How does Mirtazapine (Mirtazapine) contribute to weight gain?

From the Guidelines

Mirtazapine is associated with weight gain, particularly at lower doses, due to its ability to stimulate appetite and improve sleep quality, making it a potential option for patients requiring weight gain, as noted in a study published in Gastroenterology 1.

Mechanism of Action

Mirtazapine's weight gain effects are attributed to its pharmacological properties, including the blockade of histamine H1 receptors in the brain, which creates a sensation of hunger, and the blockade of serotonin 5-HT2C receptors, which normally suppress appetite when activated.

• The medication's ability to reduce nausea and improve sleep quality also contributes to better nutritional intake, potentially leading to weight gain.
• Weight gain typically begins within the first few weeks of treatment and is most pronounced at lower doses (15mg), as higher doses may activate noradrenergic effects that counteract the weight-promoting properties.

Clinical Considerations

For patients using mirtazapine for weight gain, it is recommended to combine the medication with regular, nutritious meals and monitor weight changes weekly.

• The medication works best when taken consistently at the same time each evening.
• Patients should be aware that weight gain varies between individuals, with some gaining 1-3kg (2-7 pounds) within the first month of treatment, as observed in clinical practice 1.

Important Considerations

While mirtazapine may be beneficial for weight gain in certain patients, its use should be carefully considered in the context of individual patient needs and medical history, taking into account potential side effects and interactions with other medications, as discussed in the context of treating obesity and related conditions 1.

From the FDA Drug Label

In U. S. controlled clinical studies, appetite increase was reported in 17% of patients treated with mirtazapine tablets, compared to 2% for placebo. In these same trials, weight gain of ≥7% of body weight was reported in 7.5% of patients treated with mirtazapine, compared to 0% for placebo.

Mirtazapine helps with weight gain by increasing appetite in some patients, which can lead to a significant weight gain of ≥7% of body weight in approximately 7.5% of patients treated with the medication.

• The exact mechanism of how mirtazapine causes weight gain is not fully understood, but it is thought to be related to its effects on appetite regulation and metabolism.
• It is essential to monitor patients taking mirtazapine for weight gain and adjust treatment as needed to minimize this potential side effect 2.

From the Research

Mechanism of Mirtazepine-Induced Weight Gain

• Mirtazepine blocks presynaptic alpha 2-adrenergic receptors and postsynaptic serotonin type 2 and type 3 receptors, which may contribute to its effects on appetite and weight gain 3.
• The drug has been shown to increase appetite and cause weight gain in several clinical trials, with patients receiving mirtazapine experiencing significantly greater weight gain compared to those receiving placebo 3, 4, 5.

Effects of Mirtazapine on Body Composition and Metabolism

• Mirtazapine treatment has been associated with significant increases in body weight, body fat mass, and leptin concentration 5.
• The drug has also been shown to increase visceral fat area and body fat ratio, suggesting that it may have a preferential effect on central fat distribution 4.
• However, mirtazapine treatment did not influence glucose homeostasis or lipid parameters in one study, suggesting that its effects on metabolism may be limited to changes in body composition 5.

Comparison with Other Antidepressants

• Mirtazapine has been compared to other antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs), in terms of its effects on weight gain and appetite 6, 7.
• Mirtazapine was found to be more likely to cause weight gain or increased appetite compared to SSRIs, but less likely to cause nausea or vomiting and sexual dysfunction 7.
• The drug has also been shown to have a faster onset of action compared to SSRIs, which may be related to its unique mechanism of action 7.