Optimizing response to desmopressin in patients with monosymptomatic nocturnal enuresis

Kamperis K, Van Herzeelee C, Rittig S, Vande Walle J. 

Pediatric nephrology. 2017 Feb;32:217–26.           

This review article sought to review best practice in selecting patients for desmopressin therapy, and to provide recommendations to optimise treatment. Desmopressin is a first-line therapy available for enuresis caused by nocturnal polyuria. A recent study demonstrated that by optimising factors surrounding treatment, even ‘resistant’ cases could be effectively treated. The authors suggest eight considerations for treatment.

Monosymptomatic nocturnal enuresis (MNE) may be due to either excess urine production overnight (nocturnal polyuria), or reduced bladder reservoir capacity or function (commonly overactive bladder). It is when either is coupled with a lack of arousal in response to a full bladder that enuresis occurs. Comprehensive data are not available, but previous estimates are that two thirds of MNE patients have nocturnal polyuria – although this has also been suggested to be overly high. Nocturnal polyuria is most often due to inadequate overnight secretion of antidiuretic hormone – usually responsible for concentrating the urine. It is this group of patients who are most likely to benefit from desmopressin, which is a synthetic analogue of antidiuretic hormone.

On reviewing the literature, the only significant demographic predictor for successful resolution was higher age; young children are more prone to a lower maximum voided volume, suggesting overactive bladder as the aetiology. It is also more difficult for them to comply with the recommended intervals following food and before bedtime. Maximum voided volume is a key discriminating factor for response – those with values of >70% of expected volume are twice as likely to respond to desmopressin, representing greater likelihood of nocturnal polyuria as the underlying pathology. A thorough assessment prior to instigating treatment should include a full history to exclude complicating factors, bladder diaries (volumes, times and fluid intake – ideally for at least 4 days) and a bedwetting diary.

The recommendations for optimisation of treatment are as follows:

1. Choose the most appropriate formulation. This is typically the oral lyophilisate formulation, as it is easier to take, is usually preferred by children <12 versus tablets, has less interaction with food and a higher bioavailability. It may be more effective, although this is currently uncertain.

2. Ensure optimal timing, and consider the impact of meals. The recommendations are for desmopressin to be administered at least two hours after the evening meal, and an hour before bed – although this may be impractical, particularly for younger children. Evidence suggests that the oral lyophilisate may be more effective and predictable after a meal compared to the tablet form. The possible impact of daytime food and fluid intake should also be considered on the osmotic load and enuresis.

3. Fluid restriction before and after administration. Data suggest a sub-optimal treatment response when fluid is given after, or in the hour before desmopressin administration.

4. Tailor dose and timing to the individual. Even at low doses maximal anti-diuresis is achieved, however the duration of action may be reduced. The inter-individual range of action is large, and a Danish study revealed that over a quarter of patients were stable on a dose below the minimum recommended. Timing may also be adjusted; a longer interval between administration and bedtime may be effective for some – although this is not backed up by data.

5. Consider the possible impact of bodyweight. Dosing may need to be adjusted when using the oral lyophilisate formulation, due to improved bioavailability. There is no demonstrable effect of bodyweight on dosing with other formulations.

6. Ensure adherence to medication and administration recommendations. In the general population, adherence to medication is poor. Desmopressin is only effective on the day that it is taken, which should be clearly emphasised to parents. Poor adherence or failure to follow administration recommendations may be a reason for treatment failure. Some data suggest a switch to oral lyophilisate may improve adherence.

7. If cessation is required, consider a structured withdrawal. Regular ‘drug holidays’ should be built into the dosing schedule to determine whether discontinuation can be attempted. A small number of studies have suggested a possible reduced relapse rate with a gradual withdrawal.

8. Consider combination therapy. Desmopressin may have an anti-diuretic, but not anti-enuretic effect, in which case adding other therapies may be necessary. Monitoring the response to treatment may establish whether it is providing adequate anti-diuresis.

This article is a useful practical resource for clinicians dealing with difficult cases of nocturnal enuresis. Ensuring treatment optimisation will allow the maximal effect from this treatment. Awareness of the appropriate indications will also prevent overtreatment.