What are the recommended first-line medications for treating depression and anxiety, specifically selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs)?

First-Line Antidepressant and Anti-Anxiety Medications

Selective serotonin reuptake inhibitors (SSRIs) are the recommended first-line pharmacotherapy for both depression and anxiety disorders in adults, with second-generation antidepressants including SSRIs and SNRIs demonstrating similar efficacy but SSRIs offering superior tolerability. 1

Primary Medication Classes

SSRIs as First-Line Treatment

SSRIs should be selected as initial pharmacotherapy based on their proven efficacy, favorable safety profile, and lower toxicity in overdose compared to first-generation antidepressants. 1

• For depression: SSRIs demonstrate modest superiority over placebo with a number needed to treat of 7-8 for achieving remission in primary care populations 1
• For anxiety disorders: SSRIs produce significant improvements in treatment response and symptom reduction across generalized anxiety disorder, social anxiety disorder, panic disorder, and separation anxiety disorder 1
• The benefit of SSRIs over placebo is most pronounced in patients with severe depression 1

Specific SSRI Recommendations by Clinical Context

For adults with depression or anxiety:

• Escitalopram and sertraline are listed as first-line options by international guidelines 1
• Fluoxetine, fluvoxamine, paroxetine, and sertraline all have established efficacy 1
• Sertraline and paroxetine transfer to breast milk in lower concentrations than other SSRIs, making them preferred in breastfeeding mothers 1

For older adults (≥60 years):

• Preferred SSRIs include citalopram, escitalopram, and sertraline using a "start low, go slow" approach 1
• Paroxetine and fluoxetine should generally be avoided in older adults due to higher rates of adverse effects 1

For children and adolescents (6-18 years):

• SSRIs as a class improve anxiety symptoms, treatment response, remission rates, and global function compared to placebo 1
• Fluoxetine is the only FDA-approved SSRI for major depression in children/adolescents aged 8 years or older 1
• Sertraline, fluoxetine, and fluvoxamine have demonstrated efficacy for anxiety disorders in this population 1

SNRIs as Alternative First-Line Treatment

SNRIs (venlafaxine and duloxetine) represent an alternative first-line option, though they carry slightly higher rates of gastrointestinal adverse effects compared to SSRIs. 1

• SNRIs are slightly more likely than SSRIs to improve depression symptoms but are associated with higher rates of nausea and vomiting 1
• For anxiety disorders, SNRIs (venlafaxine, duloxetine) demonstrate efficacy comparable to SSRIs 1
• Duloxetine is the only SNRI with FDA approval for generalized anxiety disorder in children and adolescents aged 7 years and older 1
• SNRIs have been associated with sustained clinical hypertension, increased blood pressure, and increased pulse, requiring monitoring 1

Medication Selection Algorithm

Choose initial medication based on the following hierarchy:

1. Patient-specific factors:

   • Age: Use citalopram, escitalopram, or sertraline in older adults 1
   • Pregnancy/breastfeeding: Consider sertraline or paroxetine for lower breast milk transfer 1
   • Cardiovascular status: Avoid SNRIs if hypertension is a concern 1

2. Adverse effect profile:

   • If gastrointestinal sensitivity: Prefer SSRIs over SNRIs 1
   • If sexual dysfunction is a concern: All SSRIs and SNRIs carry this risk 1
   • If activation/agitation is a concern: Monitor closely with any agent 1

3. Cost and dosing convenience:

   • All second-generation antidepressants are equally effective for treatment-naive patients 1
   • Most SSRIs permit once-daily dosing due to long half-lives 1

4. Comorbid conditions:

   • For depression with anxiety: SSRIs or SNRIs are both appropriate 1
   • For chronic pain syndromes: SNRIs may offer additional benefit 1

Treatment Monitoring and Duration

Monitor response beginning within 1-2 weeks of initiation, with treatment modification required if inadequate response by 6-8 weeks. 1

• Continue treatment for 4-9 months after satisfactory response for a first episode of major depression 1
• Patients with 2 or more episodes of depression benefit from longer duration therapy 1
• Approximately 63% of patients experience at least one adverse effect during treatment, with nausea and vomiting being the most common reasons for discontinuation 1

Critical Safety Considerations

Black box warnings apply to all SSRIs and SNRIs for treatment-emergent suicidality, particularly in adolescents and young adults through age 24. 1

• Monitor for emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, mania, worsening depression, and suicidal ideation 1
• Uncommon but serious adverse effects include serotonin syndrome (especially with concomitant serotonergic agents), seizures, abnormal bleeding, and behavioral activation 1
• Concomitant use with NSAIDs, aspirin, or warfarin increases bleeding risk 1

Common Pitfalls to Avoid

• Do not use paroxetine or fluoxetine as first-line in older adults due to higher adverse effect rates 1
• Do not combine SSRIs/SNRIs with MAOIs due to risk of serotonin syndrome 1
• Do not discontinue treatment prematurely before 6-8 weeks to assess adequate response 1
• Do not ignore drug-drug interactions: Fluoxetine and paroxetine are potent CYP2D6 inhibitors requiring dose adjustments of concomitant medications 1, 2, 3
• Do not assume all SSRIs are identical: Sertraline has minimal CYP450 inhibition compared to fluoxetine and paroxetine, reducing drug interaction risk 2, 4