What medications are used to treat depression and anxiety?

Medications for Depression and Anxiety

Start with an SSRI as first-line treatment, specifically sertraline 50 mg daily (or 25 mg if anxiety is prominent), as SSRIs demonstrate equivalent efficacy for both depression and anxiety with the best evidence base. 1, 2

First-Line Treatment: SSRIs

Preferred Agent: Sertraline

• Sertraline is the optimal first choice due to its efficacy for both depression and anxiety, favorable side effect profile, and specific advantages for melancholia and psychomotor agitation 1, 2
• Start with 50 mg daily, taken once daily (morning or evening) 1
• If the patient has prominent anxiety symptoms, start with 25 mg daily as a "test dose" for the first week before increasing to 50 mg, as SSRIs can initially worsen anxiety 1, 3
• Increase in 50 mg increments at 1-2 week intervals if inadequate response, up to maximum 200 mg daily 1
• Allow a full 6-8 weeks for adequate trial, including at least 2 weeks at maximum tolerated dose before declaring treatment failure 1

Alternative First-Line SSRIs

• Escitalopram or citalopram have the fewest drug-drug interactions due to minimal CYP450 enzyme effects, making them ideal for patients on multiple medications 1, 2
• Fluoxetine has the longest half-life (several days), which is beneficial for patients who occasionally miss doses and reduces discontinuation syndrome risk 2, 4, 5
• Paroxetine is FDA-approved for the widest range of anxiety disorders (GAD, panic disorder, social anxiety disorder, PTSD, OCD) but carries higher risk of discontinuation syndrome and requires careful tapering 1, 2

When SSRIs Are Insufficient

Switch to SNRI

• If inadequate response after 6-8 weeks at therapeutic SSRI doses, switch to venlafaxine (SNRI), which may be superior to fluoxetine specifically for patients with significant anxiety symptoms 1, 2, 6
• Venlafaxine demonstrated statistically better response rates than fluoxetine in patients with depression and concomitant anxiety (75.0% vs 50.7% response rate) 6
• One in four patients becomes symptom-free after switching medications 1, 2

Consider Mirtazapine for Specific Situations

• Mirtazapine has faster onset of action than SSRIs (statistically significant improvement within 2-4 weeks, though response rates equalize after 4 weeks) and may be more effective than fluoxetine 1, 2, 7
• Particularly useful for patients with prominent insomnia, as it has beneficial sedative effects 2, 7
• Take once daily, preferably in the evening at bedtime 7
• Cannot be combined with MAOIs (must wait 14 days after stopping MAOI before starting mirtazapine, and vice versa) 7

Critical Safety Monitoring

Black Box Warning

• All SSRIs and mirtazapine carry FDA black box warnings for increased suicidal thoughts or actions, particularly in patients under age 24, especially within the first few months of treatment or when dose is changed 1, 7, 4, 7
• Monitor closely for new or worsening depression, anxiety, agitation, panic attacks, irritability, or suicidal thoughts 7, 4, 7

Discontinuation Syndrome

• Never abruptly discontinue SSRIs or mirtazapine—always taper to prevent discontinuation syndrome (dizziness, nausea, sensory disturbances, rebound anxiety) 1, 8, 7
• Paroxetine has the highest risk of discontinuation syndrome among SSRIs 1, 2
• Fluoxetine has the lowest risk due to its long half-life 2, 5

Serotonin Syndrome Risk

• Do not combine SSRIs or mirtazapine with MAOIs, triptans, tramadol, fentanyl, or other serotonergic agents due to potentially life-threatening serotonin syndrome 7
• Symptoms include agitation, confusion, fast heart rate, tremors, muscle rigidity, seizures, hyperthermia—requires immediate emergency care 7

Dosing Considerations for Anxiety vs Depression

• Higher doses may be needed for OCD compared to depression (fluoxetine 60-80 mg, paroxetine 60 mg) 1
• For anxiety disorders, start lower and titrate more gradually than for depression alone, as SSRIs can initially increase anxiety symptoms 1, 2, 3
• Approximately 38% of patients do not achieve treatment response during 6-12 weeks, and 54% do not achieve remission—this is expected and warrants dose optimization or switching, not premature discontinuation 1

Treatment Duration

• Continue SSRI treatment for 4-9 months after satisfactory response for first-episode major depression 1
• Longer duration (often indefinite) for patients with recurrent episodes to reduce relapse risk 1

Common Pitfalls to Avoid

• Do not discontinue prematurely—partial response at 4 weeks warrants continued treatment and dose optimization, not switching 1
• Do not use SSRIs for IBS, as they lack significant benefit for global symptoms or abdominal pain 1
• Consider CYP2D6 genetic variation for fluoxetine and paroxetine, as these are metabolized through this pathway which has genetic variability 1
• Avoid benzodiazepines during SSRI/mirtazapine treatment unless specifically indicated, as they can cause additive sedation and other interactions 7

Non-Controlled Adjunctive Options

• Buspirone 5 mg twice daily (maximum 20 mg three times daily) can be added for residual anxiety symptoms, though it takes 2-4 weeks to become fully effective 8
• Beta blockers (propranolol) are not recommended as primary treatment for social anxiety disorder but may help with situational anxiety and physical symptoms (tremor, tachycardia, sweating) 9, 8
• Gabapentin can be considered when first-line treatments are ineffective or not tolerated, particularly for patients with comorbid pain 8