精 神 科實 證 期 刊 閱 讀 報 告EBM-style Journal Reading

報告人： 林政曄 Email:146102@cch.org.tw

指導臨床教師：鄭怡君醫師日期： 2012/07/19

地點：精神科討論室

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Clinical Scenario （臨床情境） A 29 years old female admitted due to depressed mood, out

side 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

1 0 0 , 3 3 7 – 3 4 5

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: 12-week, randomized, placebo-controlled, double-blind, 30 study

centres women aged ≥ 18 years predominant symptoms of OAB for ≥ 3 consecutive months

Exclusion criteria: 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 duloxetinegroup 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)

number of UI episodes/24 h (UIE)

the mean volume per void (functional bladder capacity),

number of continence pads used/24 h

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

InterventionDuloxetine 80mg for 4 weeks and 120mg for another 8 weeks

Comparison Placebo

OutcomeDecrease 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

decreases in VE24

increases in mean daytime VI,

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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