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If you're reading this, you probably know what it's like to have anxiety completely mess up your life. Can't sleep. Can't concentrate. Maybe you've tried SSRIs like Prozac or Zoloft and they either didn't work or the side effects were terrible.
So now your doctor mentions mirtazapine. Or maybe you've been googling around and found it yourself. Either way, you're wondering: is this worth trying?
I've spent way too many hours digging through research papers on this stuff. Here's what I found.
Mirtazapine (brand name Remeron) got FDA approval back in 1996. For depression. Not anxiety.
But here's the thing which is a little scary to know is doctors prescribe it for anxiety all the time. It's what they call "off-label," which sounds sketchy but actually just means the FDA hasn't officially approved it for that specific use. Lots of effective treatments started this way.
It's technically a tetracyclic antidepressant. Name aside, what matters is that it works completely differently than SSRIs.
SSRIs mess with serotonin reuptake. You've probably heard that a million times.
Mirtazapine? Total different ballgame.
It blocks these things called alpha-2 adrenergic receptors in your brain. When you block those, your brain releases more norepinephrine and serotonin. Both of those help with mood and anxiety.
But there's more going on. Research shows it also blocks certain serotonin receptors (specifically 5-HT2 and 5-HT3). That's actually why it doesn't cause nausea like SSRIs do, which are those receptors are in your gut.
And then there's the histamine thing. It blocks H1 receptors hard, which is why it makes you drowsy. If you've ever taken Benadryl, same idea. Some people hate this side effect. Others love it because anxiety has been destroying their sleep for months.
There's also this whole inflammation angle that researchers are excited about. Turns out people with anxiety and depression often have higher inflammation markers. Mirtazapine might help with that too. The jury's still out on exactly how much that matters, but it's interesting to know.
Okay so this is where it gets messy. Because mirtazapine isn't approved for anxiety, there aren't a ton of huge studies. But the ones that exist are pretty interesting and let's dive deeper into the research.
GAD and Mirtazapine studies are where the evidence is strongest.
One study published in 2005 followed 44 people with GAD for 12 weeks. They all took 30 mg of mirtazapine daily. The results? Almost 80% of them responded to treatment. More than a third went into full remission.
That's honestly better than a lot of SSRIs.
There's also this analysis from something called the MIR trial. They looked at people with treatment-resistant depression who also had bad anxiety. What they found was kind of wild where mirtazapine worked better for people who had worse anxiety to begin with.
When you have both depression and anixiety, mirtazapine seems to handle patients with this condition well.
An 8-week study compared it head-to-head with paroxetine (that's Paxil). For people dealing with both depression and high anxiety, mirtazapine worked faster, and very much noticeably faster in the first few weeks.
Another smaller study saw improvements in just one week. ONE WEEK. Most antidepressants take 4-6 weeks minimum.
For social anxiety people, this is where the results get confusing. A 10-week study in women with social anxiety found it worked way better than placebo which was promising. However, another 12-week study at higher doses showed... nothing. There was no difference from placebo and this contradictory result suggests that there needs to be more research here.
For panic disorders, the research here shows it works about as well as paroxetine. 83% of people responded by week 3, which is strong news.
This is important to understand how Mirtazapine compares to SSRIs as they're often compared and used interchangeably. A massive Cochrane review—which is basically the gold standard in medical research—looked at 29 different studies with almost 5,000 people total. Their conclusion? Mirtazapine works significantly faster than SSRIs. At the 2-week mark, there was a clear difference. By 6-12 weeks things evened out, but those first few weeks matter A LOT when you're suffering.
If anxiety is keeping you up at night and you can barely function, waiting 6 weeks for an SSRI to work feels impossible.
Even though we've gone through the research, I will be the first to share that the evidence is perfect. Most of these studies are small. A lot of them are "open-label" which means everyone knew what they were taking (not ideal for research). And pharmaceutical companies aren't funding huge trials because there's no money in it as the patent expired years ago.
This big review basically says "looks promising but we need better studies" which is fair but the long-term data especially is pretty thin.
Researchers have been finding something strange which is that people with anxiety disorders tend to have higher levels of inflammatory markers in their blood. Things like C-reactive protein and cytokines.
Why does this matter? Because inflammation affects your brain. Specifically the parts that deal with fear and emotional regulation.
Studies show that these inflammatory signals can literally make anxiety worse. And people with chronic inflammatory diseases have way higher rates of anxiety disorders.
Mirtazapine appears to reduce inflammation. How much this contributes to its anti-anxiety effects? This is still being figured out. But it's another piece of the puzzle about this drug.
The conclusion is not everyone should take this. These are the situations where this medication might make the most sense:
You've got both depression and anxiety
As mentioned above, this combo is very common. Mirtazapine hits both targets and works on both conditions.
Anxiety destroyed your sleep
The sedating effect that some people hate about anxiety meds would be a lifesaver for someone who is struggling, especially if you're lying awake with racing thoughts every single night.
Quick reality check though: medication helps you sleep NOW, but it doesn't fix WHY you can't sleep. That's where CBT-I comes in. Multiple studies prove CBT-I works as well or better than sleep meds long-term. And the benefits last after you stop.
You need fast relief
SSRIs take a very long time to work and 4-6 weeks is standard. Research shows mirtazapine can start working in 1-2 weeks, and one study even saw results in 4 days.
When you're in crisis mode, those extra weeks make all the difference so this might be a good reason to use mirtazapine over SSRIs.
You've lost weight from anxiety
Most people don't think of this as a benefit, but mirtazapine increases appetite. If anxiety has you dropping pounds because you can't eat, this side effect from mirtazapine actually helps.
SSRIs killed your sex life
This is a bit more personal where you might already know that SSRIs are notorious for sexual side effects. Low libido, inability to orgasm, the whole deal. It's awful and nobody warns you enough about it.
Mirtazapine on the other hand has way lower rates of sexual dysfunction. For some people this alone is worth switching.
Every medication has side effects. Antidepressants and sleep meds all come with baggage and you need to educate yourself so you can make the right decision for your situation!
Over half of people in trials got drowsy, especially on lower doses like 15 mg.
Weirdly, higher doses are less sedating. It's counterintuitive but it has to do with receptor binding. So if 15 mg turns you into a zombie, bumping up to 30 mg might actually help with your tiredness.
Let's be clear that the increase in appetite generally will drive weight gain: around 12% of people gain serious weight on this. We're talking 7% or more of body weight on average.
There are case reports of people gaining 14+ pounds in a week. This is not the typical situation but it can happen so be warned.
Why does this happen? The drug messes with receptors that control hunger. Your body thinks it's starving so you eat constantly.
And it gets worse as studies show it can raise your cholesterol and triglycerides even if you don't gain weight. If you've got heart disease risk factors, your doctor needs to watch this closely.
These are the other side effects: Dry mouth. Constipation. Dizziness when you stand up.
These are less dangerous but still worthy to note and be aware of.
Suicidal thoughts
Every antidepressant has a black box warning about this. Especially for people under 25. The risk is highest when you first start or change doses.
If you start having thoughts about harming yourself, call 988 (the Suicide & Crisis Lifeline) immediately. Please don't wait on this. Please also warn a loved one about this side effect before you start on this drug so they can keep an eye out too.
Serotonin syndrome
Mix mirtazapine with other serotonergic drugs and you risk serotonin syndrome. This can kill you and symptoms include confusion, rapid heart rate, high fever, muscle rigidity. It's an emergency so please be on high alert.
Mirtazapine alone rarely causes this, but combinations are risky. Never mix these drugs.
Agranulocytosis
This is very rare but I have to mention it. Your white blood cell count might crash on this drug and you become vulnerable to any infection. Warning signs include: sudden fever, sore throat, mouth sores. If this happens, get to a hospital as soon as possible.
Lots of people take mirtazapine specifically for sleep. So how does it compare to actual sleep meds?
Ambien and benzos knock you out, but they're addictiveand you build tolerance. And you also get rebound insomnia when you stop.
The evidence keeps pointing to CBT-I as the actual solution - if you're interested please reach out to us at Sleep Reset to learn more about our award-winning CBT-I based program. Unlike sleeping pills, CBT-I:
If sleep is your main issue, try CBT-I first or alongside medication.
What works:
What sucks:
Don't make this decision from a blog post. You need to meet a healthcare professional who can help look at your specific situation, check your medical history, consider what other meds you're on, monitor how you respond, and figure out if non-medication options might work better.
And if anxiety is wrecking your sleep, add CBT-I to your treatment plan. It makes a massive difference.
Mirtazapine isn't magic. But for the right person at the right time? It can really help. If you're on medication or supplements and want to understand the potential side effects, read more about supplements like l-theanine or melatonin and what a melatonin hangover means as well as medication like ambien, dayvigo and quviviq. Or if you're ready to try Sleep Reset's unique CBT-I based program, take our free sleep assessment now to begin!
Disclaimer: This blog post is for informational purposes only and should not replace professional medical advice. Always consult with a qualified healthcare provider before starting, stopping, or changing any medication.
Dr. Shiyan Yeo
Dr. Shiyan Yeo is a medical doctor with over a decade of experience treating patients with chronic conditions. She graduated from the University of Manchester with a Bachelor of Medicine and Surgery (MBChB UK) and spent several years working at the National Health Service (NHS) in the United Kingdom, several Singapore government hospitals, and private functional medicine hospitals. Dr. Yeo specializes in root cause analysis, addressing hormonal, gut health, and lifestyle factors to treat chronic conditions. Drawing from her own experiences, she is dedicated to empowering others to optimize their health. She loves traveling, exploring nature, and spending quality time with family and friends.
Fax number: (984) 888-8385
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