Carbamazepine-induced urinary retention.

Carbamazepine is one of the most commonly prescribed antiepileptic drugs and is also used in the treatment of various diseases, including trigeminal neuralgia, neuropathic pain and psychiatric disorders, particularly bipolar depression [1]. Carbamazepine adverse reactions range from minimal, dose-dependent central nervous system effects to severe, irreversible bone marrow depression, as well as idiosyncratic reactions and allergic reactions, including Stevens–Johnson syndrome and hypersensitivity syndrome. We report a patient with a 2-year history of epilepsy treated with carbamazepine who developed urinary retention under carbamazepine therapy. Urinary symptoms disappeared when carbamazepine was discontinued. A 38-year-old women, with a 2-year history of epilepsy treated with carbamazepine (200 mg twice daily), came to the emergency room because of lower abdominal discomfort and inability to void. Three days earlier she had started to complain of urgency and dribbling of urine, and then developed acute urinary retention. She reported a history of urgency, hesitancy, dribbling of urine and poor stream which began shortly after carbamazepine initiation and which she tolerated for almost 2 years without seeking medical care because of shame. She denied any previous history of haematuria, urological or gynaecological intervention. Clinical examination revealed suprapubic tenderness without guarding or rebound, suggestive of distended bladder. A urinary catheter was immediately inserted and drained 1100 ml of clear urine. Pelvic and gynaecological examinations were normal. She was apyrexial and without any other physical finding. Kidney function tests, complete blood count, glucose, albumin, sodium and potassium serum concentrations were within normal range. Urine cell count and urine chemistry were normal. Urine culture was negative. Abdomen plain X-ray and ultrasound were normal. Mechanical obstruction was ruled out by normal pelvic, genitourinary and rectal examinations. The origin of this acute urinary retention was initially intriguing, but when, subsequently, the patient reported a dry mouth with flushing and dryness of the skin that appeared several days after carbamazepine initiation, a drug-induced event seemed the most likely origin of the voiding symptoms. Carbamazepine was the only medication with anticholinergic properties taken by the patient, and the most likely causal agent. Although the carbamazepine serum concentration was 11 µg/ml (therapeutic range 4–12 µg/ml) it was withdrawn and replaced by valproic acid. Voiding symptoms and anticholinergic features did not recur over a 12-month follow-up period. Carbamazepine-induced urinary retention has been reported in the literature, but in most of the cases there was evidence of underlying disease such as longstanding diabetes mellitus with severe peripheral neuropathy in two patients [1], and Fabry's disease with autonomic dysfunction in two others [2]. It is obvious that carbamazepine might have interfered with these conditions and precipitated acute urinary retention. Therefore, these contributing factors might have biased the causality relationship between urinary retention and carbamazepine. In addition, the male gender of the patients previously reported and their advanced age raise questions about a possible prostatic contribution to the abnormalities in voiding. Fowler's syndrome represents the main differential diagnosis in our patient, but its clinical picture and natural history are completely different [3]. In our case, there are five arguments against this syndrome. First, voiding symptoms began within a few days following initiation of carbamazepine, and disappeared completely after discontinuation of the drug. Second, the urethral sphincter on the anterior vaginal wall was not enlarged on palpation. Third, the urge to void has never disappeared, and the retention of urine was painful, facts that argue for the persistence of bladder filling sensation, in contrast to Fowler's syndrome, in which the sensationof bladder filling is suppressed. Fourth, symptoms of Fowler's syndrome do not resolve spontaneously and usually require specific therapy. Fifth, anticholinergic symptoms have no reason to occur in Fowler's syndrome. Our case adds credence to previous reports of carbamazepine-induced urinary retention. Indeed, an objective causality assessment using the Naranjo rating scale has revealed that the adverse drug event was probable [4]. In addition, in contrast to previously reported cases, the female gender of our patient excluded from the start the hypothesis of prostatic-related urinary disturbances. Normal pelvic, genitourinary and rectal examinations, as well as normal medical imaging results, ruled out the possibility of mechanical obstruction of the bladder due to extrinsic compression. The absence of autonomous nervous system involvement in our patient is another difference from previously reported cases. The exact mechanism of carbamazepine-induced urinary retention is not well elucidated. However, the well-known chemical relation between carbamazepine and tricyclic antidepressants may explain the occurrence of anticholinergic effects. It is thought that urinary retention due to anticholinergics is secondary to their inhibitory effect on bladder contraction in predisposed patients, particularly in the presence of outlet obstruction and autonomic nervous system dysfunction. This effect results from antagonizing postjunctional excitatory muscarinic receptors M2 and M3 in the detrusor muscle of the bladder interfering with bladder contraction and emptying, thereby facilitating urinary storage and retention [5]. If not recognized and reversed early on, this condition can lead to urinary tract infection and damage to the kidneys [6]. The reversibility of carbamazepine-induced urinary retention by the cholinergic agent bethanecol in a previous report supports the presumed anticholinergic mechanism of this drug adverse event [1]. Carbamazepine has also been reported as a cause of overflow urinary incontinence [6, 7] and has been proposed to treat primary nocturnal enuresis [8]. Even though a rare drug adverse event, carbamazepine-induced urinary retention should be recognized not only in predisposed patients but also under normal circumstances.