What is the biggest side effect of mirtazapine?

October 11, 2025 •

3 min read

In clinical trials, drowsiness was reported by over 50% of patients taking mirtazapine, making it the most common immediate reaction. However, significant weight gain can be a more substantial long-term concern for many users, defining a complex answer to the question, what is the biggest side effect of mirtazapine?. This article explores both major side effects and other important considerations for patients.

Quick Summary

An exploration of mirtazapine's most significant side effects, detailing the prevalence and mechanisms behind both drowsiness and weight gain. Includes a comparison with other antidepressants, management strategies for common adverse reactions, and a review of less frequent but serious risks.

Key Points

Drowsiness (Somnolence): The most commonly reported side effect, affecting a high percentage of users, especially with certain amounts, due to its potent antihistamine properties.
Weight Gain: Another major side effect, and a frequent cause of long-term discontinuation, resulting from increased appetite and potential metabolic changes caused by receptor antagonism.
Pharmacological Mechanism: The sedation is linked to histamine H1 receptor blockade, while weight gain involves both H1 and serotonin 5-HT2C receptor antagonism.
Variable Sedation: The sedative effect of mirtazapine can vary depending on the amount taken, a unique feature of its pharmacology.
Comparison to SSRIs: Mirtazapine is more likely to cause sedation and weight gain but less likely to cause sexual dysfunction and nausea compared to selective serotonin reuptake inhibitors.
Management is Key: Side effects like drowsiness, dry mouth, and weight gain can often be managed through lifestyle adjustments, timing of administration, or medical consultation.
Serious but Rare Risks: Patients should be aware of rare but serious side effects, including agranulocytosis and serotonin syndrome, and report any concerning symptoms to their doctor immediately.

Mirtazapine, known by the brand name Remeron, is a tetracyclic antidepressant used to treat major depressive disorder and sometimes off-label for conditions like anxiety or insomnia. Its action involves blocking specific serotonin and histamine receptors, which influences its side effect profile. While it often has fewer sexual and gastrointestinal side effects than SSRIs, it is significantly linked to sedation and weight gain. The determination of which is the 'biggest' side effect often varies individually based on factors like the patient and duration of use.

Why Drowsiness is a Major Mirtazapine Side Effect

Sedation is the most frequently reported side effect of mirtazapine. This is mainly due to its potent effect on blocking histamine H1 receptors, which are involved in wakefulness. The level of sedation can vary. Significant drowsiness can impair daily activities. Taking the dose at bedtime and potential tolerance development may help manage drowsiness.

The Mechanism Behind Mirtazapine-Induced Weight Gain

Weight gain is another significant side effect and a major long-term concern for many. Mirtazapine is known to have one of the highest potentials for weight gain among antidepressants. Blocking histamine H1 and serotonin 5-HT2C receptors is associated with increased hunger and food intake. Mirtazapine may also affect metabolism. Weight gain can be ongoing over months. Diet and exercise are advised for management.

Less Common But Still Notable Side Effects

Beyond drowsiness and weight gain, mirtazapine can cause other side effects. These include dry mouth, constipation, dizziness, and abnormal dreams.

Serious But Rare Adverse Events

Rarely, more severe side effects can occur, requiring immediate medical attention. These include agranulocytosis, serotonin syndrome, and mania/hypomania.

Comparison of Mirtazapine vs. Common Antidepressants

The choice of antidepressant involves considering its benefits and side effects. Mirtazapine's profile can be suitable for some patients but not others. Below is a comparison of mirtazapine with SSRIs.


Side Effect	Mirtazapine	SSRIs (e.g., Fluoxetine, Sertraline)
Weight Gain	Higher risk, significant and sometimes used therapeutically.	Lower risk, though can occur with long-term use.
Drowsiness/Sedation	Higher risk, especially with certain amounts.	Lower risk, can cause insomnia or activation in some individuals.
Sexual Dysfunction	Lower risk compared to SSRIs.	Higher risk, frequently cited as a reason for discontinuation.
Nausea/Vomiting	Lower risk compared to SSRIs.	Higher risk, especially at the beginning of treatment.
Gastrointestinal Issues	Lower risk (aside from constipation).	Higher risk (nausea, diarrhea).
Agitation/Anxiety	Lower risk compared to SSRIs initially.	Higher risk, can occur at the start of treatment.

Managing Common Mirtazapine Side Effects

Managing side effects is crucial for successful treatment. Patients should consult their healthcare providers for personalized strategies.

Weight gain management: Focus on a healthy diet with plenty of fiber, fruits, and vegetables, and limit high-calorie snacks. Regular physical activity is also beneficial.
Drowsiness management: Take the medication before bedtime. Avoid alcohol, which can intensify sleepiness. Adjusting the amount, sometimes even to a higher level, might help some individuals.
Dry mouth relief: Chew sugar-free gum or candy, use saliva substitutes, and stay well-hydrated.
Constipation relief: Increase fiber and fluid intake, and engage in regular exercise.
Dizziness prevention: Stand up slowly from sitting or lying down positions to avoid lightheadedness.

Conclusion

Both drowsiness and weight gain are common mirtazapine side effects, but the most significant one is subjective. Drowsiness is frequently reported initially and often lessens over time. Weight gain can pose a more persistent challenge. Open communication with a healthcare provider is essential. While management strategies and adjustments can help, side effects should be closely monitored under medical guidance.

Frequently Asked Questions

Yes, mirtazapine is associated with a higher risk of weight gain and increased appetite compared to many other antidepressants, including SSRIs.

Mirtazapine causes drowsiness primarily by blocking histamine H1 receptors in the brain, which are involved in regulating wakefulness.

No, the sedative effect of mirtazapine is most pronounced during the first few weeks of treatment, and tolerance typically develops over time.

Managing weight gain involves maintaining a healthy, balanced diet, avoiding high-calorie snacks, and incorporating regular physical activity into your routine.

Adjusting the amount, sometimes even to a higher level, might help some individuals. Consult with a healthcare professional before making any changes.

Less common side effects include dry mouth, constipation, dizziness, and abnormal dreams. Serious but rare side effects include agranulocytosis and serotonin syndrome.

You should not stop taking mirtazapine abruptly. Your doctor will likely recommend a gradual tapering schedule to minimize withdrawal symptoms, such as dizziness, nausea, and agitation.

Yes, some patients taking mirtazapine have experienced increased cholesterol and triglyceride levels. Regular monitoring of cholesterol may be necessary.