A rare side effect of escitalopram: bilateral peripheral edema

Abstract

Escitalopram, S-isomer of sitalopram is well tolerated, rapid onset efficacy and used in the tratment of depression and other psychiatric disorders in elderly 1-3. Escitalopram is highly serotonin specific and has minimal effect on the reuptake of other neurotransmitters 4. Insomnia, headache, tremor, nausea, flushing, sweating, diarrhea, sexual dysfunction have been reported to be adverse drug reaction during escitalopram therapy 3,5,6. In elderly patients, edema is an important health problem. Heart failure, renal failure, malabsorpsion, liver failure, allergic reactions, local inflammation and infections, burns, lymphatic obstruction increased capillary permeability, venous obstruction and drugs can cause peripheral edema 7. Antihypertensive medications, nonsteroidal anti-inflammatory agents, calcium channel blockers, corticosteroids, hormones, antibiotics, beta blockers and direct vasodilators are drugs that often cause peripheral edema 7,8. Edema has been reported rarely with psychiatric medications. Premarketing trials have reported peripheral edema as an infrequent adverse event which occured less than 1/100 9. To the best of our knowladge, there are two case reports that edema associated with escitalopram. First, bilateral ankle edema in 69 year-old female patient after one month therapy with escitalopram 30 mg per day, resolved within first week after discontinuation of the drug 10. In second case, bilateral pedal edema associated with escitalopram 10 mg per day developed 9th day of the treatment and resolved within 10 days after discontinuation of the drug 11. Here, we report a case of bilateral leg edema on the 7th day of the treatment with escitalopram 10 mg/day and resolved within 12 days after discontinuation of the drug.

Drug‐induced peripheral oedema: An aetiology‐based review

“…Arteriolar vasodilatation through 5-HT2 receptors inhibition [58][59][60] Antiepileptics Carbamazepine, 61 Baclofen 86 -increased capillary permeability especially with concomitant alcohol consumption 86 -GABAergic vasodilatation through central inhibition of sympathetic tone 87,88 -myogenic response inhibition through GABA A stimulation induced by loss of selectivity 89 Cytokines G-CSF, 90 interleukin 2, 91 interferon-α2b 36 Increased capillary permeability (as these drugs are responsible for capillary leak syndrome) Progestins 10 Sodium and water retention for progestins without anti-mineralocorticoid effect 106,107 Aromatase inhibitors: anastrozole, 108 letrozole, 108 exemestane 109 Sodium and water retention by removal of oestrogen-dependent ENaC receptors inhibition 110 SERM: tamoxifen 108,111 -sodium and water retention by removal of oestrogen-dependent ENaC receptors inhibition 110 -lymphedema through disturbance of lymphatic vasculature stability mediated by oestrogen receptors α 112…”

“…An example of a drug has been selected to illustrate each of these mechanisms. 64 antiparkinsonian drugs, [75][76][77][78][79] antidepressant inhibiting 5-HT2 receptors, [58][59][60] antipsychotics with α1-adrenolytic effect and/or inhibitory effect on 5-HT2 receptors, 84,85 baclofen, 86 and endothelin receptors antagonists. 119…”

“…Drugs inducing preferential precapillary arteriolar vasodilatation increase capillary hydrostatic pressure, therefore increasing extravasation from the vascular space into the interstitium. The main causative medications include antihypertensive agents (eg, CCBs, minoxidil , hydralazine ), 64 antiparkinsonian drugs, 75–79 antidepressant inhibiting 5‐HT2 receptors, 58–60 antipsychotics with α1‐adrenolytic effect and/or inhibitory effect on 5‐HT2 receptors, 84,85 baclofen, 86 and endothelin receptors antagonists 119 …”

Drug-induced peripheral edema: an etiology-based review

“…The main causative medications include antihypertensive agents (e.g., calcium channel blockers, minoxidil, hydralazine (Messerli, 2002)), antiparkinsonian drugs (Borovac, 2016;Perez-Lloret et al, 2014;E. K. Tan & Ondo, 2000;E.-K. Tan, 2007;Wood, 2010) potentially through peripheral D1 receptors stimulation (Zeng, Zhang, Asico, Eisner, & Jose, 2007), antidepressant inhibiting 5-HT2 receptors (Ravi, Ravishankar, & Andrade, 2014;Tuman, Tuman, Tuman, & Tuman, 2018;Uguz, 2014), antipsychotics with α1-adrenolytic effect and/or inhibitory effect on 5-HT2 receptors (Hosseini & Ahmadi, 2012;Umar & Abdullahi, 2016), baclofen (Bence et al, 2014) potentially through GABAergic vasodilatation (Estato, Araújo, Bousquet, & Tibiriçá, 2004;Zhang & Mifflin, 2010), endothelin receptors antagonists (Wei et al, 2016), insulin (Lalande & Romero, 2019)).…”

Bilateral Pedal Edema After Desvenlafaxine Therapy

“…Antihypertensives, antimicrobials, steroids, dopaminergic agonists, antipsychotics, antiepileptics, hormones, and β-blockers are the drugs that often cause pedal edema 2 . There have been a few case reports of pedal edema after treatment with antidepressants such as escitalopram, mirtazapine, trazodone, paroxetine, and venlafaxine combination 2–8 . However, there was no report of pedal edema associated with desvenlafaxine in the literature, nor is it mentioned among the rare adverse effects of the drug.…”