Treatment Recommendations for Major Depressive Disorder (MDD)
Clinicians should select between cognitive behavioral therapy (CBT) or second-generation antidepressants (SGAs) as first-line treatment for major depressive disorder after discussing treatment effects, adverse effect profiles, cost, accessibility, and patient preferences. 1
Understanding MDD and Treatment Phases
- MDD is characterized by depressed mood or loss of pleasure/interest along with other symptoms (significant weight/appetite changes, sleep disturbances, psychomotor changes, fatigue, feelings of worthlessness, concentration difficulties, and suicidal thoughts) lasting at least 2 weeks and affecting normal functioning 1
- Treatment of depression follows three distinct phases 1:
- Acute phase (6-12 weeks)
- Continuation phase (4-9 months)
- Maintenance phase (≥1 year)
First-Line Treatment Options
Psychotherapy Options
- Cognitive Behavioral Therapy (CBT) is a first-line treatment with efficacy comparable to SGAs 1
- Other effective psychological interventions include acceptance and commitment therapy, interpersonal therapy, and psychodynamic therapies 1
- CBT has demonstrated lower relapse rates compared to SGAs in long-term follow-up 1
Pharmacotherapy Options
- Second-generation antidepressants (SGAs) are effective first-line medications 1
- Include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and others
- Examples: escitalopram, sertraline, fluoxetine, paroxetine, citalopram, venlafaxine, duloxetine, bupropion, mirtazapine
- Recommended starting doses 2, 3:
- Sertraline: 50 mg once daily (can be increased to maximum 200 mg/day)
- Escitalopram: typically started at 10 mg daily for adults
- Dose adjustments should not occur at intervals less than 1 week due to the elimination half-life of these medications 2
Complementary and Alternative Medicine (CAM)
- Evidence supports several CAM options for MDD 4:
- Exercise (various aerobic activities)
- Acupuncture
- Meditation
- Omega-3 fatty acids
- S-adenosyl-L-methionine (SAMe)
- St. John's wort (for mild to moderate depression)
Treatment Selection Considerations
Comparing CBT and SGAs
- Moderate-quality evidence shows CBT and SGAs have similar effectiveness for MDD 1
- Discontinuation rates are similar between CBT and SGAs 1
- SGAs have higher rates of discontinuation due to adverse events compared to CBT 1
- CBT may offer lower relapse rates than SGAs in the long term 1, 4
Adverse Effects Profile
- More than 60% of patients experience at least one adverse effect with SGAs 1
- Common SGA side effects include 1, 5:
- Sexual dysfunction (varies by medication)
- Gastrointestinal symptoms (constipation, diarrhea, nausea)
- Sleep disturbances (insomnia, somnolence)
- Headache, dizziness
- Bupropion has lower rates of sexual adverse events compared to fluoxetine and sertraline 1
- Paroxetine has higher rates of sexual dysfunction than fluoxetine, fluvoxamine, nefazodone, and sertraline 1
Treatment Response and Next Steps
- Response to treatment is typically defined as ≥50% reduction in symptom severity 1
- Up to 70% of patients do not achieve remission during initial treatment attempts 1
- For patients who don't respond to initial treatment, options include 1, 4:
- Increasing medication dose
- Switching to a different antidepressant
- Augmentation with a second medication
- Adding psychotherapy to medication (or vice versa)
- Regular monitoring using validated tools such as PHQ-9 or HAM-D is essential 1, 4
Common Pitfalls and Caveats
- Starting doses of SSRIs may sometimes be suboptimal; higher initial doses can improve response rates but also increase discontinuation due to side effects 6
- First-generation antidepressants (tricyclics, MAOIs) should be avoided as first-line due to higher toxicity in overdose despite similar efficacy 1
- St. John's wort may reduce the efficacy of other medications through cytochrome P450 induction and is contraindicated with MAOIs and serotonin reuptake inhibitors 1
- Untreated MDD increases risk of substance abuse, poor functioning, and suicidal behaviors 7
- Once remission is achieved, treatment should be continued for 6-12 months before considering a slow taper 7