What is the role of mirtazapine in treating severe depressive episodes?

From the Guidelines

Mirtazapine is an effective treatment option for severe depressive episodes, particularly when sleep disturbance, anxiety, or poor appetite are prominent symptoms, as it has a faster onset of action compared to other antidepressants like fluoxetine, paroxetine, or sertraline 1.

Key Points to Consider

• Mirtazapine is typically prescribed at a starting dose of 15 mg taken once daily at bedtime, with gradual increases up to 30-45 mg daily if needed.
• The full therapeutic effect usually takes 2-4 weeks to develop, though some symptoms like sleep and appetite may improve earlier.
• Mirtazapine works differently from SSRIs by blocking specific serotonin receptors and enhancing norepinephrine release, which helps explain its effectiveness for depression with insomnia and anxiety.
• Common side effects include sedation, increased appetite, weight gain, and dry mouth, with sedative effects being strongest at lower doses (15 mg) and may decrease at higher doses.
• Patients should be aware that mirtazapine should not be abruptly discontinued after long-term use but rather tapered gradually under medical supervision, and it's also important to avoid alcohol while taking mirtazapine as it can increase sedation.

Clinical Recommendations

• The American College of Physicians recommends selecting second-generation antidepressants, including mirtazapine, based on adverse effect profiles, cost, and patient preferences for treating acute major depression 1.
• Regular assessment of patient status, therapeutic response, and adverse effects of antidepressant therapy is recommended, starting within 1 to 2 weeks of initiation of therapy 1.
• Treatment should be modified if the patient does not have an adequate response to pharmacotherapy within 6 to 8 weeks of the initiation of therapy for major depressive disorder 1.

From the FDA Drug Label

Mirtazapine tablets, USP are indicated for the treatment of major depressive disorder The efficacy of mirtazapine in the treatment of major depressive disorder was established in 6-week controlled trials of outpatients whose diagnoses corresponded most closely to the Diagnostic and Statistical Manual of Mental Disorders-3rd edition (DSM-III) category of major depressive disorder A major depressive episode (DSM-IV) implies a prominent and relatively persistent (nearly every day for at least 2 weeks) depressed or dysphoric mood that usually interferes with daily functioning, and includes at least 5 of the following 9 symptoms: depressed mood, loss of interest in usual activities, significant change in weight and/or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, a suicide attempt, or suicidal ideation. The effectiveness of mirtazapine in hospitalized depressed patients has not been adequately studied

Mirtazapine is indicated for the treatment of major depressive disorder. The efficacy of mirtazapine was established in 6-week controlled trials of outpatients with major depressive disorder.

• Mirtazapine may be used to treat severe depressive episodes, but its effectiveness in hospitalized depressed patients has not been adequately studied 2.
• It is essential to note that mirtazapine should be used with caution, especially in patients with a history of suicidal thoughts or actions 2.
• The decision to use mirtazapine in treating severe depressive episodes should be made on a case-by-case basis, considering the individual patient's needs and medical history.

From the Research

Role of Mirtazapine in Treating Severe Depressive Episodes

Mirtazapine is a noradrenergic and specific serotonergic antidepressant (NaSSA) that has been evaluated in the treatment of major depression, including severe depressive episodes. The key points regarding its role in treating severe depressive episodes are:

• Mirtazapine has been shown to be effective in the treatment of moderate to severe major depression, with a rapid onset of action compared to selective serotonin reuptake inhibitors (SSRIs) 3, 4, 5, 6, 7.
• It has been found to be as effective as tricyclic antidepressants (TCAs) and SSRIs in the treatment of severe depression, with a better tolerability profile than TCAs 3, 5, 7.
• Mirtazapine has a unique mechanism of action, blocking presynaptic alpha 2-adrenergic receptors and postsynaptic serotonin type 2 and type 3 receptors, which contributes to its efficacy in treating depression 5, 7.
• The drug has been shown to have anxiolytic and sleep-improving effects, which may be beneficial for patients with severe depression and anxiety symptoms 3, 5, 6.
• Mirtazapine is generally well tolerated, with common adverse events including somnolence, increased appetite, weight gain, and dizziness 3, 5, 6, 7.

Efficacy in Severe Depressive Episodes

The efficacy of mirtazapine in severe depressive episodes has been demonstrated in several studies:

• A study published in 1999 found that mirtazapine was effective in the treatment of severe depression, with a rapid onset of action compared to fluoxetine 3.
• A study published in 2009 found that mirtazapine was as effective as other antidepressants in the treatment of severe depression, with a higher sustained remission rate than amitriptyline 4.
• A study published in 1998 found that mirtazapine was effective in the treatment of severe depression, with a better tolerability profile than TCAs 5.
• A study published in 1996 found that mirtazapine was effective in the treatment of severe depression, with a rapid onset of action and a better tolerability profile than TCAs 7.

Tolerability and Safety

The tolerability and safety of mirtazapine in the treatment of severe depressive episodes have been evaluated in several studies:

• Mirtazapine has been found to be generally well tolerated, with common adverse events including somnolence, increased appetite, weight gain, and dizziness 3, 5, 6, 7.
• The drug has a low potential for interaction with other medications, including antipsychotics, TCAs, and SSRIs 3, 5.
• Mirtazapine has been found to be safe in overdose, with no significant cardiovascular adverse effects reported 5, 7.