Can urinary retention be caused by antiepileptic drugs?/nA 29-year-old woman with microcephalia, se

Fråga: Can urinary retention be caused by antiepileptic drugs?

A 29-year-old woman with microcephalia, severe mental retardation and seizures has been treated with carbamazepine, phenytoin and valproate for several years. On two occasions during the last year she has had unexplained urinary retention which was previously resolved by carbacholine treatment but which now demands catheterization. The upper urinary tracts have been radiologically examined and found to be normal. The questioner has noted slightly higher phenytoin plasma concentrations than usual, but still within the therapeutic range, in relation to the episodes of urinary retention. Plasma levels of CBZ and valproate have been normal or low. Could any of these drugs cause urinary retention?

Sammanfattning: The documentation concerning urination disorders caused by antiepileptics is sparse. There are single case reports coupling carbamazepine to urinary retention, presumably due to an anticholinergic effect. Valproic acid and phenytoin have not been associated with this side-effect. The combined effect of these three drugs on the complex mechanism of micturition is, however, hard to assess, especially in a patient with brain damage. In the present case, if clinically possible, one should primarily consider lowering the carbamazepine dose or even discontinuing the CBZ treatment.

Svar: CARBAMAZEPINE. A combined case report and review article from 1985 (1) is said to describe the first well-documented case of urinary retention and overflow incontinence owing to prolonged CBZ treatment. In a 17-year-old girl with temporal lobe seizures, CBZ increased the bladder capacity and caused symptoms of urgency and frequency. After CBZ was discontinued and primidone introduced, the voiding symptoms disappeared. Different etiological, neuronal and hormonal mechanisms are discussed (1). Primarily, CBZ is said to exert an anticholinergic effect on the detrusor muscle, interfering with bladder emptying, and perhaps a sympathomimetic effect on the sphincter. Also, it may interfere with spinal reflexes. Finally, CBZ is known to induce the syndrome of inappropriate antidiuretic hormone, causing fluid retention and hyponatraemia.

In the catalogue of Swedish pharmaceutical specialities (2), urinary retention together with pollakiuria and oliguria are listed as rare (less than one per 1000) side-effects. According to the review article (1), the manufactures were aware in 1984 of only 5 cases of urinary retention caused by CBZ and the cases did not have fully established cause-effect relationships. The Swedish representative (3) cannot, at present, provide further information. Apart from the case above (1) we have found only one further published report (4) concerning this matter; a patient with multiple sclerosis developed urinary retention from CBZ that reoccurred on rechallenge. According to a recent Drug Information Centre document (5) concerning urinary incontinence caused by CBZ, there are at present (Nov 1991) only 8 such cases which have been reported to the WHO database.

VALPROIC ACID has not, according to our knowledge, been connected with urinary retention. However, pollakiuria (2) and enuresis (2,6) in children have been reported, the latter in a frequency between one and 7 per cent (6). The mechanism is unknown (1).

PHENYTOIN has not been connected with urinary retention but anecdotally with stress incontinence (2). Long-term use of phenytoin has been associated with peripheral neuropathy (6,7), but the clinical relevance seems dubious and this has not been coupled with urination disturbances. A recent determination of phenytoin concentration in this patient (8) showed an elevated free phenytoin fraction of about 19 per cent, possibly due to an interaction with valproic acid (9). The clinical relevance of this is hard to assess.

Concerning ALTERNATIVE antiepileptic drugs, clonazepam has been associated with incontinence but not with urinary retention (1) and phensuximide (but not ethosuximide) with enuresis and retention in children (1). Primidone and phenobarbital have not been convincingly associated with urinary voiding disorders (2).

The case should be reported to the Swedish Adverse Drug Reactions Advisory Committee. 1 Anders RJZ, Wang E, Radhakrishnan J, Sharifi R, Lee M: Overflow urinary incontinence due to carbamazepine. J Urolog 1985; 134: 758-759 (enclosed)

2 FASS 1992; pp 311, 330, 794-795
3 Personal communication, Erik Wosse, Ciba-Geigy AB
4 Meyler´s, Side effects of Drugs, 1972; 7th ed: 109
5 Drugline nr 07899 (year 1991)
6 Martindale, Extra pharmacopoeia, 1989; 29th ed: 407, 414
7 Levy RH, Deifuss FE, Mattson RH, Meldrum BS, Penry JK: Antiepileptic Drugs 1989; 3rd ed: 244
8 Data from TDM lab, Huddinge University Hospital

9 Hansten, Horn, Drug interactions & Updates, 1971-; pp 196-197