What is the best approach to manage a patient presenting with depression?

Management of Depression in Primary Care

For a patient presenting with depression, initiate either cognitive behavioral therapy (CBT) or a second-generation antidepressant (SSRI/SNRI) as first-line treatment, with the choice guided by depression severity: mild depression can start with CBT alone, while moderate-to-severe depression should begin with combination therapy (psychotherapy plus medication) which nearly doubles remission rates compared to medication alone. 1, 2, 3

Initial Assessment and Severity Classification

Screen systematically and assess severity using validated tools:

• Use PHQ-9 or Hamilton Depression Rating Scale to quantify symptom severity and establish baseline 2, 3
• Assess for suicidal ideation at every encounter, particularly during initial treatment and dose changes 4, 5, 6
• Rule out bipolar disorder before initiating antidepressants, as treating unrecognized bipolar depression with antidepressants alone may precipitate manic episodes 1, 6
• Screen for comorbid substance use disorders and anxiety, which worsen prognosis and require integrated treatment 1
• Evaluate for psychotic features, which necessitate immediate psychiatric consultation 1

Treatment Algorithm Based on Severity

Mild Depression

Consider active support and monitoring for 4-8 weeks before initiating formal treatment:

• Provide psychoeducation about depression and its relationship to physical health 1
• Recommend evidence-based lifestyle interventions: regular physical exercise, sleep hygiene, and adequate nutrition 1
• If symptoms persist beyond this observation period, initiate CBT or antidepressant therapy 1

Moderate Depression

Initiate either CBT or SSRI/SNRI monotherapy:

• Psychotherapy options with proven efficacy: CBT, behavioral activation, problem-solving therapy, interpersonal therapy (IPT-A for adolescents), brief psychodynamic therapy, or mindfulness-based psychotherapy all demonstrate medium-to-large effect sizes (SMD 0.50-0.73) 1, 3
• Medication options: SSRIs (fluoxetine, sertraline, escitalopram, citalopram) or SNRIs (venlafaxine, duloxetine) selected based on side effect profile, cost, and patient preference 1, 2, 3, 7
• SNRIs show slightly superior efficacy for severe symptoms but higher rates of nausea 2

Severe Depression or Treatment-Resistant Cases

Combination therapy is mandatory—do not use monotherapy:

• Initiate both psychotherapy AND antidepressant medication simultaneously, not sequentially 4, 2, 3
• Combination therapy achieves 57.5% remission versus 31.0% with medication alone (P < 0.001) 4, 2
• For adolescents with severe depression or complicating factors (substance abuse, psychosis), immediate mental health consultation is required 1

Medication Management Specifics

Starting and optimizing antidepressants:

• Begin SSRIs at standard starting doses: sertraline 50mg daily, fluoxetine 20mg daily, escitalopram 10mg daily 8, 6
• For SNRIs: venlafaxine 75mg daily, duloxetine 30-60mg daily 2
• Ensure adequate trial duration: minimum 6-8 weeks at therapeutic dose before declaring treatment failure 4, 2
• Titrate to maximum FDA-approved doses if partial response: sertraline up to 200mg, fluoxetine up to 80mg, escitalopram up to 20mg 1, 8
• Monitor for activation symptoms (agitation, anxiety, insomnia, akathisia) especially in first 1-2 months, which may precede suicidality 5, 6

Critical safety considerations:

• All antidepressants carry FDA black box warning for increased suicidality risk in patients under age 24 5, 6
• Risk differences: 14 additional cases per 1000 patients <18 years; 5 additional cases per 1000 patients ages 18-24 5, 6
• Adults ≥65 years show 6 fewer suicidality cases per 1000 compared to placebo 5, 6
• Avoid abrupt discontinuation—taper gradually to prevent withdrawal symptoms 6

Special populations:

• Cardiac patients: Sertraline is preferred due to safety profile in acute coronary syndromes and lower QTc prolongation risk compared to citalopram/escitalopram 8
• Elderly with poor appetite/insomnia: Consider mirtazapine as alternative 8
• Pregnancy: High-quality evidence is lacking; both untreated depression and antidepressants associate with preterm birth 7

Treatment-Resistant Depression (TRD)

Define TRD as failure of two adequate antidepressant trials (minimum 6-8 weeks at therapeutic dose with documented adherence): 4, 2

Before declaring treatment resistance:

• Verify medication adherence—up to 50% of patients demonstrate non-adherence 2
• Consider checking plasma drug levels if adherence uncertain 2
• Confirm adequate dose and duration of current trial 4, 2

Second-line strategies for TRD:

• Add CBT to ongoing pharmacotherapy—this is the strongest evidence-based approach for TRD 4, 2
• Switch to different antidepressant class 4, 3
• Add second antidepressant (e.g., bupropion SR 150-400mg to SSRI/SNRI) with ~50% remission rates 4
• Augment with atypical antipsychotic: aripiprazole 5-15mg daily or quetiapine 150-300mg daily 4

Collaborative Care Model

Organize practice to support systematic depression management:

• Implement proactive tracking systems for all patients with depression 1
• Establish linkages with psychiatrists, case managers, and embedded therapists 1
• Use collaborative care coordinators to provide systematic follow-up 3
• Collaborative care improves outcomes with SMD 0.42 compared to usual care 3

Monitoring and Follow-Up

Structured assessment schedule:

• Assess response within 1-2 weeks of treatment initiation for adverse effects and suicidality 2
• Formal response evaluation at 6-8 weeks: response defined as ≥50% reduction in PHQ-9 or HAM-D scores 4, 2
• If inadequate response by 6-8 weeks, modify treatment (dose adjustment, switch, or augmentation) 2

Treatment duration:

• Continue treatment minimum 4-9 months after achieving remission for first episode 2, 3, 7
• Recurrent depression requires ≥1 year maintenance therapy 2, 7
• When discontinuing, taper gradually while providing concurrent CBT to reduce relapse risk 7

Common Pitfalls to Avoid

• Inadequate dosing or premature discontinuation before 6-8 weeks at therapeutic dose 2
• Treating suspected bipolar depression with antidepressant monotherapy without mood stabilizer, risking manic switch 1, 6
• Failing to address comorbid anxiety or substance use, which significantly worsens outcomes 1
• Not monitoring for suicidality during high-risk periods (first 1-2 months, dose changes) 4, 5, 6
• Using monotherapy for severe depression when combination therapy doubles remission rates 4, 2
• Declaring treatment resistance without verifying adequate dose, duration, and adherence 4, 2