Childhood depression

Overview

Depression in children and adolescents is a significant, potentially life-threatening condition requiring prompt recognition and evidence-based management. Unlike adult depression, paediatric depression often presents with irritability rather than low mood, and comorbidities are common. It spans a spectrum from adjustment disorders and persistent depressive disorder (dysthymia) through to major depressive disorder (MDD) and treatment-resistant presentations. Effective management integrates psychotherapy, pharmacotherapy, family involvement, and appropriate use of Youth Mental Health (YMH) pathways. The HEADSS framework (Home, Education/Employment, Activities, Drugs, Sexuality, Suicide/Safety) is the cornerstone clinical tool for adolescent psychosocial assessment in Australian and New Zealand paediatric practice.

Epidemiology and Aetiology

Prevalence

Depression is a leading cause of disability and functional impairment in adolescents worldwide. Rates increase substantially at puberty, particularly in females.

Aetiological Factors

• Biological: Genetic predisposition (heritability ~40-70%), dysregulation of serotonergic and noradrenergic systems, HPA axis dysregulation, frontostriatal reward pathway dysfunction
• Psychological: Negative cognitive schemas, low self-efficacy, poor problem-solving skills, history of trauma or maltreatment, insecure attachment
• Social/environmental: Family conflict, parental depression (associated with poorer CBT response in offspring), bullying, adverse childhood experiences, socioeconomic disadvantage, social isolation
• Comorbidities: Anxiety disorders (very common, ~50-70%), ADHD, conduct disorder, substance use disorders (SUD), chronic physical illness

Pathophysiology

Depression in children and adolescents reflects the interaction of neurobiological vulnerability with developmental and environmental stressors.

• Monoamine hypothesis: Reduced serotonergic and noradrenergic neurotransmission underpins the rationale for SSRI use
• Cognitive model (Beck): Negative automatic thoughts, cognitive distortions (catastrophising, overgeneralisation, personalisation, selective abstraction), and maladaptive core beliefs perpetuate depressive symptoms, the framework targeted by CBT. Adolescents with depression demonstrate restricted behavioural repertoires and poor interpersonal problem-solving skills
• HPA axis: Elevated cortisol in response to stress, including parent-child conflict, contributes to neuroplasticity changes and hippocampal volume reduction
• Reward processing: Blunted frontostriatal activation to reward stimuli underpins anhedonia and reduced motivation
• Developmental considerations: Ongoing prefrontal cortex maturation through early adulthood alters both symptom expression and treatment response relative to adults

Clinical Features

Age-Specific Presentation

Core DSM-5-TR Criteria (≥5 symptoms for ≥2 weeks, including criterion A1 or A2)

Symptoms must cause clinically significant distress or functional impairment and not be attributable to a substance, medical condition, or better explained by another disorder.

HEADSS Assessment in Adolescent Depression

HEADSS is the structured psychosocial assessment tool recommended by RACP and endorsed in Australian clinical guidelines for adolescent health consultations. It creates a safe, rapport-building interview framework and systematically identifies risk and protective factors.

Practical notes:

• Begin with less threatening domains (Home, Education) before progressing to sensitive areas (Drugs, Sexuality, Suicide)
• Establish confidentiality parameters at the outset, including its limits (duty of care)
• Document HEADSS findings systematically; severity guides pathway (primary care, headspace, CAMHS/YMH)
• Baseline suicidal ideation is present in approximately 29% of adolescents presenting with MDD (TADS data)

Investigations

Investigations serve to exclude organic causes and assess comorbidities; there are no diagnostic tests for depression.

Validated rating scales are useful for severity assessment at baseline and for monitoring treatment response. They do not replace clinical diagnostic interviews.

Severity Classification and Initial Management Pathway

Management

Stepped-Care Approach

Step 1, Psychoeducation, supportive care, lifestyle (all severity levels)

• Psychoeducation for young person and family: depression as a medical illness, expected course, treatment rationale
• Sleep hygiene, structured routine, physical activity (robust evidence for antidepressant effect)
• Reduction of alcohol and cannabis use
• School support liaison; collaborative care with GP

Step 2, Psychological intervention (mild-moderate)

Cognitive-Behavioural Therapy (CBT) is the first-line psychological treatment for adolescent depression.

Interpersonal Therapy for Adolescents (IPT-A) targets interpersonal stressors (role transitions, loss, relationship conflict, interpersonal skills deficits, single-parent family adjustment); developmentally highly appropriate.

Family therapy, consider when family conflict is a primary driver of the depression.

Step 3, Combined pharmacotherapy and psychotherapy (moderate-severe)

First-line is combined CBT and pharmacotherapy, superior to either alone.

Pharmacotherapy

TADS Study, Key Evidence

The Treatment for Adolescents with Depression Study (TADS; March et al. JAMA 2004) compared fluoxetine, CBT, their combination, and placebo in 439 adolescents aged 12-17 years with MDD.

Key TADS findings:

• Combined treatment superior to fluoxetine alone at 12 weeks for response rate, remission rate, adaptive functioning, and speed of suicidal ideation reduction
• CBT alone was not superior to placebo at 12 weeks but reached similar outcomes to other active treatments by 18 weeks
• Combined CBT + fluoxetine had a more favourable suicidal safety profile than fluoxetine monotherapy
• Over the full 36-week study, fluoxetine alone had a significantly higher cumulative suicide event rate (14.7%) than CBT alone (6.3%); combined treatment (8.4%) was not statistically different from either
• Suicidal events peaked at a mean of 12 weeks after study onset

Fluoxetine, Agent of Choice

SSRIs in Medically Ill Adolescents

Where drug-drug interactions via CYP450 are a concern, escitalopram or citalopram may be preferable to fluoxetine (fewer CYP450 interactions, predictable elimination half-life). Sertraline is an alternative second-line agent.

Agents Avoided in Paediatric Depression

Treatment-Resistant Depression (TRD)

Definition: Persistence of depression after an adequate-quality, adequate-dose evidence-based treatment trial.

The TORDIA study (Treatment of SSRI-Resistant Depression in Adolescents; n = 334) randomised adolescents who had not responded to an adequate SSRI trial to:

Key TORDIA conclusion: Adding CBT to any medication strategy is superior to medication switch alone. The choice of SSRI or venlafaxine did not differ significantly in efficacy, but venlafaxine had a less favourable side-effect profile.

Before labelling TRD: Review adherence, diagnosis (exclude bipolar disorder), ongoing psychosocial stressors, comorbid SUD, and adequacy of the prior trial.

Depression with Comorbid Substance Use Disorder

• First-line: combined CBT (for SUD) and pharmacotherapy (fluoxetine)
• Fluoxetine showed superior efficacy over placebo on CDRS-R scores in a 16-week RCT in adolescents with comorbid MDD, conduct disorder, and SUD (Riggs et al.; n = 126; ages 13-17; 20 mg/day)
• Depression remission rates were unexpectedly high in both fluoxetine (70%) and placebo (52%) groups, suggesting that CBT targeting SUD may have contributed to depression remission even without primary focus on depression
• Remission of depression, regardless of medication assignment, was a more important predictor of reduced drug use than fluoxetine vs. placebo assignment; remitters had significant decreases in substance use, non-remitters had no change
• Fluoxetine also demonstrated efficacy and safety in reducing comorbid anxiety symptoms (GAD, SAD, PTSD) in this population
• TCAs are relatively contraindicated in adolescents with SUD (arrhythmia risk, anticholinergic effects)

Complications

Prognosis and Follow-up

Follow-up schedule:

• Within 1-2 weeks of commencing pharmacotherapy (monitor for activation, suicidality)
• Monthly for first 3 months, then 3-monthly if stable
• Structured rating scales (PHQ-A, MFQ, CDRS-R) at each visit to track response
• Review diagnosis if inadequate response at 4-6 weeks
• School liaison and GP communication in collaborative care models

When to Refer / Admit

Referral to CAMHS / Youth Mental Health Services

Inpatient Admission Criteria

• Imminent suicidal risk with inadequate safety plan or absent protective factors
• Serious suicide attempt
• Severe depression with inability to care for self
• Psychosis complicating depression
• Need for intensive monitoring during medication initiation

Australian YMH Pathways

• headspace centres: mild-moderate depression, ages 12-25 years; integrated GP, psychology, social work, and alcohol and drug services
• CAMHS (Child and Adolescent Mental Health Services): moderate-severe, complex, or high-risk presentations
• Emergency department mental health teams / CAMHS Triage: acute risk presentations
• headspace Early Psychosis / EPPIC: if psychotic features emerge
• Telehealth services: facilitate rural and remote specialist access

Key Summary Points for FRACP Examination

• Depression in adolescents may present with irritability rather than sadness, know the age-specific DSM-5-TR variations
• HEADSS is the structured psychosocial assessment framework for all adolescent mental health encounters; always include the Suicide/Safety domain; baseline suicidal ideation present in ~29% of MDD presentations (TADS)
• Fluoxetine is the first-line SSRI for paediatric MDD, the only SSRI with robust paediatric evidence and regulatory approval (TGA, FDA); the only agent statistically superior to placebo in the 2016 network meta-analysis of 14 antidepressants
• Combined CBT + fluoxetine is superior to either alone: 71% vs 61% vs 43% response at 12 weeks; superior remission, adaptive functioning, and suicidal ideation reduction (TADS)
• CBT alone was not superior to placebo at 12 weeks in TADS but reached similar outcomes to active treatments by 18 weeks; CBT appears most efficacious with ≥9 sessions, high cognitive distortion burden, and comorbid anxiety
• Minimum 4 weeks at therapeutic SSRI dose before assessing response; treat for ≥6-12 months after remission; add wellness-based CBT to continuation pharmacotherapy to further reduce relapse
• Black box warning for SSRIs and suicidality in youth, monitor closely, especially first 4 weeks; the risk of untreated moderate-severe depression outweighs this
• In treatment-resistant depression, adding CBT to a medication switch is superior to medication switch alone (TORDIA); venlafaxine is equivalent in efficacy to SSRI switch but has more adverse effects
• TCAs are contraindicated in adolescent depression, no efficacy demonstrated, QTc prolongation, anticholinergic toxicity, fatal in overdose; relatively contraindicated in comorbid SUD
• Remission of depression, regardless of medication assignment, predicts reduced comorbid substance use more than pharmacotherapy assignment alone (Riggs et al.)
• Screen for bipolar disorder before initiating SSRIs; monitor for manic activation, particularly in those with personal or family history
• Use stepped-care pathways and YMH services (headspace, CAMHS) based on severity; escitalopram or citalopram preferred over fluoxetine in medically ill adolescents due to fewer CYP450 interactions

Sources

• Royal Children's Hospital Melbourne, Clinical Practice Guidelines
• Therapeutic Guidelines (eTG)
• NHMRC clinical practice guidelines