What is the recommended treatment for depression?

Treatment of Depression: Evidence-Based Approaches

For the treatment of depression, both second-generation antidepressants (SGAs) and cognitive behavioral therapy (CBT) are recommended as first-line options with similar efficacy, with treatment selection based on patient preferences, adverse event profiles, and symptom severity. 1, 2

First-Line Treatment Options

• SGAs, including selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and others (bupropion, mirtazapine, trazodone), are commonly prescribed first-line medications for major depressive disorder (MDD) 1, 2
• Psychological interventions, particularly CBT, have demonstrated similar efficacy to antidepressants for treating moderate to severe depression 1, 2
• St. John's wort has shown comparable efficacy to antidepressants for mild to moderate depression with fewer adverse effects, though drug interactions must be considered 1, 2
• Exercise has demonstrated benefits for depression and can be recommended as part of a treatment plan 1, 3

Treatment Selection Considerations

• More than 60% of patients experience at least one adverse effect with SGAs, and up to 70% do not achieve remission during initial treatment 2
• Common side effects of SGAs include sexual dysfunction, gastrointestinal symptoms, and sleep disturbances 2, 4
• Psychological interventions like CBT have lower risks for discontinuation due to adverse events compared to antidepressants 1
• First-generation antidepressants (tricyclic antidepressants and monoamine oxidase inhibitors) are rarely used due to higher toxicity in overdose despite similar efficacy to SGAs 1

Treatment Phases

• Depression treatment consists of three phases 1:
  • Acute phase (6-12 weeks): Focus on symptom reduction
  • Continuation phase (4-9 months): Prevent relapse
  • Maintenance phase (≥1 year): Prevent recurrence

Second-Step Treatment Options

• For patients who do not respond adequately to initial treatment, evidence supports several options 1:
  • Switching to another antidepressant
  • Switching to cognitive therapy
  • Augmentation with another medication or cognitive therapy
• The 2022 VA/DoD guideline suggests ketamine and esketamine for patients who have not responded to other treatments 1
• Electroconvulsive therapy is recommended for patients with multiple prior treatment failures or who need rapid improvement 1

Complementary and Alternative Medicine (CAM) Options

• CAM treatments with some evidence include 1, 2:
  • Acupuncture
  • Meditation
  • Omega-3 fatty acids
  • S-adenosyl-L-methionine (SAMe)
  • Yoga

Special Considerations

• Treatment response should be monitored using validated tools such as the Patient Health Questionnaire-9 (PHQ-9) or Hamilton Depression Rating Scale (HAM-D) 1
• Combined therapy approaches (SGA plus CBT) may improve treatment response and remission rates compared to monotherapy 2
• Caution is advised when using antidepressants with other CNS-active drugs, as interactions may occur 4
• Patients should be informed that most studies report similar efficacy between nonpharmacologic treatments and antidepressants, though for many comparisons these results are uncertain 1

Treatment Selection Algorithm

1. Assess depression severity (mild, moderate, severe)
2. For mild to moderate depression:
   • Offer choice between CBT, SGA, or St. John's wort based on patient preference 1
   • Consider exercise as adjunctive treatment 1, 3
3. For moderate to severe depression:
   • Offer choice between CBT or SGA as first-line 1, 2
   • Consider combined approach (CBT plus SGA) for more severe cases 2
4. If inadequate response after 4-6 weeks:
   • Switch to different SGA or CBT, or
   • Augment current treatment with additional medication or therapy 1
5. For treatment-resistant depression:
   • Consider ketamine/esketamine or electroconvulsive therapy 1