Urinary Frequency: Clonazepam vs Diazepam
Clonazepam (Klonopin) causes more urinary frequency than diazepam, with micturition frequency reported in 2% of clonazepam-treated patients compared to 1% in placebo in controlled trials, while diazepam's FDA labeling does not list urinary frequency as a notable adverse effect. 1
Direct Evidence from FDA Drug Labeling
The FDA label for clonazepam explicitly lists "micturition frequency" occurring in 2% of patients treated with clonazepam (0.5-4 mg/day) versus 1% in placebo-treated patients during 6-9 week controlled trials for panic disorder 1
Clonazepam's FDA label also documents other urinary adverse effects including dysuria, enuresis, nocturia, and urinary retention, though these are listed under general adverse events rather than the most common treatment-emergent effects 1
Diazepam's primary documented adverse effects from the American Gastroenterological Association include phlebitis at injection sites, respiratory depression, coughing, and dyspnea, with no specific mention of urinary frequency as a notable side effect 2, 3
Clinical Context and Mechanism
Both benzodiazepines work through non-selective GABA-A receptor activation, but their side effect profiles differ based on pharmacokinetic properties and tissue distribution 3
Diazepam has high lipid solubility and a very long half-life (20-120 hours) with active metabolites, leading to prolonged sedation and accumulation rather than urinary symptoms 3
The urinary effects of clonazepam appear dose-related and occur early in treatment, as demonstrated in the controlled trial data where 2% of patients experienced this side effect at therapeutic doses 1
Important Clinical Considerations
The 2% incidence of micturition frequency with clonazepam, while seemingly low, represents a doubling of the placebo rate and is clinically significant enough to be listed among treatment-emergent adverse events in FDA labeling 1
Clonazepam's long half-life (30-40 hours) means urinary frequency effects may persist throughout the dosing interval 3, 4
In elderly patients, both medications require dose reductions due to decreased clearance, but diazepam's active metabolites pose greater risks for prolonged sedation, confusion, and falls rather than urinary symptoms 3