What are the treatment options for individuals experiencing symptoms of Major Depressive Disorder (MDD)?

Treatment Options for Major Depressive Disorder (MDD)

For individuals experiencing Major Depressive Disorder, clinicians should select between either cognitive behavioral therapy (CBT) or second-generation antidepressants (SGAs) as first-line treatment after discussing treatment effects, adverse effect profiles, cost, accessibility, and preferences with the patient. 1

Diagnostic Criteria and Assessment

• MDD is defined as depressed mood or loss of pleasure/interest along with other symptoms that last for at least 2 weeks and affect normal functioning 2
• Diagnosis requires at least 5 symptoms during a 2-week period, including depressed mood, anhedonia, sleep disturbances, psychomotor changes, fatigue, feelings of worthlessness, concentration difficulties, or suicidal thoughts 2
• Assessment tools include the Patient Health Questionnaire-9 (PHQ-9) and Hamilton Depression Rating Scale (HAM-D) to measure severity and monitor treatment response 2

First-Line Treatment Options

Pharmacological Options

• Second-generation antidepressants (SGAs) including selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), and others like bupropion, mirtazapine, and trazodone are recommended first-line medications 2, 3
• SSRIs (fluoxetine, sertraline, escitalopram, paroxetine, citalopram) are typically the preferred initial pharmacological treatment due to their favorable safety profile 2, 4
• Starting doses for SSRIs include fluoxetine 20mg/day, escitalopram 10mg/day, sertraline 50mg/day, and paroxetine 20mg/day 5, 6
• More than 60% of patients experience at least one adverse effect with SGAs, and up to 70% do not achieve remission during initial treatment 3

Psychotherapeutic Options

• Cognitive Behavioral Therapy (CBT) has moderate-quality evidence supporting its effectiveness as equivalent to SGAs 1
• Other effective psychological interventions include interpersonal therapy and psychodynamic therapies 2
• Moderate-quality evidence from multiple trials showed no difference in response when comparing SGAs with CBT in patients with MDD after 8 to 52 weeks of treatment 1

Treatment Phases

• Acute phase (6-12 weeks): Focus on symptom reduction 2
• Continuation phase (4-9 months): Prevent relapse 2
• Maintenance phase (≥1 year): Prevent recurrence, especially important for patients with multiple episodes 2

Combination Therapy

• Low-quality evidence shows no significant difference in response or remission rates between SGA monotherapy and combination therapy with SGA plus CBT 2
• However, one trial showed improved work functioning with combination therapy compared to SGA monotherapy 2
• Long-term follow-up studies suggest that concomitant CBT with SSRI treatment may reduce recurrence rates (59.0%) compared to SSRI-only treatment (82.0%) 7

Complementary and Alternative Medicine (CAM)

• St. John's Wort: Low-quality evidence from multiple trials showed no difference in response or remission compared to SGAs 2
• Acupuncture: Low-quality evidence shows combination therapy of SGAs with acupuncture improved treatment response compared to SGA monotherapy 2
• Other CAM options include meditation, omega-3 fatty acids, and S-adenosyl-L-methionine (SAMe) 3

Special Considerations

• SGAs have lower toxicity in overdose compared to first-generation antidepressants (tricyclics, MAOIs) 1
• Common side effects of SGAs include sexual dysfunction, gastrointestinal symptoms, sleep disturbances, anxiety, and insomnia 3, 5
• Hyponatremia may occur as a result of treatment with SSRIs and SNRIs, particularly in elderly patients 5
• Activation of mania/hypomania has been reported in a small proportion of patients with MDD treated with antidepressants 5
• Patients should be cautioned about the risk of bleeding associated with the concomitant use of SSRIs and NSAIDs, aspirin, or other drugs that affect coagulation 5

Treatment Algorithm

1. Initial Assessment: Determine severity using validated tools (PHQ-9, HAM-D) 2
2. First-line Treatment: Choose between SGA (SSRI preferred) or CBT, considering patient preference, previous treatment response, side effect profile, and comorbidities 1, 2
3. Monitor response: Response to treatment is typically defined as ≥50% reduction in measured severity using validated tools 2
4. If insufficient response after several weeks, consider:
   • For pharmacotherapy: Dose increase or switching to another agent 5
   • For psychotherapy: Adjusting approach or considering combination therapy 2
5. For treatment-resistant depression (failure to respond to two or more adequate antidepressant trials), consider specialized approaches or combination therapy 8