Nocturia: a blinded, randomized, parallel placebo-controlled self-study of the effect of 5 different sedatives and analgesics

Can Urol Assoc J. 2008 Dec;2(6):604-8.

Abstract

Background: In a previous study I noted that, when taken occasionally as a nighttime sedative, the benzodiazepine (BZD) oxazepam decreased nocturia. The objective of the present study was, using placebo and other sedatives and analgesics, to assess whether oxazepam decreases nocturia and, if so, how?

Methods: I conducted a prospective, randomized, placebo-controlled self-study over a period of 10 months using oxazepam, zopiclone and trazodone as sedatives, and naproxen and oxycodone as analgesics. I assessed each medication 10 times, for a total of 60 tests. Each test included assessment of sleep adequacy, number and volume of overnight voidings and chemistries. Every test was a "first-time" or "naive" event.

Results: All medications differed in several parameters from placebo, but nocturia only showed a significant reduction with naproxen and oxazepam. Nocturia occurred a mean (standard deviation [SD]) of 1.6 (0.84) times nightly with placebo and fell to 0.6 (0.5) with oxazepam, which was a 63% decrease without any change in urine volume. Naproxen reduced nocturia to a mean (SD) of 0.7 (0.8) times nightly by reducing water, salt and potassium excretion. Compared with placebo, all medications had less urine sodium loss and decreased fractional sodium excretion (FENa), suggesting increased renal tubular sodium reabsorption. This effect was most marked with naproxen. Neither improved sleep quality with zopiclone nor pain relief with oxycodone resulted in reduced nocturia.

Conclusion: The effect of naproxen was probably a direct one on the kidney. The reduction of electrolyte excretion produced by the other medications is possibly a central effect on sympathetic activity, and the effect was too small to change urine volume. The effect of oxazepam was to make the bladder less irritable and could not be attributed to a decrease in urine volume, electrolyte change, sedation or analgesia. A central gamma-aminobutyric acid-mediated effect in the cord or brain could explain the results observed with oxazepam.