How do psychiatrists choose which antidepressants to use for a patient?

How Psychiatrists Choose Antidepressants for Patients

Psychiatrists should select second-generation antidepressants (SGAs) such as SSRIs as first-line treatment for most patients with depression due to their better side effect profile compared to first-generation antidepressants, while considering individual patient factors like comorbidities, side effect profiles, and potential drug interactions. 1

Initial Medication Selection Framework

First-Line Options

• Second-generation antidepressants (SGAs) are generally considered first-line treatment for depression due to:
  • Better adverse effect profiles than first-generation antidepressants
  • Similar efficacy across the class (remission rates of 42-49%) 1
  • Lower toxicity in overdose
  • Better patient compliance

Key Patient Factors That Guide Selection

1. Severity of Depression

   • Patients with severe depression show more robust responses to antidepressants compared to those with mild-moderate depression 1
   • The STAR*D trial found that higher baseline depression severity was associated with lower likelihood of achieving remission 1

2. Comorbid Conditions

   • Pain disorders: SNRIs may provide marginally superior remission rates (49% vs 42%) compared to SSRIs 1
   • Anxiety: Avoid activating agents like bupropion 2
   • Bipolar disorder: Avoid SSRIs due to risk of triggering mania 2
   • Obesity: Consider bupropion which promotes weight loss 1

3. Side Effect Profiles

   • Sexual dysfunction: Bupropion has decreased risk compared to escitalopram and paroxetine 1
   • Weight concerns:
     • Fluoxetine and sertraline: Weight loss with short-term use, weight neutrality long-term 1
     • Paroxetine and amitriptyline: Higher risk of weight gain 1
     • Bupropion: Consistently promotes weight loss 1

4. Age Considerations

   • Young adults (18-24): Higher risk of suicidality (OR = 2.30) - requires closer monitoring 1, 2
   • Adults 25-64: Neutral effect on suicidality 1
   • Adults 65+: Protective effect against suicidality (OR = 0.06) 1

5. Pregnancy/Breastfeeding Status

   • Fluoxetine has demonstrated safety in pregnancy 3
   • Sertraline and paroxetine transfer in lower concentrations to breast milk 1
   • Fluoxetine and citalopram produce higher infant plasma concentrations 1

Pharmacokinetic Considerations

• Drug Interactions: Consider patient's current medications

  • Paroxetine: Potent inhibitor of CYP2D6 4
  • Fluoxetine: Potent inhibitor of CYP2D6 4
  • Fluvoxamine: Potent inhibitor of CYP1A2 and CYP2C19 4
  • Sertraline: Moderate drug interaction issues 5
  • Escitalopram: Fewer drug interactions 5

• Half-life differences:

  • Fluoxetine: 1-4 days (7-15 days for active metabolite norfluoxetine) 4
  • Paroxetine: 21 hours 4
  • Citalopram: 36 hours 4

Specific Medication Selection Algorithm

1. For uncomplicated depression:

   • Start with an SSRI (fluoxetine, sertraline, escitalopram) due to favorable side effect profile 1, 2
   • Evidence suggests escitalopram may be more effective than other antidepressants with better tolerability 5

2. For patients with sexual dysfunction concerns:

   • Consider bupropion (100-400 mg/day) 1

3. For patients with comorbid pain:

   • Consider an SNRI for marginally superior efficacy 1

4. For patients with weight concerns:

   • Weight gain concerns: Consider fluoxetine, sertraline, or bupropion 1
   • Weight loss desired: Bupropion is consistently associated with weight loss 1

5. For patients with high suicide risk:

   • Choose medications with lower toxicity in overdose (SGAs over TCAs) 2
   • Implement closer monitoring, especially in young adults 1, 2

Monitoring and Follow-up

• Assess treatment response beginning within 1-2 weeks of starting treatment 2
• Monitor for side effects and emergence of suicidal thoughts 2
• If inadequate response after 6-8 weeks, consider:
  • Dose adjustment
  • Switching to a different antidepressant
  • Adding psychotherapy
  • Adding another medication 2

Common Pitfalls to Avoid

• Underestimating drug interactions: Particularly with paroxetine and fluoxetine which strongly inhibit CYP2D6 4, 5
• Ignoring age-related risks: Young adults have increased suicidality risk with antidepressants 1, 2
• Abrupt discontinuation: Can lead to withdrawal symptoms, particularly with shorter-acting agents 2
• Overlooking bipolar disorder: SSRIs can trigger mania in bipolar patients 2
• Assuming all SSRIs are identical: Despite similar efficacy, they have important differences in side effect profiles and drug interactions 5