How to increase response- rate 1) Fluid restriction 1 hour before desmopressin administration Evidence ??? NO Rationale with indirect evidence : Yes

Fluid load reduces desmopressin response * * * 30% lower U osmol results in 30% higher diuresis-rate .. and bedwetting dDAVP 2 nasal spray * p < O.O1 EVIDENCE OF PARTIAL dDAVP RESPONSE RELATED TO POOR PHARMACODYNAMIC EFFECTS OF dDAVP NASAL SPRAY (De Guchtenaere J Urology,2009)

How to increase response- rate 2)Diet advice Normal protein and sodium intake diet Spreading over the day Avoid highest osmotic load in the evening No food after evening meal Evidence ??? NO Rationale with indirect evidence : Yes

But high nocturnal excretion of osmol and water Group 2: (high) Normal 24 h intake, normal 24 h excretion But high nocturnal excretion of osmol and water high osmotic load in the evening J.Dehoorne Desmopressin resistant nocturnal polyuria secundary to increased osmotic excretion J Urology 2006

How to increase response- rate 3) Desmopressin 1 hour before last void

effet anti-diuretique maximale rapide Fast Anti-diuretic effect first hour Additional effect 2nd and 3rd hour Vermindering van diurese van 0,05 ml/kg/min naar 0,02 gedurende 2 uur lijkt niet veel….doch voor een kind van 30 kg betekent dit een afname van 0,03*120*30 wat betekent een winst van een volume van 108 ml, hetgeen natuurlijk wel het verschil kan maken tussen nat of droog….

Concentration capacity Fast effect first hour Additional increased effect 2nd and 3rd hour Zelfde voor osmolaliteit, een stijging van 650 naar 900 in uur 2 en uur 3 na medicatie-inname Pharmacodynamic studies of dDAVP melt during water-load Vande Walle JG et al. BJU Int 2006;97(3):603–9

How to increase response- rate 4) Sleep Hygiëne Last hour before bedtime No strong stimuli light or music = ipad /television/ computer / games Void just before bedtime Once in bed No light No reading No other activities

How to increase response- rate 5) Compliance

What about adherence? The study clearly demonstrated that a high adherence is associated with a high response rate. Low adherence is associated with a low response rate. This study demonstrates the importance of non-adherence as a possible reason for therapyresistance.

What about adherence? The study also demonstrates that even when patients know that adherence will be measured, the group with the 100% adherence decreases over time, to 77% after 3 months and even to 71% of the patients after 6 months who are fully adherent.

How to increase response- rate 6) Select the right patient

High nocturnal urinary volumes predict good DDAVP response 500 Full responders (N=13) Desmopressin i.n. 20 mg 40 mg Partial responders (N=19) 400 Non responders (N=84) Night urinary volume (mL) 300 200 100 5 10 15 20 25 30 Time (days) Rittig et al. Scand J Urol Nephrol 1998

Re-analysis: Do screening parameters predict response to desmopressin? Enuretic predictors: nocturnal diuresis (p<0.0001)

Enuresis is not a benign condition Results of the sleep study

Before and after desmopressin melt Results: Enuretic parameters Response desmopressin melt (ICCS)

Before and after desmopressin melt Results: enuresis / sleep Time alarm Response volgens ICCS criteria: 25/30 minstens 50% reductie in aantal natte nachten = desmopressin 17

Before and after desmopressin melt Results: Sleep PLMS index PLMS-index ↓ (p<.001)

Before and after desmopressin melt Results: Sleep Cortical arousals Arousal-index ↓ (p<.01) Arousal Awakening-index ↓ (p<.05)

Before and after desmopressin melt Results: Psychology QoL ADHD-symptoms (attention - hyperactivity/impulsivity) Internalizing problems Externalizing problems Executive functions Self-esteem Memory

Before and after desmopressin melt Results: Psychology QoL ↑ PinQ Child ↓ (p<.01) PedsQL Parents ↑ (p<.01)

Enuresis is not a benign condition Results of the sleep study Comorbidity with Disrupted sleep Restless legs symptoms Attention deficit Poor QOL Burden toi the patie,nts Ameliorating during desmopressin trherapy

WAIT and SEE attitude Is not defendable