The most common side effect of mirtazapine is drowsiness, reported by 54% of patients in clinical trials, compared to 18% on placebo. Increased appetite (17%) and weight gain (12%) are the next most frequent, followed by dizziness (7%). These four side effects occur at rates at least double those seen with a placebo, making them the defining experiences of taking this medication.
Drowsiness and Sedation
More than half of people taking mirtazapine experience noticeable drowsiness, making it the side effect you’re most likely to encounter. The medication blocks histamine receptors in the brain, the same receptors targeted by over-the-counter sleep aids, which explains why the sedation can feel significant. Many doctors suggest taking mirtazapine at bedtime specifically to work with this effect rather than against it.
There’s a widely held belief among prescribers that lower doses (under 30 mg) are more sedating than higher doses, and that increasing the dose can actually reduce sleepiness. This idea is commonly repeated in prescribing references, but the evidence behind it is thin. The FDA requested a study examining this dose-sedation relationship after approval, and no adequate trial was ever completed. So while some people do report less drowsiness at higher doses, it’s not something you should count on.
The sedation tends to be strongest when you first start the medication. During those initial days, it’s wise to avoid driving or cycling until you understand how it affects you. Alcohol and cannabis both amplify mirtazapine’s sedative effects, particularly in the early weeks.
Appetite and Weight Changes
Mirtazapine increases appetite in about 1 in 6 people who take it. This isn’t a subtle shift for many. In clinical trials, 17% of patients reported increased appetite versus just 2% on placebo, one of the starkest differences between the drug and a sugar pill.
Weight gain follows predictably from the appetite increase. About 12% of patients gain weight overall, and when researchers looked specifically at clinically meaningful weight gain (7% or more of body weight), 7.5% of mirtazapine patients hit that threshold compared to 0% on placebo. In longer-term use, the typical weight gain is modest: roughly 1.4 kg (about 3 pounds) over 40 weeks of treatment, with most of that appearing within the first 8 to 12 weeks. For some people, though, the gain is considerably more. This side effect is one reason mirtazapine is sometimes deliberately chosen for patients who are underweight or have lost their appetite due to illness.
Dizziness and Blood Pressure Drops
About 7% of patients experience dizziness, which is often related to a temporary drop in blood pressure when standing up from a seated or lying position. Getting up slowly helps. This effect is more pronounced in older adults, who are also more likely to experience confusion or unusual drowsiness at standard doses.
Cholesterol and Triglyceride Changes
A side effect that gets less attention is mirtazapine’s effect on blood lipids. In clinical trials, 15% of patients saw their cholesterol rise by 20% or more, compared to 7% on placebo. Triglyceride levels jumped to clinically elevated levels in 6% of patients, versus 3% on placebo. These changes don’t produce symptoms you’d notice, but they can show up on routine bloodwork and matter for long-term cardiovascular health.
Low Sodium in Older Adults
Mirtazapine can lower sodium levels in the blood, a condition called hyponatremia. This is more common in older adults, especially those taking diuretics (water pills) for blood pressure or those who are dehydrated from vomiting or diarrhea. Symptoms of low sodium include headache, confusion, weakness, and in severe cases, seizures. It’s not common in younger, otherwise healthy adults.
Rare but Serious Blood Cell Changes
In premarketing trials, 3 out of 2,796 patients developed dangerously low white blood cell counts, a condition that leaves the body unable to fight infections. That translates to roughly 1 in 1,000 patients. The onset happened within the first two months of treatment, and all three patients recovered after stopping the medication. Signs to watch for include unexplained fever, sore throat, or mouth sores that don’t heal, particularly in the first few weeks.
Suicidal Thoughts in Young Adults
Like all antidepressants, mirtazapine carries a boxed warning about increased suicidal thoughts and behaviors in people under 25. Pooled data from roughly 77,000 adult patients and 4,500 pediatric patients across multiple antidepressant trials showed 14 additional cases of suicidal thoughts or behaviors per 1,000 patients treated among those under 18, and 5 additional cases per 1,000 among 18- to 24-year-olds. The risk is highest in the first few months and during dose changes. Mirtazapine is not approved for use in children.
What Happens When You Stop
Stopping mirtazapine abruptly can trigger discontinuation symptoms: flu-like feelings, insomnia, nausea, dizziness, sensory disturbances (like electric shock sensations), and a general sense of being on edge. These aren’t dangerous, but they’re uncomfortable enough that a gradual taper over six to eight weeks is typically recommended rather than stopping cold. Mirtazapine is considered safe for long-term use, with no known lasting harmful effects from months or years of treatment.
How Side Effects Change Over Time
The first few weeks are generally the roughest. Drowsiness, dizziness, and a general feeling of being “off” tend to peak early and improve as your body adjusts. Some people feel worse overall before the antidepressant benefits kick in. Weight gain and appetite changes, by contrast, tend to persist for as long as you take the medication, though the rate of gain usually slows after the first couple of months. Cholesterol and triglyceride changes also persist with continued use and are worth monitoring through periodic blood tests.