What are the side effects, contraindications, and best administration cases for citalopram, venlafaxine, mirtazapine, and sertraline in treating depression and anxiety disorders?

Antidepressant Medication Guide: Side Effects, Contraindications, and Optimal Use

Sertraline (First-Line Choice)

Sertraline is the preferred first-line medication for depression and anxiety due to its optimal balance of efficacy, safety, and tolerability, with lower cardiac risk than citalopram and lower discontinuation syndrome risk than other SSRIs 1, 2.

Dosing Strategy

• Start at 50 mg daily (or 25 mg as a "test dose" for highly anxious patients to minimize initial activation) 1
• Increase in 50 mg increments at 1-2 week intervals if inadequate response 1
• Maximum dose: 200 mg daily 1
• Allow 6-8 weeks for adequate trial, including at least 2 weeks at maximum tolerated dose 1

Common Side Effects (FDA Data)

• Gastrointestinal: Nausea (26% vs 11% placebo), diarrhea (20% vs 10%), dyspepsia (8% vs 4%) 2
• Sexual dysfunction: Ejaculatory delay (14% vs 1% in men), decreased libido (6% vs 1%) 2
• CNS: Insomnia (21% vs 11%), somnolence (13% vs 7%), dizziness (12% vs 7%) 2
• Autonomic: Dry mouth (14% vs 8%), sweating (7% vs 2%) 2

Absolute Contraindications

• Concurrent MAOI use or within 2 weeks of MAOI discontinuation (serotonin syndrome risk) 1
• Pimozide use (QT prolongation) 2

Critical Safety Monitoring

• Suicidality: Monitor closely during first 1-2 weeks after initiation or dose changes, especially in patients under age 24 (FDA black box warning) 1
• Serotonin syndrome risk: Exercise caution with tramadol, triptans, other antidepressants, St. John's wort 1
• Discontinuation: Never stop abruptly—taper gradually to minimize withdrawal symptoms (dizziness, nausea, sensory disturbances) 1, 2

Treatment Duration

• Continue for 4-9 months minimum after satisfactory response for first-episode depression 1
• ≥1 year for recurrent episodes 1

Best Clinical Scenarios

• Depression with comorbid anxiety 1
• Patients with cardiac risk factors (lower QT prolongation risk than citalopram) 1
• Older patients ≥60 years (favorable tolerability, no age-based dose adjustment needed) 1
• When drug interactions are a concern (minimal CYP450 effects) 1

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Citalopram (Alternative First-Line)

Citalopram has the least effect on CYP450 enzymes and lowest propensity for drug interactions among SSRIs, making it ideal when polypharmacy is a concern 1.

Dosing Strategy

• Start at 20 mg daily 3
• Titrate to 40 mg daily maximum (20 mg maximum in patients >60 years, hepatic impairment, or CYP2C19 poor metabolizers) 1

Common Side Effects

• Similar SSRI profile: nausea, diarrhea, insomnia, sexual dysfunction 1
• Sweating more common than with mirtazapine 4

Absolute Contraindications

• Concurrent MAOI use 1
• QT prolongation or congenital long QT syndrome 1

Critical Safety Monitoring

• Cardiac: Higher QT prolongation risk than sertraline; avoid in patients with cardiac arrhythmias or on QT-prolonging medications 1
• Suicidality: Same FDA black box warning as all SSRIs 1

Best Clinical Scenarios

• Patients on multiple medications requiring minimal drug-drug interactions 1
• Generalized anxiety disorder with comorbid depression 3
• Patients who failed other SSRIs (may still respond to citalopram) 3

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Venlafaxine (SNRI for Treatment-Resistant Cases)

Venlafaxine demonstrates statistically superior response rates compared to SSRIs specifically for depression with prominent anxiety symptoms, making it the preferred second-line agent when SSRIs fail 1, 5.

Dosing Strategy

• Start at 37.5-75 mg extended-release daily 6
• Titrate to 75-225 mg daily based on response 6
• Has ascending dose-response curve (unlike SSRIs' flat curve) 6
• Low doses predominantly affect serotonin; higher doses add norepinephrine reuptake inhibition 6

Common Side Effects

• At low doses: Similar to SSRIs—nausea, diarrhea, fatigue, sexual dysfunction 6
• At higher doses: Hypertension (dose-dependent), diaphoresis, tachycardia, tremors, anxiety 6
• Discontinuation rates: 40-67% higher than SSRIs due to adverse effects 1

Absolute Contraindications

• Concurrent MAOI use (serotonin syndrome risk) 6
• Uncontrolled hypertension 6

Critical Safety Monitoring

• Blood pressure: Monitor at each dose increase; dose-dependent elevation (infrequent below 225 mg/day) 6
• Discontinuation syndrome: Higher risk than SSRIs; requires careful tapering 6
• CYP2D6 interactions: Venlafaxine metabolized by CYP2D6; subject to drug-drug interactions with CYP2D6 inhibitors 6

Best Clinical Scenarios

• Treatment-resistant depression/anxiety after SSRI failure 5
• Depression with prominent anxiety symptoms 1, 5
• When greater efficacy at higher doses is needed (ascending dose-response) 6
• Generalized anxiety disorder, social anxiety disorder, panic disorder 6

Common Pitfalls

• SNRIs cause significantly higher rates of nausea and vomiting than SSRIs 1
• Not first-line due to higher adverse effect burden 1

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Mirtazapine (Rapid-Onset Alternative)

Mirtazapine has statistically faster onset of action than SSRIs (1-2 weeks vs 4 weeks) and is superior for early anxiety relief, making it the preferred choice when rapid symptom control is critical 5, 4.

Dosing Strategy

• Start at 15 mg at bedtime 5
• Increase to 30-45 mg daily based on response 5
• Paradoxically, lower doses (15 mg) may be more sedating than higher doses 5

Common Side Effects

• Metabolic: Increased appetite, weight gain (clinically significant and more frequent than SSRIs) 4
• Sedation: Somnolence (dose-dependent, more at lower doses) 4
• Less common than SSRIs: Nausea, sweating, sexual dysfunction 4

Absolute Contraindications

• Concurrent MAOI use (serotonin syndrome risk) 5

Critical Safety Monitoring

• Weight gain: Monitor weight at each visit; clinically relevant increases common 4
• Sedation: May impair driving/operating machinery, especially initially 4
• Suicidality: Same FDA black box warning as all antidepressants 1

Best Clinical Scenarios

• When rapid onset is critical (statistically significant improvement by week 2) 5, 4
• Depression with prominent insomnia (improves sleep quality and alertness upon awakening) 4
• Patients who cannot tolerate SSRI gastrointestinal or sexual side effects 4
• Augmentation strategy when duloxetine/venlafaxine fails 5
• Elderly patients with poor appetite or weight loss 5

Common Pitfalls

• Weight gain is a major limitation for long-term use 4
• Not ideal for patients with obesity or metabolic syndrome 4

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Comparative Treatment Algorithm

First-Line Approach

1. Start with sertraline 50 mg daily for most patients with depression/anxiety 1
2. Use citalopram 20 mg daily if multiple drug interactions are a concern 1
3. Consider mirtazapine 15-30 mg if rapid onset is critical or insomnia is prominent 5, 4

Second-Line (After 6-8 Weeks Without Response)

1. Switch to venlafaxine XR 75-225 mg for treatment-resistant cases, especially with prominent anxiety 5
2. Augment with mirtazapine if partial response to SSRI/SNRI 5

Response Monitoring Timeline

• Assess at 4 weeks and 8 weeks using standardized scales 1
• 38% of patients don't respond to initial trials; 54% don't achieve remission 1, 5
• Allow full 6-8 weeks before declaring treatment failure 1

Universal Safety Principles

• All agents carry FDA black box warnings for suicidality in adolescents and young adults 1
• Never combine with MAOIs (minimum 2-week washout) 1, 6
• Always taper when discontinuing (except fluoxetine, which has longest half-life) 1
• Combination with CBT is superior to either alone when available 1