Can mirtazapine help with anxiety? Understanding its off-label use

October 10, 2025 •

4 min read

Anxiety disorders affect nearly 40 million adults in the United States, and while standard treatments exist, some individuals don't respond to them. In these cases, the antidepressant mirtazapine can help with anxiety, particularly when it is co-occurring with depression, sleep problems, or appetite issues. This usage is considered "off-label," meaning it is prescribed for a condition other than its FDA-approved indication for major depressive disorder.

Quick Summary

Mirtazapine is an antidepressant often prescribed off-label for anxiety, especially when standard treatments are ineffective. It is uniquely beneficial for patients with co-occurring insomnia or low appetite. Its sedative effects can provide rapid relief for sleep problems, while the full anxiolytic effects typically take several weeks to manifest.

Key Points

Off-Label Use: Mirtazapine is an antidepressant, not FDA-approved for anxiety, but is commonly prescribed off-label for it.
Unique Benefits: Its sedative and appetite-stimulating effects make it particularly useful for anxiety accompanied by insomnia or weight loss.
Distinct Mechanism: Mirtazapine boosts serotonin and norepinephrine differently than SSRIs, by blocking specific receptors instead of reuptake.
Effective for Comorbid Conditions: It is often a strong option for patients dealing with both anxiety and depression.
Common Side Effects: The most frequent side effects are drowsiness, weight gain, increased appetite, and dry mouth.
Requires Patience: While sedative effects are quick, the full anti-anxiety benefits can take 4 to 6 weeks to appear.
Not First-Line Treatment: It is generally considered a second-line option for anxiety, used after first-line treatments like SSRIs have failed or caused intolerable side effects.

How mirtazapine works for anxiety

Mirtazapine is classified as a tetracyclic antidepressant and has a unique mechanism of action compared to more common selective serotonin reuptake inhibitors (SSRIs). Instead of simply blocking the reuptake of neurotransmitters, mirtazapine works by blocking specific receptors in the brain to increase the activity of mood-enhancing chemicals.

Alpha-2 receptor antagonism: Mirtazapine blocks presynaptic alpha-2 adrenergic autoreceptors. This action prevents the brain from inhibiting the release of norepinephrine and serotonin, ultimately boosting their levels in the synaptic cleft.
Serotonin receptor blockade: It also potently blocks specific serotonin receptors, namely 5-HT2 and 5-HT3 receptors. This blockage is believed to contribute to its reduced risk of sexual side effects and gastrointestinal issues often associated with SSRIs.
Antihistamine effect: Mirtazapine's strong blocking effect on H1 histamine receptors is responsible for its powerful sedative properties, which is particularly useful for anxiety-related insomnia.

Its efficacy for various anxiety disorders

Clinical research and practice have shown mirtazapine to be effective in treating various forms of anxiety, especially when used as a second-line or adjunctive treatment. Studies have noted benefits for:

Generalized Anxiety Disorder (GAD): Research has indicated significant improvement in GAD symptoms for a majority of participants in some trials, particularly in patients with more severe anxiety.
Social Anxiety Disorder (SAD): Some studies suggest mirtazapine can reduce SAD symptoms, although results can be inconsistent, possibly due to factors like the severity of the anxiety at the study's start.
Panic Disorder: Evidence suggests mirtazapine can be comparable in effectiveness to some first-line panic disorder treatments, showing benefits for global anxiety symptoms.
Comorbid anxiety and depression: Mirtazapine is particularly well-regarded for patients who suffer from both anxiety and depression. Its broad action on different neurotransmitter systems can address symptoms of both conditions.

Dosage and administration guidelines

Mirtazapine is available in tablet and orally disintegrating tablet (ODT) formulations. It is typically taken once daily, usually at night, due to its sedating effects. A healthcare provider will determine the appropriate dosage for an individual, starting with a lower dose and potentially adjusting it based on response and tolerability. Dosage adjustments are typically made at intervals of at least a week to allow time for the body to respond.

Comparison: mirtazapine vs. SSRIs for anxiety

While SSRIs and SNRIs are generally considered first-line treatments for anxiety, mirtazapine's unique profile offers distinct advantages for certain patients, as highlighted in the table below.


Feature	Mirtazapine	SSRIs (e.g., escitalopram, sertraline)
Mechanism	Blocks specific serotonin (5-HT2, 5-HT3) and histamine (H1) receptors, and presynaptic α2-adrenergic receptors to increase serotonin and norepinephrine.	Blocks the reuptake of serotonin, increasing its availability in the brain.
Onset for Anxiety Relief	Sedative effect is rapid (first few days), but full anxiolytic effects typically take 4–6 weeks.	Can take 4–8 weeks for full effects; some individuals may experience a temporary increase in anxiety initially.
Effect on Sleep	Highly effective for insomnia due to sedative properties, especially at lower doses.	Can cause sleep disturbances like insomnia or somnolence.
Effect on Appetite	Often increases appetite and can lead to weight gain, making it beneficial for patients with appetite loss.	Variable effect on appetite; weight changes can occur but are not as consistently pronounced.
Sexual Side Effects	Lower risk of sexual dysfunction.	Sexual side effects like decreased libido are common.
Gastrointestinal (GI) Side Effects	Lower risk of nausea and GI issues due to receptor blocking.	Nausea and other GI upset are common, especially early in treatment.
Typical Use	Often used for treatment-resistant anxiety, or anxiety with comorbid insomnia or weight loss.	Standard first-line treatment for many anxiety disorders.

Important considerations and side effects

As with any medication, mirtazapine has potential side effects. The most common ones include:

Drowsiness and sedation, especially when starting treatment.
Increased appetite and associated weight gain.
Dizziness.
Dry mouth.
Constipation.

More rare but serious side effects can occur, and it is crucial to seek immediate medical attention if they appear. These include Serotonin Syndrome, low white blood cell counts, and severe skin reactions. Additionally, mirtazapine carries a black box warning from the FDA concerning the increased risk of suicidal thoughts and behaviors in adolescents and young adults. Patients should be closely monitored for any changes in mood or behavior, particularly at the beginning of treatment or after a dose change. Do not stop taking mirtazapine suddenly without consulting a healthcare provider, as this can lead to withdrawal symptoms.

Conclusion: weighing the pros and cons

Mirtazapine is not an FDA-approved first-line treatment for anxiety, but it can be a highly effective off-label option for specific patient populations. Its unique mechanism of action provides a distinct advantage for those experiencing anxiety accompanied by insomnia or loss of appetite, as its sedative and appetite-stimulating properties can directly address these issues. While it offers benefits like a lower risk of sexual side effects compared to SSRIs, common side effects like weight gain and sedation require careful consideration. The decision to use mirtazapine should always be made in consultation with a qualified healthcare professional, who can determine if it is the right choice based on an individual's specific symptoms, medical history, and treatment goals. For those with treatment-resistant depression and severe anxiety, evidence suggests it may be a particularly effective strategy. Read more about mirtazapine's pharmacology on the NCBI Bookshelf.

Disclaimer: This information is for general knowledge and should not be taken as medical advice. Consult with a healthcare professional before starting any new medication.

Frequently Asked Questions

While you may notice the sedating effects quickly, often within the first few days, the full anti-anxiety effects of mirtazapine typically take 4 to 6 weeks to develop.

No, mirtazapine is not a first-line treatment for anxiety. First-line options typically include SSRIs and SNRIs. Mirtazapine is often used as a second-line or alternative option when first-line medications are ineffective or not tolerated.

Mirtazapine is typically taken once daily, usually in the evening, due to its sedative properties.

Yes, mirtazapine is particularly effective for anxiety-related insomnia. Its potent sedative properties can help patients fall asleep faster and stay asleep longer.

Yes, weight gain is a common side effect of mirtazapine. It can increase appetite, which may lead to weight gain for many users. This can be beneficial for those who have experienced appetite loss due to anxiety.

No, you should never stop taking mirtazapine suddenly. This can cause withdrawal symptoms. Any changes to your dosage, including stopping, must be managed gradually and with the guidance of a healthcare professional.

Mirtazapine is less likely to cause sexual side effects and GI upset compared to many SSRIs. However, it is more commonly associated with drowsiness and weight gain. It is often a better option for patients who experience insomnia or appetite problems with their anxiety.

If you experience any concerning side effects while taking mirtazapine, you should contact your healthcare provider. They can assess your symptoms and determine the best course of action.

Mirtazapine may not be suitable for everyone. A healthcare professional will evaluate your medical history and current health status to determine if mirtazapine is a safe and appropriate treatment option for you.

Mirtazapine is FDA-approved for the treatment of major depressive disorder. It may also be used off-label for other conditions under the guidance of a healthcare professional.