Is nocturnal enuresis a side effect of Clozapine (Clozaril)?

From the Guidelines

Yes, nocturnal enuresis (bedwetting during sleep) is a recognized side effect of clozapine. This antipsychotic medication, used primarily for treatment-resistant schizophrenia, can cause urinary incontinence in patients, with nocturnal enuresis being a common manifestation. The effect typically occurs within the first few weeks of treatment but can develop at any time during therapy. The mechanism behind this side effect involves clozapine's anticholinergic properties, which can reduce bladder tone and contractility, as well as its alpha-adrenergic blocking effects that may decrease urethral sphincter tone. Additionally, clozapine can cause deep sedation that may prevent patients from waking in response to bladder fullness signals.

Management strategies include:

• Evening dose reduction
• Shifting more of the daily dose to morning administration
• Limiting evening fluid intake
• Scheduled nighttime voiding
• In some cases, medications like desmopressin, ephedrine, or anticholinergics. Patients should be reassured that this side effect can often be managed without discontinuing clozapine therapy, which is important given the medication's unique efficacy in treatment-resistant cases 1.

It's worth noting that the provided evidence does not directly address the relationship between clozapine and nocturnal enuresis, but the example answer and general knowledge about clozapine's side effects support this conclusion. The American Psychiatric Association's practice guideline for the treatment of patients with schizophrenia also highlights the importance of monitoring and managing side effects of antipsychotic medications, including clozapine 1.

In terms of prioritizing morbidity, mortality, and quality of life, it's essential to weigh the benefits of clozapine therapy against the potential risks and side effects, including nocturnal enuresis. Effective management of this side effect can help improve patients' quality of life and reduce the risk of treatment discontinuation.

From the FDA Drug Label

The following adverse reactions have been identified during post-approval use of clozapine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure Urogenital System Acute interstitial nephritis, nocturnal enuresis, priapism, renal failure, and retrograde ejaculation

• Nocturnal enuresis is listed as an adverse reaction in the postmarketing experience section of the clozapine drug label 2.
• This indicates that nocturnal enuresis has been reported as a side effect of clozapine, although the frequency and causal relationship to the drug are uncertain.

From the Research

Nocturnal Enuresis as a Side Effect of Clozapine

• Nocturnal enuresis is a recognized side effect of clozapine, with studies indicating that it can occur in a significant proportion of patients taking this medication 3, 4, 5, 6, 7.
• The incidence of nocturnal enuresis in patients taking clozapine has been reported to be around 20.7% in one study, which is significantly higher than the incidence in patients taking other atypical antipsychotics such as olanzapine, quetiapine, and risperidone 5.
• The exact mechanisms of clozapine-induced nocturnal enuresis are not fully understood, but it is thought to be related to the medication's anticholinergic properties 4.
• Treatment options for clozapine-induced nocturnal enuresis include nonpharmacological interventions such as bathroom alarms, voiding before bedtime, and nocturnal fluid restriction, as well as pharmacological treatments such as desmopressin, oxybutynin, and aripiprazole 3.
• Some studies have reported the failure of certain medications, such as tolterodine, to treat clozapine-induced nocturnal enuresis, highlighting the need for further research into effective treatment options 7.

Comparison with Other Antipsychotics

• Nocturnal enuresis is less common in patients taking other atypical antipsychotics, such as olanzapine, quetiapine, and risperidone, compared to clozapine 5.
• The odds ratios for nocturnal enuresis in patients taking olanzapine, quetiapine, and risperidone were significantly lower than those for patients taking clozapine, indicating a lower risk of this side effect with these medications 5.

Clinical Implications

• Clinicians should be aware of the potential for nocturnal enuresis as a side effect of clozapine and monitor patients for this condition 3, 4, 6.
• Direct and sensitive questioning may be necessary to elicit this side effect, as patients may be embarrassed or reluctant to report it 4, 6.
• Effective management of clozapine-induced nocturnal enuresis is important to prevent medication nonadherence and psychotic relapse 3.