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

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.

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

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.

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.