Effects of imipramine on enuretic frequency and sleep stages
Kales, A.; Kales, J.D.; Jacobson, A.; Humphrey, F.J.; Soldatos, C.R.
Pediatrics 60(4): 431-436
1977
ISSN/ISBN: 0031-4005 PMID: 198735 Document Number: 121644
Four children with a history of primary enuresis were evaluated in both the sleep laboratory and at home in a 68 consecutive-night protocol with successive conditions of 10 placebo-baseline nights, 27 drug (imipramine) nights and 31 placebo-withdrawal nights. On the placebo conditions, 2/3 of the enuretic events occurred during the 1st third of the night. Enuretic events occurred out of each sleep stage in approximate proportion to the time spent in that sleep stage for each third of the night. Thus, primary enuresis was chiefly related to time of night and not to any specific sleep stage such as stage 3 or 4 (slow wave) sleep. Administration of imipramine in a mammer simulating clinical drug use resulted in marked decrease in overall enuretic frequency. The reduction of enuretic frequency was not related to the effects of imipramine on sleep stages. There was a reduction of enuretic events in the first 2/3 of the night with an increase in enuretic events in the last 3rd of the night. With long-term drug administration, there was a significant increase in wakefulness in the last 3rd of the night. Early in the night when sleep is deepest, imipramine decreases bladder excitability and/or increases the child's bladder capacity. This allows the child to continue to sleep without micturition and later in the night when sleep is lighter, to be more aware of the stimuli from the bladder. Immediately following withdrawal of imipramine, enuretic frequency approximated baseline levels. Imipramine administration resulted in a moderate degree of rapid eye movement (REM) suppression. With long-term administration, there was a diminution of the REM suppressant effect. Initial withdrawal of imipramine produced a marked REM rebound.