Is Mirtazapine a Good Antidepressant? Uses, How it Works, and What to Expect

If your doctor has brought up mirtazapine (brand name Remeron) or you’re looking into your options, you might wonder how it stacks up against more well-known drugs like sertraline (Zoloft) or fluoxetine (Prozac). Mirtazapine is a different kind of antidepressant. It doesn’t work the same way as SSRIs, and for many people, that’s a good thing.

A large 2018 meta-analysis in The Lancet compared 21 antidepressants across hundreds of trials. Mirtazapine came out as one of the more effective options compared to placebo and some other medications. Here’s what you need to know about how it works, who it’s best for, and what side effects to watch for.

Key Takeaways

• Mirtazapine is FDA-approved for major depressive disorder (MDD) and works about as well as other common antidepressants. Some studies show it starts working faster — within one to two weeks — compared to SSRIs, although it could take 4-6 weeks for full therapeutic effect.

• Mirtazapine may be helpful if you have depression along with trouble sleeping, low appetite, or anxiety. It works through a different pathway than SSRIs.

• The main side effects of mirtazapine are drowsiness, increased appetite, and weight gain. On the plus side, it’s less likely to cause nausea or sexual problems, which are common with SSRIs.

What is Mirtazapine?

Mirtazapine is an atypical antidepressant, not an SSRI. It’s also called a tetracyclic antidepressant or a noradrenergic and specific serotonergic antidepressant (NaSSA). The FDA approved it for major depressive disorder in 1996. Doctors also use it off-label for insomnia, anxiety, panic disorder, PTSD, nausea, and migraines.

How Does it Work?

Selective serotonin reuptake inhibitors (SSRIs) work by blocking the serotonin transporter protein (SERT) responsible for the reuptake of serotonin into the neuron. This increases serotonin levels in the brain, which improves mood and stabilizes emotions.

Mirtazapine takes a different route. It is an alpha-2 antagonist, which means it blocks alpha-2 receptors in the brain that normally slow down the release of two key chemicals: serotonin and norepinephrine. By blocking these receptors, mirtazapine allows the brain to release more of both chemicals at once. Higher levels of serotonin and epinephrine are associated with improved mood, focus, and energy, which creates the antidepressant effect.

Mirtazapine also blocks a few other receptors:

• Histamine receptors: This is why it makes you sleepy and hungry. It’s the same system that allergy medicines like Benadryl target.

• Certain serotonin receptors (5-HT2A, 5-HT2C, and 5-HT3): Blocking these reduces nausea and may lower the risk of sexual side effects and anxiety.

The distinct mechanism of action explains why mirtazapine feels so different from an SSRI. It can help with sleep, boost appetite, ease nausea, and fight depression. For this reason, mirtazapine may be considered for people with depression, insomnia, and weight loss. Does Mirtazapine Actually Work?

There is strong evidence supporting the effectiveness of mirtazapine for depression.

A Cochrane review of 29 studies involving nearly 5,000 patients found that mirtazapine worked better than SSRIs at two weeks and was still slightly ahead at the end of acute treatment (6–12 weeks). It was also significantly more effective than venlafaxine (Effexor), a serotonin norepinephrine reuptake inhibitor (SNRI), at both time points. It worked about the same as older tricyclic antidepressants like amitriptyline, but with fewer side effects.

The 2018 Lancet study found that about 50% of people on the antidepressants used in the study, including mirtazapine, saw their depression scores cut in half (compared to 35% on placebo). That placed mirtazapine in the more effective group among all 21 drugs studied.

A meta-analysis of pooled data also confirmed that mirtazapine was clearly better than placebo for both moderate and severe depression.

Another review of studies showed that mirtazapine was equally effective as the SSRIs fluoxetine (Prozac), citalopram (Celexa), sertraline (Zoloft), and paroxetine (Paxil), as well as the SNRI venlafaxine (Effexor), with a significantly earlier onset of action. Early effects of mirtazapine were seen within 1-2 weeks of initiation of treatment.

Possible Early Action

Results from different studies comparing mirtazapine with other SSRI antidepressants suggest its therapeutic benefits may begin earlier than those of SSRIs. 

A comparative study between mirtazapine and sertraline showed that mirtazapine was more effective than sertraline on several counts during the first two weeks of the study, as measured in the Hamilton Depression Rating Scale (HDRS). Thereafter, the results were similar for both drugs.

In a later study of 60 MDD patients with a high level of anxiety symptoms, mirtazapine was more effective in reducing anxiety within the first two weeks of treatment compared to paroxetine. Improvement in depression measured by HDRS scores was, however, similar for both medications.

Who is Mirtazapine More Suitable For?

SSRIs are still the first-line treatment for depression because they work well for many people and are generally better tolerated with a safer side effect profile compared to first-generation antidepressants (TCAs and MAOIs). But mirtazapine may be a better option in certain situations.

Depression with Insomnia

Mirtazapine has a calming and sedating effect, mainly because it blocks histamine (H1) receptors. This side effect can actually be helpful for people with insomnia. 

Low doses of mirtazapine (15 mg) are generally prescribed for depression with insomnia, as it is understood that higher doses (up to 45 mg) may cause a noradrenergic effect, producing activation instead of sedation. 

However, newer research suggests that this inverse relationship between dose and sedation may only last for the first week of treatment, indicating that higher doses at bedtime may not be a concern for insomnia. 

Depression with Low Appetite or Weight Loss

Mirtazapine boosts appetite; that’s one of its most consistent effects. In six-week clinical trials on patients with MDD, increased appetite was reported in 17% of patients on mirtazapine vs 2% on placebo.

If depression has caused weight or appetite loss, this can be a real benefit. Doctors sometimes choose mirtazapine for cancer patients,  elderly people, or those with a low body weight profile who need to gain weight while also treating depression.

Depression with Anxiety

Mirtazapine is one of the options available for the treatment of coexisting depression and anxiety. 

Although SSRIs such as escitalopram, sertraline, and fluoxetine are first-line treatments for these co-occurring conditions, they can actually make anxiety worse in the first week or two before things get better. 

Due to its unique mechanism of action, mirtazapine may provide faster anxiety relief compared to SSRIs, which is why some doctors prefer it for anxious patients.

People Who Can’t Handle SSRIs

SSRIs can cause side effects such as nausea, sexual dysfunction, and an increase in anxiety, which usually get better after 1-2 weeks. For some people, these side effects can persist. On the other hand, mirtazapine has a very different side effect profile. 

The Cochrane review found it causes less nausea, less vomiting, and fewer sexual problems than SSRIs. Its 5-HT3 receptor blocking action actually produces an anti-nausea and anti-emetic effect, the opposite of what many SSRIs do.

Mirtazapine may be considered for patients who experience severe side effects on SSRIs or those who don’t respond sufficiently to SSRIs.

Older Adults

Mirtazapine is generally well-tolerated in older people. It’s a good match when depression comes with poor appetite, weight loss, and trouble sleeping, a common pattern in this age group. But the drowsiness can raise fall risk, so careful dosing is important.

Side Effects of Mirtazapine

Mirtazapine’s side effects are quite different from those of SSRIs. Here’s what to expect.

Drowsiness (Somnolence)

This is the most common side effect. In 6-week clinical trials on patients with MDD, 54% of people on mirtazapine reported drowsiness as a side effect, as opposed to 18% on a placebo. Taking it at bedtime may be beneficial if you have trouble sleeping. Over time, most people adjust.

Weight Gain and Increased Appetite

This is the side effect that bothers people the most. The Cochrane review confirmed it causes more weight gain than SSRIs. During the clinical trials, 17% of patients reported increased appetite and 12% reported weight gain, whereas these side effects were observed in only 2% of patients on a placebo. If weight is a big concern for you, talk to your doctor about this before starting.

Other Common Side Effects

• Dry mouth: Usually mild. Drinking water and chewing sugar-free gum can help.

• Constipation: Eating more fiber and drinking plenty of fluids can ease this.

• Dizziness: Usually mild and goes away after the first few weeks.

• Higher cholesterol: Mirtazapine has been associated with increases in cholesterol and triglycerides in some patients. Your doctor may check labs now and then.

What About Sexual Side Effects?

Mirtazapine is associated with significantly lower sexual side effects, unlike many SSRI and SNRI antidepressants, although individual response may vary. 

Due to its unique pharmacology, it increases the levels of serotonin and norepinephrine, while deactivating certain receptors, including 5-HT2A and 5-HT2C. This function contributes to its antidepressant and anti-anxiety properties while reducing the risk of sexual dysfunction. 

On the other hand, SSRIs activate these receptors initially, which leads to an increase in anxiety and sexual side effects in the first few weeks.

Mirtazapine Dosing

According to FDA prescribing information:

• Starting dose: 15 mg at bedtime

• Range: 15–45 mg a day (increase dosage only if the initial dose doesn’t produce sufficient response during the first 1-2 weeks)

• Dose changes: Usually go up by 15 mg every one to two weeks

• Max dose: 45 mg a day

A dose-response study found that going above 30 mg doesn’t add much benefit for depression but does increase side effects. For most people, 15–30 mg is the sweet spot. However, in some cases, providers may advise going up to 45 mg depending on response.

Mirtazapine comes as regular tablets (15 mg, 30 mg, and 45 mg) and as tablets that dissolve on your tongue without water. The disintegrating tablets are helpful if you have trouble swallowing pills.

Mirtazapine vs. SSRIs: How Do They Compare?

Here’s a quick side-by-side look:

How well they work: About the same overall. Mirtazapine may have a slight edge in the first two weeks. In the comparative study of 21 antidepressants, some SSRIs, such as escitalopram, were more effective and tolerable than mirtazapine.

Speed: Mirtazapine may work faster at first. By 6–8 weeks, they’re about equal.

Nausea: Less with mirtazapine. More with SSRIs, during the first few weeks.

Sexual side effects: Less with mirtazapine. More with SSRIs, especially during the first few weeks.

Weight gain: More with mirtazapine. Some SSRIs are weight-neutral initially, but some may cause weight gain over time.

Sleep: Mirtazapine helps with sleep. SSRIs can sometimes make insomnia worse.

The “best” choice depends on your symptoms and treatment concerns. Your doctor can help you weigh the trade-offs and make an informed choice.

Can You Combine Mirtazapine with Other Antidepressants?

Sometimes doctors add mirtazapine to an SSRI or SNRI when one drug alone isn’t enough. The combination of mirtazapine plus venlafaxine (Effexor) is informally called “California rocket fuel” in psychiatry.

But the evidence for this is weaker than the nickname suggests. A Phase-III randomized, placebo-controlled study found that adding mirtazapine to an SSRI or SNRI didn’t improve depression much, but it did increase side effects. Such adjunctive treatments should only be tried under close medical supervision after single-drug options have been given a fair shot.

How to Stop Taking Mirtazapine

Don’t stop mirtazapine all at once. Quitting suddenly can cause discontinuation symptoms like irritability, nausea, dizziness, vivid dreams, and anxiety. Your doctor will lower your dose slowly over several weeks. If you’ve been on it for more than six months, the taper may need to be even slower.

Medical Disclaimer

This article is for informational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified healthcare provider with any questions you may have regarding a medical condition. If you are experiencing a mental health crisis, contact the 988 Suicide and Crisis Lifeline by calling or texting 988.

Sources

1. Jilani, T. N., Gibbons, J. R., Faizy, R.M., et al. Mirtazapine. [Updated 2024 Nov 9]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK519059/

2. U.S. Food and Drug Administration. (2021). Remeron (mirtazapine) tablets, for oral use: Prescribing information (Reference ID: 4878026). https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/020415s038,021208s028lbl.pdf 

3. Watanabe, N., Omori, I. M., Nakagawa, A., Cipriani, A., Barbui, C., Churchill, R., & Furukawa, T. A. (2011). Mirtazapine versus other antidepressive agents for depression. The Cochrane database of systematic reviews, (12), CD006528. https://pmc.ncbi.nlm.nih.gov/articles/PMC4158430/ 

4. Kasper S. (1995). Clinical efficacy of mirtazapine: a review of meta-analyses of pooled data. International clinical psychopharmacology, 10 Suppl 4, 25–35. https://pubmed.ncbi.nlm.nih.gov/8930007/ 

5. Alam, A., Voronovich, Z., & Carley, J. A. (2013). A review of therapeutic uses of mirtazapine in psychiatric and medical conditions. The primary care companion for CNS disorders, 15(5), PCC.13r01525. https://pmc.ncbi.nlm.nih.gov/articles/PMC3907331/ 

6. Fawcett, J., & Barkin, R. L. (1998). Review of the results from clinical studies on the efficacy, safety and tolerability of mirtazapine for the treatment of patients with major depression. Journal of affective disorders, 51(3), 267–285. https://pubmed.ncbi.nlm.nih.gov/10333982/ 

7. Cipriani, A., Furukawa, T. A., Salanti, G., et al. (2018). Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet (London, England), 391(10128), 1357–1366. https://pubmed.ncbi.nlm.nih.gov/29477251/ 

8. Behnke, K., Søgaard, J., Martin, S., et al. (2003). Mirtazapine orally disintegrating tablet versus sertraline: a prospective onset of action study. Journal of clinical psychopharmacology, 23(4), 358–364. https://pubmed.ncbi.nlm.nih.gov/12920411/ 

9. Kim, J. E., Yoon, S. J., Kim, J., et al. (2011). Efficacy and tolerability of mirtazapine in treating major depressive disorder with anxiety symptoms: an 8-week open-label randomised paroxetine-controlled trial. International journal of clinical practice, 65(3), 323–329.                       https://pubmed.ncbi.nlm.nih.gov/21314870/ 

10. Shuman, M., Chukwu, A., Van Veldhuizen, N., & Miller, S. A. (2019). Relationship between mirtazapine dose and incidence of adrenergic side effects: An exploratory analysis. The mental health clinician, 9(1), 41–47. https://pmc.ncbi.nlm.nih.gov/articles/PMC6322815 

11. Kessler, D., Burns, A., Tallon, D., Lewis, G., et al. (2018). Combining mirtazapine with SSRIs or SNRIs for treatment-resistant depression: the MIR RCT. Health technology assessment (Winchester, England), 22(63), 1–136. https://pmc.ncbi.nlm.nih.gov/articles/PMC6287172/ 

12. Furukawa, T. A., Cipriani, A., Cowen, P. J., et al. (2019). Optimal dose of selective serotonin reuptake inhibitors, venlafaxine, and mirtazapine in major depression: A systematic review and dose-response meta-analysis. The Lancet Psychiatry, 6(7), 601–609. https://doi.org/10.1016/S2215-0366(19)30217-2 

13. Holm, K. J., Markham, A. Mirtazapine: a review of its use in major depression. 1999. In: Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK67759/

14. National Institute of Mental Health. (n.d.). Mental health medications. U.S. Department of Health and Human Services, National Institutes of Health. https://www.nimh.nih.gov/health/topics/mental-health-medications 

15. Hassanein, E. H. M., Althagafy, H. S., Baraka, M. A., et al. (2024). Pharmacological update of mirtazapine: A narrative literature review. Naunyn-Schmiedeberg’s Archives of Pharmacology, 397(5), 2603–2619. https://link.springer.com/article/10.1007/s00210-023-02818-6