|Year : 2019 | Volume
| Issue : 2 | Page : 114-117
Carbamazepine-associated urinary incontinence: A case report and literature review
Jamir P Rissardo, Ana L Fornari Caprara
Department of Medicine, Federal University of Santa Maria, Santa Maria, Rio Grande do Sul, Brazil
|Date of Web Publication||18-Nov-2019|
Mr. Jamir P Rissardo
Department of Medicine, Federal University of Santa Maria, Santa Maria, Rio Grande do Sul.
Source of Support: None, Conflict of Interest: None
Carbamazepine (CBZ) is an anticonvulsant approved for the management of many neurological and psychiatric disorders. We present a case of an adult male with epilepsy who reported new seizures, and the dose of CBZ administered was 1600mg daily. CBZ dose was increased to 1800mg daily. The subject complained of urinary incontinence without dysuria that started after the CBZ dose increase. It was associated with urgency, hesitancy, dribbling of urine, and poor stream. Laboratory tests were within normal limits. He admitted dry mouth, flushing, constipation, and accommodation paralysis starting after CBZ increase. Assuming that these symptoms were an adverse drug reaction, CBZ was withdrawn and valproate was started. The individual had full recovery within four weeks. To the best of our knowledge, only two case reports of similar nature are available, but this is the first one to be reported with young male adult.
Keywords: Carbamazepine, epilepsy, incontinence, urinary
|How to cite this article:|
Rissardo JP, Fornari Caprara AL. Carbamazepine-associated urinary incontinence: A case report and literature review. Int J Med Health Dev 2019;24:114-7
|How to cite this URL:|
Rissardo JP, Fornari Caprara AL. Carbamazepine-associated urinary incontinence: A case report and literature review. Int J Med Health Dev [serial online] 2019 [cited 2023 Feb 5];24:114-7. Available from: https://www.ijmhdev.com/text.asp?2019/24/2/114/271089
| Introduction|| |
Carbamazepine (CBZ) is an anticonvulsant approved by the Food and Drug Administration for the management of bipolar type 1 disorder, epilepsy, and trigeminal or glossopharyngeal neuralgia. It is an iminostilbene derivative, of which, the carbamyl group at the first position is responsible for its anti-seizure activity. In this context, CBZ is generally well tolerated with only mild adverse effects. Commonly reported side effects are drowsiness, fatigue, dizziness, nausea, and skin rashes.,
Only a few cases of CBZ-associated urinary incontinence have been reported in the literature. To the best of our knowledge, only two case reports of similar nature are available, but this is the first one to be reported with young male adult., To date, urinary incontinence has been associated with other anticonvulsant agents such as valproate, gabapentin, and topiramate.,,
Here, we report a case of an adult male diagnosed with epilepsy, in which CBZ was increased due to uncontrolled seizures. A week later, the subject complained of urinary symptoms. After a thorough investigation, CBZ was withdrawn, and the symptoms of the individual ameliorated.
| Case Report|| |
A 20-year-old man with a two-year history of secondary epilepsy due to a traumatic brain injury was seizure free. He was in use of CBZ (1600mg a day). But during a routine visit in our neurology department, the subject reported new seizures that started within the last four months. The ictal episodes were of focal onset with impaired awareness. An electroencephalogram showed left temporal spike waves with typical phase inversion. The neurological exam was normal. Laboratory tests were within normal limits. CBZ dose was increased.
After two weeks, he was in use of CBZ (200mg, three capsules) three times a day. However, the subject complained of urinary incontinence without dysuria that started seven days after the CBZ dose was increased. It was associated with urgency, hesitancy, dribbling of urine, and poor stream. Neither a history of pelvic trauma nor an antecedent of urinary tract symptoms was revealed. Physical examination was normal. Laboratory tests and urinalysis were requested. Ciprofloxacin (500mg) twice a day over five days was started.
After two weeks, he reported the same previous urinary symptoms, and that the medication prescribed did not ameliorate them. Complete blood cell count, glucose, creatinine, urea, sodium, and potassium serum concentrations were within normal limits. Urine cell count and urine chemistry were normal. Urine culture was negative. Physical examination revealed suprapubic tenderness without guarding or rebound, which was suggestive of a distended bladder. The subject was presented at the emergency department, and a urinary catheter was inserted, which drained 1000mL of clear urine. Abdomen plain X-ray and ultrasound were normal. A voiding cystourethrogram showed retention of a large volume of contrast material in the bladder without bladder outlet obstruction or ureteral reflux. Magnetic resonance imaging of the brain and spine was normal.
On further questioning, he admitted the appearance of dry mouth, flushing, constipation, and accommodation paralysis starting after CBZ dose increase. Assuming that these anticholinergic symptoms were an adverse drug reaction, CBZ was tapered and valproate was started. The individual had a full recovery, including from urinary incontinence symptoms, within four weeks. One year later, in the follow-up, the subject still remains continent, and he was seizure free with valproic acid.
| Discussion|| |
Epilepsy is described by chronically abnormal brain activity associated with unprovoked and probable recurrent seizures. In this context, CBZ is one of the most commonly prescribed drugs in the management of this disorder. It is indicated for focal aware or impaired awareness and generalized tonic but not for absence seizures.,, The probable mechanism of antiepileptic action of CBZ is considered to be its inhibitory effect on voltage-dependent sodium channels, which could reduce action potentials and inhibit the generation of rapid action., Also, this inhibition has a positive correlation with neuronal depolarizing rates.,,
The low cost and its proven therapeutic benefits explain the common use of CBZ in clinical practice, although, approximately one in every four patients discontinue the treatment with CBZ because of adverse drug reactions., In fact, these effects can widely vary from mild to severe. Moreover, the central nervous system effects are dose dependent and more frequent in the elderly population.,, Thus, physicians prescribing CBZ should be aware of these possible adverse effects and communicate them to patients and their caregivers.,,
CBZ-associated urinary incontinence has been reported in the literature. But there was evidence of underlying pathology or situation in these reports, which per se could better explain the incontinence of the subjects, such as diabetes mellitus, Fabry’s disease, or male advanced age due to prostate-related urinary disturbances.,, We identified two case reports without any other main explanation for the individuals' symptoms than the CBZ use, published in English, and we compared them with the present case [Table 1]., A literature search was performed in Google Scholar, LILACS, and MEDLINE, on a set of terms that included “incontinence,” “urinary,” and “carbamazepine.”
|Table 1: Case reports of carbamazepine-associated urinary incontinence without evidence of underlying pathology, which per se could explain the urinary symptoms of the subjects|
Click here to view
As per the cases in [Table 1], the predominance of female sex was 2:1., As already hypothesized with other anticonvulsants, Kibar et al. explained that the occurrence of incontinence is more commonly found in females due to their vaginal parity. In our study, we could not support this assumption because the cases reported by Anders et al. and Hmouda et al. did not mention the vaginal parity of their subjects, and the subject of our study was a male. Another interesting fact is that to date, all patients reported with CBZ-associated urinary incontinence had a diagnosis of epilepsy (two of the temporal lobe and one case without a clear description of seizures). However, CBZ is a drug, which is clinically used in many other neurological and psychiatric disorders such as trigeminal neuralgia, bipolar mania, and restless legs syndrome. Also, it is worth mentioning that all the individuals had a full recovery after CBZ withdrawal.,
The urinary incontinence started when the dose of CBZ was increased in Anders et al. study and in the present case. In this way, we hypothesized that the urinary incontinence associated with CBZ could be a dose-dependent side effect as well as an adverse effect of the central nervous system. Therefore, titrated doses with near clinical monitoring are probably beneficial, when it is being planned to increase CBZ's dose.
The mechanism to explain the urinary incontinence secondary to CBZ is the anticholinergic effect. It is an iminostilbene derivative that is chemically related to tricyclic antidepressants (TCAs). This hypothesis is supported by their structural similarities and studies showing cross-reactivity of the TCAs immunoassay for CBZ with Abbot assay even in therapeutic levels. Thus, CBZ may have TCA-like side effects, and as with TCAs, incontinence is probably caused by anticholinergic pathways.,,,
The pathophysiology of TCA-like effect leading to urinary retention could be explained by three hypotheses. First, CBZ probably antagonizes postjunctional excitatory muscarinic (M2 and 3) receptors in the detrusor muscle of the bladder decreasing bladder contraction, which can facilitate urine storage and lead to overflow incontinence., This assumption is supported by the reversibility of CBZ-induced urinary symptoms by bethanechol, which is a cholinergic agonist that selectively stimulates muscarinic receptors. Second, a presynaptic norepinephrine reuptake block, which is a TCA-like effect, can contribute to the incontinence as this fact could increase the tone of the internal urethral sphincter, leading to the inhibition of the bladder emptying., Third, CBZ is an anticonvulsant so it can interfere with the somatosensory cortex projections of the ventral posterior lateral thalamic nucleus, which notifies the brain with the issues in the bladder or urethra. Furthermore, this drug can interfere with the spinal reflex associated with micturition by the same mechanism.,
| Conclusion|| |
Urinary incontinence is a known adverse reaction of other anticonvulsants such as valproate, gabapentin, and topiramate. Our report supports that CBZ should be listed as a probable cause of urinary incontinence. Although not life-threatening, clinicians need to have a high index of suspicion while reviewing patients because this adverse effect can be very embarrassing to patients and can lead to poor adherence to the therapy.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Tomson T, Johannessen SI. Carbamazepine. In: Simon S, Emilo P, editor. The treatment of epilepsy. 4th ed. Chichester, UK: John Wiley & Sons; 2016. pp. 431-46.
Marson AG, Al-Kharusi AM, Alwaidh M, Appleton R, Baker GA, Chadwick DW, et al
; SANAD Study group. The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: An unblinded randomised controlled trial. Lancet 2007;369:1000-15.
Anders RJ, Wang E, Radhakrishnan J, Sharifi R, Lee M. Overflow urinary incontinence due to carbamazepine. J Urol 1985;134:758-9.
Hmouda H, Ben Salem C, Grira M, Slim R, Bouraoui K. Carbamazepine-induced urinary retention. Br J Clin Pharmacol 2007;64:833-4.
Wang CF, Ho PS, Tseng YT, Liang CS. Topiramate-associated urinary incontinence: A case verified by rechallenge. Clin Neuropharmacol 2014;37:149-50.
Rissardo JP, Caprara ALF. Gabapentin-associated urinary incontinence: A case verified by rechallenge. Clin Neuropharmacol 2019;42:91-3.
Sudan YS, Bansal AR. Urine incontinence induced by valproic acid. Indian J Pediatr 2017;84:867-8.
Steiner I, Birmanns B. Carbamazepine-induced urinary retention in long-standing diabetes mellitus. Neurology 1993;43:1855-6.
Filling-Katz MR, Merrick HF, Fink JK, Miles RB, Sokol J, Barton NW. Carbamazepine in Fabry's disease: Effective analgesia with dose-dependent exacerbation of autonomic dysfunction. Neurology 1989;39:598-600.
Kibar S, Demir S, Sezer N, Köseoğlu BF, Dalyan Aras M, Kesikburun B. Gabapentin-induced urinary incontinence: A rare side effect in patients with neuropathic pain. Case Rep Neurol Med 2015;2015:341573.
Chattergoon DS, Verjee Z, Anderson M, Johnson D, McGuigan MA, Koren G, et al
. Carbamazepine interference with an immune assay for tricyclic antidepressants in plasma. J Toxicol Clin Toxicol 1998;36:109-13.
Hegde SS. Muscarinic receptors in the bladder: From basic research to therapeutics. Br J Pharmacol 2006;147:S80-7.
Merrill DC, Markland C. Vesical dysfunction induced by the major tranquilizers. J Urol 1972;107:769-71.
Holstege G, Collewijn H. Central nervous system control of micturition. Spinal Cord 2009;130-47.