Can increasing the dose of Remeron (mirtazapine) cause depression?

Increasing Mirtazapine (Remeron) Dose and Depression Risk

Increasing the dose of mirtazapine (Remeron) is not likely to cause depression; rather, it is used to treat depression and may actually improve depressive symptoms with proper dosing.

Mechanism and Therapeutic Role

Mirtazapine is a noradrenergic and specific serotonergic antidepressant (NaSSA) that works by:

• Enhancing both noradrenergic and serotonergic neurotransmission through presynaptic alpha-2 antagonism
• Blocking postsynaptic 5-HT2 and 5-HT3 receptors, which helps reduce serotonin-related side effects 1
• Promoting sleep, appetite, and weight gain at therapeutic doses 2

Dosing Considerations

Mirtazapine is typically initiated at lower doses and gradually increased:

• Starting dose: 7.5-15 mg at bedtime 2
• Maximum therapeutic dose: 30-45 mg at bedtime 2
• Dosage adjustments should be made gradually, typically using increments of the initial dose every 5-7 days until therapeutic benefits are achieved 2

Important Dosing Observations

• At lower doses (7.5-15 mg), mirtazapine's antihistaminic (H1) effects predominate, causing sedation 3
• At higher doses (30-45 mg), the noradrenergic and serotonergic effects become more prominent, which enhances the antidepressant effect 3
• Interestingly, somnolence (the most common side effect) appears to be less frequent at higher dosages 3

Potential Concerns When Changing Doses

When increasing mirtazapine dosage, clinicians should be aware of:

1. Suicidality risk: There is an FDA warning about increased risk of suicidal thoughts or actions, particularly in young adults during the first few months of treatment or when the dose is changed 1

2. Common side effects: Increased appetite, weight gain, and transient somnolence are the most commonly reported adverse events 3

3. Monitoring needs: Patients should be monitored for:

   • New or worsening depression symptoms
   • Agitation, irritability, or unusual changes in behavior
   • Sleep disturbances
   • Changes in appetite or weight 1

Clinical Evidence on Dose Adjustments

A study examining mirtazapine in severely depressed patients found that:

• Mirtazapine at doses of 15-60 mg/day was as effective as fluoxetine in treating severe depression
• More mirtazapine-treated patients exhibited early response (≥50% decrease in depression scores) at day 7 compared to fluoxetine 4
• Mirtazapine produced significantly better improvements in sleep compared to fluoxetine 4

Practical Recommendations

1. Dose optimization: If a patient is not responding adequately to a lower dose, increasing to the therapeutic range of 30-45 mg may improve antidepressant efficacy 2

2. Timing of administration: Administer mirtazapine at bedtime to take advantage of its sedative properties for patients with insomnia 2

3. Duration of treatment: After 9 months of successful treatment, consider gradual dosage reduction over 10-14 days to reassess the need for continued medication and to limit withdrawal symptoms 2

4. Monitoring schedule: Assess therapeutic response and adverse effects regularly, particularly within the first 1-2 weeks after any dose change 5

Special Considerations

• Elderly or debilitated patients: Use lower doses and titrate more gradually 2
• Hepatic impairment: Consider dose reduction 2
• Concomitant medications: Be aware of potential drug interactions, although mirtazapine has fewer drug interactions compared to some other antidepressants 6

In conclusion, increasing mirtazapine dose within the therapeutic range is more likely to improve depression rather than cause it, provided the dose is appropriately adjusted and the patient is properly monitored for adverse effects.