) are characterized by clusters of psychiatric symptoms that fall short of meeting full diagnostic criteria for formal mental disorders in terms of symptom count, duration, or severity, yet still lead to significant distress and functional impairment.
                <sup>
                    <xref ref-type="bibr" rid="ref1">1</xref>,
                    <xref ref-type="bibr" rid="ref2">2</xref>
                </sup> Despite growing recognition of SMDs, the lack of consensus has resulted in terminological diversity within the literature,
                <sup>
                    <xref ref-type="bibr" rid="ref3">3</xref>,
                    <xref ref-type="bibr" rid="ref4">4</xref>
                </sup> including terms such as &#x201c;subsyndromal disorders&#x201d;,
                <sup>
                    <xref ref-type="bibr" rid="ref2">2</xref>
                </sup> &#x201c;subthreshold psychiatric symptoms&#x201d;,
                <sup>
                    <xref ref-type="bibr" rid="ref5">5</xref>
                </sup> and &#x201c;minor psychiatric disorders&#x201d;.
                <sup>
                    <xref ref-type="bibr" rid="ref6">6</xref>
                </sup> However, this heterogeneity of terminology converges on an intermediary nosological category between normative mental functioning and diagnosable psychiatric disorders.
                <sup>
                    <xref ref-type="bibr" rid="ref7">7</xref>
                </sup> These conditions are clinically classified under the &#x201c;other specified&#x201d; categories of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) or the &#x201c;not otherwise specified&#x201d; categories of DSM-IV, operationalizing terminological diversity into standardized diagnostic frameworks.
                <sup>
                    <xref ref-type="bibr" rid="ref8">8</xref>&#x2013;
                    <xref ref-type="bibr" rid="ref10">10</xref>
                </sup> Numerous epidemiological studies worldwide have consistently demonstrated that SMDs are more common than diagnosed mental disorders in general population and primary care.
                <sup>
                    <xref ref-type="bibr" rid="ref11">11</xref>
                </sup> In a meta-analysis, the pooled prevalence of subthreshold depression is reported at 11.1%,
                <sup>
                    <xref ref-type="bibr" rid="ref12">12</xref>
                </sup> which exceeds the prevalence of depressive disorders, reported as 6.38% in the general population.
                <sup>
                    <xref ref-type="bibr" rid="ref13">13</xref>
                </sup> Similarly, 10% of the Chinese population exhibits symptoms of a subthreshold anxiety disorder, significantly higher than the 3.5% who fulfill the criteria for a clinically diagnosed anxiety disorder.
                <sup>
                    <xref ref-type="bibr" rid="ref14">14</xref>
                </sup> SMDs, while not meeting full diagnostic criteria, can still affect both individual functionality and broader socioeconomic development. In a representative sample from the UK, 12.6% of individuals exhibiting SMDs at baseline were found to develop a new functional disability, a rate significantly higher than the 7.7% observed among healthy individuals.
                <sup>
                    <xref ref-type="bibr" rid="ref15">15</xref>
                </sup> Additionally, SMDs were responsible for over 32 million days of work lost in the year prior to the study.
                <sup>
                    <xref ref-type="bibr" rid="ref15">15</xref>
                </sup> A study in Norway found that about 20% of medical leave episodes and a third of all disability pensions are attributed to SMDs.
                <sup>
                    <xref ref-type="bibr" rid="ref16">16</xref>
                </sup> The exacerbation of risk associated with SMDs is particularly evident in the progression to full-blown mental disorders. Specifically, the incidence of major depression was observed at a rate of 17.6% among individuals with subthreshold depression, markedly higher than the 6.1% observed among healthy individuals.
                <sup>
                    <xref ref-type="bibr" rid="ref12">12</xref>
                </sup> The high prevalences of SMDs and their impacts on functioning impose a noteworthy socioeconomic burden that should not be disregarded.</p>
            <p>Significant challenges exist in managing SMDs in the mental health field. While psychotherapeutic interventions demonstrate a moderate effect size of 0.42 in alleviating SMDs,
                <sup>
                    <xref ref-type="bibr" rid="ref17">17</xref>
                </sup> and are recommended as one of the first-line treatment in clinical guidelines,
                <sup>
                    <xref ref-type="bibr" rid="ref18">18</xref>
                </sup> the shortage of mental health professionals, especially in primary care where SMDs are most commonly seen, can lead to delayed and underprovided treatment.
                <sup>
                    <xref ref-type="bibr" rid="ref19">19</xref>,
                    <xref ref-type="bibr" rid="ref20">20</xref>
                </sup> The WHO&#x2019;s Mental Health Atlas 2020 underscores this issue, reporting a mean of fewer than 3 mental health workers per 100,000 population in the Southeast Asia and African regions. This figure is considerably lower than the global median of 13.
                <sup>
                    <xref ref-type="bibr" rid="ref21">21</xref>
                </sup> This scarcity of mental health professionals also manifests in highly developed areas like Hong Kong, where the waiting period for psychiatric appointments in public hospitals can extend beyond two years for mild cases such as SMDs.
                <sup>
                    <xref ref-type="bibr" rid="ref22">22</xref>
                </sup> Additionally, the current healthcare paradigm frequently overlooks preventive screening for such cases, resulting in missed opportunities for early intervention.
                <sup>
                    <xref ref-type="bibr" rid="ref23">23</xref>
                </sup> Active monitoring is recommended for SMDs in the National Institute for Health and Care Excellence (NICE) clinical guidelines.
                <sup>
                    <xref ref-type="bibr" rid="ref24">24</xref>,
                    <xref ref-type="bibr" rid="ref25">25</xref>
                </sup> However, studies have shown that active monitoring may be insufficient compared to proactive treatment in subthreshold states.
                <sup>
                    <xref ref-type="bibr" rid="ref26">26</xref>
                </sup> Initiating pharmacological interventions at these early and subthreshold stages may be considered premature and can lead to treatment failures with no significant difference in outcomes compared to placebo.
                <sup>
                    <xref ref-type="bibr" rid="ref27">27</xref>
                </sup> Another challenge is the often delayed or completely absent help-seeking, which exacerbates the problem.
                <sup>
                    <xref ref-type="bibr" rid="ref28">28</xref>,
                    <xref ref-type="bibr" rid="ref29">29</xref>
                </sup> Stigma is one of the most significant contributors to this issue. A meta-analysis has shown that stigma related to mental health services is directly associated with less active help-seeking for mental problems in the general population (Odds ratio (OR) = 0.80, 95% Confidence interval (CI) 0.73&#x2013;0.88).
                <sup>
                    <xref ref-type="bibr" rid="ref30">30</xref>
                </sup> Cultural familiarity also plays a significant role in healthcare decisions. Although Cognitive Behavioral Therapy (CBT) is effective, it was originally developed in a Western context and exhibits smaller effect sizes in Chinese populations,
                <sup>
                    <xref ref-type="bibr" rid="ref31">31</xref>
                </sup> and its effectiveness is reduced without cultural adaptation.
                <sup>
                    <xref ref-type="bibr" rid="ref32">32</xref>
                </sup> Therefore, it is imperative to identify alternative treatments for SMDs that are effective, offer sufficient workforce provision and are less stigmatized compared to conventional treatments. In confronting these challenges, Chinese medicine (CM) presents as one of the promising first-line treatment options in primary care for the management of SMDs, particularly within primary care systems that have existing infrastructure and high public acceptance, such as those in mainland China and Hong Kong.</p>
        </sec>
        <sec id="sec2">
            <title>2. Chinese Medicine and Subthreshold Mental Disorders</title>
            <p>CM, with its roots spanning thousands of years, has a rich history of treating mental disorders.
                <sup>
                    <xref ref-type="bibr" rid="ref33">33</xref>
                </sup> It has been incorporated into the healthcare system in numerous Asian countries and viewed as a complementary medical system in many Western nations.
                <sup>
                    <xref ref-type="bibr" rid="ref34">34</xref>,
                    <xref ref-type="bibr" rid="ref35">35</xref>
                </sup> CM aims to rectify imbalances and restore patients&#x2019; holistic wellness, encompassing both the physical and mental aspects of patients&#x2019; health.
                <sup>
                    <xref ref-type="bibr" rid="ref36">36</xref>
                </sup> Several CM practices are recognized for their potential in preventing and treating mental disorders. For instance, acupuncture is considered as adjunctive treatment to antidepressant medication for depression by the American Psychological Association (APA).
                <sup>
                    <xref ref-type="bibr" rid="ref37">37</xref>
                </sup> Chinese herbal medicine and acupuncture are recommended to treat insomnia in the Hong Kong Chinese Medicine Clinical Practice Guideline.
                <sup>
                    <xref ref-type="bibr" rid="ref38">38</xref>
                </sup> The NICE has also reviewed the efficacy of combining acupuncture with antidepressants for depression.
                <sup>
                    <xref ref-type="bibr" rid="ref24">24</xref>
                </sup> Moreover, various CM treatments, including herbal medicine, acupuncture, cupping, and tuina, are endorsed for treating anxiety in clinical guidelines published by the National Administration of Traditional Chinese Medicine.
                <sup>
                    <xref ref-type="bibr" rid="ref39">39</xref>
                </sup> Systematic reviews and meta-analyses have indicated the promising therapeutic effects of acupuncture on treating depression and anxiety. The effect sizes were estimated to be Hedges&#x2019; g of 0.41 (95% CI 0.18 to 0.63; p&lt;0.001) for depression
                <sup>
                    <xref ref-type="bibr" rid="ref40">40</xref>
                </sup> and a standard mean effect size of 0.41(95% CI 0.31 to 0.50; p&lt;0.001) for anxiety,
                <sup>
                    <xref ref-type="bibr" rid="ref41">41</xref>
                </sup> which both were of small to moderate magnitude.
                <sup>
                    <xref ref-type="bibr" rid="ref42">42</xref>
                </sup> These findings are consistent with earlier systematic reviews that included 12 randomized controlled trials showing that acupuncture is beneficial for treating anxiety disorders and perioperative anxiety, especially in auricular acupuncture.
                <sup>
                    <xref ref-type="bibr" rid="ref43">43</xref>
                </sup> Crucially, network meta-analyses suggest that electroacupuncture is as effective as CBT in alleviating depressive symptoms in subthreshold depression.
                <sup>
                    <xref ref-type="bibr" rid="ref44">44</xref>
                </sup> However, acupuncture&#x2019;s key advantage lies in its scalability. Even with similar session requirements,
                <sup>
                    <xref ref-type="bibr" rid="ref45">45</xref>
                </sup>
                <sup>,</sup>
                <sup>
                    <xref ref-type="bibr" rid="ref46">46</xref>
                </sup> acupuncture benefits from a larger workforce and the availability of efficient models like community acupuncture, where one practitioner can treat multiple patients simultaneously. In contrast, CBT relies on a limited workforce of therapists for either individual or intensive group facilitation.</p>
            <p>Chinese herbal formula such as Xiao Yao San (Free Wanderer Powder), Chai Hu Shu Gan San (Bupleurum Liver-Soothing Powder), and Gan Mai Da Zao Tang (Licorice, Wheat and Jujube Decoction) have also been demonstrated to elicit comparable efficacy as antidepressants in reducing the depression severity measured by Hamilton Depression Rating Scale (HDRS).
                <sup>
                    <xref ref-type="bibr" rid="ref47">47</xref>
                </sup> In a randomized controlled trial (RCT), Lycium barbarum polysaccharide, an active extract derived from the herbal medicine Goji berries, significantly reduced depressive symptoms compared to placebo in patients with subthreshold depression, demonstrating a large effect size (Cohen&#x2019;s d = 0.86, p = 0.014).
                <sup>
                    <xref ref-type="bibr" rid="ref48">48</xref>
                </sup> Furthermore, the Chinese herbal medicine has been reported to be associated with fewer adverse events compared to psychotropic medications. A meta-analysis revealed that subjects taking herbal medicine were less likely to report adverse events than those taking antidepressants (pooled rate ratio (RAR) = 0.23, 95% CI: 0.16 to 0.33, p &lt; 0.00001, I
                <sup>2</sup> = 59%). Additionally, the combination of Chinese herbal medicine and antidepressants was associated with fewer adverse events compared to antidepressants alone (pooled RAR = 0.43, 95% CI: 0.35 to 0.52, p &lt; 0.00001, I
                <sup>2</sup> = 64%) in the treatment of depression.
                <sup>
                    <xref ref-type="bibr" rid="ref47">47</xref>
                </sup> Another meta-analysis indicated that the incidence of adverse events in the herbal formula Xiao Yao San group was lower than in the anxiolytics group, and the rates of adverse events in the group combining Xiao Yao San with anxiolytics were significantly lower than in the anxiolytics-only group.
                <sup>
                    <xref ref-type="bibr" rid="ref49">49</xref>
                </sup> Given this evidence of efficacy and safety, leveraging established, evidence-based formulas is recommended for treatment in primary care.</p>
            <p>Beyond acupuncture and herbal therapies, other CM modalities also demonstrate robust therapeutic potential. For instance, acupressure has been shown to significantly reduce anxiety (a reduction in standardized mean difference (SMD) of 1.152, 95% CI 0.847 to 1.459; p&lt;0.001), particularly effective in providing immediate relief for pretreatment anxiety.
                <sup>
                    <xref ref-type="bibr" rid="ref50">50</xref>
                </sup> CM-based integrated health interventions had larger effects on reducing depressive symptoms (SMD = &#x2212;2.05, 95% CI: &#x2212;2.74 to &#x2212;1.37; p &lt; 0.00001) compared with usual care, and showed no significant differences in reducing depression symptoms compared to CBT.
                <sup>
                    <xref ref-type="bibr" rid="ref51">51</xref>
                </sup> Similarly, mind-body exercises rooted in CM, such as Tai Chi, have outperformed non-mindful exercises in improving anxiety (Hedges&#x2019;s d = 0.28, 95% CI, 0.08 to 0.48, p = 0.008), depression (Hedges&#x2019;s d = 0.20, 95% CI, 0.04 to 0.36, p = 0.018), and general mental health (Hedges&#x2019;s d = 0.40, 95% CI, 0.08 to 0.73, p = 0.017) with small-to-moderate effect sizes.
                <sup>
                    <xref ref-type="bibr" rid="ref52">52</xref>
                </sup> Reviewing these aspects, CM offers promising potential for managing and alleviating a variety of symptoms associated with SMDs.</p>
        </sec>
        <sec id="sec3">
            <title>3. Benefits of Chinese Medicine as a First-line Subthreshold Mental Disorders Treatment in Primary Care</title>
            <p>The Lancet Commission report suggests that task-shifting to non-specialist health workers can be an effective strategy to improve the availability of interventions in mental health care.
                <sup>
                    <xref ref-type="bibr" rid="ref18">18</xref>
                </sup> Integrating CM as one of the first-line treatments in primary care for SMDs aligns with these objectives and offers several additional benefits. Firstly, in terms of workforce availability and accessibility, East Asian regions such as mainland China and Hong Kong present a compelling model for integration. The National Administration of Traditional Chinese Medicine reports that there are over 1.5 million licensed CM practitioners already embedded in primary care in China, with an annual growth rate of 6.6% since 2015.
                <sup>
                    <xref ref-type="bibr" rid="ref53">53</xref>
                </sup> This growth rate surpasses that of primary health-care physicians in all other specialties combined over the past decade in China.
                <sup>
                    <xref ref-type="bibr" rid="ref54">54</xref>
                </sup> Hong Kong boasts a well-regulated CM industry, with over 10,000 CM practitioners significantly contributing to primary care.
                <sup>
                    <xref ref-type="bibr" rid="ref55">55</xref>
                </sup> This infrastructure enables CM to immediately address workforce shortages in resource-limited areas with established CM systems but inadequate mental health staffing.
                <sup>
                    <xref ref-type="bibr" rid="ref56">56</xref>
                </sup>
            </p>
            <p>Second, cultural congruence and reduced stigma play a pivotal role in help-seeking behavior. Psychiatric labels often trigger self-stigma, deterring individuals from seeking conventional mental health care.
                <sup>
                    <xref ref-type="bibr" rid="ref57">57</xref>
                </sup> In contrast, CM employs a holistic framework that conceptualizes mental and physical health as interconnected aspects of overall well-being.
                <sup>
                    <xref ref-type="bibr" rid="ref58">58</xref>
                </sup> By emphasizing balance restoration, preventive care, and symptom management without pathological labeling,
                <sup>
                    <xref ref-type="bibr" rid="ref59">59</xref>
                </sup> CM is perceived as a form of &#x201c;health maintenance&#x201d; rather than &#x201c;mental illness treatment.&#x201d;
                <sup>
                    <xref ref-type="bibr" rid="ref60">60</xref>
                </sup> Research has demonstrated that Chinese Americans perceive greater community attitudes of shame when accessing Western psychiatric services as opposed to CM for treating mental disorders.
                <sup>
                    <xref ref-type="bibr" rid="ref61">61</xref>
                </sup> The medical paradigm of CM reduces barriers to care and fosters earlier intervention.</p>
            <p>Third, integrating CM offers a compelling economic advantage. In mainland China, basic public health insurance schemes have progressively expanded their coverage to include CM treatments.
                <sup>
                    <xref ref-type="bibr" rid="ref62">62</xref>
                </sup> Similarly, the government of Hong Kong subsidizes care in its 18 territory-wide Chinese Medicine Clinics for Training and Research, providing a clear precedent for publicly supported services that could be scaled to include SMD management.
                <sup>
                    <xref ref-type="bibr" rid="ref63">63</xref>
                </sup> Beyond funding, CM demonstrates strong potential for cost-effectiveness compared to standard interventions. For instance, a trial found that while acupuncture and counseling for depression yielded similar health gains as measured in Quality-Adjusted Life Years (QALYs), acupuncture incurred significantly lower total costs to the health system (&#x00a3;1,227 vs. &#x00a3;1,450) over 12 months.
                <sup>
                    <xref ref-type="bibr" rid="ref64">64</xref>
                </sup> The Incremental Cost-Effectiveness Ratio (ICER) further underscored this, indicating that adopting counseling over acupuncture would cost the health service over &#x00a3;71,000 for each additional QALY gain, a figure exceeding standard thresholds for value in healthcare.
                <sup>
                    <xref ref-type="bibr" rid="ref64">64</xref>
                </sup> By integrating CM into first-line primary stepped-care models, health systems can provide earlier, cost-effective, and less stigmatized interventions while preserving specialist resources for higher-acuity needs (
                <xref ref-type="fig" rid="f1">
Figure 1</xref>).</p>
            <fig fig-type="figure" id="f1" orientation="portrait" position="float">
                <label>
Figure 1. </label>
                <caption>
                    <title>Integrating Chinese medicine in primary care to address subthreshold mental disorders challenges.</title>
                </caption>
                <graphic id="gr1" orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/189428/52d030c7-45aa-4c40-b29c-d641be110107_figure1.gif"/>
            </fig>
        </sec>
        <sec id="sec4">
            <title>4. Challenges and Solutions in Integrating Chinese Medicine into Primary Care</title>
            <p>Even in regions where CM is well-established, integrating it into primary care for mental health faces three significant challenges. First, there is a public lack of recognition regarding the role of CM in treating mental disorders. For instance, despite CM&#x2019;s prevalence in Hong Kong, a territory-wide psychiatric epidemiological study in Hong Kong showed that a mere 1.8% of patients dealing with mental health issues would seek help from CM.
                <sup>
                    <xref ref-type="bibr" rid="ref65">65</xref>
                </sup> This is four times less than the proportion of patients seeking help for other health conditions, highlighting a significant underutilization and a lack of perceived legitimacy in the context of mental health.
                <sup>
                    <xref ref-type="bibr" rid="ref65">65</xref>
                </sup> Second, there is a lack of collaboration and defined referral pathways between CM and mental health specialties in secondary care.
                <sup>
                    <xref ref-type="bibr" rid="ref66">66</xref>
                </sup> The absence of clear, standardized procedures to guide CM practitioners and conventional healthcare providers in referring patients to each other can lead to disjointed and ineffective care. This deficiency often leads to delays in accessing advanced treatments for treatment-resistant patients, inadequate management of comorbid conditions, and insufficient specialist assessments or diagnoses needed for legal compliance. Such inefficiencies not only obstruct the integration of CM into mainstream mental health care but also potentially place CM at a disadvantage within the primary care setting. Third, owing to different theological and cultural backgrounds and knowledge gaps, other healthcare providers in the mental health field often have varying perceptions of CM&#x2019;s efficacy, which can hinder its integration.
                <sup>
                    <xref ref-type="bibr" rid="ref67">67</xref>
                </sup> Addressing these challenges requires a multi-pronged approach. Public education campaigns can raise awareness about the potential benefits of CM in treating mental disorders, presenting scientific evidence to enhance its perceived legitimacy. Concurrently, research should be encouraged to further explore and validate the efficacy of CM treatment in this field. Furthermore, the development of collaborative frameworks and referral pathways is essential to facilitate collaboration between CM and other mental health specialties. This could be realized through policy changes and the formulation of clear collaboration and referral guidelines. Lastly, cross-disciplinary education can play a pivotal role in improving understanding of CM among other mental health practitioners. By embedding CM into medical curricula, conducting joint training programs, and promoting regular dialogues and interdisciplinary exchanges, practitioners&#x2019; knowledge and acceptance of CM can be improved, thus paving the way for its successful integration into primary mental healthcare.</p>
        </sec>
        <sec id="sec5" sec-type="conclusion">
            <title>5. Conclusion</title>
            <p>In conclusion, SMDs represent a significant public health burden, and current management strategies are often hindered by workforce shortages and stigma. This perspective has argued that CM emerges as a promising first-line option, particularly in primary care settings with established infrastructure and public acceptance. With its holistic approach, growing evidence of efficacy, and potential to be a less-stigmatized alternative, integrating CM in these systems could enhance help-seeking and alleviate workforce gaps. The successful integration of CM in these model regions could provide a valuable, evidence-based blueprint for other healthcare systems to consider in the future. To realize this potential, a focused strategy encompassing public education, rigorous research, policy reform to create clear referral pathways, and interdisciplinary training is essential.</p>
        </sec>
        <sec id="sec6">
            <title>Ethical approval</title>
            <p>Ethical approval and consent were not required.</p>
        </sec>
        <sec id="sec7">
            <title>Declaration of generative AI and AI-assisted technologies in the writing process</title>
            <p>The authors declare that they have not used generative AI and AI-assisted technologies in the writing process.</p>
        </sec>
    </body>
    <back>
        <sec id="sec10" sec-type="data-availability">
            <title>Data availability statement</title>
            <p>No data associated with this article.</p>
        </sec>
        <ack>
            <title>Acknowledgements</title>
            <p>Not applicable.</p>
        </ack>
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                            <surname>Makanjuola</surname>
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                        <etal/>
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                    <article-title>The role of global traditional and complementary systems of medicine in the treatment of mental health disorders.</article-title>
                    <source>

                        <italic toggle="yes">Lancet Psychiatry.</italic>
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                    <year>2015</year>;<volume>2</volume>(<issue>2</issue>):<fpage>168</fpage>&#x2013;<lpage>177</lpage>.
                    <pub-id pub-id-type="pmid">26052502</pub-id>
                    <pub-id pub-id-type="doi">10.1016/S2215-0366(15)00013-9</pub-id>
                    <pub-id pub-id-type="pmcid">PMC4456435</pub-id>
                </mixed-citation>
            </ref>
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                        <name name-style="western">
                            <surname>Hollenberg</surname>
                            <given-names>D</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Muzzin</surname>
                            <given-names>L</given-names>
                        </name>
</person-group>:
                    <article-title>Epistemological challenges to integrative medicine: An anti-colonial perspective on the combination of complementary/alternative medicine with biomedicine.</article-title>
                    <source>

                        <italic toggle="yes">Health Sociol. Rev.</italic>
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                    <year>2010</year>;<volume>19</volume>(<issue>1</issue>):<fpage>34</fpage>&#x2013;<lpage>56</lpage>.
                    <pub-id pub-id-type="doi">10.5172/hesr.2010.19.1.034</pub-id>
                </mixed-citation>
            </ref>
        </ref-list>
    </back>
    <sub-article article-type="reviewer-report" id="report473351">
        <front-stub>
            <article-id pub-id-type="doi">10.5256/f1000research.189428.r473351</article-id>
            <title-group>
                <article-title>Reviewer response for version 2</article-title>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author">
                    <name>
                        <surname>Choi</surname>
                        <given-names>Yujin</given-names>
                    </name>
                    <xref ref-type="aff" rid="r473351a1">1</xref>
                    <role>Referee</role>
                    <uri content-type="orcid">https://orcid.org/0000-0001-5257-2340</uri>
                </contrib>
                <aff id="r473351a1">
                    <label>1</label>Korea Institute of Oriental Medicine, Daejeon, South Korea</aff>
            </contrib-group>
            <author-notes>
                <fn fn-type="conflict">
                    <p>
                        <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>21</day>
                <month>4</month>
                <year>2026</year>
            </pub-date>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2026 Choi Y</copyright-statement>
                <copyright-year>2026</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <related-article ext-link-type="doi" id="relatedArticleReport473351" related-article-type="peer-reviewed-article" xlink:href="10.12688/f1000research.163621.2"/>
            <custom-meta-group>
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                    <meta-name>recommendation</meta-name>
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        </front-stub>
        <body>
            <p>This revised manuscript presents a well-structured and focused argument for integrating Chinese medicine as a first-line treatment for subthreshold mental disorders in primary care settings. I have the following minor comments for the authors' consideration. 
                <list list-type="order">
                    <list-item>
                        <p>The abbreviation "SMD" is used in this manuscript to denote both "subthreshold mental disorders" (as a population category) and "standardized mean difference" (as a statistical effect size measure). These dual uses appear in close proximity throughout the text and may cause confusion for readers. The authors should consider differentiating these.</p>
                    </list-item>
                    <list-item>
                        <p>Several effect sizes cited in Section 2 to support the efficacy of CM interventions are drawn from studies enrolling patients with diagnosed mental disorders or other clinical populations (e.g., perioperative anxiety), rather than individuals with subthreshold presentations specifically. Given that the manuscript's central argument concerns SMDs, a brief clarification of the extent to which these estimates can be extrapolated to subthreshold populations is required.</p>
                    </list-item>
                </list>
            </p>
            <p>Is the topic of the opinion article discussed accurately in the context of the current literature?</p>
            <p>Yes</p>
            <p>Are arguments sufficiently supported by evidence from the published literature?</p>
            <p>Yes</p>
            <p>Are all factual statements correct and adequately supported by citations?</p>
            <p>Yes</p>
            <p>Are the conclusions drawn balanced and justified on the basis of the presented arguments?</p>
            <p>Yes</p>
            <p>Reviewer Expertise:</p>
            <p>Integrative medicine, Korean medicine, Neuropsychiatry</p>
            <p>I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.</p>
        </body>
    </sub-article>
    <sub-article article-type="reviewer-report" id="report411863">
        <front-stub>
            <article-id pub-id-type="doi">10.5256/f1000research.180003.r411863</article-id>
            <title-group>
                <article-title>Reviewer response for version 1</article-title>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author">
                    <name>
                        <surname>Deng</surname>
                        <given-names>Li</given-names>
                    </name>
                    <xref ref-type="aff" rid="r411863a1">1</xref>
                    <role>Referee</role>
                    <uri content-type="orcid">https://orcid.org/0000-0002-1522-4184</uri>
                </contrib>
                <aff id="r411863a1">
                    <label>1</label>Jinan University, Guangzhou, Guangzhou, China</aff>
            </contrib-group>
            <author-notes>
                <fn fn-type="conflict">
                    <p>
                        <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>17</day>
                <month>9</month>
                <year>2025</year>
            </pub-date>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2025 Deng L</copyright-statement>
                <copyright-year>2025</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <related-article ext-link-type="doi" id="relatedArticleReport411863" related-article-type="peer-reviewed-article" xlink:href="10.12688/f1000research.163621.1"/>
            <custom-meta-group>
                <custom-meta>
                    <meta-name>recommendation</meta-name>
                    <meta-value>approve</meta-value>
                </custom-meta>
            </custom-meta-group>
        </front-stub>
        <body>
            <p>This perspective article presents a forward-looking and practically significant proposition: utilizing Chinese Medicine (CM) as a first-line treatment option for Subthreshold Mental Disorders (SMDs) within primary care. With a clear structure, the article systematically elaborates on the disease burden of SMDs, current treatment challenges, the potential efficacy and advantages of CM, as well as the obstacles and solutions related to its integration.</p>
            <p> As Reviewer 1 pointed out, the overly broad scope of the research constitutes a significant limitation. In most Western developed countries, challenges such as the lack of unified practice standards and regulatory frameworks, disparities between efficacy evaluation systems and biomedical models, potential skepticism among Western medical practitioners, and the high costs associated with cultural translation and patient education remain unresolved. These issues render the proposed integration strategies abstract and lacking in operational practicality, making it difficult to translate them into concrete practice guidelines across different contexts.</p>
            <p> Although the authors mention that Chinese medicine may be "cost-effective" and cite a limited number of studies (such as one acupuncture trial), this argument lacks sufficient depth and persuasiveness. More rigorous pharmacoeconomic evidence is needed. This entails conducting strict cost-effectiveness analyses (CEA) or cost-utility analyses (CUA) that directly compare Chinese medicine interventions with currently recommended first-line treatment options&#x2014;such as cognitive behavioral therapy (CBT), mindfulness-based interventions (MBIs), or active monitoring. The key is not only to demonstrate the efficacy of Chinese medicine but also to prove that it can reduce overall healthcare costs or societal resource burdens while achieving equivalent or better health outcomes. At present, such high-quality economic evaluations remain relatively scarce in the field of Chinese medicine. If the article were to adequately address this gap, its value would be significantly enhanced.</p>
            <p> While the authors list various Chinese medicine therapies (e.g., acupuncture, specific herbal formulas, tai chi, etc.) and summarize evidence of their efficacy, they fail to elaborate in depth on how to standardize and scale these applications in primary care settings. Furthermore, a critical question remains unaddressed: Should standardized fixed formulas, which facilitate quality control, RCT execution be recommended, or should traditional pattern-based diagnosis and treatment&#x2014;which allows for individualized care aligned with Chinese medicine theory but introduces complexity and challenges to standardization&#x2014;be permitted? The article does not engage with this essential decision-making dilemma.</p>
            <p>Is the topic of the opinion article discussed accurately in the context of the current literature?</p>
            <p>Yes</p>
            <p>Are arguments sufficiently supported by evidence from the published literature?</p>
            <p>Yes</p>
            <p>Are all factual statements correct and adequately supported by citations?</p>
            <p>Yes</p>
            <p>Are the conclusions drawn balanced and justified on the basis of the presented arguments?</p>
            <p>Yes</p>
            <p>Reviewer Expertise:</p>
            <p>The article is already &#x200b;largely comprehensive&#x200b; in its current state.</p>
            <p>I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.</p>
        </body>
    </sub-article>
    <sub-article article-type="reviewer-report" id="report383877">
        <front-stub>
            <article-id pub-id-type="doi">10.5256/f1000research.180003.r383877</article-id>
            <title-group>
                <article-title>Reviewer response for version 1</article-title>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author">
                    <name>
                        <surname>Frost</surname>
                        <given-names>Rachael</given-names>
                    </name>
                    <xref ref-type="aff" rid="r383877a1">1</xref>
                    <role>Referee</role>
                    <uri content-type="orcid">https://orcid.org/0000-0003-3523-0052</uri>
                </contrib>
                <aff id="r383877a1">
                    <label>1</label>Liverpool John Moores University, Liverpool, England, UK</aff>
            </contrib-group>
            <author-notes>
                <fn fn-type="conflict">
                    <p>
                        <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>27</day>
                <month>5</month>
                <year>2025</year>
            </pub-date>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2025 Frost R</copyright-statement>
                <copyright-year>2025</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <related-article ext-link-type="doi" id="relatedArticleReport383877" related-article-type="peer-reviewed-article" xlink:href="10.12688/f1000research.163621.1"/>
            <custom-meta-group>
                <custom-meta>
                    <meta-name>recommendation</meta-name>
                    <meta-value>approve-with-reservations</meta-value>
                </custom-meta>
            </custom-meta-group>
        </front-stub>
        <body>
            <p>This opinion article advocates for the inclusion of Chinese Medicine as a first line treatment for SMDs. It demonstrates an interesting and generally well supported argument for greater inclusion of CM, and highlights relevant potential benefits and challenges. I feel it would benefit from considering the following:</p>
            <p> 1) A narrower focus on which countries the authors are recommending integration in, as there are many different systems and consequent issues globally.&#x00a0;It seems integration should first be recommended in China as somewhere with existing infrastructure and high CM acceptance/interest? The countries should be clear as it has implications for how integration would happen - for example in Western countries there would be a greater challenge of integrating private services into publicly funded care. Alleviating workforce gaps would be good but this is only likely to occur in specific Asian countries where there are high rates of well trained CM practitioners - they may also face a shortage in other countries!</p>
            <p> 2) More economic consideration is needed.&#x00a0;Who are the authors proposing should pay for the integration?&#x00a0;There is some economic evidence cited but it would be good to expand this, particularly in comparison to existing interventions.</p>
            <p> 3)&#x00a0;It would be good to comment on the comparability in terms of delivery of acupuncture vs CBT with regards to&#x00a0; N sessions needed per person for effects, given that the effect sizes are very similar but different session duration or number has workforce and delivery implications. For this reason antidepressants are often given instead of CBT. Are the authors proposing CM herbal mixes be individually tailored or using established products only?</p>
            <p> 4)&#x00a0;Section 2 would benefit from being split into 2 paragraphs to enhance readability.&#x00a0;</p>
            <p> 5) Statement "acupressure has been shown to significantly reduce anxiety (standardized mean difference (SMD) = 1.152, 95% CI 0.847 to 1.459; p&lt;0.001)" - number is positive, implying an increase? It ma be worth restating as "a reduction of 1.152" for clarity.</p>
            <p>Is the topic of the opinion article discussed accurately in the context of the current literature?</p>
            <p>Yes</p>
            <p>Are arguments sufficiently supported by evidence from the published literature?</p>
            <p>Partly</p>
            <p>Are all factual statements correct and adequately supported by citations?</p>
            <p>Yes</p>
            <p>Are the conclusions drawn balanced and justified on the basis of the presented arguments?</p>
            <p>Yes</p>
            <p>Reviewer Expertise:</p>
            <p>Western herbal medicine, primary care, mental health, depression, anxiety</p>
            <p>I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.</p>
        </body>
        <sub-article article-type="response" id="comment14733-383877">
            <front-stub>
                <contrib-group>
                    <contrib contrib-type="author">
                        <name>
                            <surname>Tang</surname>
                            <given-names>Hiu To</given-names>
                        </name>
                        <aff>Hong Kong Baptist University, Hong Kong, Hong Kong</aff>
                    </contrib>
                </contrib-group>
                <author-notes>
                    <fn fn-type="conflict">
                        <p>
                            <bold>Competing interests: </bold>I have no competing interests to declare.</p>
                    </fn>
                </author-notes>
                <pub-date pub-type="epub">
                    <day>7</day>
                    <month>10</month>
                    <year>2025</year>
                </pub-date>
            </front-stub>
            <body>
                <p>Dear Dr. Frost,</p>
                <p> </p>
                <p> "Chinese Medicine as First-Line Treatment for Subthreshold Mental Disorders in Primary Care: Opportunities and Challenges"</p>
                <p> </p>
                <p> Thank you for your time and the thorough reading of our manuscript. We are grateful for the insightful and favourable comments. We have revised the manuscript taking into consideration all the feedback received. For clarity, the reviewers&#x2019; comments are presented in bold, our responses are in regular font, and the corresponding changes in the manuscript are in italic. We believe these revisions have significantly strengthened the manuscript's argument. We hope we have successfully addressed all the concerns and that the revised manuscript is now suitable for publication in F1000Research. Thank you for your time and consideration.</p>
                <p> </p>
                <p> Yours sincerely,</p>
                <p> Tang Hiu To</p>
                <p> </p>
                <p> </p>
                <p> 
                    <bold>1) A narrower focus on which countries the authors are recommending integration in, as there are many different systems and consequent issues globally. It seems integration should first be recommended in China as somewhere with existing infrastructure and high CM acceptance/interest? The countries should be clear as it has implications for how integration would happen - for example in Western countries there would be a greater challenge of integrating private services into publicly funded care. Alleviating workforce gaps would be good but this is only likely to occur in specific Asian countries where there are high rates of well trained CM practitioners - they may also face a shortage in other countries!</bold>
                </p>
                <p> </p>
                <p> 
                    <bold>Response:</bold> Thank you for this insightful comment. We agree that a global recommendation is too broad and overlooks critical systemic differences. Accordingly, we have substantially revised the manuscript to narrow our focus to regions where integration is most feasible due to existing infrastructure, public acceptance, and a robust workforce. Our recommendation now centers on East Asian regions, specifically using mainland China and Hong Kong as primary examples. This revised focus allows for a more nuanced discussion of the implementation model and its potential to alleviate workforce gaps in these specific contexts. We have also added a brief discussion acknowledging the distinct challenges that integration would face in other healthcare systems.</p>
                <p> </p>
                <p> 
                    <bold>Revise</bold>
                    <bold>d manuscript: </bold> 
                    <list list-type="bullet">
                        <list-item>
                            <p>
                                <italic>
                                    <bold>Abstract:</bold> This perspective advocates for the integration of Chinese medicine (CM) as a first-line treatment for SMDs, focusing specifically on primary care settings in regions with established CM infrastructure and high public acceptance.</italic>
                            </p>
                        </list-item>
                        <list-item>
                            <p>
                                <italic>
                                    <bold>Introduction:</bold> In confronting these challenges, Chinese medicine (CM) presents as one of the promising first-line treatment options in primary care for the management of SMDs, particularly within primary care systems that have existing infrastructure and high public acceptance, such as those in mainland China and Hong Kong.</italic>
                            </p>
                        </list-item>
                        <list-item>
                            <p>
                                <italic>Similarly, 10% of the Chinese population exhibits symptoms of a subthreshold anxiety disorder, significantly higher than the 3.5% who fulfill the criteria for a clinically diagnosed anxiety disorder. </italic>
                            </p>
                        </list-item>
                        <list-item>
                            <p>
                                <italic>
                                    <bold>Benefits of Chinese Medicine as a First-line Subthreshold Mental Disorders Treatment in Primary Care:</bold> Integrating CM as one of the first-line treatments in primary care for SMDs aligns with these objectives and offers several additional benefits. Firstly, in terms of workforce availability and accessibility, East Asian regions such as mainland China and Hong Kong present a compelling model for integration. The National Administration of Traditional Chinese Medicine reports that there are over 1.5 million licensed CM practitioners already embedded in primary care in China, with an annual growth rate of 6.6% since 2015. 
                                    <sup>53</sup>&#x00a0;This growth rate surpasses that of primary health-care physicians in all other specialties combined over the past decade in China. 
                                    <sup>54</sup> Hong Kong boasts a well-regulated CM industry, with over 10,000 CM practitioners significantly contributing to primary care. 
                                    <sup>55</sup> This infrastructure enables CM to immediately address workforce shortages in resource-limited areas with established CM systems but inadequate mental health staffing. 
                                    <sup>56</sup>
                                </italic>
                            </p>
                        </list-item>
                        <list-item>
                            <p>
                                <italic>
                                    <bold>Challenges and Solutions in Integrating Chinese Medicine into Primary Care</bold>
                                    <bold>:</bold> Even in regions where CM is well-established, integrating it into primary care for mental health faces three significant challenges.</italic>
                            </p>
                        </list-item>
                        <list-item>
                            <p>
                                <italic>For instance, despite CM's prevalence in Hong Kong, a territory-wide psychiatric epidemiological study in Hong Kong showed that a mere 1.8% of patients dealing with mental health issues would seek help from CM. 
                                    <sup>65</sup>
                                </italic>
                            </p>
                        </list-item>
                        <list-item>
                            <p>
                                <italic>
                                    <bold>Conclusion:</bold> In conclusion, SMDs represent a significant public health burden, and current management strategies are often hindered by workforce shortages and stigma. This perspective has argued that CM emerges as a promising first-line option, particularly in primary care settings with established infrastructure and public acceptance. With its holistic approach, growing evidence of efficacy, and potential to be a less-stigmatized alternative, integrating CM in these systems could enhance help-seeking and alleviate workforce gaps. The successful integration of CM in these model regions could provide a valuable, evidence-based blueprint for other healthcare systems to consider in the future. To realize this potential, a focused strategy encompassing public education, rigorous research, policy reform to create clear referral pathways, and interdisciplinary training is essential.</italic>
                            </p>
                        </list-item>
                    </list> </p>
                <p> </p>
                <p> 
                    <bold>2) More economic consideration is needed. Who are the authors proposing should pay for the integration? There is some economic evidence cited but it would be good to expand this, particularly in comparison to existing interventions.</bold>
                </p>
                <p> </p>
                <p> 
                    <bold>Response:</bold> Thank you for this crucial feedback. We agree that a discussion on funding models and a more direct comparative economic analysis is essential to the manuscript's argument. We have now explicitly identified existing public funding pathways in the proposed model regions and strengthened the cost-effectiveness evidence by including a direct comparison from a key clinical trial, comparing non-pharmacological treatments- acupuncture and counseling.</p>
                <p> </p>
                <p> 
                    <bold>Revise</bold>
                    <bold>d manuscript:</bold> 
                    <list list-type="bullet">
                        <list-item>
                            <p>
                                <italic>
                                    <bold>Benefits of Chinese Medicine as a First-line Subthreshold Mental Disorders Treatment in Primary Care:&#x00a0;</bold>Third, integrating CM offers a compelling economic advantage. In mainland China, basic public health insurance schemes have progressively expanded their coverage to include CM treatments.&#x00a0;
                                    <sup>62</sup> Similarly, the government of Hong Kong subsidizes care in its 18 territory-wide Chinese Medicine Clinics for Training and Research, providing a clear precedent for publicly supported services that could be scaled to include SMD management. 
                                    <sup>63</sup>&#x00a0;Beyond funding, CM demonstrates strong potential for cost-effectiveness compared to standard interventions. For instance, a trial found that while acupuncture and counseling for depression yielded similar health gains as measured in Quality-Adjusted Life Years (QALYs), acupuncture incurred significantly lower total costs to the health system (&#x00a3;1,227 vs. &#x00a3;1,450) over 12 months. 
                                    <sup>64</sup>&#x00a0;The Incremental Cost-Effectiveness Ratio (ICER) further underscored this, indicating that adopting counseling over acupuncture would cost the health service over &#x00a3;71,000 for each additional QALY gain, a figure exceeding standard thresholds for value in healthcare. 
                                    <sup>64</sup>&#x00a0;By integrating CM into first-line primary stepped-care models, health systems can provide earlier, cost-effective, and less stigmatized interventions while preserving specialist resources for higher-acuity needs( Figure 1).</italic>
                            </p>
                        </list-item>
                    </list> </p>
                <p> </p>
                <p> 
                    <bold>3) It would be good to comment on the comparability in terms of delivery of acupuncture vs CBT with regards to&#x00a0; N sessions needed per person for effects, given that the effect sizes are very similar but different session duration or number has workforce and delivery implications. For this reason antidepressants are often given instead of CBT. Are the authors proposing CM herbal mixes be individually tailored or using established products only?</bold>
                </p>
                <p> </p>
                <p> 
                    <bold>Response:</bold> Thank you for your insightful feedback. You raised an important point regarding the practical delivery of acupuncture versus CBT, particularly concerning session numbers and workforce implications. Addressing this point strengthens our argument for integrating CM. While the effect sizes are similar, the delivery models have distinct workforce implications. A typical course of CBT involves 8&#x2013;16 weekly sessions of approximately 50 minutes each, requiring a highly trained therapist (Cuijpers et al., 2013). Acupuncture protocols for depression or anxiety often involve a similar number of sessions, such as 10&#x2013;12 sessions over 8&#x2013;12 weeks, with each session lasting 30&#x2013;60 minutes (MacPherson, 2013). However, the larger and more rapidly growing workforce of licensed CM practitioners makes acupuncture a more scalable intervention in settings like mainland China and Hong Kong. Furthermore, models like community acupuncture, where one practitioner can treat multiple patients in a shared space, offer a highly efficient delivery method that can alleviate workforce pressures&#x2014;a significant advantage over the one-on-one format or intensive group facilitation required for CBT. To clarify our proposed approach to CHM, we now specify that our model prioritizes established, evidence-based formulas for first-line treatment in primary care. This approach is crucial for ensuring the safety, scalability, and standardization required for broad implementation. Accordingly, we have added the following text in Section 2:</p>
                <p> </p>
                <p> 
                    <bold>Revised manuscript: </bold> 
                    <list list-type="bullet">
                        <list-item>
                            <p>
                                <bold>
                                    <italic>Chinese Medicine and Subthreshold Mental Disorders:&#x00a0;</italic>
                                </bold>
                                <italic>Crucially, network meta-analyses suggest that electroacupuncture is as effective as CBT in alleviating depressive symptoms in subthreshold depression. 
                                    <sup>44 </sup>However, acupuncture's key advantage lies in its scalability. Even with similar session requirements, 
                                    <sup>45,46 </sup>acupuncture benefits from a larger workforce and the availability of efficient models like community acupuncture, where one practitioner can treat multiple patients simultaneously. In contrast, CBT relies on a limited workforce of therapists for either individual or intensive group facilitation.&#x00a0;</italic>&#x00a0;</p>
                        </list-item>
                        <list-item>
                            <p>
                                <italic>Given this evidence of efficacy and safety, leveraging established, evidence-based formulas is recommended for treatment in primary care.&#x00a0;</italic>&#x00a0;</p>
                        </list-item>
                    </list> 
                    <bold>References</bold>
                </p>
                <p> Cuijpers, P., Berking, M., Andersson, G., Quigley, L., Kleiboer, A., &amp; Dobson, K. S. (2013). A meta-analysis of cognitive-behavioural therapy for adult depression, alone and in comparison with other treatments. The Canadian Journal of Psychiatry, 58(7), 376-385.</p>
                <p> MacPherson, H., Richmond, S., Bland, M., Brealey, S., Gabe, R., Hopton, A., ... &amp; Watt, I. (2013). Acupuncture and counselling for depression in primary care: a randomised controlled trial. PLoS medicine, 10(9), e1001518.</p>
                <p> </p>
                <p> </p>
                <p> 
                    <bold>4) Section 2 would benefit from being split into 2 paragraphs to enhance readability.</bold>
                </p>
                <p> </p>
                <p> 
                    <bold>Response: </bold>Thank you for this suggestion to improve readability. We agree and have restructured Section 2 accordingly, dividing it into four focused paragraphs. The new structure now separately covers the evidence for clinical guidelines, acupuncture, Chinese herbal medicine, and other CM modalities. We believe this provides a clearer and more logical progression of the evidence presented.</p>
                <p> </p>
                <p> </p>
                <p> 
                    <bold>5) Statement "acupressure has been shown to significantly reduce anxiety (standardized mean difference (SMD) = 1.152, 95% CI 0.847 to 1.459; p&lt;0.001)" - number is positive, implying an increase? It ma be worth restating as "a reduction of 1.152" for clarity.</bold>
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                <p> </p>
                <p> 
                    <bold>Response: </bold>Thank you for this observation. To improve the clarity of this statement, we have revised the sentence in the manuscript. 
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                                <bold>Revised manuscript: </bold>
                                <italic>For instance, acupressure has been shown to significantly reduce anxiety (a reduction in standardized mean difference (SMD) of = 1.152, 95% CI 0.847 to 1.459; p&lt;0.001), particularly effective in providing immediate relief for pretreatment anxiety.&#x00a0;</italic>
                                <sup>50</sup>
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