nocturia is defined as waking at night to void urine , and nocturia has been reported in 58 - 90% of people over 50 years of age , with the prevalence of nocturia increasing with age .
this condition can significantly impair a patient 's perception of their well being and often warrants treatment , especially when the patient must wake twice or more per night [ 15 ] .
nocturia is associated with impaired health , deterioration in sleep , and quality of life .
it has also been associated with an increased risk of death after adjusting for age , cardiac disease , diabetes mellitus and stroke .
the increased mortality may to some extent be explained by an increased risk of falls , which is one consequence of nocturia [ 7 , 8 ] .
a quarter of the falls occur at night , and more than a quarter of these nocturnal falls occur during trips to the toilet .
nocturia is often attributed to benign prostatic hyperplasia ( bph ) in men , but a causal relation is uncertain , although the two conditions may be associated in older individuals .
nocturia is often found to respond less satisfactorily than other lower urinary tract symptoms ( luts ) after medical or surgical treatment of bph .
sleep disturbance is a common experience of older adults , many of whom depend on prescribed sedatives .
although one report outlines the improvement of nocturia through the use of a hypnotic agent , there are no reports , to our knowledge , that address the actual effect of hypnotic agents on patients with nocturia after a diagnosis of insomnia .
the aim of the present study was to determine whether zolpidem , a nonbenzodiazepine hypnotic agent , would be useful for patients dissatisfied with nocturia and suspected to have sleep disturbance after monotherapy with tamsulosin .
a total of 35 male outpatients ( age 50 years ) with a complaint of nocturia with luts suggestive of bph were enrolled in the present study from september 2005 to august 2006 .
the enrolled patients experienced 2 or more episodes of nocturia per night and had a nocturia - quality of life ( qol ) score of 4 or more .
nocturia  qol score ( table 1 ) was used as a simple tool to measure the satisfaction of patients with symptoms of nocturia .
uroflowmetry studies were performed on each patient according to the criteria of the international continence society .
abdominal ultrasonography was performed on each patient to determine prostate volume and post - voided residual and to rule out any urinary system abnormality .
patients with prostate cancer , abnormal prostate findings on digital rectal examination ( nodularity or induration ) , or psa values of 4 ng / ml were excluded from the study .
the exclusion criteria also included the use of medications for the control of bladder symptoms and use of hypnotics . 
 
quality of life the patients were assessed using the score for the seventh question of the international prostate symptom score ( ipss ) , the athens insomnia scale ( ais ) and the nocturia - qol score .
the ais , an instrument that measures the intensity of sleep - related problems , was used as a screening tool for the diagnosis of insomnia .
enrollment and follow - up of patients in the present study are shown in figure 1 .
after assessment at baseline , the 35 patients were administered tamsulosin ( 0.2 mg / day ) for 4 weeks before re - assessment .
a nocturia - qol score of 3 was regarded as indicating patient satisfaction with nocturia ( defined as group a ) , and a nocturia - qol score of 4 was regarded as indicating patient dissatisfaction with nocturia .
patients dissatisfied with nocturia and with sleep disturbances ( ais 6 ) received additional treatment with zolpidem 5 - 10 mg once per night for 2 weeks ( defined as group b ) .
all values are expressed as the mean ( sd ) , with statistical significance inferred at a value of p < 0.05 unless otherwise specified .
demographic and other baseline characteristics of all patients ( n = 35 ) and group a ( n = 15 ) and group b ( n = 16 ) patients are presented in table 2 .
mean prostate volume was 19.59.8 ml , and mean max flow rate and post - voided residual were 11.3 3.6 ml / s and 47.2 29.8 ml , respectively .
differences in mean values of age , prostate volume , max flow rate and post - voided residual were not significant between group a and group b. 
  demographics and other baseline characteristics ns - not significant ( mann - whitney u test ) the score at baseline and post - treatment for the ipss , qol index , nocturia episodes , nocturia - qol and ais are shown in table 3 . in all patients ,
monotherapy with tamsulosin for 4 weeks significantly improved ipss ( 18.9 3.8 to 9.9 3.0 , p < 0.001 ) , qol ( 4.5 0.9 to 3.2 0.9 , p < 0.001 ) , nocturia episodes ( 3.4 0.7 to 2.6 1.0 , p < 0.001 ) , nocturia - qol ( 5.5 0.6 to 4.3 1.5 , p < 0.001 ) and ais ( 11.7 3.6 to 9.1 3.1 , p 0.001 ) . 
 
effects of tamsulosin / zolpidem on nocturia in patients with benign prostatic hyperplasia ipss - international prostate symptom score , qol - quality of life , ais - athens insomnia scale , all and group a - monotherapy with tamsulosin for 4 weeks , group b - combination therapy with tamsulosin and zolpidem for 2 weeks , after treatment - after treatment with tamsulosin , after additional treatment - after treatment with tamsulosin and zolpidem .
p < 0.001 , ns : p 0.05 ( wilcoxon signed - rank test ) among all patients , a reduction in the nocturia - qol score ( 3 ) was observed in 15 patients ( group a ) , but 20 patients were not satisfied with symptoms of nocturia ( nocturia - qol 4 ) . in group
a , monotherapy with tamsulosin significantly reduced the ipss ( 18.3 3.7 to 8.7 3.2 , p < 0.001 ) , qol ( 4.4 0.6 to 2.5 0.6 , p < 0.001 ) , nocturia episodes ( 3.3 0.6 to 1.7 0.5 , p < 0.001 ) and ais ( 11.2 3.6 to 7.9 3.1 , p < 0.001 ) . among the 20 patients
not satisfied with symptoms of nocturia ( nocturia - qol 4 ) , 16 patients ( group b ) were suspected of having sleep disturbances ( ais 6 ) . in group b ,
treatment with tamsulosin only did not result in a significant reduction in nocturia episodes ( 3.4 0.9 to 3.3 0.8 ) and nocturia - qol score ( 5.7 0.5 to 5.6 0.5 ) , although significant reductions in ipss ( 18.9 4.1 to 10.4 2.6 , p < 0.001 ) , qol ( 4.6 1.0 to 3.8 0.6 , p < 0.001 ) and ais ( 12.9 3.3 to 10.6 2.9 , p <
after additional treatment with tamsulosin and zolpidem for 2 weeks , significant decreases in nocturia episodes ( 3.3 0.8 to 1.9 0.7 , p < 0.001 ) , nocturia - qol ( 5.6 0.5 to 3.6 1.1 , p < 0.001 ) and ais ( 10.6 2.9 to 6.8 2.5 , p <
bph can cause bladder outlet obstruction and induce secondary bladder overactivity and reduction of functional bladder capacity , which may result in filling symptoms including nocturia .
therefore , urologists often treat patients whose chief symptom is nocturia with modalities for bph , including conservative medical treatment and surgical intervention . in regard to degrees of improvement , nocturia is the lowest among the seven individual symptoms included in the ipss . unlike the other six symptoms
, nocturia is markedly influenced by various factors other than bph , and other approaches might be required for the treatment of nocturia [ 10 , 12 ] .
nocturia is associated with various factors of pathologic conditions such as cardiovascular disease and diabetes mellitus , anxiety and primary sleep disorders , and behavioral and environmental factors .
the underlying pathophysiologic process of nocturia consists of three main conditions : polyuria , nocturnal polyuria , and bladder storage problems .
however , nocturia can be secondary to awakening and sleep disturbances rather than to nocturnal polyuria in patients with sleep disturbances from other causes .
the present study showed that monotherapy with tamsulosin significantly improved the ipss and qol scores , and a reduction in the nocturia - qol score ( 3 ) was observed in 15 ( 43% ) group a patients .
interestingly , a significant improvement in ais was also seen in group a. djavan et alreported that tamsulosin improves nocturia and sleep disturbances ( by increasing the number of hours of undisturbed sleep ) in luts / bph .
thus , the results of the present study suggest that the improvement of nocturia by monotherapy with tamsulosin may improve sleep disturbances .
the ais was developed as a brief and easily administered selfassessment questionnaire for estimating the severity of insomnia encountered in a large variety of clinical and research settings .
the ais can be used in clinical practice and research , not only to reliably measure the intensity of sleep difficulty , but also to assist in establishing the diagnosis of insomnia . when diagnosing individuals with a score of 6 or higher as insomniacs , the scale has a sensitivity of 93% and specificity of 85% .
subjectively , sleep disturbances were observed in 80% ( 16/20 ) of patients who did not show a decrease in nocturia - qol score of 3 ) by monotherapy with tamsulosin . in these patients ( group b ) , additional 2-week combination therapy with tamsulosin and zolpidem significantly reduced nocturia episodes , ais and nocturia - qol score , indicating that improvement of sleep disturbances may contribute to improve symptoms of nocturia .
in addition , these results suggest that improvement in the number of nocturia episodes may be closely related to improvement in the nocturia - qol score .
recently , song and ku showed that zolpidem improved the frequency of nocturia unresponsive to treatment by an alpha - blocker ( terazosin or tamsulosin ) in men with luts . in the present study
, patients were selected in whom sleep disturbance appeared to be a cause of nocturia after evaluation using the nocturia - qol score and the ais .
the nocturia - qol score is a simple and useful tool for evaluating disease - specific qol related to nocturia .
a problem identified in the present study was that objective efficacy , determined by assessing nocturia episodes from the frequency - volume chart , was not evaluated .
there may be poor agreement between the subjectively estimated nocturnal frequency from the ipss and chart - determined nocturnal frequency .
however , the change in qol related to nocturnal frequency could be evaluated with the nocturia - qol score .
yoshimura et al . reported that sleep and general - related qol in the mildly nocturic patient were more greatly affected by trouble sleeping due to night - time frequency than by the frequency of nocturnal urinary voiding per se 
 .
they suggest that the strategy for treatment of nocturia may be improved if urologists clearly distinguish whether nocturic patients are bothered by trouble sleeping .
therefore , we believe that it is beneficial to use the nocturia - qol score and ais to identify the cause of deterioration in qol by nocturia - related sleep disturbance and to treat with hypnotic agents . the present study is limited in that we could not directly compare the effect of combination therapy ( tamsulosin with zolpidem ) with monotherapy ( tamsulosin alone ) in group b after monotherapy with tamsulosin for 4 weeks . however , after additional treatment with tamsulosin and zolpidem for 2 weeks , significant decreases in episodes of nocturia and nocturia - qol and ais scores were observed , whereas ipss and qol scores did not decrease significantly . therefore , the effect is not due to the longer exposure to tamsulosin but rather to the addition of zolpidem . in this study , patients were given 0.2 mg tamsulosin once daily .
a 0.4-mg dose of tamsulosin is routinely used in north america and europe to treat bph . however , previous studies show that lower doses of tamsulosin than those used in western countries are equally effective for treating symptomatic bph in asian patients .
hypnotics such as zolpidem may be useful as additional treatment in patients unresponsive to treatment by an alpha 1-blocker such as tamsulosin in patients in whom the etiology of nocturia is associated with sleep disturbances .
the zolpidem used in the present study has a low propensity to cause clinical next - day residual effects , withdrawal , dependence or tolerance . in animal studies , zolpidem has weaker myorelaxant and anticonvulsant effects than the benzodiazepines because of the selectivity of zolpidem for benzodiazepine 1 receptors .
reported that zolpidem increased bladder capacity via a gaba - ergic mechanism in cerebral infarction rats and suppressed urine excretion via a pathway that was not through activation of vasopressin v2 receptors in water - loaded and brattleboro rats .
therefore , zolpidem may improve nocturia via an increase in bladder capacity and a decrease in urine excretion . in the present study , no remarkable side effects or voiding disturbances
therefore , we believe that zolpidem is considered safe for bph patients and is suitable for use as a hypnotic agent in patients complaining of nocturia .
the ais is useful for evaluating patients with sleep disturbance that appears to be a cause of nocturia .
the effectiveness of tamsulosin on nocturia in patients with bph is limited when the etiology of nocturia is associated with sleep disturbances . in such patients , hypnotic agents such as zolpidem
 introductionwe examined the efficacy of combination therapy with 1-blocker tamsulosin and hypnotic zolpidem in patients who had suffered from sleep disturbance associated with nocturia.material and methodsa total of 35 patients diagnosed with nocturia with lower urinary tract symptoms ( luts ) suggestive of benign prostatic hyperplasia ( bph ) were studied . 
 after treatment with tamsulosin for 4 weeks , 16 patients dissatisfied with nocturia ( nocturiaquality of life index 4 ) and suspected to have sleep disturbance ( athens insomnia scale 6 ) received additional treatment with tamsulosin and zolpidem for 2 weeks . 
 outcomes were evaluated by the international prostate symptom score ( ipss ) and quality of life index ( qol ) , athens insomnia scale ( ais ) and nocturia - quality of life index ( nocturia - qol).resultsafter monotherapy with tamsulosin , significant reductions in ipss ( 18.9 3.8 to 9.9 3.0 , p < 0.001 ) , qol ( 4.5 0.9 to 3.2 0.9 , p < 0.001 ) and nocturia episodes ( 3.4 0.7 to 2.6 1.0 , p < 
 0.001 ) were observed . 
 however 20 patients were dissatisfied with nocturia ( nocturia- qol 4 ) . among 20 patients , 16 patients were suspected to have sleep disturbances ( ais 6 ) . in these patients , additional therapy with tamsulosin and zolpidem significantly reduced nocturia episodes ( 3.3 0.8 to 1.9 0.7 , p < 0.001 ) , ais ( 10.6 2.9 to 6.8 25 , p < 0.001 ) and nocturia  qol ( 5.6 0.5 to 3.6 1.1 , p 
 < 0.001 ) compared with patients after treatment with tamsulosin only.conclusionscombination therapy with tamsulosin and zolpidem may be useful for patients with bph dissatisfied with nocturia and suspected to have sleep disturbance . 
INTRODUCTION
METHODS
RESULTS
DISCUSSION
CONCLUSION