Prim Care Companion CNS Disord 2023;25(6):23cr03605
Venlafaxine belongs to a class of antidepressants that act by inhibiting reuptake of serotonin, norepinephrine, and some amount of dopamine.1 It has theoretically no anticholinergic activity, unlike the classic tricyclic antidepressants. Therefore, it lacks anticholinergic side effects such as dry mouth, glaucoma, constipation, and urinary retention. The most common side effects are nausea, somnolence, hypertension, anxiety, and sexual dysfunction.2
The indirect effect on the urinary bladder due to adrenergic effects from norepinephrine reuptake blockade can lead to urinary incontinence in some cases.3 Venlafaxine-induced urinary incontinence has been reported in the literature.4–7 This specific drug-induced effect is likely to mediate the possible therapeutic use of venlafaxine for reducing postvoiding residual volume in patients with a spinal cord lesion.8
However, urinary retention is not a commonly reported adverse effect of venlafaxine. In our literature review, we found only a few case reports of acute urinary retention with venlafaxine.9–11 The reported cases of urinary retention were either with a higher dose or use of venlafaxine in conjunction with other psychotropic drugs.9–11 We describe a case of urinary retention in a young man with use of lower doses of venlafaxine.
Case Report
A 33-year-old man presented to the outpatient clinic with symptoms suggestive of severe depressive episode12 following a financial setback. The patient was started on venlafaxine, which had been increased from 75 mg/d to 112.5 mg/d over 4 weeks. The patient reported difficulty urinating at the subsequent follow-up. There was nothing suggestive of genitourinary system pathology or neurologic involvement in the past. There was no abnormality on imaging of the bilateral kidney and urinary bladder. Urine microscopy and urodynamic study reports were within normal limits. The urologist advised for psychiatry consultation given the possibility that the recent increase in venlafaxine dose led to urinary retention.
We reduced the dose of venlafaxine to 75 mg/d, which resulted in improvement in urinary symptoms. We then completely stopped venlafaxine and started the patient on mirtazapine 15 mg/d. There was complete resolution of the inability to urinate, and the patient was stabilized on mirtazapine along with cognitive-behavioral therapy over 9 months.
Discussion
Lower urinary system symptoms can have a significant impact on quality of life. The common causes of urinary retention include vesical stone, urethral strictures, neurologic insult, acute prostatitis, or medications such as α-adrenergic agonists.13 Antidepressants such as duloxetine have been used to treat stress urinary incontinence in women.14 In animal models, venlafaxine has produced an effect on the bladder quantitatively similar to duloxetine.15 In our case, based on a probability scale for causality assessment by Naranjo et al,16 urinary retention was possibly due to the increase in dose of venlafaxine. The increased sympathetic stimulus likely resulted in an indirect reduction in parasympathetic tone, causing urinary retention.17 We considered mirtazapine as the next best choice in view of its peripheral α-1 adrenergic antagonist effects leading to direct relaxation of urinary bladder muscles.18–20 The limitation of our report is that there was no quantitative method to objectify the findings.
Conclusion
The reported case highlights the need to consider urinary side effects while prescribing venlafaxine. Clinicians should exercise caution when considering venlafaxine as a therapeutic agent for managing vesico-sphincter dyssynergia in patients with spinal cord lesions.
Horst WD, Preskorn SH. Mechanisms of action and clinical characteristics of three atypical antidepressants: venlafaxine, nefazodone, bupropion. J Affect Disord. 1998;51(3):237–254. PubMedCrossRef
Rudolph RL, Derivan AT. The safety and tolerability of venlafaxine hydrochloride: analysis of the clinical trials database. J Clin Psychopharmacol. 1996;16(suppl 2):54S–59S, discussion 59S–61S. PubMedCrossRef
Selvaraj V, Gunasekar P, Kumar S, et al. Urinary incontinence due to overactive detrusor muscle: a rare side effect of venlafaxine. Case Rep Urol. 2015;2015:690931. PubMedCrossRef
Polimeni G, Salvo F, Cutroneo P, et al. Venlafaxine-induced urinary incontinence resolved after switching to sertraline. Clin Neuropharmacol. 2005;28(5):247–248. PubMedCrossRef
Cavanaugh GL, Martin RE, Stenson MA, et al. Venlafaxine and urinary incontinence: possible association. Ann Pharmacother. 1997;31(3):372. PubMedCrossRef
Votolato NA, Stern S, Caputo RM. Serotonergic antidepressants and urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct. 2000;11(6):386–388. PubMedCrossRef
Hansen LK. Venlafaxine-induced increase in urinary frequency in 3 women. J Clin Psychiatry. 2004;65(6):877–878. PubMedCrossRef
Inghilleri M, Conte A, Frasca V, et al. Venlafaxine and bladder function. Clin Neuropharmacol. 2005;28(6):270–273. PubMedCrossRef
Tuman TC. Venlafaxine-induced urinary retention. Prim Care Companion CNS Disord. 2021;23(1):20l02702. PubMedCrossRef
Demirdöğen ŞO, Yıldırım Demirdöğen E, Adanur Ş. Acute urinary retention after venlafaxine use. Arch Ital Urol Androl. 2017;89(2):160–161. PubMedCrossRef
Benazzi F. Urinary retention with venlafaxine‐fluoxetine combination. Hum Psychopharmacol. 1998;13(2):139–140. CrossRef
World Health Organization. International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10). 1992.
Irwin DE, Milsom I, Hunskaar S, et al. Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: results of the EPIC study. Eur Urol. 2006;50(6):1306–1314, discussion 1314–1315. PubMedCrossRef
Norton PA, Zinner NR, Yalcin I, et al; Duloxetine Urinary Incontinence Study Group. Duloxetine versus placebo in the treatment of stress urinary incontinence. Am J Obstet Gynecol. 2002;187(1):40–48. PubMedCrossRef
Katofiasc MA, Nissen J, Audia JE, et al. Comparison of the effects of serotonin selective, norepinephrine selective, and dual serotonin and norepinephrine reuptake inhibitors on lower urinary tract function in cats. Life Sci. 2002;71(11):1227–1236. PubMedCrossRef
Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30(2):239–245. PubMedCrossRef
Stahl SM. Personalized medicine, pharmacogenomics, and the practice of psychiatry: on the threshold of predictive therapeutics in psychopharmacology? CNS Spectr. 2008;13(2):115–118. PubMedCrossRef
Lenze EJ. Reversal of SSRI-associated urinary retention with mirtazapine augmentation. J Clin Psychopharmacol. 2012;32(3):434. PubMedCrossRef
Thor KB, Katofiasc MA, Danuser H, et al. The role of 5-HT(1A) receptors in control of lower urinary tract function in cats. Brain Res. 2002;946(2):290–297. PubMedCrossRef
Delbressine LP, Vos RM. The clinical relevance of preclinical data: mirtazapine, a model compound. J Clin Psychopharmacol. 1997;17(suppl 1):29S–33S. PubMedCrossRef