Insomnia Disorder Increases the Risk of Mortality: Pooled Analysis of Annual Cumulative Time-to-Event Data.

The association of mortality risk and insomnia disorder with daytime impairments has been plausible. The purpose of this study was to evaluate the strength of evidence for this relationship. We performed a comprehensive literature search for clinical Cohort trials including annual cumulative time-to-event data that evaluated the risk of mortality in insomnia disorder patients with daytime impairments. We used pooled hazard ratio (HR) as the main outcome measure and Kaplan-Meier survive curve to display outcome measures. The weighted cumulative mortality of 4.5% for patients with insomnia disorder was higher than that of 2.6% for those without insomnia (p<0.001). Higher risk of mortality presented in patients with insomnia disorder when compared to those without insomnia (HR = 1.66, 95% CI = 1.25-2.19, p<0.001). Patients with duration of more than 10 years were at a greater risk of annual cumulative mortality (R2 = 0.891, p<0.001). Insomnia disorder with daytime impairments increased the risk of mortality, and patients with duration of more than 10 years were at a greater risk of annual cumulative mortality.

Short- and long-term mortality following hypnotic use.

Potential long-term consequences of hypnotics remain controversial. We used the prospective Swedish National March Cohort, a study based on 41,695 participants with a mean follow-up duration of 18.9 years. Logistic regression models and Cox proportional hazards models with attained age as timescale were used to assess associations of hypnotic use with short- and long-term mortality. The proportion of subjects who initiated or discontinued hypnotic use during follow-up was substantial. All groups of hypnotics were associated with increased mortality within 2 years after a first prescription, with an overall OR of 2.38 (95% CI, 2.13-2.66). The association was more pronounced among subjects younger than 60 years (OR, 6.16; 95% CI, 3.98-9.52). There was no association between hypnotic use and long-term mortality. The association between hypnotic use and increased mortality was thus restricted to a relatively short period after treatment initiation, and may be explained in terms of confounding by indication.

Associations of Benzodiazepine With Adverse Prognosis in Heart Failure Patients With Insomnia.

Background The prognostic impact of benzodiazepines has been unclear in patients with heart failure (HF). Methods and Results This was a historical observational cohort study. A total of 826 patients who had been hospitalized for HF and were being treated for insomnia with either benzodiazepines or Z-drugs (zolpidem, zopiclone, or eszopiclone), were enrolled and divided on the basis of their hypnotics: benzodiazepine group (n=488 [59.1%]) and Z group (n=338 [40.9%]). We compared the patient characteristics and postdischarge prognosis between the groups. The primary end points were rehospitalization for HF and cardiac death. The benzodiazepine group was older (age, 72.0 versus 69.0 years; P=0.010), had a higher prevalence of depression (17.4% versus 8.9%; P<0.001), and showed a higher use of loop diuretics (77.9% versus 67.8%; P=0.001). In the laboratory data, the benzodiazepine group demonstrated lower levels of hemoglobin (12.3 versus 13.0 g/dL; P=0.001), sodium (139.0 versus 140.0 mEq/L; P=0.018), and albumin (3.7 versus 3.9 g/dL; P=0.003). Kaplan-Meier analysis showed that both end points were higher in the benzodiazepine group (rehospitalization for HF, log-rank P=0.001; cardiac death, log-rank P=0.043). Multiple Cox proportional hazard analysis revealed that the use of benzodiazepines was an independent predictor of rehospitalization for HF (hazard ratio, 1.530; 95% CI, 1.025-2.284; P=0.038). Furthermore, rehospitalization for HF was higher in the benzodiazepine group after propensity score matching (log-rank P=0.036). Conclusions Benzodiazepine is associated with higher risk of rehospitalization for HF compared with Z-drugs in patients with HF.

Insomnia and risk of mortality from all-cause, cardiovascular disease, and cancer: Systematic review and meta-analysis of prospective cohort studies.

Growing evidence indicates that insomnia may be associated with mortality. However, these findings have been inconsistent. We systematically searched MEDLINE and EMBASE to identify prospective cohort studies that assessed the association between insomnia disorder/individual insomnia symptoms and the risk of mortality among adults aged ≥18 yrs. We addressed this association using summary hazard ratios (HRs) and 95% confidence intervals (CIs) calculated using random-effects meta-analysis, and the GRADE approach to rate the certainty of evidence. Twenty-nine cohorts including 1,598,628 individuals (55.3% men; mean age 63.7 yrs old) with a median follow-up duration of 10.5 yrs proved eligible. Difficulty falling asleep (DFA) and non-restorative sleep (NRS) were associated with an increased risk of all-cause mortality (DFA: HR = 1.13, 95%CI 1.03 to 1.23, p = 0.009, moderate certainty; NRS: HR = 1.23, 95%CI 1.07 to 1.42, p = 0.003, high certainty) and cardiovascular disease mortality (DFA: 1.20, 95%CI: 1.01, 1.43; p = 0.04, moderate certainty; NRS: HR = 1.48, 95%CI 1.06 to 2.06, p = 0.02, moderate certainty). Convincing associations between DFA and all-cause mortality were restricted to the mid to older-aged population (moderate credibility). Insomnia disorder, difficulty maintaining sleep, and early morning awakening proved to be unassociated with all-cause and cardiovascular disease mortality. No insomnia symptoms proved to be associated with cancer-related mortality.

The relationship between sleep quality and all-cause, CVD and cancer mortality: the Southall and Brent REvisited study (SABRE).

BACKGROUND: Both long and short sleep duration increase risk of mortality. Most previous studies have been performed in Europeans and have focused on sleep duration. Thus, we aimed to investigate the association between sleep quality and mortality across three different ethnic groups. METHODS: We used data from the Southall and Brent REvisited Study (SABRE) cohort, which comprises first generation migrant South Asian and African Caribbean men and women, aged 40-69 years, recruited between 1988 and 1991. In sum, 4399 participants provided complete data at baseline and follow-up. Of those, 1656 died by December 2017. Our exposures (eg, difficulty falling asleep, early morning waking and waking up tired in the morning) were self-reported and our primary outcome was mortality. We used Cox proportional hazards models to analyse our data, adjusting for baseline-measured confounders. RESULTS: None of the sleep measures were strongly associated with all-cause mortality in Europeans or African Caribbeans, whilst in South Asians difficulty falling asleep was related to an increased risk of all-cause mortality (HR = 1.28, 95%CI = 1.01; 1.61). In Europeans, early morning waking was associated with a moderately increased risk of cardiovascular death (HR = 1.31, 95%CI = 1.05; 1.63); alternately, this association was not as strong in the other groups. CONCLUSION: Our findings suggest that the relationship between sleep quality and mortality may differ by ethnic group, but formal heterogeneity tests indicated that the strongest difference in HRs was observed for early morning waking and cardiovascular disease (CVD) mortality across the three groups (Cochran's Q test p = 0.036). As such, these results are novel and provide support for ethnic differences in sleep quality and mortality, and may have implications for precision medicine.

Insomnia and mortality: A meta-analysis.

The purpose of this review was to evaluate the strength of evidence for a relationship between risk of mortality and frequent and ongoing insomnia using a meta-analytic strategy. Seventeen studies, including a total of 36,938,981 individuals followed up for a mean of 11.6 y, reporting the investigation of the association between mortality and frequent (≥3 nights/wk), ongoing (≥1 mo) insomnia were identified. There was no difference in the odds of mortality for those individuals with symptoms of insomnia when compared to those without symptoms (OR = 1.06, 95%CI = 0.61-1.84, p = .84). This finding was echoed in the assessment of the rate of mortality in those with and without symptoms of insomnia using the outcomes of multivariate models, with the most complete adjustment for potential confounders, as reported by the individual studies included in this meta-analysis (HR = 1.07, 95%CI = .96-.1.19, p = .22). Additional analyses revealed a tendency for an increased risk of mortality associated with hypnotic use. The current evidence reinforces the use of cognitive therapy, within a CBTi framework, as a frontline non-pharmacological treatment for insomnia to reassure patients their longevity will not be impacted as a consequence of suffering from insomnia.

Insomnia with objective short sleep duration and risk of incident cardiovascular disease and all-cause mortality: Sleep Heart Health Study.

Study Objectives: To quantify the association between insomnia or poor sleep with objective short sleep duration and incident cardiovascular disease (CVD) and mortality in the general population. Methods: We conducted a time-to-event analysis of Sleep Heart Health Study data. Questionnaires and at-home polysomnography (PSG) were performed between 1994 and 1998. Participants were followed for a median of 11.4 years (Q1-Q3, 8.8-12.4 years) until death or last contact. The primary exposure was insomnia or poor sleep with short sleep defined as follows: difficulty falling asleep, difficulty returning to sleep, early morning awakenings, or sleeping pill use, 16-30 nights per month; and total sleep of <6 hr on PSG. We used proportional hazard models to estimate the association between insomnia or poor sleep with short sleep and CVD, as well as all-cause mortality. Results: Among 4994 participants (mean age: 64.0 ± 11.1 years), 14.1 per cent reported insomnia or poor sleep, of which 50.3 per cent slept <6 hr. Among 4437 CVD-free participants at baseline, we observed 818 incident CVD events. After propensity adjustment, there was a 29 per cent higher risk of incident CVD in the insomnia or poor sleep with short sleep group compared with the reference group (HR: 1.29, 95% CI: 1.00, 1.66), but neither the insomnia or poor sleep only nor short sleep only groups were associated with higher incident CVD. Insomnia or poor sleep with objective short sleep was not associated with all-cause mortality (HR: 1.07, 95% CI: 0.86, 1.33). Conclusions: Insomnia or poor sleep with PSG-short sleep was associated with higher risk of incident CVD. Future studies should evaluate the impact of interventions to improve insomnia with PSG-short sleep on CVD.

Insomnia is associated with increased mortality in patients with first-ever stroke: a 6-year follow-up in a Chinese cohort study.

Objective: Insomnia is a highly prevalent disorder among patients suffering from stroke. The association between insomnia and stroke mortality is less studied, particularly using the latest diagnostic criteria. The current study examined the relationship between insomnia and mortality among patients with first-evonal hazard models were used to calculate HRs for stroke er stroke in China. Methods: Patients with acute cerebrovascular diseases (stroke) were recruited from 56 hospitals in mainland China. Insomnia was defined as difficulty falling asleep, or difficulty staying asleep or waking up early, for at least two consecutive visits. Demographic data, medical history and clinical data were collected. Four follow-up visits occurred within the first year after stroke, and the last follow-up call was conducted 6 years later. Cox proportional hazard models were used to calculate HRs for stroke mortality. Results: Insomnia was reported by 38.4% (489/1273) of patients at baseline. During the 6 years of follow-up, after adjusting for all confounders, insomnia was found to be associated with increased mortality (HR=1.66, 95% CI 1.10 to 2.48). Old age (HR=1.08, 95% CI 1.06 to 1.10), stroke recurrence in the first year of follow-up (HR=2.53, 95% CI 1.48 to 4.31) and stroke survivors with hypertension (HR=1.62, 95% CI 1.04 to 2.53) had substantially higher risk of mortality. Conclusions: Besides old age, stroke recurrence in the first year of follow-up and hypertension, insomnia is associated with increased risk of mortality in patients with first-ever stroke in China. More studies about prompt and efficient interventions for insomnia are expected in the future. Trial registration number: rctn62169508.

An investigation into the association between demographic and morbidity factors, and sleep disturbance.

BACKGROUND: The recognition of sleep disorders is important because in the long term, they are associated with numerous deleterious health outcomes. Despite the high prevalence of sleep disorders, they are widely under-diagnosed at general practice level. AIM: This study aims to investigate the association between demographic and morbidity factors, and self-reported sleep disturbance symptoms. METHODS: A quantitative cross-sectional study design was used. The data collection tool was an anonymous questionnaire consisting of 22 sleep symptoms categorised into four subscales: 1. Insomnia, 2. Daytime Distress, 3. Sleep Disorder, 4. Psychological Distress. Participants were adults ≥18 years of age attending their general practitioner. RESULTS: A total of 281 questionnaires were analysed (70.3% response rate). Participants with a diagnosis of depression and those who experienced low mood 'very frequently' had significantly higher median scores on all four subscales. Those with a body mass index (BMI) >30 kg/m2 had a higher median score on subscale 3, compared to those with lower BMIs. Smokers had higher median scores on subscales 1-3 compared to non-smokers. Participants >65 years of age had lower median scores on all subscales compared to younger participants. Married participants had lower median scores on subscales 1-3 compared to unmarried participants. A total of 37% reported that they would be willing to participate in an overnight sleep study, and 5.3% had been formally diagnosed with a sleep disorder. CONCLUSIONS: A number of factors are significantly associated with sleep disturbance, particularly depression, low mood, elevated BMI and smoking. General practitioners should consider these factors to increase recognition of patients who would benefit from sleep disorder investigation.

Insomnia and Risk of Cardiovascular Disease.

Insomnia is the most prevalent sleep disorder in the United States and has high comorbidity with a number of cardiovascular diseases (CVDs). In the past decade, a number of observational studies have demonstrated an association between insomnia and incident cardiovascular disease (CVD) morbidity and mortality, including hypertension (HTN), coronary heart disease (CHD), and heart failure (HF). Despite some inconsistencies in the literature, likely due to variations in how insomnia is defined and measured, the existing data suggest that insomnia, especially when accompanied by short sleep duration, is associated with increased risk for HTN, CHD and recurrent acute coronary syndrome, and HF. Purported mechanisms likely relate to dysregulation of the hypothalamic-pituitary axis, increased sympathetic nervous system activity, and increased inflammation. This paper reviews the most recent studies of insomnia and CVD and the potential pathophysiological mechanisms underlying this relationship and highlights the need for randomized trials to further elucidate the nature of the relationship between insomnia and CVD.

Hypnotic Medications and Suicide: Risk, Mechanisms, Mitigation, and the FDA.

OBJECTIVE: Insomnia is associated with increased risk for suicide. The Food and Drug Administration (FDA) has mandated that warnings regarding suicide be included in the prescribing information for hypnotic medications. The authors conducted a review of the evidence for and against the claim that hypnotics increase the risk of suicide. METHOD: This review focused on modern, FDA-approved hypnotics, beginning with the introduction of benzodiazepines, limiting its findings to adults. PubMed and Web of Science were searched, crossing the terms "suicide" and "suicidal" with each of the modern FDA-approved hypnotics. The FDA web site was searched for postmarketing safety reviews, and the FDA was contacted with requests to provide detailed case reports for hypnotic-related suicide deaths reported through its Adverse Event Reporting System. RESULTS: Epidemiological studies show that hypnotics are associated with an increased risk for suicide. However, none of these studies adequately controlled for depression or other psychiatric disorders that may be linked with insomnia. Suicide deaths have been reported from single-agent hypnotic overdoses. A separate concern is that benzodiazepine receptor agonist hypnotics can cause parasomnias, which in rare cases may lead to suicidal ideation or suicidal behavior in persons who were not known to be suicidal. On the other hand, ongoing research is testing whether treatment of insomnia may reduce suicidality in adults with depression. CONCLUSIONS: The review findings indicate that hypnotic medications are associated with suicidal ideation. Future studies should be designed to assess whether increases in suicidality result from CNS impairments from a given hypnotic medication or whether such medication decreases suicidality because of improvements in insomnia.

Increased Mortality in Relation to Insomnia and Obstructive Sleep Apnea in Korean Patients Studied with Nocturnal Polysomnography.

STUDY OBJECTIVES: To elucidate the links between the two most prevalent sleep disorders, insomnia and obstructive sleep apnea (OSA), and mortality. METHODS: We studied 4,225 subjects who were referred to the Center for Sleep and Chronobiology, Seoul National University Hospital, from January 1994 to December 2008. We divided the subjects into five groups: mild OSA (5 ≤ AHI < 15), moderate OSA (15 ≤ AHI < 30), severe OSA (AHI ≥ 30), insomnia, and a no-sleep-disorder group consisting of subjects without sleep disorders. Standardized mortality ratio (SMR), hazard ratio, and the survival rates of the five groups were calculated and evaluated. RESULTS: The SMR of all-cause mortality was significantly higher in the severe OSA group than in the general population (1.52, 95% CI 1.23-1.85, p < 0.05). The SMR of cardiovascular mortality increased progressively with the severity of OSA (no-sleep-disorder: 0.09, mild: 0.40, moderate: 0.52, severe: 1.79, p < 0.05). Statistical analyses of the hazard ratios indicated that severe OSA is a risk factor for all-cause mortality (HR 3.50, 95% CI 1.03-11.91, p = 0.045) and cardiovascular mortality (HR 17.16, 95% CI 2.29-128.83, p = 0.006). Cardiovascular mortality was also significantly elevated in the insomnia group (HR 8.11, 95% CI 1.03-63.58, p = 0.046). CONCLUSIONS: Severe OSA was associated with increased all-cause mortality and cardiovascular mortality compared to the no-sleep-disorder group. Insomnia was associated with increased cardiovascular mortality compared to the no-sleep-disorder group.

Prognostic Significance of Insomnia in Heart Failure.

BACKGROUND: Insomnia is associated with incident heart failure (HF), but the clinical significance and impact of insomnia on HF remain unclear. METHODS AND RESULTS: Consecutive 1,011 patients admitted for HF were divided into 2 groups according to the presence of insomnia: HF with insomnia (insomnia group, n=519) and HF without insomnia (non-insomnia group, n=492). We compared (1) cardiac event rates including cardiac death and worsening HF; and (2) underlying clinical background including laboratory data, echocardiographic data, and cardiopulmonary exercise test between the 2 groups. On Kaplan-Meier analysis, cardiac event rate was significantly higher in the insomnia group than in the non-insomnia group (39.1 vs. 23.4%, P<0.001). The insomnia group, as compared with the non-insomnia group, had (1) higher plasma renin activity (P=0.042), renin concentration (P=0.007), and aldosterone (P=0.047); (2) lower peak V̇O2(14.9 vs. 16.3 ml/kg/min, P=0.002) and higher V̇E/V̇CO2slope (36.0 vs. 33.5, P=0.001); and (3) similar B-type natriuretic peptide and left ventricular ejection fraction. Importantly, on multivariate Cox proportional hazard analysis after adjusting for potential confounding factors, insomnia was an independent predictor of cardiac events in HF patients (hazard ratio, 1.899; P<0.001). CONCLUSIONS: Insomnia is an independent predictor of cardiac events in HF patients. HF patients with insomnia have activated renin-angiotensin-aldosterone system and lower exercise capacity. (Circ J 2016; 80: 1571-1577).

Nocturia, Insomnia Symptoms and Mortality among Older Men: The Health, Aging and Body Composition Study.

STUDY OBJECTIVES: To examine the association between nocturia (walking up from sleep for urination) and mortality risk among community dwelling older men. METHODS: This is a secondary data analysis using data obtained from the Health Aging Body Composition (Health ABC) study. Frequency of nocturia was determined at baseline using a questionnaire. RESULTS: A total of 1,478 older men, mean (SD) age 73.8 (2.9) years, were included in the analysis. During a follow up period of 9.9 years, a total of 760 deaths were reported. Mortality rate was significantly higher for participants with 3 or more nocturia episodes per night, in comparison to those with 0-1 episodes (HR [CI] : 1.21 [1.00-1.47], p = 0.055), even after controlling for baseline characteristics which included demographic variables, body mass index, lower urinary tract symptoms, use of loop diuretics, insomnia symptoms, feeling excessively sleepy during the day/daytime naps, sleep duration, and use of sleep medications. However, the association between ≥ 3 nocturia episodes per night and mortality risk was no longer statistically significant once prevalent diabetes mellitus and cardiovascular disease were included in the model (HR [CI]: 1.18 [0.97- 1.44], p = 0.100). CONCLUSIONS: Nocturia is associated with mortality independent of insomnia symptoms and sleep duration. The relationship is explained in part by prevalent cardiovascular disease and diabetes mellitus. The results underscore the impact of these medical conditions on the association between 3 or more nocturia episodes and increased mortality risk among older men.

Insomnia symptoms and mortality: a register-linked study among women and men from Finland, Norway and Lithuania.

Evidence on the association between insomnia symptoms and mortality is limited and inconsistent. This study examined the association between insomnia symptoms and mortality in cohorts from three countries to show common and unique patterns. The Finnish cohort comprised 6605 employees of the City of Helsinki, aged 40-60 years at baseline in 2000-2002. The Norwegian cohort included 6236 participants from Western Norway, aged 40-45 years at baseline in 1997-1999. The Lithuanian cohort comprised 1602 participants from the City of Palanga, aged 35-74 years at baseline in 2003. Mortality data were derived from the Statistics Finland and Norwegian Cause of Death Registry until the end of 2012, and from the Lithuanian Regional Mortality Register until the end of 2013. Insomnia symptoms comprised difficulties initiating sleep, nocturnal awakenings, and waking up too early. Covariates were age, marital status, education, smoking, alcohol, physical inactivity, obesity, diabetes, cardiovascular diseases, depression, shift work, sleep duration, and self-rated health. Cox regression analysis was used. Frequent difficulties initiating sleep were associated with all-cause mortality among men after full adjustments in the Finnish (hazard ratio 2.51; 95% confidence interval 1.07-5.88) and Norwegian (hazard ratio 3.42; 95% confidence interval 1.03-11.35) cohorts. Among women and in Lithuania, insomnia symptoms were not statistically significantly associated with all-cause mortality after adjustments. In conclusion, difficulties initiating sleep were associated with mortality among Norwegian and Finnish men. Variation and heterogeneity in the association between insomnia symptoms and mortality highlights that further research needs to distinguish between men and women, specific symptoms and national contexts, and focus on more chronic insomnia.

The Use of Hypnotics and Mortality--A Population-Based Retrospective Cohort Study.

BACKGROUND: Sleep disorders, especially chronic insomnia, have become major health problem worldwide and, as a result, the use of hypnotics is steadily increasing. However, few studies with a large sample size and long-term observation have been conducted to investigate the relationship between specific hypnotics and mortality. METHODS: We conducted this retrospective cohort study using data from the National Health Insurance Research Database in Taiwan. Information from claims data including basic characteristics, the use of hypnotics, and survival from 2000 to 2009 for 1,320,322 individuals were included. The use of hypnotics was divided into groups using the defined daily dose and the cumulative length of use. Hazard ratios (HRs) were calculated from a Cox proportional hazards model, with two different matching techniques to examine the associations. RESULTS: Compared to the non-users, both users of benzodiazepines (HR = 1.81; 95% confidence interval [CI] = 1.78-1.85) and mixed users (HR = 1.44; 95% CI = 1.42-1.47) had a higher risk of death, whereas the users of other non-benzodiazepines users showed no differences. Zolpidem users (HR = 0.73; 95% CI = 0.71-0.75) exhibited a lower risk of mortality in the adjusted models. This pattern remained similar in both matching techniques. Secondary analysis indicated that zolpidem users had a reduced risk of major cause-specific mortality except cancer, and that this protective effect was dose-responsive, with those using for more than 1 year having the lowest risk. CONCLUSIONS: The effects of different types of hypnotics on mortality were diverse in this large cohort with long-term follow-up based on representative claims data in Taiwan. The use of zolpidem was associated with a reduced risk of mortality.

Sleeping difficulty, disease and mortality in older women: a latent class analysis and distal survival analysis.

The aim of this study is to identify patterns of sleep difficulty in older women, to investigate whether sleep difficulty is an indicator for poorer survival, and to determine whether sleep difficulty modifies the association between disease and death. Data were from the Australian Longitudinal Study on Women's Health, a 15-year longitudinal cohort study, with 10 721 women aged 70-75 years at baseline. Repeated-measures latent class analysis identified four classes of persistent sleep difficulty: troubled sleepers (N = 2429, 22.7%); early wakers (N = 3083, 28.8%); trouble falling asleep (N = 1767, 16.5%); and untroubled sleepers (N = 3442, 32.1%). Sleep difficulty was an indicator for mortality. Compared with untroubled sleepers, hazard ratios and 95% confidence intervals for troubled sleepers, early wakers, and troubled falling asleep were 1.12 (1.03, 1.23), 0.81 (0.75, 0.91) and 0.89 (0.79, 1.00), respectively. Sleep difficulty may modify the prognosis of women with chronic diseases. Hazard ratios (and 95% confidence intervals) for having three or more diseases (compared with 0 diseases) were enhanced for untroubled sleepers, early wakers and trouble falling asleep [hazard ratio = 1.86 (1.55, 2.22), 1.91 (1.56, 2.35) and 1.98 (1.47, 2.66), respectively], and reduced for troubled sleepers [hazard ratio = 1.57 (1.24, 1.98)]. Sleep difficulty in older women is more complex than the presence or absence of sleep difficulty, and should be considered when assessing the risk of death associated with disease.

Intrarectal ice application prior to transrectal prostate biopsy: a prospective randomised trial accessing pain and collateral effects

Objectives To analyze the efficacy of intrarectal ice application as an anesthetic method prior to transrectal ultrasound (TRUS) guided prostate biopsy. Materials and Methods A total of 120 consecutive men were included into the study prospectively. Patients were equally randomized as group 1 and 2 with 60 patients each. Ice was applied as an anesthetic method 5 minutes before procedure to the patients in group 1. Patients in group 2 were applied 10 ml of 2% lidocaine gel 10 minutes before procedure. Twelve core biopsy procedure was performed for all patients. The pain level was evaluated using a visual analogue scale (VAS). Results Median pain score was 3.5 (1-8) in group 1 and 5 (1-8) in group 2. There is significantly difference between groups regarding the mean sense of pain level during the procedure. (p=0.007) There was also no difference in complications between two groups about presence and duration of macroscopic hematuria and rectal bleeding. Conclusions Intrarectal ice application prior to TRUS prostate biopsy has an effect on reducing pain. Development of new techniques about cold effect or ice can make this method more useful and decrease complication rates. .