Which medication, Pramipexole (Dopamine Agonist), Tizanidine (Muscle Relaxant), or Mirtazapine (Antidepressant), is most likely to cause increased edema?

From the Guidelines

Mirtazapine is most likely to cause increased edema among the three medications listed. Mirtazapine is an atypical antidepressant that works by blocking certain serotonin and norepinephrine receptors. One of its known side effects is peripheral edema, which occurs in approximately 8-14% of patients taking the medication, as reported in studies such as 1. The edema typically manifests as swelling in the lower extremities, particularly the ankles and feet. This side effect is thought to be related to mirtazapine's antagonism of alpha-1 adrenergic receptors, which can cause vasodilation and fluid retention. Some key points to consider when evaluating the risk of edema with mirtazapine include:

• The risk of edema appears to be dose-dependent, with higher doses carrying a greater risk than lower doses.
• In comparison, pramipexole (a dopamine agonist used for Parkinson's disease and restless legs syndrome) and tizanidine (a centrally acting alpha-2 adrenergic agonist used as a muscle relaxant) have much lower incidences of edema as side effects.
• Patients taking mirtazapine who develop edema should be monitored, and if the edema becomes problematic, dose reduction or switching to an alternative antidepressant may be necessary, as suggested by studies such as 1 and 1. It's also worth noting that while other medications, such as pregabalin, have been associated with peripheral edema as a side effect, as reported in studies such as 1, the available evidence suggests that mirtazapine is more likely to cause increased edema among the three medications listed.

From the FDA Drug Label

Peripheral Edema 2% 1% Edema 1% 0%

• Mirtazapine is the medication most likely to cause increased edema, as it is listed in the drug label with a frequency of 2% for peripheral edema and 1% for edema, which is higher than the placebo group 2.
• The other medications, Pramipexal and Tizanidine, are not mentioned in the provided drug label, therefore, no conclusion can be drawn about their potential to cause edema.
• Key points:
  • Mirtazapine is associated with an increased risk of edema.
  • The frequency of peripheral edema is 2% and edema is 1% in patients taking mirtazapine.

From the Research

Medications and Edema

• The medications in question are pramipexal, tizanidine, and mirtazapine.
• Among these, mirtazapine is the most likely to cause increased edema, as evidenced by several studies 3, 4, 5.

Mirtazapine and Edema

• Mirtazapine has been reported to cause peripheral edema in some patients 3, 4, 5.
• A systematic review of case reports found that mirtazapine was one of the most implicated antidepressants in causing peripheral edema 5.
• The exact mechanism of mirtazapine-induced edema is not fully understood, but it may be related to the drug's antagonism of α1 adrenergic receptors and 5HT2A receptors, leading to vasodilation and edema 5.

Comparison with Other Medications

• There is limited evidence on the association between pramipexal and tizanidine and edema.
• In contrast, mirtazapine has been consistently reported to cause edema in various studies 3, 4, 5.
• Therefore, based on the available evidence, mirtazapine is the most likely to cause increased edema among the three medications 3, 4, 5.