Recommended Therapy Options for Depression
For initial treatment of major depressive disorder, offer either cognitive behavioral therapy (CBT) or second-generation antidepressants (SSRIs, SNRIs, bupropion, mirtazapine) as first-line options, with combination therapy providing superior outcomes in moderate-to-severe or recurrent depression. 1, 2
First-Line Treatment Selection
Monotherapy Options
Cognitive Behavioral Therapy (CBT) demonstrates equivalent efficacy to antidepressants with fewer adverse effects and lower relapse rates. 1
- CBT and second-generation antidepressants produce similar response rates (RR 0.90,95% CI 0.76-1.07) and remission rates (RR 0.98,95% CI 0.73-1.32) 1
- CBT provides an enduring effect that reduces subsequent risk after treatment termination, unlike medications which only prevent symptom return while continued 3
- Discontinuation rates are similar between CBT and antidepressants, though adverse event-related discontinuation is higher with medications 1
Alternative psychotherapy approaches include interpersonal therapy (IPT), psychodynamic therapy, and acceptance and commitment therapy, all demonstrating comparable efficacy. 1
- IPT may specifically improve interpersonal functioning 3
- These modalities are appropriate when CBT is unavailable or patient preference dictates 1
Second-generation antidepressants (SSRIs, SNRIs, bupropion, mirtazapine, trazodone) provide rapid symptom relief but require ongoing use to prevent relapse. 1, 2
- Bupropion has lower rates of sexual adverse events compared to SSRIs 1
- Paroxetine has higher rates of sexual dysfunction than fluoxetine, fluvoxamine, nefazodone, and sertraline 1
- Monitor within 1-2 weeks for suicidal ideation, agitation, irritability, and unusual behavioral changes, particularly in patients under age 24 4, 5
Combination Therapy
Combination therapy with psychotherapy plus antidepressants achieves significantly higher remission and response rates than monotherapy and should be prioritized for moderate-to-severe or recurrent depression. 2, 6, 7
- Combined treatment outperforms antidepressants alone at six months or longer (OR 2.93,95% CI 2.15-3.99) 7
- In severe recurrent depression, combined therapy shows highly significant advantage over psychotherapy alone 6
- Combined maintenance treatment results in better-sustained response compared to antidepressants alone (OR 1.61,95% CI 1.14-2.27) 7
Treatment for Comorbid Depression and Anxiety
When patients present with both depression and anxiety symptoms, prioritize treatment of depressive symptoms first, or use a unified protocol combining CBT treatments for both conditions. 1
Monitoring Protocol
Assess treatment response at 4 weeks and 8 weeks using standardized validated instruments (PHQ-9 or HAM-D). 1, 4
- Begin monitoring within 1-2 weeks focusing on suicidal ideation, agitation, irritability, and behavioral changes 4, 5
- If symptoms are stable or worsening at 8 weeks despite good adherence, adjust the regimen 1
Second-Step Treatment for Non-Response
After 8 weeks without improvement, modify treatment by adding a psychological or pharmacologic intervention, changing medication, or switching from group to individual therapy. 1
- Different switching and augmentation strategies provide similar symptom relief 1
- Avoid starting a third sequential antidepressant trial, as this worsens mortality risk and increases suicide deaths 2
- Consider lithium augmentation, which effectively lowers suicide risk independent of mood-stabilizing effects 2
Treatment Duration
Continue treatment for 4-9 months after achieving satisfactory response in first-episode depression. 1, 4
- For patients with 2 or more depressive episodes, consider years to lifelong maintenance therapy 4
- Ongoing treatment with IPT or CBT further reduces relapse risk 3
Critical Safety Considerations
Antidepressants increase suicidality risk in patients under age 24, with 14 additional cases per 1000 patients treated in those under 18, and 5 additional cases per 1000 in ages 18-24. 5
- Risk decreases in adults 25-64 (1 fewer case per 1000) and adults ≥65 (6 fewer cases per 1000) 5
- Prescribe the smallest quantity consistent with good management to reduce overdose risk 5
Comorbid substance use significantly increases suicide risk and requires heightened monitoring. 2
Complementary and Alternative Options
Exercise, omega-3 fatty acids, SAMe, St. John's wort, acupuncture, meditation, and yoga show efficacy compared to placebo, though evidence comparing them directly to antidepressants is limited. 1
- These options may be considered when first-line treatments are unavailable, declined, or contraindicated 1
- Concerns exist about adequate dosing and purity of St. John's wort preparations in U.S. studies 1
Treatment-Resistant Depression
For severe treatment-resistant depression, electroconvulsive therapy (ECT) demonstrates a 50% reduction in suicide risk during the first year post-discharge. 2