# Special Populations: Three Age Cohorts — APA 2023

## Overview

The APA Clinical Practice Guideline uniquely addresses depression treatment across three developmental cohorts: children/adolescents, adults, and older adults (age 60 and over). Each cohort has distinct evidence bases, treatment considerations, and recommendations. This section provides cohort-specific decision pathways.

## Cohort 1: Children and Adolescents

### Scope of Recommendations

- The panel made treatment recommendations for **adolescents** with MDD
- The panel did **not** make specific treatment recommendations for **children** (pre-adolescent) due to insufficient evidence
- The guideline covers MDD, persistent depressive disorder, and subsyndromal depressive symptoms

### Recommended First-Line Treatments

#### Psychotherapy

- **CBT** is the most evidence-supported psychotherapy for adolescent MDD (Strong Recommendation)
- CBT alone showed a response rate of **43.2%** in the TADS trial (vs. 35% placebo)
- CBT should be delivered by a trained therapist using a structured, manualized protocol

#### Pharmacotherapy

- **Fluoxetine** is the first-line medication for adolescents with MDD (Strong Recommendation)
  - FDA-approved for patients age 8 years and older
  - Starting dose: 10 mg/day PO; target dose: 20 mg/day; maximum: 60 mg/day in adolescents
  - Response rate: **60.9%** in TADS trial (fluoxetine alone vs. 35% placebo)
- **Escitalopram** is FDA-approved for adolescent MDD (age 12 and older)
  - Starting dose: 10 mg/day PO; maximum: 20 mg/day
  - The APA panel noted a less robust evidence base compared to fluoxetine
- The panel **recommends against** using several other medications for adolescents; when other options are not available, effective, or acceptable to the patient, shared decision-making between patient and clinician is recommended

#### Combined Treatment

- **Fluoxetine + CBT** is the most effective initial treatment strategy for adolescent MDD
  - Response rate: **71%** in the TADS trial
  - This combined approach is recommended when resources and clinical infrastructure allow
  - Combined treatment was also associated with faster response and greater functional improvement

### Safety Monitoring

- All antidepressants carry an **FDA black-box warning** regarding increased risk of suicidal thoughts and behaviors in patients under age 25
- Enhanced monitoring schedule:
  - Weekly for the first 4 weeks
  - Biweekly for weeks 5-8
  - At week 12 and as clinically indicated
- Educate patients, families, and caregivers about warning signs: worsening depression, agitation, irritability, unusual behavior changes, and suicidal ideation
- A safety plan should be documented before initiating antidepressant treatment

### Decision Pathway: Adolescent MDD

1. **Diagnosis confirmed:** Adolescent meets criteria for MDD
2. **Mild depression (PHQ-9 5-9):** Consider active monitoring, supportive counseling, or CBT
3. **Moderate depression (PHQ-9 10-19):**
   - Offer CBT or fluoxetine, based on shared decision-making
   - If moderate-to-severe and resources allow, consider combined fluoxetine + CBT
4. **Severe depression (PHQ-9 >= 20):**
   - Recommend combined fluoxetine + CBT
   - Implement enhanced suicidality monitoring
5. **Inadequate response at 6-8 weeks:**
   - If on monotherapy, consider adding the complementary modality
   - If on fluoxetine, optimize dose (up to 40-60 mg/day) before switching
   - Consider escitalopram as an alternative
6. **Safety concern:** Any positive suicidality screening requires immediate clinical assessment and safety planning

## Cohort 2: Adults (Age 18-59)

### Recommended First-Line Treatments

#### Psychotherapy or Pharmacotherapy

- For initial treatment, the panel recommends offering either psychotherapy or a second-generation antidepressant (Strong Recommendation)
- Effectiveness studies demonstrated **comparable effects** across psychotherapy modalities; no single modality is recommended above others
- No superiority established among second-generation antidepressants (SSRIs, SNRIs, bupropion, mirtazapine, trazodone, vilazodone, vortioxetine)

#### Combined Treatment Indications

Combined psychotherapy and pharmacotherapy is recommended for:
- **Severe depression** (PHQ-9 >= 20)
- **Persistent depression** (duration > 2 years)
- **Recurrent depression** (two or more episodes)
- If combined treatment is selected: **CBT or IPT** plus a second-generation antidepressant (Strong Recommendation)

### Decision Pathway: Adult MDD

1. **Diagnosis confirmed:** Adult meets criteria for MDD
2. **Determine severity and chronicity:**
   - Mild to moderate (PHQ-9 < 20): monotherapy (psychotherapy OR pharmacotherapy)
   - Severe (PHQ-9 >= 20), persistent, or recurrent: combined treatment recommended
3. **Select treatment via shared decision-making:**
   - If psychotherapy: CBT, BA, IPT, or psychodynamic therapy
   - If pharmacotherapy: second-generation antidepressant selected by side effect profile, patient preference, cost, and prior response
4. **Monitor response at 6-8 weeks** using PHQ-9
5. **If inadequate response:**
   - Add psychotherapy to pharmacotherapy (IPT, CBT, or psychodynamic therapy)
   - OR augment with another antidepressant
   - Insufficient evidence to recommend specific switching vs. augmentation strategies
6. **If remission achieved (PHQ-9 < 5):**
   - Continue treatment for 4-9 months (continuation phase)
   - For recurrent depression, consider longer maintenance and relapse prevention psychotherapy (CBT, IPT, or MBCT)

### Relapse Prevention in Adults

- Continuing antidepressant medication at the same dose for **4-9 months** after remission reduces relapse by approximately one-third
- **CBT, IPT, or MBCT** during remission reduces relapse risk (Conditional Recommendation)
- Particularly recommended for patients with:
  - Unstable remission
  - Two or more prior episodes
  - Residual symptoms despite remission
- Before discontinuation, establish a relapse monitoring plan with the patient

## Cohort 3: Older Adults (Age 60+)

### Unique Considerations

- Depression in older adults is frequently comorbid with medical illness, cognitive decline, social isolation, and functional impairment
- Altered pharmacokinetics (reduced hepatic metabolism, renal clearance) require dose adjustments
- Polypharmacy increases the risk of drug-drug interactions
- Presentation may differ: somatic complaints, cognitive symptoms ("pseudodementia"), and functional decline may predominate over sadness
- Suicide risk is highest among older white men; careful assessment is essential

### Recommended First-Line Treatments

#### Psychotherapy

- **Group life-review therapy** or **group CBT** (either alone or added to usual care) over no treatment (Strong Recommendation)
- **Combined pharmacotherapy and IPT** over IPT alone (Strong Recommendation)
- **Behavioral activation** (individual) for mild to moderate depression (Conditional Recommendation)
- **Problem-solving therapy** (individual) for MDD with executive dysfunction (Conditional Recommendation)
- **Problem-solving behavioral therapy** or **pleasant events behavioral therapy** for depression in older adults with dementia (Conditional Recommendation)

#### Pharmacotherapy

- SSRIs are generally preferred as first-line medication due to favorable side effect profile
- **Start low, go slow:** initiate at lower doses and titrate gradually
- **Citalopram:** maximum dose limited to **20 mg/day** in patients over 60 due to QTc prolongation risk
- Avoid medications with significant anticholinergic effects (e.g., paroxetine, tricyclic antidepressants) due to cognitive and falls risk
- Consider drug-drug interactions carefully due to polypharmacy
- Monitor for hyponatremia (SIADH), especially with SSRIs in older adults

### Decision Pathway: Older Adult Depression

1. **Diagnosis confirmed:** Older adult meets criteria for depressive disorder
2. **Screen for comorbidities:**
   - Cognitive screening (e.g., MoCA) to differentiate depression from neurodegenerative disease
   - Review medication list for depressogenic medications (beta-blockers, corticosteroids, etc.)
   - Assess falls risk, social isolation, and functional status
3. **Mild to moderate depression:**
   - Group CBT or group life-review therapy
   - Behavioral activation (individual)
   - If executive dysfunction is present: problem-solving therapy
   - If comorbid dementia: problem-solving behavioral therapy or pleasant events behavioral therapy
4. **Moderate to severe depression:**
   - Combined pharmacotherapy (SSRI preferred, start low) + IPT
   - Enhanced monitoring for side effects and drug interactions
5. **Monitor response at 6-8 weeks** using PHQ-9 and functional status measures
6. **If inadequate response:**
   - Optimize dose (within age-appropriate limits)
   - Add or switch psychotherapy modality
   - Consider augmentation strategies
   - Reassess for medical comorbidities contributing to treatment resistance

### Medications to Use with Caution in Older Adults

| Concern | Medications to Avoid/Use Cautiously | Rationale |
|---|---|---|
| **Anticholinergic effects** | Paroxetine, TCAs (amitriptyline, nortriptyline) | Cognitive impairment, constipation, urinary retention, delirium |
| **QTc prolongation** | Citalopram (>20 mg/day), TCAs | Cardiac arrhythmia risk |
| **Falls and orthostatic hypotension** | TCAs, trazodone (high doses), mirtazapine | Hip fracture risk |
| **Hyponatremia (SIADH)** | All SSRIs and SNRIs (monitor sodium) | More common in older adults, especially with diuretics |
| **Bleeding risk** | SSRIs with anticoagulants or NSAIDs | Platelet dysfunction; assess bleeding risk |

## Cross-Cutting Themes Across All Cohorts

### Shared Decision-Making

- The guideline mandates shared decision-making for all treatment decisions across all age cohorts
- Clinicians should present the evidence on benefits and harms and collaborate with patients (and caregivers, where appropriate) to select treatments aligned with patient values and preferences

### Exercise as Adjunctive Treatment

- The guideline recognizes exercise (aerobic exercise and resistance training) as beneficial for mood symptoms across age cohorts
- Particularly recommended for older adults with comorbid medical conditions
- Considered a complementary/alternative treatment option rather than a standalone primary treatment

### Cultural and Diversity Considerations

- The guideline panel considered applicability of evidence across demographic groups and settings
- Clinicians should be attentive to cultural factors influencing depression presentation, treatment preferences, and help-seeking behavior
- Access barriers (insurance, geographic, linguistic) may influence treatment modality selection

## Limitations

- The panel did not make specific treatment recommendations for **children** (pre-adolescent) due to insufficient evidence, representing a significant gap
- Evidence for pharmacotherapy in older adults is less extensive than in the general adult population
- The guideline does not address treatment-resistant depression protocols (e.g., electroconvulsive therapy, esketamine, transcranial magnetic stimulation) in detail for any age cohort, as these were outside the scope of the systematic reviews
- Most evidence supporting age-specific recommendations comes from studies conducted in high-income countries, limiting global generalizability
- The guideline does not address depression in the context of bipolar disorder, perinatal depression, or depression secondary to substance use disorders
