What to discuss with a patient when initiating mirtazapine (tetracyclic antidepressant) therapy, including safety precautions?

Counseling Patients Starting Mirtazapine

Start mirtazapine at 15 mg once daily at bedtime, warn patients about sedation and weight gain as the most common side effects, and schedule close follow-up within the first week to monitor for suicidal ideation, especially in patients under 25 years of age. 1

Critical Safety Information to Discuss

Black Box Warning: Suicidal Thoughts and Behaviors

• Patients under 24 years have increased risk of suicidal thoughts or actions, particularly in the first few months of treatment or when doses change 1
• Instruct patients and family members to immediately report new or worsening: 1
  • Depression or suicidal thoughts
  • Unusual changes in behavior or mood
  • Panic attacks, agitation, or restlessness
  • Acting aggressive or violent
  • Extreme increase in activity or talking (mania)
  • Trouble sleeping
• Schedule follow-up contact (in-person or telephone) within the first week after initiation 2, 1

Common Side Effects to Expect

• Sedation/somnolence is the most frequently reported adverse effect (23% vs 14% placebo) 3, 4
  • Warn patients not to drive or operate machinery until they know how the medication affects them 1
  • Explain that sedation may be less prominent at higher doses due to dose-dependent antihistaminic effects 2, 3
• Increased appetite (11% vs 2% placebo) and weight gain (10% vs 1% placebo) 3, 4
• Dry mouth (25% vs 16% placebo) 3, 4

Serious but Rare Adverse Events

Agranulocytosis/Low White Blood Cell Count:

• Instruct patients to immediately contact you if they develop fever, chills, sore throat, mouth ulcers, or flu-like symptoms 1

Serotonin Syndrome:

• Warn about risk when combining with other serotonergic medications (SSRIs, SNRIs, triptans, tramadol, St. John's Wort) 1
• Tell patients to seek emergency care if they experience agitation, confusion, rapid heart rate, high fever, muscle rigidity, or tremor 1

QTc Prolongation:

• Inform patients to report immediately if they feel faint, lose consciousness, or have heart palpitations 1
• This is particularly important if taking other QT-prolonging medications (certain antibiotics, antipsychotics, ondansetron, escitalopram) 2, 1

Dosing Instructions

• Start at 15 mg once daily at bedtime 1, 3, 5
• Effective dose range is 15-45 mg daily 1, 3
• If inadequate response after 2-4 weeks, may increase to 30 mg, then 45 mg if needed 1, 5
• Take at the same time each day, preferably at bedtime 1

Important Drug Interactions and Contraindications

Absolute Contraindications:

• Do not use with MAOIs or within 14 days of stopping an MAOI 1
• Do not start an MAOI until at least 14 days after stopping mirtazapine 1
• Avoid with linezolid or IV methylene blue 1

Avoid Concurrent Use:

• Alcohol - significantly increases sedation and impairs cognitive/motor function 1, 4
• Benzodiazepines - additive sedative effects 1, 4

What to Expect for Therapeutic Effect

• Sleep disturbances and anxiety may improve within the first week 3, 6
• Full antidepressant effect typically takes 2-4 weeks 3, 5
• Continue medication even after feeling better to prevent relapse 6, 7

Discontinuation Warning

• Never stop abruptly - must taper gradually to avoid withdrawal symptoms 1
• Discuss any tapering plan with your healthcare provider before making changes 1

Special Populations

Pregnancy and Breastfeeding:

• Notify your provider if pregnant, planning pregnancy, or breastfeeding 1
• Consider enrolling in the National Pregnancy Registry for Antidepressants (1-844-405-6185) 1
• Mirtazapine passes into breast milk 1

Angle-Closure Glaucoma:

• Mirtazapine can cause mild pupillary dilation, which may trigger angle-closure glaucoma in susceptible individuals 1
• Patients with risk factors should be examined before starting treatment 1

Advantages Over Other Antidepressants

• No sexual dysfunction, unlike SSRIs 6, 7
• Minimal cardiovascular and anticholinergic effects compared to tricyclic antidepressants 3, 6
• No gastrointestinal side effects typical of SSRIs 3, 6
• May be particularly helpful if you have comorbid anxiety, insomnia, or poor appetite 2, 6, 7

Follow-Up Schedule

• Initial contact within 1 week of starting 2, 1
• Regular monitoring especially during first few months and after any dose changes 1
• Report any new or concerning symptoms between scheduled visits 1