Treatment of Major Depressive Disorder
The recommended first-line treatment for major depressive disorder (MDD) is either cognitive behavioral therapy (CBT) or a second-generation antidepressant (SGA), with the choice between them based on discussing treatment effects, adverse effect profiles, cost, accessibility, and patient preferences. 1
Treatment Selection Algorithm
Step 1: Initial Assessment and Treatment Selection
- Evaluate severity of depression using standardized measures (e.g., PHQ-9)
- Choose between two equally effective first-line options:
Cognitive Behavioral Therapy (CBT)
- Fewer adverse effects than SGAs
- Lower relapse rates
- Similar efficacy to SGAs in short-term
- Potentially better long-term outcomes
Second-Generation Antidepressants (SGAs)
Step 2: Monitoring and Dose Adjustment
- Assess patient status within 1-2 weeks of starting therapy 1
- Evaluate treatment efficacy at approximately 6 weeks and 12 weeks
- Monitor for suicidal ideation, especially in first weeks of treatment
- If inadequate response after 6-8 weeks, consider:
- Increasing dose (SGAs may show slightly better response at higher doses, though with increased side effects) 4
- Switching to a different SGA
- Adding CBT if on medication only
- Augmenting with a second pharmacologic agent
Step 3: Maintenance Treatment
- Continue treatment for 4-9 months after satisfactory response for a first episode 1
- For recurrent depression, longer maintenance may be necessary
- Regularly reassess to determine need for continued treatment
Comparative Efficacy
- Moderate-quality evidence shows no difference in response rates between SGAs (fluoxetine, fluvoxamine, paroxetine, or sertraline) and CBT after 8-52 weeks of treatment 5
- Low-quality evidence shows no difference in remission rates between SGAs and CBT 5
- Combination therapy (SGA plus CBT) shows no significant difference in response or remission compared to SGA monotherapy, though some evidence suggests improved work functioning with combination therapy 5
Adverse Effects Considerations
- CBT has fewer adverse effects than SGAs and lower relapse rates 1
- More than 60% of patients experience at least one adverse effect when taking SGAs 1
- Common SGA side effects include:
- Constipation, diarrhea, dizziness, headache
- Insomnia, nausea, somnolence
- Sexual dysfunction (varies by medication)
- Risk of suicidality (requires monitoring)
Special Considerations
Medication Selection
- Bupropion has lower rates of sexual adverse events than fluoxetine and sertraline 1
- Paroxetine has higher rates of sexual dysfunction than fluoxetine, fluvoxamine, and sertraline 1
- For elderly patients, consider medications with favorable side effect profiles:
- Sertraline (25-50 mg initial, max 200 mg)
- Citalopram (10 mg initial, max 20 mg in elderly due to QT prolongation risk)
- Escitalopram (10 mg initial, max 20 mg) 1
Common Pitfalls to Avoid
- Inadequate dose or duration: Up to 70% of patients don't achieve remission during initial treatment 1
- Failure to monitor: Regular assessment using standardized measures is essential
- Overlooking drug interactions: Particularly important in elderly patients on multiple medications
- Premature discontinuation: Treatment should continue for 4-9 months after satisfactory response
- Ignoring comorbidities: Anxiety disorders frequently coexist with depression and require evaluation
Treatment Response
- Approximately 60-70% of patients respond to SGA treatment 1
- Higher doses of SSRIs appear slightly more effective in MDD, with benefits plateauing at around 50 mg of fluoxetine equivalents 4
- However, higher initial doses are associated with higher discontinuation rates due to side effects 6
By following this structured approach to MDD treatment, clinicians can optimize outcomes while minimizing adverse effects, ultimately improving patients' morbidity, mortality, and quality of life.