the largest systematic review to date of the use of botulinum toxin for the management of both neurogenic and idiopathic detrusor overactivity ( ndo and ido ) revealed that 300iu onabotulinumtoxina was the most commonly reported dose in the former and 200u in the latter . with the initial off  licence use of this therapy , well designed dosing studies were lacking and therefore , a dose of 300iu was commonly utilised in patients with proven detrusor overactivity . subsequently , data emerged which showed the efficacy of lower doses of onabotulinumtoxina for both ndo and ido [ 2 , 3 ] . we had been treating all patients with either ndo or ido with 300iu in our institution . in light of the new evidence , a decision was made in july 2008 to switch all new patients to an initial dose of 200iu . we found no evidence in the literature describing the feasibility of down  titrating patients who had already received 300iu down to 200iu onabotulinumtoxina . therefore our aim was to assess treatment efficacy and longevity after switching from 300iu to 200iu in patients with either ndo or ido . all patients admitted prior to june 2008 with detrusor overactivity ( do ) received 300iu onabotulinumtoxina at our institute . all 79 patients were started on 300iu onabotulinumtoxina and had proven detrusor overactivity prior to injection . after july 2008 , due to the emergence of new evidence , we down  titrated the administered dose to 200iu onabotulinumtoxina in all patients with do . a retrospective notes review was performed for all patients ( group b ) that had received 200iu after 300iu up to april 2011 , to assess the efficacy and tolerability of dose reduction . onabotulinumtoxina 100iu ( allergan , irvine ca ) was dissolved in 5 ml of normal saline , making a concentration of 20iu / ml . all patients were injected using a flexible cystoscope and an olympus needle using intraurethral 2% lidocaine hydrochloride gel anesthesia only . injection volume was 0.5 ml resulting in 30 injections with 300iu and 20 injections with 200iu . we injected with evenly distributed intramural injections in the base and the posterolateral walls of the urinary bladder and spared the dome and trigone . all patients received a prophylactic course of antibiotic ; ciprofloxacin 500 mg twice a day for three days is the preferred choice of antibiotic unless contraindicated . all patients were educated on the use of clean intermittent self  catheterization ( cisc ) prior to receiving the injections . all patients were taught to record symptoms such as frequency of voids , urgency episodes , and incontinence episodes in a voiding diary . urinary tract infections , which settled with antibiotic therapy  microbiological evidence of bacteriuria were defined as appropriate urinary symptoms . patients were instructed to telephone the continence specialist nurse when symptoms ( frequency , urgency , and incontinence ) returned and further injections were required . in order to assess overall perception of treatment satisfaction , at a three year follow up visit patients were also asked the following question : compared to previous injections , how much has this new dose changed your symptoms ? possible replies included : better than before , same as before , or worse than before . from 79 patients in group a , who started with 300iu onabotulinumtoxina injections , 44 patients went on to receive 200iu onabotulinumtoxina ( 36 female and 8 male ) . of these , 16 patients had a diagnosis of ndo ( figure 1 shows the underlying neurological diagnoses ) and 28 patients of ido . table 1 lists the reasons why 35 patients in group a did not receive any further injections . underlying diagnoses in patients with ndo . the underlying reasons for which patients from group  a did not proceed to receive further onabotulinumtoxina therapy after switching ndo patients to 200iu , 15 ( 94% ) patients continued to report symptomatic improvement . four patients ( all with ndo ) reverted back to receiving onabotulinumtoxina 300iu with good effect and two patients had another 200iu of onabotulinumtoxina after five months and reported good efficacy . only one patient noticed shorter longevity of treatment with onabotulinumtoxina 200iu ( 3 months ) compared to 300iu ( 5 months ) . reduction rates of daytime frequency and nocturia in patients receiving 200iu onabotulinumtoxina were 87.5% and 81.3% respectively vs. 75% and 75% in the same group of patients when they were receiving 300iu onabotulinumtoxina . significant or complete improvement in urgency was reported by 81% and 75% of patients receiving 300iu and 200iu respectively ( figure 2 ) . subjective improvement in the urgency symptom in ndo patients while they were receiving 300iu and 200iu respectively . at three year follow  up , 82% of ndo patients who had switched to the lower dose were happy with their symptomatic improvement and were keen to continue receiving 200iu onabotulinumtoxina . after switching ido patients to 200iu , 22 ( 79% ) patients continued to report symptomatic improvement ; five ( 18% ) patients reported mild deterioration of their symptoms when they received 200iu onabotulinumtoxina , compared to their symptoms while they were receiving 300iu , and one patient did not attend follow  up . the median longevity of efficacy was 67 months with both doses and only two patients noticed a shorter longevity of efficacy with 200iu ( 2 and 6 months ) compared to 300iu ( 7 and 8 months ) . reduction rates of daytime frequency and nocturia in patients receiving 200iu onabotulinumtoxina were 50% and 64% respectively , compared to 60.7% and 71.4% respectively in the same group of patients when they had previously received 300iu onabotulinumtoxina . the majority of ido patients reported either a significant or complete improvement in their urgency symptoms while they were receiving onabotulinumtoxina 300iu ( 82.2% ) and 200iu ( 75% ) ( figure 3 ) . subjective improvement in the urgency symptom in ido patients while they were receiving 300iu and 200iu respectively . * 2 patients wished for no further treatments and 1 patient was unable to perform cisc . three ( 7% ) patients , all with ido , had to commence intermittent self follow  up , 75% of ido patients who had switched to the lower dose were happy with their symptomatic improvement and were keen to continue receiving 200iu onabotulinumtoxina . twelve out of 44 patients ( both groups a&b ) developed symptoms of uti , of which eight had positive urine culture . rate of uti 's and other complications ( including cough , suprapubic pain , and lethargy ) were comparable between both groups ( table 2 ) . 
  outcomes of injecting onabotulinumtoxina 300iu and 200iu in patients with ndo and ido patients experienced uti symptoms . abdominal pain ( 1 patient ) , cough ( 1patient ) and lethargy ( 1 patient ) after switching ndo patients to 200iu , 15 ( 94% ) patients continued to report symptomatic improvement . four patients ( all with ndo ) reverted back to receiving onabotulinumtoxina 300iu with good effect and two patients had another 200iu of onabotulinumtoxina after five months and reported good efficacy . only one patient noticed shorter longevity of treatment with onabotulinumtoxina 200iu ( 3 months ) compared to 300iu ( 5 months ) . reduction rates of daytime frequency and nocturia in patients receiving 200iu onabotulinumtoxina were 87.5% and 81.3% respectively vs. 75% and 75% in the same group of patients when they were receiving 300iu onabotulinumtoxina . significant or complete improvement in urgency was reported by 81% and 75% of patients receiving 300iu and 200iu respectively ( figure 2 ) . subjective improvement in the urgency symptom in ndo patients while they were receiving 300iu and 200iu respectively . at three year follow  up , 82% of ndo patients who had switched to the lower dose were happy with their symptomatic improvement and were keen to continue receiving 200iu onabotulinumtoxina . after switching ido patients to 200iu , 22 ( 79% ) patients continued to report symptomatic improvement ; five ( 18% ) patients reported mild deterioration of their symptoms when they received 200iu onabotulinumtoxina , compared to their symptoms while they were receiving 300iu , and one patient did not attend follow  up . the median longevity of efficacy was 67 months with both doses and only two patients noticed a shorter longevity of efficacy with 200iu ( 2 and 6 months ) compared to 300iu ( 7 and 8 months ) . reduction rates of daytime frequency and nocturia in patients receiving 200iu onabotulinumtoxina were 50% and 64% respectively , compared to 60.7% and 71.4% respectively in the same group of patients when they had previously received 300iu onabotulinumtoxina . the majority of ido patients reported either a significant or complete improvement in their urgency symptoms while they were receiving onabotulinumtoxina 300iu ( 82.2% ) and 200iu ( 75% ) ( figure 3 ) . subjective improvement in the urgency symptom in ido patients while they were receiving 300iu and 200iu respectively . * 2 patients wished for no further treatments and 1 patient was unable to perform cisc . three ( 7% ) patients , all with ido , had to commence intermittent self follow  up , 75% of ido patients who had switched to the lower dose were happy with their symptomatic improvement and were keen to continue receiving 200iu onabotulinumtoxina . twelve out of 44 patients ( both groups a&b ) developed symptoms of uti , of which eight had positive urine culture . rate of uti 's and other complications ( including cough , suprapubic pain , and lethargy ) were comparable between both groups ( table 2 ) . outcomes of injecting onabotulinumtoxina 300iu and 200iu in patients with ndo and ido patients experienced uti symptoms . abdominal pain ( 1 patient ) , cough ( 1patient ) and lethargy ( 1 patient ) to our knowledge , this cohort study is the first to evaluate the feasibility of switching patients with ndo from 300iu to 200iu onabotulinumtoxina in real life clinical practice and the first to assess the longevity of this treatment . a recent abstract presented at the 2012 eau congress reported similar efficacy and quality of life improvements in 46 neurogenic patients with do who switched from 300iu to 200iu . we found a similar subjective efficacy with onabotulinumtoxina 200iu among ndo patients when compared to 300iu , once an effective dose had been administered . confirmation of this finding is provided by a study reported in abstract form by ginsberg et al . , which has reported similar findings to ours in terms of longevity of treatment . they reported that the median time until repeated treatment was not different between 200iu and 300iu at 36.6 weeks and no significant differences were seen in the improvements over baseline in the bladder diary parameters . however , in that study both groups of patients were exclusive and the patients were not switched to the lower dose . cruz et al . have compared 200iu or 300iu onabotulinumtoxina against placebo . by two weeks , both doses had led to significant improvements in urgency incontinence episodes per week in patients with multiple sclerosis and spinal cord injury . although at two weeks the difference between urgency incontinence episodes was less than three per week ( 10% ) in favour of 300iu , this was not deemed significant , and by 12 weeks there was no difference between the doses . median time until repeated treatment for both doses was 42 weeks compared to 16 weeks for placebo . in patients catheterisation , increases in post void residue were reported in 12 , 30 and 42% of the placebo , 200iu and 300iu groups respectively . only one serious , treatment related , similarly , apostolidis et al . have assessed 50iu , 100iu and 200iu onabotulinumtoxina in ndo patients , randomised against placebo in 19 , 21 , 17 and 16 patients respectively . significant symptomatic improvements compared to placebo were only seen in the 200iu group , however due to the low power of the study , significant differences in the use of the lower doses were not seen over 54 weeks . a different formula of 1012iu / kg is utilised . with this , zeino et al . similarly to ndo , we did not find any clinical difference in the subjective efficacy among the ido patients when they received onabotulinumtoxina at a dose of both 300iu and 200iu . this was also noted in the dmochowski study , where they reported the proportion of patients requiring intermittent catheterisation were 21% and 16% in the 200iu and 300iu groups respectively . however , we feel that this is not a significant finding in an underpowered retrospective study ; since , in the dmochowski study , a lower dose of onabotulinumtoxina was similarly efficacious with a lower retention rate . our study is limited by the relatively small number of patients involved . the lack of randomisation of patients to different therapeutic dose groups and lack of variation in the baseline demography of patients are also limiting factors . , has also reported significant improvements in frequency , incontinence , and quality of life ( qol ) scores over placebo for 100iu , 150iu , 200iu and 300iu onabotulinumtoxina . response curve revealed that doses greater than 150iu did not impart further significant symptomatic improvements . fifty units were shown to lead to significant improvements in incontinence episodes but the proportion of patients who were completely dry was less than with higher doses . denys et al . have investigated even lower doses of onabotulinumtoxina ( 50iu , 100iu and 150iu ) versus placebo in ido patients with greater than three urgency or urgency incontinence episodes in a three day diary . reduction of urgency and/or urgency incontinence rates by 50% were 29% , 37% , 65% and 56% for the placebo , 50iu , 100iu and 150iu groups . only three patients with a post  void residual volume over 200ml were reported in the 150iu group . although the authors state that a greater number of incontinent patients became dry with 150iu , this was not deemed significant . the limitation of this sub limitations of our study include its retrospective nature and the fact that it relies on the accuracy of past documentation . in addition , there was a 1/3 reduction in the volume of injection and number of injection sites with 200iu . data from guinea  pig bladders has shown 2iu dissolved in 20 ml led to increased cleaving of snap25 compared to 2iu in 2 ml both given as single injections . although we did not find significant differences in outcomes , it must be recognised that the dose was not the only parameter altered in this study . furthermore , it has been suggested that injection of the trigone improves outcomes without adverse events [ 13 , 14 ] . we spared the trigone due to earlier concerns regarding the possible occurrence of ureteric reflux if the trigone was injected . one study has shown no differences between intradetrusor and suburothelial injections , however the number of patients for each was only 15 and therefore limited information can be gained from this . in real life to our knowledge , this cohort study is the first to evaluate the feasibility of switching patients with ndo from 300iu to 200iu onabotulinumtoxina in real life clinical practice and the first to assess the longevity of this treatment . a recent abstract presented at the 2012 eau congress reported similar efficacy and quality of life improvements in 46 neurogenic patients with do who switched from 300iu to 200iu . we found a similar subjective efficacy with onabotulinumtoxina 200iu among ndo patients when compared to 300iu , once an effective dose had been administered . confirmation of this finding is provided by a study reported in abstract form by ginsberg et al . , which has reported similar findings to ours in terms of longevity of treatment . they reported that the median time until repeated treatment was not different between 200iu and 300iu at 36.6 weeks and no significant differences were seen in the improvements over baseline in the bladder diary parameters . however , in that study both groups of patients were exclusive and the patients were not switched to the lower dose . cruz et al . have compared 200iu or 300iu onabotulinumtoxina against placebo . by two weeks , both doses had led to significant improvements in urgency incontinence episodes per week in patients with multiple sclerosis and spinal cord injury . although at two weeks the difference between urgency incontinence episodes was less than three per week ( 10% ) in favour of 300iu , this was not deemed significant , and by 12 weeks there was no difference between the doses . median time until repeated treatment for both doses was 42 weeks compared to 16 weeks for placebo . in patients catheterisation , increases in post void residue were reported in 12 , 30 and 42% of the placebo , 200iu and 300iu groups respectively . only one serious , treatment related , similarly , apostolidis et al . have assessed 50iu , 100iu and 200iu onabotulinumtoxina in ndo patients , randomised against placebo in 19 , 21 , 17 and 16 patients respectively . significant symptomatic improvements compared to placebo were only seen in the 200iu group , however due to the low power of the study , significant differences in the use of the lower doses were not seen over 54 weeks . a different formula of 1012iu / kg is utilised . with this , zeino et al . similarly to ndo , we did not find any clinical difference in the subjective efficacy among the ido patients when they received onabotulinumtoxina at a dose of both 300iu and 200iu . this was also noted in the dmochowski study , where they reported the proportion of patients requiring intermittent catheterisation were 21% and 16% in the 200iu and 300iu groups respectively . however , we feel that this is not a significant finding in an underpowered retrospective study ; since , in the dmochowski study , a lower dose of onabotulinumtoxina was similarly efficacious with a lower retention rate . our study is limited by the relatively small number of patients involved . the lack of randomisation of patients to different therapeutic dose groups and lack of variation in the baseline demography of patients are also limiting factors . the dose ranging study , by dmochowski et al . , has also reported significant improvements in frequency , incontinence , and quality of life ( qol ) scores over placebo for 100iu , 150iu , 200iu and 300iu onabotulinumtoxina . response curve revealed that doses greater than 150iu did not impart further significant symptomatic improvements . fifty units were shown to lead to significant improvements in incontinence episodes but the proportion of patients who were completely dry was less than with higher doses . denys et al . have investigated even lower doses of onabotulinumtoxina ( 50iu , 100iu and 150iu ) versus placebo in ido patients with greater than three urgency or urgency incontinence episodes in a three day diary . reduction of urgency and/or urgency incontinence rates by 50% were 29% , 37% , 65% and 56% for the placebo , 50iu , 100iu and 150iu groups . only three patients with a post  void residual volume over 200ml were reported in the 150iu group . although the authors state that a greater number of incontinent patients became dry with 150iu , this was not deemed significant . the limitation of this sub limitations of our study include its retrospective nature and the fact that it relies on the accuracy of past documentation . in addition , there was a 1/3 reduction in the volume of injection and number of injection sites with 200iu . data from guinea  pig bladders has shown 2iu dissolved in 20 ml led to increased cleaving of snap25 compared to 2iu in 2 ml both given as single injections . although we did not find significant differences in outcomes , it must be recognised that the dose was not the only parameter altered in this study . furthermore , it has been suggested that injection of the trigone improves outcomes without adverse events [ 13 , 14 ] . we spared the trigone due to earlier concerns regarding the possible occurrence of ureteric reflux if the trigone was injected . one study has shown no differences between intradetrusor and suburothelial injections , however the number of patients for each was only 15 and therefore limited information can be gained from this . in real life this study shows that down  titrating ndo and ido patients treated with 300iu to 200iu onabotulinumtoxina leads , in 90% of cases , to similar efficacy with no apparent reduction in longevity of treatment . patients with ndo may need up titrating back to 300iu . larger , multi  centre studies investigating effects of lower doses would support these observations . although it has some weaknesses , to our knowledge this is the first study which explores the feasibility of dose down  titration in real life clinical practice
introductionto assess the feasibility of converting from 300iu to 200iu onabotulinumtoxina in patients diagnosed with either idiopathic detrusor overactivity ( ido ) or neurogenic detrusor overactivity ( ndo).material and methodsretrospective case  notes review of patients who were converted from 300iu to 200iu onabotulinumtoxina . 
 subjective patient reported improvements at interview and bladder diary reported parameters of urgency , urgency incontinence , frequency and nocturia.resultsfortyfour patients had received 300iu onabotulinumtoxina and were switched to 200iu after july 2008 , 28 for ido and 16 for ndo . 
 thirty  seven patients reported ongoing improvement with 200iu onabotulinumtoxina , six patients had worsening in their symptoms since down  titrating to 200iu and one patient did not attend follow  up . 
 improvement in urgency and urgency incontinence episodes per day were 82% and 72% , respectively , in patients who received 200iu . 
 of the 44 patients , 39 continued to receive 200iu , four requested up 
 titration to 300iu ( due to decreased effect ) and one did not attend after the 1st treatment . after converting from 300iu to 200iu , additional three patients were started on cisc for de novo voiding difficulty.conclusionsseventynine percent of patients were satisfied with their symptoms after switching from 300iu to 200iu onabotulinumtoxina . 
 only 9% of patients ( all with ndo ) reverted back to receiving 300iu . 
 this study showed similar efficacy and longevity in the majority of patients ( 90% ) using 200iu in both ndo and ido .