Clinical guidelines for adolescent depression: An integrated traditional Chinese and Western medicine approach

Abstract

The management of adolescent depressive disorder faces significant challenges, including insufficient societal, educational, and familial attention to students’ mental health issues, as well as inadequate capacity for early detection, diagnosis, and intervention. There is an urgent need to explore effective, comprehensive solutions. Based on published evidence and panel consensus, we developed this guideline, providing recommendations for the diagnosis and treatment of adolescent depression using an integrated Chinese and Western medicine approach. Integrated traditional Chinese and Western medicine effectively alleviates the somatic symptoms of adolescent depression and mitigates adverse drug reactions, thereby promoting restored social functioning and lowering risk of recurrence. This guideline emphasizes the importance of screening and prevention of depressive disorders in adolescents, with close monitoring and prevention of non-suicidal self-injury and suicidal behaviors during diagnosis and treatment. In terms of treatment, priority should be given to psychotherapy and social support, while an integrated approach combining traditional Chinese and Western medicine is recommended to alleviate symptoms and reduce adverse reactions.

Key Words: Adolescent depressive disorder; Integrated traditional Chinese and Western medicine; Guideline; Diagnosis; Therapy

Core Tip: This guideline addresses the critical challenges of delays in identification and inadequate intervention in adolescent depression. It underscores the importance of systematic screening and crisis monitoring while advocating for integrated traditional Chinese and Western medicine as a core strategy to deliver safer and more comprehensive care.

INTRODUCTION

The prevalence of psychological and behavioral problems as well as mental disorders among adolescents has been continuously increasing, emerging as a prominent global public health issue with significant implications for a sustainable societal future. However, the diagnosis and management of adolescent depressive disorders pose multiple challenges, including insufficient attention to students’ mental health issues from society, schools, and families, as well as inadequate capacity for early detection, diagnosis, and intervention. There is an urgent need to explore comprehensive and effective solutions to address these gaps.

Integrated traditional Chinese and Western medicine (TCM-WM) refers to a comprehensive diagnostic and therapeutic strategy that combines effective interventions from both medical systems for adolescent depressive disorder. This approach enhances treatment efficacy by managing somatic symptoms and drug adverse effects, thereby promoting functional recovery and reducing relapse risk. Currently, established consensus, standardized protocols, and formal guidelines are lacking for the integrated TCM-WM approach to preventing and treating depressive disorders in adolescents. We have developed this guideline which draws upon domestic and international treatment plans for adolescent depressive disorders involving TCM, Western medicine, and integrated TCM-WM approaches. Following evidence-based medicine methodology, we evaluated clinical research literature on adolescent depressive disorders, provided graded recommendations, and established expert consensus to formulate a clinical practice guideline for the integrated TCM-WM prevention and treatment of adolescent depressive disorders. This guideline was developed by adhering to the fundamental methodology prescribed in the relevant Chinese Medical Association document (2022 edition)[1], and was subsequently registered on the International Practice Guideline Registry Platform (Registration No. PREPARE-2023CN061). The guideline emphasizes the integration of TCM-WM, recommending therapeutic strategies supported by robust empirical evidence. It serves as a standardized reference to optimize clinical decision-making and improve outcomes in adolescents with depressive disorder.

GUIDELINE DEVELOPMENT METHODS

Formulation of clinical questions

A combination of patient interviews, expert interviews, and questionnaire surveys was conducted to collect opinions and suggestions regarding clinical issues and outcome indicators from three patients, four experts, and 105 physicians practicing TCM, Western medicine, and integrated Chinese and Western medicine across 17 provinces (including direct-administered municipalities). Through online expert voting, the following 10 clinical questions to be addressed in this guideline were finalized (Table 1).

Table 1 Clinical questions.

	Clinical questions
1	What is the prevalence of adolescent depressive disorder?
2	What are the risk factors for adolescent depressive disorder?
3	Which diseases should be differentiated from adolescent depressive disorder?
4	What are the TCM syndrome types of adolescent depressive disorder?
5	How should adolescent depressive disorder be screened?
6	What are the treatment objectives and precautions for adolescent depressive disorder?
7	What are the treatments for mild to moderate adolescent depressive disorder, and what are their efficacy and safety profiles?
8	What are the treatments for moderate to severe adolescent depressive disorder, and what are their efficacy and safety profiles?
9	How should the treatment duration for adolescent depressive disorder be defined?
10	What are the preventive measures for adolescent depressive disorder?

TCM: Traditional Chinese medicine.

Literature inclusion criteria

Literature retrieval for the final included guideline questions was conducted by employing a combination of subject headings and free-text terms, based on the PICOS framework with the population defined as adolescents (12-18 years) meeting diagnostic criteria for depressive disorders. Intervention: Treatment modalities including TCM, Western medicine, or integrated TCM-WM therapy. Comparison: Control measures such as Western medicine monotherapy, vehicle control, or combination therapy. Outcome: Response rate, Hamilton Depression Scale (HAMD), TCM Syndrome Score Scale, Adverse reactions, Reynolds Adolescent Depression Scale, Children’s Depression Inventory, Depression Self-Rating Scale for Children, Clinical Global Impression (CGI), Treatment Emergent Symptom Scale (TESS), Patient Health Questionnaire (PHQ)-2 or PHQ-9, Self-Rating Depression Scale, Kutcher Adolescent Depression Scale, Beck Depression Inventory-II. Study design: Study types including randomized controlled trials (RCTs), cohort studies, case-control studies, case series, systematic reviews, and meta-analyses. The HAMD and Self-Rating Depression Scale were not originally developed for adolescent populations, and evidence supporting their reliability and validity in this age group is limited[2-6]. In light of this limitation and the scarcity of high-quality studies on integrated Chinese-Western medicine for adolescent depression, a consensus was reached among the research experts to include these outcomes in the present study. Although used to objectively track efficacy data, these scales are not a clinical recommendation for adolescents.

Exclusion criteria

The exclusion criteria were as follows: (1) Literature in which diagnostic criteria for adolescent depressive disorder were unclear; (2) Duplicate reports; or publications identified as stemming from the same clinical trial; (3) Reviews, animal studies, theoretical research, or conference papers; (4) Abstract-only publications or literature for which the full text could not be accessed; and (5) Studies from which relevant data could not be extracted.

Search strategy

A systematic search was performed in the following databases: China National Knowledge Infrastructure, Wanfang, VIP Information, SinoMed, PubMed, Cochrane Library, and EMBASE. The search period spanned from the inception of each database to July 2023. The search terms included: “Adolescent”, “Adolescence”, “Teen”, “Teenager”, “Youth”, “Depression”, “Depressive Disorder”, “Depressive Symptom”, “Randomized Controlled Trial”, “Clinical Trials”, “RCT”, “Cohort study”, “Case control”, “Evidence-based”, “meta”, “meta-analysis”, “System evaluation”, and “systematic review”. The search was restricted to articles published in Chinese and English. The search strategy combined subject headings with free-text terms and was adapted as required by the specific features of each database.

Literature screening and data extraction

The guideline working group carried out the literature screening based on the pre-defined inclusion and exclusion criteria. Retrieved literature citations were imported into the NoteExpress (version 3.7.0.9296) reference management software. After removing duplicate records, preliminary screening and full-text screening were performed. A stepwise screening based on titles, abstracts, and full texts was conducted in accordance with the criteria. After the full-text review, an excel-based data extraction form was devised to gather relevant information from the final set of included studies. The screening and data extraction for each article were performed independently by two reviewers, with a third individual responsible for verification and examination of the extracted data. In cases of disagreement, the controversial articles were submitted to the secretariat and discussed collectively by expert members of the collaboration group via online meetings to reach a consensus.

Evidence evaluation

The evidence assessment was conducted by the working group under the guidance of methodological experts. Based on the study type, corresponding evaluation criteria were applied to assess the methodological quality of the literature. The Risk of Bias tool from the Cochrane Handbook for Systematic Reviews of Interventions was used to evaluate the methodological quality of RCTs. Existing systematic reviews and meta-analyses were appraised for methodological quality with the AMSTAR 2 instrument.

Quality assessment of evidence and recommendation criteria

This guideline adopts the GRADE methodology to evaluate and grade the synthesized evidence and recommendations (Supplementary Table 1). During the evidence grading process, five downgrading factors - risk of bias, imprecision, inconsistency, indirectness, and publication bias - as well as three upgrading factors - large effect size, dose-response relationship, and plausible confounding factors - were considered. Given the characteristics of integrated TCM-WM in the diagnosis and treatment of adolescent depressive disorders and the domestic clinical context, the strength of recommendations in this guideline was determined by weighing three key factors: The balance of benefits and harms of interventions, clinical feasibility, and patient values and preferences. In this guideline, recommendation refer to guidance directly derived from existing research evidence; consensus recommendation refers to collective judgments reached by the guideline expert panel through formal procedures, such as the nominal group technique, in the absence of high-quality evidence. The final recommendations and consensus recommendations were established through voting using the GRADE grid. The GRADE recommendation strength classification and corresponding expressions are detailed in Supplementary Table 2.

Formulation of recommendations

The nominal group technique was employed to conduct voting on evidence-supported opinions based on the GRADE grid, followed by the formulation of recommendations. For insufficient evidence, a majority voting rule was applied to generate recommendations. The voting criteria were as follows: If > 50% of participants selected a single voting option, a consensus was reached, directly determining both the recommendation direction (for/against) and strength (strong/weak); If the combined votes of two adjacent options on one side of the “neutral” category exceeded 70%, a consensus was achieved, establishing the recommendation direction, with the strength classified as either “weak recommendation” or “weak against”. Cases not meeting the above criteria were deemed non-consensus, and the recommendation underwent additional voting rounds. If no consensus was reached after three rounds, the statement was classified as “no recommendation formed”.

SCOPE

In this guideline, adolescents are defined as individuals aged 12 years to 18 years. It is intended for broad application within the healthcare system by clinical physicians, nursing staff, and other professionals engaged in the prevention and management of depression disorder in adolescents across relevant departments including Traditional Chinese Medicine, Integrated Traditional Chinese and Western Medicine, Psychiatry and Psychology, Pediatrics, Sleep Medicine, Psychosomatic Medicine, General Practice, as well as administrative management and health education personnel.

EPIDEMIOLOGY

Depression significantly impairs the healthy development of adolescents and imposes a substantial economic burden on families and society[7]. According to the 2019 Global Burden of Disease study, the incidence rate of depressive disorders among adolescents aged 10-19 years has reached 3.67%[8]. This high occurrence rate leads to substantial health consequences, making depressive disorders the second leading cause of years lived with disability in this age group. Furthermore, the prevalence of depressive disorders increases markedly from early to late adolescence[8]. The prevalence of depressive disorders among adolescents aged 6-16 years in China is 2%[9].

RISK FACTORS

The risk of developing depression in adolescents is influenced by multiple factors, among which the genetic component plays a significant role. Studies have shown that parental depression is an important risk factor for the offspring, and adolescents with a family history of depression have a significantly elevated risk of developing the condition[10-12].

At the biological level, neurodevelopmental mismatch and sex differences constitute potential risk factors. During adolescence, rapid physical development occurs, yet the maturation of neurocognitive and emotional regulation systems lags behind, thereby increasing susceptibility to anxiety and depression[13]. Epidemiological data indicate that the risk ratios for mild and severe depression symptom in females are 12.5% and 5.0%, respectively, both higher than those rates of 9.2% and 3.0% in males[14]. From a neurochemical perspective, the predominant hypothesis posits that depression is closely associated with dysfunction of neurotransmitter systems, particularly involving imbalances in the noradrenergic, dopaminergic, and serotonergic systems[15,16]. Neuroendocrine abnormalities are also frequently observed, especially dysregulation of the hypothalamic-pituitary-adrenal axis, characterized by elevated cortisol levels and disrupted hormonal secretion rhythms. Other hormones, including growth hormone, prolactin, melatonin, and sex hormones, are also commonly dysregulated[17-21]. Alterations in neuroplasticity are also implicated, as evidenced by abnormal expression of brain-derived neurotrophic factor[22]. At the neural circuit level, magnetic resonance imaging studies have revealed abnormalities in the serotonergic emotion-regulation circuit centered on the amygdala-medial prefrontal cortex, as well as dysfunction in the dopaminergic reward pathway involving the ventral striatum-prefrontal cortex in patients with depression[23-25]. Furthermore, neuroelectrophysiological studies have demonstrated a negative correlation between depression severity and the amplitude of interhemispheric integrated electroencephalographic signals[26,27]. Mitochondrial dysfunction, encompassing impaired energy metabolism, oxidative stress, and apoptosis, is also regarded as a significant pathological mechanism in depression[28]. Additionally, some studies suggest that gut microbiota dysbiosis and neuroinflammation may contribute to the pathogenesis, although a consensus has not yet been reached regarding these findings[29,30].

Environmental factors are also pivotal in triggering adolescent depression. Within the family environment, lower socioeconomic status, single-parent family structure, later birth order, authoritarian parenting styles, parental mental health issues, and high levels of interparental conflict significantly increase the risk of depression[14,31-37]. At the interpersonal level, poor peer relationships and experiences of either in-school bullying or cyberbullying are strong predictors of depression[38-40]. Academic pressure should not be overlooked; as adolescents progress through school and face increasing academic demands, their vulnerability of depression rises accordingly. Insufficient sleep and lack of physical activity associated with these pressures further exacerbate this trend[14,32,38].

CLINICAL MANIFESTATIONS AND DIAGNOSIS

Medical diagnosis

Adolescent depressive disorder typically presents with a persistent low mood and anhedonia. Unlike in adults with depression, its core symptoms often manifest as irritability, emotional reactivity, and mood lability[41]. The disorder is also frequently accompanied by neurovegetative disturbances (e.g., sleep and appetite disturbances, fatigue), along with behavioral problems and functional impairments. Common behavioral problems include self-harm and internet addiction, while frequent functional impairments encompass academic decline and interpersonal conflicts.

Diagnostic criteria

Adolescents with depressive disorder are diagnosed using the International Classification of Diseases-11 criteria[42].

Symptom criteria: A diagnosis of a depressive episode in adolescents requires, first, the presence of a core symptom: Either a persistently depressed mood or a markedly diminished interest in activities, which must occur nearly daily for a minimum of two weeks. Additionally, the clinical presentation may include several other symptoms, such as irritable mood; diminished pleasure; fatigue; psychomotor changes; feelings of worthlessness or guilt; impaired concentration; recurrent thoughts of death; sleep disturbances; and changes in appetite or weight. Crucially, this symptom cluster must result in clinically significant distress or functional impairment and cannot be attributed to substance use or another medical condition.

Severity criteria: The severity of a depressive episode is determined by the number of symptoms and the degree of functional impairment they cause. A mild episode meets the basic diagnostic criteria and results in some, but not substantial, difficulty in daily academic task, social interactions, or household activities. In a moderate episode, symptoms are more pronounced, and individuals experience considerable difficulty in these activities, although they may retain functionality in some domains. Finally, a severe episode is characterized by a majority of symptoms being pronounced or particularly intense, leading to a near-complete inability to maintain functionality or severe impairment across critical domains such as personal, family, social, and occupational life.

Duration criteria: The symptom criteria must be met continuously for at least two weeks.

Exclusion criteria: Individuals diagnosed with organic mental disorders, schizophrenia, bipolar disorder, or substance-induced depressive disorders were not included in the study.

Differential diagnosis

Depressive symptoms are frequently overlap with other psychiatric conditions such as bipolar disorder, schizophrenia, generalized anxiety disorder, and disruptive mood dysregulation disorder. Therefore, distinguishing adolescent depressive disorder from these conditions is crucial in clinical diagnosis.

Bipolar disorder: Bipolar disorder presents with episodes of mania/hypomania and depression that alternate over time. The manic phase typically presents with elevated mood, racing thoughts, and increased activity; the depressive phase manifests as depressed mood, slowed thinking, and reduced activity. Bipolar disorder is often misdiagnosed as depressive disorder during its depressive phase. For differential diagnosis, it is important to note that adolescent patients with bipolar disorder frequently have a family history, exhibit hypomanic features, and experience an acute onset, short course, and high relapse rate. Furthermore, when treating adolescents diagnosed with depressive disorder, clinicians must maintain a high level of vigilance for the risk of switching to mania. Close monitoring of symptom changes is essential to achieve early identification and early intervention[42,43].

Schizophrenia: Schizophrenia is a progressive disorder characterized by primary positive symptoms (e.g., hallucinations, delusions) and negative symptoms (e.g., affective flattening, avolition), which reflect a core discoordination between thought, emotion, and behavior. The co-occurring depressive symptoms in schizophrenia are predominantly secondary and transient, lasting for a shorter duration than the disorder’s primary symptoms[42,43].

Generalized anxiety disorder: The core presentation of anxiety disorders involves excessive and uncontrollable fear and worry. This is accompanied by somatic manifestations, including autonomic dysfunction and psychomotor agitation. Symptom severity often fluctuates in response to identifiable stressors, leading to urgent help-seeking. Depressive symptoms associated with anxiety disorders are often subsequent to prolonged tension and mental exhaustion, manifesting as irritability, fatigue, and difficulty concentrating, although core motivation may not be entirely lost[42,43].

Disruptive mood dysregulation disorder: Characteristic of disruptive mood dysregulation disorder are severe temper outbursts, occurring frequently (≥ 3 days weekly), which are markedly disproportionate to the context. The emotional experience is often characterized by irritability and intolerance to frustration, rather than the core symptoms of depressive disorders such as low mood and loss of interest. Between these outbursts, the individual’s mood is persistently irritable or angry. To meet diagnostic criteria, the following must be satisfied: Symptom onset before age 10; a duration of at least 12 months; and no prior manic or hypomanic episode exceeding one day in length[42,43].

TCM diagnostic criteria and treatment based on syndrome differentiation

TCM diagnosis: Adolescent depressive disorder falls under the TCM diagnostic categories of “yu zheng” (depression syndrome) or “yu bing” (depression disease). According to the TCM theory, this condition is characterized primarily by symptoms including persistent sadness with frequent crying, mental restlessness, irritability with insomnia, reduced appetite, and mental confusion.

Adolescent depression in TCM is closely linked to the constitutional tendency of “frequently excessive liver and frequently deficient spleen”[44]. The core pathogenesis is liver qi stagnation, which initially presents as an excess pattern. This stagnation may transform into fire that harasses the mind, leading to irritability and insomnia. Moreover, stagnant liver qi often invades the spleen, impairing its transformation and transportation functions and generating internal phlegm-dampness. If the condition persists, it evolves into a deficiency pattern that consumes heart and spleen qi, resulting in qi and blood deficiency that fails to nourish the spirit. Consequently, the clinical presentation is typically a complex interplay of deficiency and excess, characterized by intertwined qi stagnation, phlegm coagulation, and fire depression[45]. The TCM syndrome differentiation and treatment approach are summarized in Table 2.

Table 2 Traditional Chinese medicine syndrome differentiation and treatment of adolescent depressive disorder.

Syndrome diagnosis	Core symptoms	Tongue and pulse	Medication
Liver qi stagnation	Main symptoms: Depressed mood, restlessness. Secondary symptoms: Slowed thinking, self-blame and low self-esteem, aversion to learning, or reticence, delayed response, distending pain in the hypochondrium, epigastric stuffiness with belching, poor appetite, dull complexion	Pale tongue with thin white coating; wiry and thready pulse	Modified Chaihu shugan powder
Stagnation of qi transforming into fire	Main symptoms: Depressed mood, irritability, distending pain in the chest and hypochondrium. Secondary symptoms: Aggressive behavior, social withdrawal, restlessness and agitation, poor concentration, bitter taste in the mouth, dry mouth, loss of appetite, or headache, red eyes, tinnitus, constipation	Red tongue with thin white or yellow coating; wiry and rapid pulse	Modified Danzhi xiaoyao san
Syndrome of phlegm-qi stagnation	Main symptoms: Low mood, sensation of a foreign body in the throat that cannot be swallowed or expected. Secondary symptoms: Chest tightness, distending pain in the hypochondrium, cough with sputum, or sputum production without cough, or accompanied by stabbing pain in the chest and hypochondrium	Pale red tongue with white greasy coating; wiry and slippery pulse	Modified Banxia houpu decoction
Liver stagnation and spleen deficiency	Main symptoms: Low mood, distension and fullness in the hypochondria, frequent sighing. Secondary symptoms: Sentimentality, excessive rumination, reticence, insomnia, forgetfulness, social withdrawal, fatigue, decreased appetite, weight loss, or accompanied by dizziness, abdominal distension, diarrhea, or constipation	Pale tongue with thin white coating; wiry and thready pulse	Modified Xiaoyao powder
Deficiency of heart and spleen	Main symptoms: Excessive contemplation and worry, poor appetite, fatigue. Secondary symptoms: Palpitations, dream-disturbed sleep, sallow complexion, numbness in the limbs, dizziness, spontaneous sweating, abdominal distension, loose stools, irregular menstruation	Pale tongue and tender with white coating; thready and weak pulse	Modified Guipi decoction

SCREENING

Screening scope and frequency

Consensus recommendation 1: It is recommended that adolescents aged 12-18 years undergo annual screening for depressive symptoms, with repeated screening for those at high risk of depressive disorders (recommendation 82.14%, neutral 17.86%).

Early screening for depressive disorders allows for timely intervention in adolescents. The United States Preventive Services Task Force recommends screening for individuals aged 12-18, citing a moderate net benefit[36]. Key high-risk groups include adolescents with a personal or family history of depression, other mental disorders, trauma, or substance use[46]. However, evidence on the optimal interval for repeated screening is currently unavailable.

Selection of screening scales

Consensus recommendation 2: The PHQ-9 is recommended for screening depressive disorders in adolescents (recommendation 75.00%, neutral 25.00%).

The internationally recognized screening tool for adolescent depression is the PHQ-9, which has been recommended by organizations such as the International Consortium for Health Outcomes Measurement and the United States Preventive Services Task Force[46,47]. Its brevity and ease of comprehension make them suitable for depression screening in adolescents[46,47].

Post-screening management

Consensus recommendation 3: Adolescents identified as being at risk for depressive disorders through screening should be referred to specialized institutions for comprehensive assessment and diagnosis (recommendation 100.00%).

Adolescents at risk of depression should be promptly referred to mental health specialists for comprehensive evaluation and treatment. This applies to individuals identified through screening tools, those reporting emotional distress, or cases where clinicians suspect depression irrespective of screening outcomes[48].

Based on the aforementioned consensus recommendations, a stepped screening and crisis monitoring pathway is proposed to enhance clinical operability: Annual universal PHQ-9 screening; operationalized positive screening criteria (PHQ-9 total score ≥ 10 or item 9 score ≥ 1); same-day multi-source comprehensive risk assessment for screening positive cases integrating standardized scales, clinical interviews, and behavioral observations; risk-stratified interventions whereby high-risk cases or those presenting with suicide risk are referred to psychiatric services, whereas low-risk cases receive school-based psychosocial support with 1-2 weeks of active monitoring; and reassessment to determine the final management plan. The screening and monitoring pathway is shown in Figure 1.

Figure 1 Adolescent depression screening and monitoring pathway. PHQ-9: Patient Health Questionnaire-9.

TREATMENT

Treatment objectives and considerations

Consensus recommendation 4: The primary objectives of treating depressive disorders in adolescents are symptom alleviation, functional recovery, and reduction of relapse risk (recommendation 100.00%).

The central aims in managing adolescent depression are to reduce symptomatology, achieve functional recovery, and mitigate the risk of future relapse[49]. As recommended by the Guidelines for Adolescent Depression in Primary Care, progress toward these goals should be systematically and regularly monitored[50]. Aimed at achieving distinct clinical goals, antidepressant therapy is therefore categorized into acute, continuation, and maintenance phases. The objective shifts from symptom remission in the acute phase to preventing relapse and recurrence in the later stages. Treatment outcomes are defined as follows: (1) Response: Significant symptom reduction sustained for at least 2 weeks; (2) Remission: Minimal or absent symptoms lasting at least 2 weeks but less than 2 months; (3) Recovery: Defined as a period of 2 months or longer during which significant symptoms are absent; (4) Relapse: Recurrence of depressive episodes during remission; and (5) Recurrence: Recurrence of depressive episodes after recovery[51]. The treatment protocol consists of three phases: The acute phase lasting 4-12 weeks or until symptom remission is achieved, with monitoring every 1-2 weeks; the consolidation phase lasting 6-12 months with monitoring every 2-4 months; and the maintenance phase lasting 1-3 years with monitoring every 1-3 months[50-54]. In clinical practice, treatment is dynamically adjusted based on the patient’s specific condition, syndrome differentiation results, treatment response, and medication adherence.

Consensus recommendation 5: Close monitoring and prevention of non-suicidal self-injury and suicidal behaviors should be implemented throughout the treatment of depressive disorders in adolescents (recommendation 100.00%).

To manage the safety risks associated with antidepressants in adolescents, such as suicidal ideation, clinicians must thoroughly inform patients and their families about the treatment plan, expected timeline, and potential side effects. Close and continuous monitoring for any adverse events is essential, especially during the initial phase of pharmacotherapy[55].

Treatment of mild adolescent depressive disorder

Consensus recommendation 6: For adolescents diagnosed with mild depressive disorder, it is recommended to first actively improve relationships within family, school, and interpersonal contexts, while strengthening social support and implementing regular monitoring (recommendation 96.43%, neutral 3.57%).

For adolescents diagnosed with mild depressive disorder, a period of active support and monitoring is often advisable before treatment commencement. The recommended monitoring frequency involves active surveillance conducted every 1-2 weeks over a period of 6-8 weeks[50]. Active support is a critical and effective treatment for adolescent depression, requiring a collaborative alliance among the family, school, and community. This approach focuses on reducing stressors, monitoring symptoms, and fostering an understanding and accepting environment for the adolescent. Adolescents with mild depression are encouraged to adopt a healthy lifestyle, including maintaining a regular sleep schedule, ensuring adequate sleep, having a balanced diet, and engaging in regular aerobic exercise (3-5 times per week, 30-45 minutes per session)[56].

Treatment of moderate adolescent depressive disorder

Consensus recommendation 7: Psychotherapy is recommended as the first-line treatment for adolescents with mild depressive disorder, with cognitive-behavioral therapy (CBT), interpersonal therapy (IPT), and family therapy being prioritized (recommendation 96.43%, neutral 3.57%).

For mild-to-moderate depression in adolescents, psychotherapy, particularly CBT or IPT, is recommended as the first-line intervention (once a week for a duration of 8-16 weeks)[50,54,55]. As an effective therapeutic intervention for adolescent depression, CBT enhances clinical symptoms and improves daily functioning. It works with two main techniques. Cognitive restructuring: Helping patients identify and change habitual negative thought patterns. Behavioral activation: Encouraging patients to set goals and engage in enjoyable, rewarding activities to boost motivation and mood[55].

IPT is a structured psychotherapy that treats adolescent depression by improving social functioning and reducing stress within key relationships. Treatment typically unfolds in three phases. Initial phase: The therapist and patient build an alliance and identify one primary interpersonal problem area to focus on, such as grief, interpersonal conflicts, role transitions, or social deficits. Middle phase: They actively work together to address and resolve issues within the chosen problem area. Termination phase: The focus shifts to maintaining the patient’s progress, reinforcing skills, and preventing future relapse[55].

Consensus recommendation 8: For mild-to-moderate adolescent depressive disorder, treatment with syndrome differentiation-based Chinese herbal medicine (CHM), Chinese patent medicine, or acupuncture therapy is recommended (recommendation 85.71%, neutral 14.29%).

CHM, Chinese patent formulas and acupuncture are all viable treatments for moderate adolescent depressive disorder. TCM helps alleviate persistent energy metabolism disorders and overall functional impairment, such as fatigue, decreased appetite, and lack of motivation, by improving mitochondrial function[57,58]. Additionally, TCM has demonstrated definitive therapeutic effects on anxiety/somatization, cognitive function, psychomotor retardation, and sleep disturbances[59]. The selection of CHM is based on TCM syndrome differentiation. In the selection of Chinese patent medicines, Shugan granules are used for liver qi stagnation with irritability, sighing, and chest-flank pain; Shugan Jieyu capsules or Xiaoyao pills for liver depression and spleen deficiency with anorexia, bloating, and loose stools; Morinda officinalis oligosaccharide capsules for kidney yang deficiency with aversion to cold, cold extremities, lower back soreness, and nocturia; and Wuling capsules for associated insomnia[60].

As a simple, convenient, effective, and cost-efficient non-pharmacological therapy, acupuncture exhibits multi-target and multi-pathway therapeutic effects. Studies have shown that 4 weeks of acupuncture monotherapy can reduce HAMD-24 scores by 10 points and significantly improve factor scores including anxiety/somatization, cognitive impairment, sleep disturbance, psychomotor retardation, body weight, diurnal variation, and feelings of despair[53]. Furthermore, acupuncture can rapidly regulate autonomic nervous function and modulate the activity of the brain’s default mode network[61-64]. A meta-analysis demonstrated that, compared with sham acupuncture, acupuncture significantly reduced the HAMD scores in adult patients with depressive disorder [920 cases, mean difference (MD) = -4.49, 95% confidence interval (CI): -5.93 to -3.04][2]. For adolescents, acupuncture can be used as a monotherapy for moderate depression, while for severe cases, it may be combined with CHM or antidepressants. Commonly selected acupoints for soothing liver qi stagnation, nourishing the heart, and regulating the spirit include Baihui (GV20), Yintang (EX-HN3), Taichong (LR3), Shenmen (HT7), and Neiguan (PC6). Additional acupoints may be selected based on syndrome differentiation: Danzhong (CV17) and Qimen (LR14) for liver qi stagnation; Xingjian (LR2) and Xiaxi (GB43) for qi stagnation transforming into fire; Fenglong (ST40) and Zhongwan (CV12) for phlegm-qi stagnation; Ganshu (BL18) and Zusanli (ST36) for liver depression and spleen deficiency; and Sanyinjiao (SP6) and Xinshu (BL15) for heart-spleen deficiency.

Drug interactions among herbal medicines and between herbal and Western medications should be monitored during TCM treatment. Prior to acupuncture, the risk of needle sickness should be assessed, and patients should be closely monitored during treatment. Acupuncture is contraindicated at sites of skin damage, infection, scarring, or tumors.

Consensus recommendation 9: For adolescents with moderate depressive disorder who exhibit no significant symptomatic improvement after 4 weeks of monotherapy, a combination of two or more therapeutic approaches may be considered (recommendation 85.71%, neutral 14.29%).

For adolescents with moderate depressive disorder who show no significant symptomatic improvement after 4 weeks of monotherapy - such as psychotherapy, syndrome differentiation-based CHM, Chinese patent medicine, or acupuncture, or repetitive transcranial magnetic stimulation (rTMS) - a combination of two or more therapeutic approaches may be considered.

Recommendation 1: Acupuncture combined with psychotherapy is recommended for the treatment of moderate adolescent depression to alleviate depressive symptoms (evidence level: GRADE 1C; strong recommendation 53.57%, weak recommendation 32.14%, neutral 10.71%, weak recommendation against 3.57%).

Compared with conventional antidepressant pharmacotherapy combined with psychotherapy, acupuncture combined with psychotherapy significantly reduces the HAMD score (RCT, 60 cases, MD = -4.36, 95%CI: -7.78 to -0.94)[65].

Recommendation 2: CHM combined with psychotherapy is recommended for the treatment of moderate adolescent depressive disorder to alleviate depressive symptoms (evidence level: GRADE 1C; strong recommendation 64.29%, weak recommendation 35.71%).

When adjunctive to psychotherapy (CBT), CHM (e.g., Shugan Jieyu capsule) significantly reduces the HAMD score (RCT, 60 cases, MD = -6.38, 95%CI: -7.80 to -4.96)[66].

Recommendation 3: For moderate adolescent depression, acupuncture combined with syndrome-differentiated CHM is recommended to alleviate depressive symptoms (evidence level: GRADE 1C; strong recommendation 57.14%, weak recommendation 32.14%, neutral 10.71%).

Compared with antidepressant monotherapy (fluoxetine), the combination of acupuncture and CHM (Chaihu Jia Longgu Muli Tang) demonstrated superior outcomes: Reduction in HAMD scores (RCT, 120 cases, MD = -2.70, 95%CI: -5.34 to -0.06), and improved response rate [RCT, 120 cases, risk ratio (RR) = 1.22, 95%CI: 1.04-1.42][67].

Treatment of severe adolescent depressive disorder

Recommendation 4: Pharmacotherapy with Western medicine antidepressants is recommended for moderate-to-severe adolescent depressive disorder, with fluoxetine and sertraline as the preferred first-line agents (evidence level: GRADE 1C; strong recommendation 82.14%, weak recommendation 17.86%).

For severe adolescent depressive disorder, selective serotonin reuptake inhibitors (SSRIs) antidepressants, such as fluoxetine and sertraline, should be the first-choice treatment[55,68,69]. A meta-analysis demonstrated that, compared with vehicle, fluoxetine significantly reduced the Depression Self-Rating Scale for Children scores in adolescents with depressive disorders (meta, 1183 cases, MD = -2.72, 95%CI: -3.96 to -1.48) and decreased the CGI scores (meta, 957 cases, MD = -0.21, 95%CI: -0.36 to -0.06)[70]. No statistically significant difference was observed in the incidence of adverse events between fluoxetine and vehicle (meta, 1038 cases, RR = 1.03, 95%CI: 0.95-1.11)[70]. A network meta-analysis indicated that among 14 antidepressant medications for acute-phase treatment of adolescent depression, fluoxetine exhibited significantly superior efficacy compared with vehicle (MD = -0.51, 95%CI: -0.99 to -0.03)[71]. Additionally, compared with vehicle, sertraline significantly reduced the CGI-improvement scores in adolescents with depressive disorders (meta, 376 cases, MD = -3.16, 95%CI: -3.46 to -2.86)[71]. No statistically significant difference was found in the incidence of adverse events between sertraline and vehicle (meta, 199 cases, RR = 2.33, 95%CI: 0.94-5.76)[72].

Consensus recommendation 10: The use of citalopram, escitalopram, or fluvoxamine is recommended for the treatment of severe adolescent depressive disorder (recommendation 67.86%, neutral 32.14%).

If the initial antidepressant fails to achieve full efficacy, treatment should be adjusted based on the patient’s response. For patients with a partial response and good tolerability, the dose should be increased to the maximum level or psychotherapy should be added. However, if there is no response at the maximum dose, clinicians should consider switching to an alternative antidepressant. According to the Guidelines for Adolescent Depression in Primary Care, the American Academy of Child and Adolescent Psychiatry guidelines, and the Canadian Network for Mood and Anxiety Treatments guidelines, alternative SSRIs such as citalopram, escitalopram, or fluvoxamine are recommended options, supported by their established safety profiles and pharmacokinetic suitability in adolescent populations[50,51,73].

During the initial 4 weeks of fluvoxamine administration, patients may experience activation symptoms, including hyperactivity, irritability, agitation, and anxiety. To mitigate these symptoms, short-term concomitant use of benzodiazepine sedatives may be considered, with careful attention to risks of dependence and cognitive effects, and a tapering plan upon discontinuation[74]. Antidepressant therapy requires dose titration to the therapeutic level over 4-6 weeks (acute phase), with weekly monitoring for adverse effects and treatment response evaluation[55]. If no significant clinical improvement is observed after 4-6 weeks, either increasing the initial SSRIs dosage or switching to an alternative SSRIs should be considered[55]. Table 3 presents clinically recommended antidepressants and their approved dosages for adolescent depressive disorders[50]. Dose adjustment must be individualized and cautious to maintain the lowest effective dose[73].

Table 3 Selective serotonin reuptake inhibitors titration schedule (mg/day).

Medication	Starting dose	Increments	Effective dose	Maximum dose	Titration period	Safety instructions
Fluoxetine	10	10-20	20	60	Titrate to 20 mg/day after 1 week; consider lower dose for low-weight adolescent	Monitor for suicidal ideation and behavior
						Contraindicated with MAOIs
						Long half-life
						Monitor for activation syndrome
						Refer to prescribing information for complete safety data
Sertraline	25	12.5-25	50	200	Titrate over 2-4 weeks, intervals ≥ 1 week	Monitor for suicidal ideation and behavior
						Contraindicated with MAOIs
						QT prolongation risk; ECG monitoring when indicated
						Monitor for manic switch
						Monitor for abnormal bleeding
						Periodic hepatic and renal function monitoring
						Refer to prescribing information for complete safety data
Escitalopram	10	5	10	20	Titrate over 2-4 weeks, intervals ≥ 1 week	Monitor for suicidal ideation and behavior
						Contraindicated with MAOIs
						Monitor for manic switch
						Monitor for abnormal bleeding
						Monitor for serotonin syndrome
						Monitor for hyponatremia
						Refer to prescribing information for complete safety data
Citalopram	10	10	20	40	Titrate over 2-4 weeks, intervals ≥ 1 week	Monitor for suicidal ideation and behavior
						Contraindicated with MAOIs
						Monitor for manic switch
						Monitor for serotonin syndrome
						Monitor for hyponatremia
						Refer to prescribing information for complete safety data
Fluvoxamine	25	25	50	200	Titrate by 25 mg every 4-7 days	Monitor for suicidal ideation and behavior
						Contraindicated with MAOIs
						Monitor for manic switch
						CYP450 inhibitor; multiple drug interactions
						Refer to prescribing information for complete safety data

MAOIs: Monoamine oxidase inhibitors; QT: QT interval; ECG: Electrocardiogram.

Recommendation 5: The combination of Western antidepressants with rTMS is recommended for adolescents with severe depressive disorder to enhance therapeutic efficacy (evidence level: GRADE 1C; strong recommendation 67.86%, weak recommendation 28.57%, neutral 3.57%).

Combination therapy with antidepressants and rTMS is also an option for treating severe depressive disorder. A meta-analysis confirmed that combining rTMS with antidepressants is significantly more effective at reducing HAMD scores [meta, 464 cases, standardized mean difference (SMD) = -1.50, 95%CI: -2.16 to -0.84] than using antidepressants alone, and had significantly greater response (meta, 406 cases, RR = 1.35, 95%CI: 1.04-1.76) and remission (meta, 306 cases, RR = 1.35, 95%CI: 1.03-1.77), without increasing side effects[4,75]. Standard rTMS protocols typically employ either high-frequency (10 Hz) stimulation applied to the left dorsolateral prefrontal cortex or low-frequency (1 Hz) stimulation applied to the right dorsolateral prefrontal cortex. Treatment sessions are usually administered once daily or every other day, with no more than two days between sessions. A typical course consists of 14 sessions to 30 sessions, delivered over a period of 2 weeks to 8 weeks[3,76-80]. Contraindications for rTMS include: History of epilepsy or seizures; metallic or electronic implants in close contact with the stimulation coil, including cochlear implants, cardiac pacemakers, medication pumps, and cerebrospinal fluid shunts; and intracranial pathological conditions such as vascular, traumatic, neoplastic, infectious, or metabolic brain lesions[81].

Consensus recommendation 11: For adolescents with severe depressive disorder, a combination of Western antidepressants with syndrome-differentiated CHM, Chinese patent medicine, or acupuncture is recommended to enhance therapeutic efficacy and reduce adverse effects (recommendation 67.86%, neutral 32.14%).

Antidepressants can be combined with CHM, patent formulas, or acupuncture to enhance efficacy and reduce adverse reactions[69,82]. This synergy leads to a faster antidepressant response, better medication adherence, fewer side effects, and an overall improved quality of life, ultimately enhancing treatment efficacy and safety while lowering the risk of relapse[83,84].

Recommendation 6: Acupuncture combined with antidepressant drugs is recommended for the treatment of severe adolescent depressive disorder to alleviate depressive symptoms and reduce adverse effects (evidence level: GRADE 1C; strong recommendation 57.14%, weak recommendation 32.14%, neutral 7.14%).

Compared with antidepressant drugs alone, adjunctive acupuncture therapy significantly reduced HAMD scores (RCT, 198 cases, MD = -4.67, 95%CI: -5.24 to -4.11)[82,85] and improved response rate (RCT, 120 cases, RR = 1.16, 95%CI: 1.04-1.30)[82]. In one of the included studies, which assessed adverse effects using the TESS, the combination of acupuncture and antidepressants significantly reduced TESS scores compared to antidepressants alone (RCT, 120 cases, MD = -6.69, 95%CI: -7.68 to -5.70)[82].

Recommendation 7: The combination of syndrome differentiation-based TCM and Western antidepressant drugs is recommended for the treatment of severe adolescent depression to alleviate depressive symptoms, reduce anxiety, and improve sleep quality (evidence level: GRADE 1C; strong recommendation 75%, weak recommendation 21.43%, neutral 3.57%).

When combined with Western antidepressant therapy (sertraline), adjunctive TCM treatments (including Wuling capsule, Shugan Jieyu capsule, Shumian capsule, and syndrome differentiation-based TCM formulations) demonstrated the following effects: (1) Reduction in HAMD scores (RCT, 355 cases, MD = -1.69, 95%CI: -2.79 to -0.59)[5,86-89]; (2) Reduction in Hamilton Anxiety Scale scores (RCT, 60 cases, MD = -3.05, 95%CI: -3.67 to -2.43)[5]; (3) Reduction in Insomnia Severity Index scores (RCT, 60 cases, MD = -3.05, 95%CI: -3.59 to -2.51)[5]; (4) Reduction in TCM syndrome scores (RCT, 50 cases, MD = -2. 68, 95%CI: -3.59 to -1.77)[89]; and (5) Improvement in response rate (RCT, 294 cases, RR = 1.16, 95%CI: 1.06-1.27)[86,88-90]. Compared with antidepressant drugs alone, the combination of TCM and antidepressant drugs showed no significant difference in reducing TESS scores (RCT, 190 cases, MD = -2.21, 95%CI: -4.98 to 0.56)[5,87,88].

Recommendation 8: The combination of antidepressants and psychotherapy (CBT) is recommended for adolescents with severe depressive disorder to prevent relapse or recurrence (evidence level: GRADE 1B; strong recommendation 96.43%, weak recommendation 3.57%).

In adolescents with depressive disorder who responded to fluoxetine during the acute phase, the addition of CBT to continued fluoxetine treatment was more effective in preventing relapse/recurrence than fluoxetine alone[55]. A meta-analysis demonstrated that fluoxetine, either as monotherapy or in combination with psychotherapy, is the optimal choice for the acute treatment of severe depressive disorder in adolescents[91]. Multiple guidelines recommend the combination of SSRIs and psychotherapy for adolescents with moderate or severe depressive disorder[50,54]. Meta-analysis results indicated that, compared with fluoxetine monotherapy, the combination of fluoxetine and CBT significantly reduced the relapse rate in adolescent patients with depressive disorder, based on relapse data from included studies (meta, 648 cases, RR = 0.44, 95%CI: 0.34-0.56)[92,93]. Additionally, combination therapy reduced HAMD scores (meta, 604 cases, SMD = -1.01, 95%CI: -1.39 to -0.63), and CGI scores (meta, 568 cases, SMD = -0.22, 95%CI: -0.54 to -0.10), increased response rate (meta, 628 cases, RR = 1.12, 95%CI: 1.04-1.21), reduced suicide risk (meta, 568 cases, RR 0.94, 95%CI: 0.74-1.20), and decreased the incidence of adverse reactions (meta, 850 cases, RR = 0.62, 95%CI: 0.4-0.96)[92].

Consensus recommendation 12: Modified electro-convulsive therapy (MECT) is recommended only for adolescents with severe major depressive disorder (recommendation 60.71%, neutral 32.14%, non-recommendation 7.14%).

MECT is a last-resort treatment for adolescents with the most severe, life-threatening, or treatment-resistant depression. It is highly effective but carries risks, including cognitive impairment, and should only be considered when all other therapies have failed[54]. A standard course of ECT typically comprises 6-12 sessions administered at a frequency of twice a week[54]. The absolute contraindication for MECT in adolescents with depression is allergy to the anesthetic agents or muscle relaxants used. Relative contraindications include central nervous system tumors, increased intracranial pressure, space-occupying lesions, recent myocardial infarction, unstable angina, uncontrolled hypertension, severe cardiac arrhythmias, recent stroke, cerebral aneurysm, severe respiratory disease, and pheochromocytoma. In the presence of relative contraindications, treatment should only be administered after careful consideration of the benefits and risks[94]. Table 4 summarizes the efficacy and safety of combined treatment with SSRIs for adolescent depression.

Table 4 Efficacy and safety of combined treatment with selective serotonin reuptake inhibitors for adolescent depression.

Treatment	Outcomes	Response/remission	Adverse events/rate
SSRIs + CBT vs SSRIs	Relapse rate (504, RR = 0.27, 95%CI: 0.16-0.45). HAMD (604, SMD = -1.01, 95%CI: -1.39 to -0.63). CGI (568, SMD = -0.22, 95%CI: -0.54 to -0.10)	Response (628, RR = 1.12, 95%CI: 1.04-1.21)	850, RR = 0.62, 95%CI: 0.4-0.96. Headache, nausea, hyperhidrosis, dizziness, lethargy and incidents of suicide or NSSI
SSRIs + rTMS vs SSRIs	HAMD (464, SMD = -1.50, 95%CI: -2.16 to -0.84)	Response (406, RR = 1.35, 95%CI: 1.04-1.76). Remission (306, RR = 1.35, 95%CI: 1.03-1.77)	Without increasing side effects (P = 0.14-0.82). Headache, loss of appetite, dizziness and nausea
SSRIs + syndrome-differentiated CHM vs SSRIs	HAMD (355, MD = -1.69, 95%CI: -2.79 to -0.59). HAMA (RCT, 60, MD = -3.05, 95%CI: -3.67 to -2.43). ISI (RCT, 60, MD = -3.05, 95%CI: -3.59 to -2.51). TCM syndrome scores (50, MD = -2.68, 95%CI: -3.59 to -1.77)	Response (294, RR = 1.16, 95%CI: 1.06-1.27)	TESS (190, MD = -2.21, 95%CI: -4.98 to 0.56). Loss of appetite, diarrhea, insomnia, hypersomnia
SSRIs + acupuncture vs SSRIs	HAMD (198, MD = -4.67, 95%CI: -5.24 to -4.11)	Response (120, RR = 1.16, 95%CI: 1.04-1.30)	TESS (120, MD = -6.69, 95%CI: -7.68 to -5.70)

SSRIs: Selective serotonin reuptake inhibitors; CBT: Cognitive-behavioral therapy; RR: Risk ratio; CI: Confidence interval; HAMD: Hamilton Depression Scale; SMD: Standardized mean difference; CGI: Clinical Global Impression; HAMA: Hamilton Anxiety Scale; MD: Mean difference; ISI: Insomnia Severity Index; rTMS: Repetitive transcranial magnetic stimulation; CHM: Chinese herbal medicine; RCT: Randomized controlled trial; TCM: Traditional Chinese medicine; TESS: Treatment Emergent Symptom Scale.

Consensus recommendation 13: It is recommended that adolescent patients with depressive disorder continue antidepressant treatment for 6-12 months after symptom remission (recommendation 89.29%, neutral 10.71%).

To prevent relapse, adolescents should continue antidepressant therapy for 6-12 months after their symptoms resolve, followed by a gradual tapering of the medication[54,68,95]. During this tapering period, adjunctive treatments like TCM or acupuncture can be used to help manage withdrawal and reduce adverse effects[60].

PREVENTION

Consensus recommendation 14: Early screening and intervention are recommended for adolescents with risk factors (recommendation 96.43%, neutral 3.57%).

Comprehensive screening for depressive symptoms in adolescents aged 12 years and older[95], in conjunction with an assessment of risk factors, facilitates the early identification of depressive disorders, enabling timely detection, diagnosis, and intervention.

Consensus recommendation 15: It is recommended that all adolescents receive mental health education and behavioral guidance (recommendation 100.00%).

Good psychological resilience enables adolescents to adapt quickly to environmental stressors, and such resilience can be enhanced through health education[96]. Health education refers to fostering positive emotional responses, correcting negative cognitive patterns, adjusting stress-coping strategies, improving interpersonal relationships, enhancing social functioning and life skills, ensuring regular and adequate sleep, engaging in appropriate physical activity, and pursuing enjoyable and meaningful activities[51,97,98]. The “Healthy China Initiative-Mental Health Action Plan for Children and Adolescents (2019-2022)” proposed the “Two Ones” campaign, encouraging students to engage in 15 minutes of effective daily communication with peers or family members and to participate in at least one hour of physical activity per day to promote adolescent mental health.

Good behavioral habits contribute to the prevention of depressive disorders in adolescents and facilitate recovery in those affected. Adolescents are advised to cultivate healthy sleep habits by shifting their sleep rhythm from a late-to-bed, late-to-rise pattern to an early-to-bed, early-to-rise pattern. Maintaining a regular daily schedule with fixed sleep-wake times is recommended. A balanced diet should be ensured, incorporating whole grains, vegetables, fruits, legumes, and dairy products, while consuming fish, poultry, eggs, and lean meats in moderation. Intake of spicy, greasy, and highly processed foods should be minimized. Appropriate application of TCM techniques - such as moxibustion, auricular acupressure, foot baths, massage, gua sha, five-tone therapy, and the six-healing sounds (Liu Zi Jue) - may be utilized to promote health and enhance physical and mental resilience. A reasonable exercise plan should be established to ensure daily physical activity without excessive fatigue. Recommended activities include jogging, Tai Chi, Baduanjin, and yoga.

Family education plays a pivotal role in protecting students’ mental health and personality development. It is recommended that parents receive family mental health education to enhance their awareness of psychological well-being, reinforce the importance of their children’s mental health, and adopt appropriate parenting philosophies. Additionally, parents should be equipped with scientifically validated educational methods to ensure that family-based psychological education aligns with school mental health initiatives. Such coordinated efforts will establish a supportive environment conducive to children’s healthy growth. A summary of recommended treatment methods for adolescent depressive disorder is presented in Figure 2.

Figure 2 Recommended treatment methods for adolescent depression. ICD-11: The 11^th revision of the International Classification of Diseases; TCM: Traditional Chinese medicine; CBT: Cognitive-behavioral therapy; IPT: Interpersonal therapy; CHM: Chinese herbal medicine; MECT: Modified electroconvulsive therapy; rTMS: Repetitive transcranial magnetic stimulation.

CONCLUSION

This document provides expert consensus guidelines on TCM-WM integrated management for adolescent depressive disorders. By standardizing these approaches, the guideline aims to enhance clinical efficacy, improve therapeutic outcomes, optimize healthcare services, and ultimately reduce the disease burden for this vulnerable population. While this guideline provides a critical framework, several evidence gaps highlight key directions for future research. Firstly, there is a need for more high-quality clinical trials, particularly multicenter, large-sample, randomized, and appropriately controlled studies on TCM-WM interventions. Secondly, more precise integrated Chinese and Western medicine treatment plans need to be defined, such as the frequency and duration of acupuncture treatment cycles. Finally, establishing a comprehensive data-sharing platform for adolescent depression is essential, as leveraging these data with artificial intelligence and machine learning could significantly accelerate the development of new diagnostic and therapeutic technologies. This guideline provides directional guidance for the design and implementation of future high-quality research by systematically synthesizing existing evidence and identifying research gaps.

Rooted in Chinese clinical practice and cultural contexts, this guideline’s global applicability and effectiveness necessitate rigorous cross-cultural validation. Future research must extend beyond mere efficacy verification to investigate the cross-cultural acceptability and adherence to therapies like acupuncture and herbal medicine, alongside strategies for their innovative integration with established Western treatments such as cognitive behavioral therapy. A comprehensive assessment should also encompass biopsychosocial disparities, international variations in healthcare policy, and degrees of cultural integration. Therefore, promoting international multicenter studies to systematically compare the therapeutic mechanisms and outcomes of this integrated model across diverse populations is imperative. Such efforts are fundamental to the guideline’s successful global dissemination, its precise localization, and the advancement of a truly personalized, globally-informed diagnostic and treatment framework.

ACKNOWLEDGEMENTS

The expert group for the Guidelines, listed alphabetically by last name, includes: Jun-Ling Cao; Gang Chen; Jian-Hua Chen; Jue Chen; Sheng-Liang Chen; Rong-Jing Ding; Yan-Ping Duan; Jian-Qun Fang; Li-Yun He; Zhen-Yun Han; Li-Juan He; Xia Hong (A); Xia Hong (B); Jun-Shan Huang; Fu-Jun Jia; Hong-Xiao Jia; Xue-Jing Jin; Li Kuang; Yuan-Yuan Li; Feng Li; Shu-Ying Li; Xiu-Yu Li; Yan Li; Qiao Lin; Cui-Lian Liu; Hua-Qing Liu; Jian-Ping Liu; Xiang-Zhe Liu; Zhong-Chun Liu; Zheng Lu; Guo-Lin Mi; Hong-Mei Ni; Tie-Liang Pang; Xue-Mei Qin; Xin-Hua Shen; Lu Sun; Qi-Sheng Tang; Hong Tao; Jing Teng; He-Qiu Wang; Jia-Lin Wang; Jian-Xin Wang; Shi-Liang Wang; Yong-Yan Wang; Xue-Qin Wang; Jing Wei; Zhen-Ping Xian; Jian Xie; Jia Xing; Jian Xu; Hong Yan; Dong-Dong Yang; Zhi-Jian Yao; Shu-Qin Zhan; Bo-Hua Zhang; Gui-Qing Zhang; Jie Zhang; Yan Zhang; Peng Zhao; Yong-Hou Zhao; Bo Zhou; Gang Zhu; Xiao-Chen Zhu.