Mirtazapine associated tender pitting pedal oedema

To the Editor

Although relatively uncommon, dermatological reactions to psychotropic medications may hinder treatment and reduce compliance. Among psychotropic medications, antidepressants can cause dermatological side effects at an incidence of 0.05%, the most common culprit being Bupropion (Mitkov et al., 2013). Mirtazapine, has been reported to rarely cause dermatitis, alopecia, acneiform eruptions (Degner et al., 2004) and very rarely, peripheral oedema (non-pitting and non-tender) (Lin and Chen, 2010). We report the first case of a mirtazapine associated pitting tender pedal oedema.

Ms. GA was a 48-year-old female admitted due to recurrence of her major depressive episode with suicidal ideation. She denied history of surgery or any significant medical problems, as well as insect bite, drug rash, allergy to medication or food, and exposure to sexually transmitted disease (STDs). A general physical and neurological examination was unremarkable as were the results of comprehensive urine and blood tests. Mirtazapine 15mg/day was added to her existing medications of venlafaxine, and increased a week later to 30mg/day. She started complaining of swelling and tender feet. On examination, she was noted to have bilateral tender pitting pedal oedema, which was circumscribed up to ankle level; otherwise the physical examination was unremarkable. Mirtazapine dosage was reduced to 15mg/day, which improved oedema but did not resolve it. Finally, mirtazapine was ceased and within 48 hours, the tender pitting oedema resolved completely. All tests (blood and urine) repeated at this time were unremarkable. She was diagnosed to have mirtazapine associated bilateral, tender, pitting pedal oedema, with a Naranjo ADR score of 7, which makes it highly probable that mirtazapine was the offending agent.

Various physiologic processes can produce pedal oedema, including medical conditions, allergic reactions and drugs. The patient was concurrently taking venlafaxine which has independently been associated with peripheral oedema (Mitkov et al., 2013; Degner et al., 2004). However, she had been taking venlafaxine for the past two years without any adverse effect making a direct association unlikely. The development of pedal oedema may be attributed to a variety of non–immune-mediated mechanisms as well as the direct release of mediators from mast cells, production and accumulation of toxic metabolites, and phototoxicity (Mitkov et al., 2013). It is also possible that addition of mirtazapine possibly produced the pharmacodynamic or pharmacokinetic interaction detailed above. However, it is not possible to either confirm or deny this effect. Such side effects can carry significant morbidity and affect compliance, it is important for clinicians to recognize it so that proper management of the presenting patient can be achieved.