Transcript The Study: （研究效度）

精神科
實證期刊閱讀報告
EBM-style Journal Reading
報告人： 林政曄
Email:[email protected]
指導臨床教師：鄭怡君醫師
日期：2012/07/19
地點：精神科討論室
Clinical Scenario （臨床情境）
 A 29 years old female admitted due to depressed mood,
outside wandering since 1 week before admission.
 She presented with depressed mood, reference delusion,
delusional atmosphere, illogical thinking and multiple somatic
complain.
 Obvious urinary tract symptoms such as urgency and
frequency.
 Family history: Sister schizophrenia
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Clinical Uncertainty → PICO 問題
 If antidepressant agent decreases urinary
symptoms like frequency and urgency in
depressive patient ?
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臨床個案的PICO
Patient / Problem
Depressive patient with
urgency and frequency
Intervention
Antidepressant
Comparison
Placebo
Outcome
Improvement of frequency
Type of Question＆: Therapy
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Search Terms & Strategy:
（搜尋關鍵字與策略）
 資料庫：PubMed
 搜尋日期： 2012/07/10
 搜尋關鍵字與策略：
 Search #1 Overactive bladder
 Search #2 Serotonin
 #1 and #2  34
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Best available evidence:
（挑選可獲得之最佳研究證據）
 Citation/s:
 Duloxetine compared with placebo for
treating women with symptoms of
overactive bladder
 2 0 07 B J U I N T E R N A T I O N A L
100,337–345
 Lead author's name :
 William D. Steers, Sender Herschorn*, Karl J. Kreder, Kate Moore, Kris
Strohbehn,Ilker Yalcin§ and Richard C. Bump§for the Duloxetine OAB
Study Group
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The Study: （研究效度）- 1
 Inclusion criteria:
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12-week, randomized, placebo-controlled, double-blind, 30 study
centres
 women aged ≥ 18 years
 predominant symptoms of OAB for ≥ 3 consecutive months
 Exclusion criteria:
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a postvoid residual urine volume (PVR) of >100 ml
a mean 24-h total voided volume of ≥3 L
documented on a 2-day frequency-volume chart (FVC)
a positive urine culture (>100 000 colony-forming units/mL) or four or more UTIs during the year
regular use of medications for OAB symptoms within a month
any previous use of duloxetine
continence surgery within 6 months or any major surgery within 3 months of enrolment
pelvic organ prolapse greater than ICS Stage II
Any nonpharmacological intervention (e.g. electrical stimulation, bladder training,
continence devices) within 3 months of enrolment
pelvic floor muscle training that had not been stable for 3 months or would not remain stable during the
trial
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The Study: （研究效度）- 2
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The Study: （研究效度）- 3
A significantly higher proportion of patients in the placebo than in the duloxetine
group completed the study (78% vs 59%, P< 0.001), the result of a significantly higher
discontinuation rate because of AEs in the duloxetine than in the placebo group.
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The Study: （研究效度）- 4
 Efficacy analyses considered one primary efficacy variable, the
change in the number of voiding episodes/24-h (VE24, reflecting
the overall effect of treatment on frequency)
 Secondary variables

Mean daytime (awake hours) VI (reflecting the frequency symptom with the
greatest effect while awake)
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number of UI episodes/24 h (UIE)
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the mean volume per void (functional bladder capacity),
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number of continence pads used/24 h
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number of nocturic (sleep hours) episodes/24h (reflecting the frequency
symptom with the greatest effect while asleep).
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The Study: （研究效度）- 12本篇
文獻的PICO (T)
Patient /
Problem
Patients with overactive bladder and
urodynamic detrusor overactivity
Intervention
Duloxetine 80mg for 4 weeks and 120mg
for another 8 weeks
Comparison Placebo
Outcome
Decrease in voiding episode, and increase
in daytime voiding interval
Time
12 weeks
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The Evidence: （研究重要結果）-1
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The Evidence: （研究重要結果）-2
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The Evidence: （研究重要結果）-3
 There were significant treatment differences favouring duloxetine
over placebo
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decreases in VE24
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increases in mean daytime VI,
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decreases in UIE overall
 Of patients whose mean VI were < 2 h on the FVC completed
before randomization, 48.2% of duloxetine-treated and 21.3% of
placebo-treated patients had VIs of ≥ 2 h during treatment
(P<0.001).
 Level of Evidence: 2b
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Comment & Discussion: -1
 The positive efficacy results in the present study differ
from the negative results in three earlier phase 2
duloxetine clinical trials, completed between 1995 and
1997.
 The lack of response to duloxetine in these trials was
probably the result of the low doses used.
 The short duration of active treatment and relatively
few patients might also contribute to the differences.
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Comment & Discussion: -2
 This implied that any benefit of duloxetine might
require higher drug exposures.
 Thus, in the present proof-of-concept study we
increased the dose of duloxetine from 40-mg twice
daily (the optimally effective dose for SUI) to 60-mg
twice daily after 4 weeks, to be certain that, had
efficacy not been apparent at 4 weeks, it was not
because of an inadequate dose.
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Comment & Discussion: -3
 Figure 3A,B suggests some progressive improvement
in VE24 and daytime VI between visit 4 (when
patients were taking duloxetine 80 mg/day) and visits
5 and 6 (when patients were taking duloxetine 120
mg/day).
 This could be a result of progressive improvement
over time or could reflect enhanced efficacy at the
higher dose of duloxetine.
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回到臨床個案情境
Clinical bottom line 臨床決策底線
 In patient with depression and overactive
bladder, Duloxetine decrease in voiding
episode, and increase in daytime voiding
interval
 證據等級 2b 建議等級:B
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References:
1.
Cardozo L, Drutz HP, Baygani SK, Bump RC, for the Duloxetine Severe
UI Study Group. Pharmacological treatment of women awaiting surgery
for stress urinary incontinence. Obstet Gynecol 2004; 104: 511–9
2.
Hurley DJ, Turner CL, Yalcin I, Viktrup L, Saygani SK. Duloxetine for the
treatment of stress urinary incontinence: an integrated analysis of safety.
Eur J Obstet Gynecol Reprod Biol 2006; 125: 120–8
3.
Lubeck DP, Prebil LA, Peeples P, Brown JS. A health related quality of
life measure for use in patients with urge urinary incontinence: a
validation study. Qual Life Res 1999; 8: 337–44
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結 論 （標題 Title）
Duloxetine was better than placebo for
treating women with ‘wet’ and ‘dry’
symptoms of overactive bladder
associated with detrusor overactivity.
Kill or Update By（下次更新日期）:
Jan. 19, 2013
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