Is Mirtazapine (an antidepressant) recommended for treating depression?

Mirtazapine for Depression Treatment

Yes, mirtazapine is recommended as an effective second-generation antidepressant for treating major depressive disorder in adults, with FDA approval and guideline support from the American College of Physicians. 1, 2

FDA-Approved Indication

• Mirtazapine is FDA-approved specifically for the treatment of major depressive disorder (MDD) in adults 2
• Clinical trials demonstrated superiority over placebo on multiple depression rating scales including the Hamilton Depression Rating Scale (HDRS), Clinical Global Impression (CGI) severity scores, and Montgomery-Asberg Depression Rating Scale (MADRS) 2
• Effective dosing ranges from 15-45 mg/day, with mean effective doses of 21-32 mg/day in clinical trials 2

Comparative Efficacy

Mirtazapine demonstrates equivalent efficacy to other second-generation antidepressants and tricyclic antidepressants for treating major depression. 1, 3

• Shows comparable effectiveness to amitriptyline, clomipramine, and doxepin based on depression rating scales 4, 5
• Equivalent efficacy to selective serotonin reuptake inhibitors (SSRIs) for treating depression with accompanying anxiety symptoms (moderate strength of evidence) 3

Unique Clinical Advantages

Faster Onset of Action

Mirtazapine demonstrates a statistically significantly faster onset of action compared to SSRIs, which is particularly valuable for patients requiring rapid symptom relief. 3

• More effective than fluoxetine at weeks 3 and 4 of therapy 4
• More effective than paroxetine at week 1 and citalopram at week 2 in short-term assessments 4
• This rapid onset may be attributed to its dual noradrenergic and serotonergic enhancement mechanism 5, 6

Depression with Insomnia

Mirtazapine is particularly useful for patients with depression accompanied by insomnia due to its beneficial effects on sleep disturbances. 1, 3

• Demonstrated superiority over placebo on the HDRS sleep disturbance factor 2
• Can be considered as a sedating low-dose antidepressant option when insomnia is a prominent feature 1
• The American Academy of Sleep Medicine recognizes mirtazapine for its sleep-improving effects 3

Depression with Anxiety

• Equally effective as other second-generation antidepressants for treating depression with accompanying anxiety symptoms 3
• Demonstrated superiority over placebo on the HDRS anxiety/somatization factor 2
• May be particularly useful in patients with cardiovascular disease who have comorbid anxiety, as it is considered safe in this population 3

Mechanism of Action

• Mirtazapine is classified as a noradrenergic and specific serotonergic antidepressant (NaSSA) 7, 4
• Blocks presynaptic alpha-2 adrenergic receptors, increasing both noradrenergic and serotonergic neurotransmission 5, 6
• Blocks postsynaptic 5-HT2 and 5-HT3 receptors while enhancing 5-HT1 receptor-mediated transmission 5, 6
• Has minimal anticholinergic activity compared to tricyclic antidepressants 4, 5

Tolerability Profile

Mirtazapine is generally well tolerated with fewer anticholinergic, cardiac, and neurological adverse events compared to tricyclic antidepressants. 4, 5

Common Adverse Effects

• Most commonly reported: somnolence, increased appetite, and weight gain 2, 8, 4
• Somnolence appears to be less frequent at higher dosages 6
• Weight gain and increased appetite are more common with mirtazapine than with comparator antidepressants 1, 4

Advantages Over Other Antidepressants

• Fewer anticholinergic events (dry mouth, constipation) compared to tricyclic antidepressants 4, 5
• Does not appear to be associated with sexual dysfunction, unlike SSRIs 6
• No significant cardiovascular adverse effects at therapeutic doses 6
• Safe in overdose with very low potential for inducing seizures 5

Guideline Recommendations

The American College of Physicians includes mirtazapine among the recommended second-generation antidepressants for treating major depressive disorder. 1

• Should be considered for moderate to severe depressive episodes 1
• Not recommended for initial treatment of mild depressive episodes 1
• Treatment should not be stopped before 9-12 months after recovery to prevent relapse 1

Long-Term Efficacy

• Patients receiving continued mirtazapine treatment experienced significantly lower relapse rates over 40 weeks compared to placebo 2
• Sustained remission rates may be higher with mirtazapine than with amitriptyline 4
• This pattern of relapse prevention was demonstrated in both male and female patients 2

Clinical Considerations

When selecting mirtazapine, prioritize patients with depression accompanied by insomnia, anxiety symptoms, or those requiring rapid symptom relief. 3, 2

• Avoid in patients where weight gain would be particularly problematic 1
• Consider as an alternative in patients who do not respond to or are intolerant of SSRIs or tricyclic antidepressants 6
• Low potential for drug-drug interactions via cytochrome P450 enzymes makes it suitable for patients requiring polytherapy 4