clozapine and Urination-Disorders

Urinary incontinence and enuresis are well-known side effects of clozapine. However, clinical experience has shown that patients also suffer from diverse lower urinary tract symptoms (LUTS). The natural course of clozapine-related LUTS is unclear. Thus, a longitudinal follow-up study is needed. A total of 101 subjects who were taking clozapine initially participated. Their LUTS were evaluated using the International Prostate Symptom Score (IPSS), other questionnaires, and a medical records review. After 2 years, 87 of the original subjects could be contacted, and the status of their LUTS was re-evaluated. The average IPSS total was 7.4 +/- 5.9 at the initial evaluation. Although only 11 subjects (10.9%) reported actual incontinence, 42 subjects (41.6%) were found to have clinically significant LUTS (IPSS total score > or =8). No influencing factors could be found among the demographic and clinical variables. At the follow-up, the average IPSS total (7.9 +/- 6.0) and the percentage of subjects with clinically significant LUTS (43.7%) had both increased, although the change was not statistically significant. The prevalence of LUTS in clozapine-medicated patients was higher than in the general population of the same age. However, the prevalence of incontinence was only a quarter of that of LUTS. If clinicians focus only on incontinence, distress from LUTS will not receive appropriate attention. Furthermore, contrary to literature observations, clozapine-related LUTS did not remit easily but rather persisted even into the long-term maintenance phase. More concern should be directed at these troublesome and often neglected side effects.

Topics: Adult; Antipsychotic Agents; Clozapine; Female; Follow-Up Studies; Humans; Male; Medical Records; Prospective Studies; Quality of Life; Stress, Psychological; Surveys and Questionnaires; Time Factors; Urinary Incontinence; Urination Disorders; Young Adult

Clozapine therapy has been associated with a high degree of urinary disturbances. The purpose of this study is to examine the effect of clozapine on urodynamic parameters and on the activity of the external urethral sphincter in anesthetized rats. Single cystometrograms (CMG) were performed on urethane-anesthetized female Sprague-Dawley rats, while also recording the EMG from the external urethral sphincter. Clozapine (0, 0.1, 1, 10 mg/kg) was administered intravenously. In addition, the peripheral end of the pudendal nerve was stimulated in order to determine if clozapine was exerting peripheral effects directly on the external urethral sphincter. Clozapine increased the bladder capacity while reducing the micturition volume thus resulting in a marked increase in the residual volume. The pressure threshold was increased but the peak pressure during contraction remained unchanged. The expulsion time and contraction time were decreased and the amplitude of the high frequency oscillations (HFO) seen during the expulsion phase were markedly reduced and even abolished. The EMG from the external urethral sphincter also showed marked decreases after clozapine, and the bursting pattern seen during HFO was abolished. Clozapine had no effect on the activity elicited from electrical stimulation of the pudendal nerve. Clozapine inhibits several urodynamic parameters and inhibits the activity of the external urethral sphincter in anesthetized rats. These effects may help explain the urinary disturbances reported in the clinical literature.

Topics: Animals; Antipsychotic Agents; Clozapine; Dose-Response Relationship, Drug; Electromyography; Female; Muscle, Skeletal; Perineum; Rats; Rats, Sprague-Dawley; Transducers, Pressure; Urethra; Urinary Bladder; Urination; Urination Disorders

Clozapine, an atypical antipsychotic, has resulted in a number of reports of urinary disturbances in the clinical literature. We examined the effects of clozapine on urodynamic parameters in the anesthetized rat and compared the effects to those of the typical antipsychotic haloperidol and the selective D2 and D4 antagonists, raclopride and L-745,870, respectively. Clozapine abolished high-frequency oscillations (HFO) during the expulsion phase, and profoundly altered a number of other parameters (e.g., intercontraction interval and resting pressure). Clozapine did not affect the peak contraction pressure during cystometrograms but displayed peripheral inhibition of bladder contractions elicited by electrical stimulation of the pelvic nerve (possibly mediated via clozapine's anti-muscarinic effects). Haloperidol had less potent effects than clozapine since it reduced the amplitude of HFO to 25% of control and also affected several other parameters but without peripheral bladder inhibition. Raclopride only resulted in a modest decrease (approximately 70% of control) in the HFO and no alteration in other parameters. L-745,870 was effective only at highest dose tested suggesting that it might not be acting selectively at D4 receptors. Therefore, we propose that clozapine primarily interferes with the function of the external urethral sphincter. These effects can only be partly explained through antagonism of D2 receptors. Since both clozapine and haloperidol have interactions with other transmitter systems beside dopamine, we suggest that central antagonism of D2 receptors, coupled to central antagonism of another receptor system and peripheral muscarinic receptor blockade, may account for clozapine's potent effects on micturition.

Topics: Anesthesia; Animals; Antipsychotic Agents; Clozapine; Dopamine Antagonists; Dopamine D2 Receptor Antagonists; Electric Stimulation; Female; Haloperidol; Hypogastric Plexus; Pyridines; Pyrroles; Raclopride; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D4; Urinary Bladder; Urination; Urination Disorders

Topics: Adult; Clozapine; Deamino Arginine Vasopressin; Enuresis; Female; Humans; Male; Mandelic Acids; Parasympatholytics; Prevalence; Psychotic Disorders; Urination Disorders