What is the initial treatment approach for a patient presenting with depression?

Case Study: Initial Treatment Approach for Major Depressive Disorder

Patient Presentation

A 42-year-old woman presents with a 3-month history of persistent low mood, loss of interest in previously enjoyed activities, difficulty concentrating at work, early morning awakening, decreased appetite with 8-pound weight loss, and daily fatigue. She denies suicidal ideation, prior depressive episodes, substance use, or manic symptoms. PHQ-9 score is 18 (moderately severe depression).

Initial Treatment Selection

For this treatment-naive patient with moderate-to-severe depression, initiate a second-generation antidepressant selected based on her predominant symptom profile, adverse effect tolerance, cost considerations, and patient preference. 1

Medication Choice Based on Target Symptoms

Since this patient's primary complaint includes cognitive symptoms (difficulty concentrating, mental fog):

• First choice: Bupropion starting at 150 mg once daily in the morning, with potential increase to 150 mg twice daily after 3-4 days if tolerated 2

  • Bupropion is most effective for cognitive symptoms due to dopaminergic and noradrenergic effects 2
  • Lower rates of sexual adverse events compared to SSRIs 1, 2
  • Avoid if seizure history or eating disorder present

• Second choice: SNRI (duloxetine 30-60 mg daily or venlafaxine 75-150 mg daily) if bupropion is contraindicated 2

  • Noradrenergic component improves attention and concentration better than SSRIs 2

• Alternative: SSRI (sertraline 50 mg or citalopram 20 mg daily) if patient prefers most-studied option 1, 2

  • All second-generation antidepressants show equal efficacy for general depressive symptoms 2
  • Number needed to treat for remission is 7-8 2

Critical Pre-Treatment Discussion

Before prescribing, discuss with the patient:

• Approximately 63% will experience at least one adverse effect 2
• Most common: nausea, diarrhea, dizziness, headache, sexual dysfunction 2
• Full therapeutic effect may require 4 weeks or longer 3
• Cost differences between generic and brand options 1

Monitoring Protocol

Begin close monitoring within 1-2 weeks of treatment initiation to assess for:

• Suicidal ideation or behavior (highest risk during first 1-2 months) 1, 4
• Emergence of agitation, irritability, or unusual behavioral changes 1
• Treatment response using PHQ-9 or HAM-D scores 1, 5
• Adverse effects impacting adherence 1

Continue regular assessments every 2-4 weeks during acute phase 1

Treatment Response Assessment

At 6-8 Weeks

If inadequate response (less than 50% symptom reduction), modify treatment 1:

Options include:

• Increase dose to therapeutic maximum 1
• Switch to different antidepressant class 1
• Add psychotherapy (CBT, interpersonal therapy, or behavioral activation) 1, 5
• Augment with second medication 1

Do not continue ineffective treatment beyond 8 weeks 1

If Adequate Response Achieved

Continue treatment for 4-9 months after symptom resolution for this first episode 1, 2

• This continuation phase prevents relapse (return of symptoms from same episode) 1
• For patients with 2 or more prior episodes, consider longer-term maintenance therapy (≥1 year) 1

Specific Dosing Example for This Patient

Given cognitive symptoms, prescribe bupropion SR 150 mg once daily in morning 2:

• Week 1: 150 mg once daily
• Week 2 onward: Increase to 150 mg twice daily (morning and early afternoon) if tolerated 3
• Maximum dose: 400 mg/day in divided doses if needed after 6-8 weeks 3

Schedule follow-up at week 2 to assess for:

• Suicidal thoughts or behavioral changes 1
• Adverse effects (insomnia, agitation, dry mouth) 2
• Early treatment response 1

Schedule follow-up at week 6-8 to determine:

• Treatment response (target: ≥50% PHQ-9 reduction) 1
• Need for dose adjustment or treatment modification 1

Critical Pitfalls to Avoid

• Do not prescribe antidepressants for mild depression or subsyndromal symptoms without current moderate-to-severe episode 2
• Do not use tricyclic antidepressants as first-line due to higher adverse effects and overdose risk 2
• Do not assume all SSRIs are identical—paroxetine has notably higher anticholinergic effects and sexual dysfunction rates, making it less preferred 1, 2
• Do not stop monitoring after initial prescription—regular assessment beginning within 1-2 weeks is mandatory 1
• Do not continue ineffective treatment—modify approach if inadequate response by 6-8 weeks 1

Enhanced Treatment Approach

Consider adding evidence-based psychotherapy from treatment initiation, particularly for moderate-to-severe depression 1, 5:

• Combined treatment shows greater symptom improvement than either modality alone (SMD 0.30-0.33) 5
• CBT, behavioral activation, interpersonal therapy, or problem-solving therapy all demonstrate medium-to-large effect sizes 1, 5