What are the recommended antidepressants for treating depression?

Recommended Antidepressants for Treating Depression

Second-generation antidepressants (SSRIs, SNRIs, and others) are the recommended first-line pharmacological treatments for depression, with selection based primarily on side effect profiles, cost, and patient preferences rather than efficacy differences.

Types of Antidepressants

First-Line Options (Second-Generation Antidepressants)

Selective Serotonin Reuptake Inhibitors (SSRIs)

• Sertraline (Zoloft): Often recommended as first-line treatment with initial dosage of 25-50 mg daily and maximum of 200 mg daily 1
• Citalopram (Celexa): 10-20 mg daily (maximum 20 mg in elderly due to QT prolongation risk)
• Escitalopram (Lexapro): 10-20 mg daily
• Fluoxetine (Prozac)
• Paroxetine (Paxil)
• Fluvoxamine (Luvox)

Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)

• Venlafaxine (Effexor)
• Duloxetine (Cymbalta)
• Desvenlafaxine (Pristiq)
• Levomilnacipran (Fetzima)
• Milnacipran (Savella)

Other Second-Generation Antidepressants

• Bupropion (Wellbutrin): Notable for promoting weight loss 1
• Mirtazapine (Remeron): Associated with weight gain 1
• Trazodone (Desyrel)
• Nefazodone
• Vilazodone (Viibryd)
• Vortioxetine (Trintellix)

Second-Line Options (First-Generation Antidepressants)

• Tricyclic Antidepressants (TCAs): Amitriptyline, clomipramine, nortriptyline
• Monoamine Oxidase Inhibitors (MAOIs)

Selection Criteria

The American College of Physicians strongly recommends selecting second-generation antidepressants based on 2:

1. Adverse effect profiles
2. Cost
3. Patient preferences

Evidence shows no significant differences in efficacy between second-generation antidepressants for treating major depressive disorder 2, 1. Even for severe depression, SSRIs have been found to be as effective as TCAs 3.

Special Considerations for Medication Selection

Side Effect Considerations

• Weight concerns:

  • For patients concerned about weight gain: Consider bupropion (promotes weight loss) 1
  • Avoid mirtazapine and paroxetine (associated with weight gain) 1

• Sexual dysfunction:

  • Bupropion has lower rates of sexual adverse events than fluoxetine or sertraline 2
  • Paroxetine has higher rates of sexual dysfunction than fluoxetine, fluvoxamine, nefazodone, or sertraline 2

• Elderly patients:

  • Preferred options include sertraline, citalopram, and escitalopram due to favorable side effect profiles and lower risk of drug interactions 1

Drug Interactions

• Sertraline has less prominent inhibitory effect on CYP2D6 at lower doses compared to some other SSRIs, though still has potential for clinically important interactions 4
• Monitor closely when combining SSRIs with:
  • Triptans (risk of serotonin syndrome) 4
  • TCAs (may need TCA dose reduction) 4
  • Warfarin and NSAIDs (increased bleeding risk) 4

Treatment Protocol

Treatment Phases

1. Acute phase (6-12 weeks): Goal is symptom remission
2. Continuation phase (4-9 months): Prevent relapse
3. Maintenance phase (≥1 year): Prevent recurrence, especially for patients with multiple episodes 2, 1

Monitoring and Adjustment

• Begin monitoring within 1-2 weeks of starting therapy 2
• Assess for improvement in depressive symptoms and emergence of side effects
• Modify treatment if inadequate response within 6-8 weeks 2
• Up to 38% of patients do not achieve response and 54% do not achieve remission with initial treatment 2

Duration of Treatment

• For first episode: Continue treatment for 4-9 months after satisfactory response 2
• For patients with 2+ episodes: Longer duration of therapy is beneficial 2

Treatment-Resistant Depression

For the approximately one-third of patients who don't respond adequately to first-line treatment:

• Consider switching to a different antidepressant class
• Consider augmentation strategies, particularly atypical antipsychotics (aripiprazole, brexpiprazole, cariprazine, quetiapine, olanzapine-fluoxetine combination) 5
• Weigh benefits against potential adverse events such as weight gain, akathisia, and tardive dyskinesia 5

Common Pitfalls to Avoid

• Inadequate duration of treatment: Ensure full trial of 6-8 weeks before concluding ineffectiveness
• Inadequate dosing: Titrate to therapeutic doses
• Premature discontinuation: Continue treatment for recommended duration to prevent relapse
• Ignoring side effects: Address side effects promptly to improve adherence
• Overlooking drug interactions: Particularly with medications metabolized by CYP2D6
• Failing to monitor for suicidality: Risk for suicide attempts is greater during the first 1-2 months of treatment 2