Antipsychotic drugs and QT interval prolongation

The QTc prolongation by antipsychotic drugs is of major concern, especially in light of the data indicating an increased risk of sudden death in psychiatric patients taking these drugs. Sudden death in psychiatric patients could be partially attributed to drug-induced torsades de pointes and for this reason careful evaluation of QTc prolonging properties of antipsychotic drugs is needed. Antipsychotic drugs prolong QT interval usually by blocking the potassium I_Kr current. Improved understanding of ion channel structure and kinetics and its role in repolarization has tremendous impact on understanding of the mechanisms of drug-induced QT prolongation and torsades de pointes. Proarrhythmia caused by a QT-prolonging drug occurs infrequently, and usually multiple factors need to operate to precipitate such an event including a combination of two or more drugs affecting the same pathway, hypokalemia, and possibly genetic predisposition. Currently prescribed antipsychotics might cause QT prolongation ranging from 4–6 ms for haloperidol and olanzapine to 35 ms for thioridazine. The response of a patient to a drug is very individual and therefore an individualized system of drug administration and monitoring needs to be developed which takes into account baseline QTc duration and its changes after a drug was introduced. A systematic approach while stratifying psychiatric patients as those with short QTc (QTc 0.41 sec), borderline QTc (QTC = 0.42–0.44 sec), and prolonged QTc ( 0.45 sec) is being proposed to improve the safety of administering antipsychotic drugs and to decrease the risk of drug-related sudden death in psychiatric patients.     

QT interval prolongation related to psychoactive drug treatment: a comparison of monotherapy versus polytherapy

Background  

Several antipsychotic agents are known to prolong the QT interval in a dose dependent manner. Corrected QT interval (QTc) exceeding a threshold value of 450 ms may be associated with an increased risk of life threatening arrhythmias. Antipsychotic agents are often given in combination with other psychotropic drugs, such as antidepressants, that may also contribute to QT prolongation. This observational study compares the effects observed on QT interval between antipsychotic monotherapy and psychoactive polytherapy, which included an additional antidepressant or lithium treatment.     

The QTc interval and its dispersion in patients receiving two atypical antipsychotics

Objective  Treatment with atypical antipsychotics may prolong the rate-corrected Q–T interval (QTc) on electrocardiogram and increase the risk of dangerous ventricular arrhythmias. Polytherapy with atypical antipsychotics is becoming common, but the effect of this practice on the QTc has not been explored in detail. Methods  Among 364 adults treated with atypical antipsychotics randomly selected from consecutive admissions to a single hospital, electrocardiograms with measurable Q–T intervals in at least six leads were available for 38 of 49 patients receiving polytherapy with two atypical antipsychotics. Daily chlorpromazine equivalent, QTc duration and QTc dispersion were assessed in this group and in 73 closely matched patients receiving atypical antipsychotic monotherapy. Results  The daily chlorpromazine equivalent of atypical antipsychotics was significantly greater in the polytherapy group (525.2 vs. 244.7 mg, P = 0.0003). Polytherapy and monotherapy patients were similar with regard to QTc duration, QTc dispersion and proportion of patients with gender-adjusted QTc prolongation (7.9% vs. 9.6%). The QTc duration had only a modest correlation with the total antipsychotic dose (P = 0.064). The presence of hypokalemia (3.0–3.5 mEq/l) was not associated with longer QTc intervals. Conclusions  The common practice of polytherapy with two atypical antipsychotics does not seem to lead to significant QTc prolongation compared to monotherapy. Grant Support: The Zucker Hillside Hospital Advanced Center for Intervention and Services Research for the Study of Schizophrenia (MH074543-01) from the National Institute of Mental Health, Bethesda, Maryland.     

A pilot study of antipsychotic prescribing decisions for acutely-Ill hospitalized patients

Background

Evidence on antipsychotic prescribing decisions is limited. This pilot study quantified factors considered in choosing an antipsychotic and evaluated the influence of metabolic status on treatment decisions.

Methods

Prescribing decisions by 4 psychiatrists were examined based on 80 adult patients initiated on antipsychotic medication diagnosed with schizophrenia, schizoaffective disorder or bipolar disorder by DSM-IV criteria, who were admitted to an acute inpatient psychiatric program of an urban Veterans Affairs Medical Center. The primary analysis examined the association between antipsychotic treatment choice and predictions of symptom control and metabolic risk. Secondary analyses included comparison of the chosen and next best treatments in predicted symptom control and metabolic risk, the frequency of reasons cited for drug choice, and the association between treatment choice and patients' baseline metabolic parameters. Mean differences and odds-ratios (OR) with 95% confidence intervals were used to compare relationships between treatment choice, ratings of risk and metabolic data.

Results

Antipsychotic choice correlated significantly with ratings of predicted symptom control (OR = .92, p = 0.02) and metabolic risk (OR = .88, p = 0.01). Mean differences between the chosen and next best drugs were significant but small in predicted symptom control (F = 2.81, df = 3, 76; p < 0.05) compared with larger differences in anticipated metabolic risk (F = 14.80, df = 3, 76; p = 0.0001). Nevertheless, among 24 identified reasons influencing drug selection, anticipated metabolic risk of chosen antipsychotics was cited less often than efficacy measures. In contrast to psychiatrists' expectations of metabolic risk with selected treatments, we found that patients' actual baseline BMI, fasting glucose, blood pressure, and Framingham risk levels did not necessarily predict antipsychotic treatment choice independent of other factors.

Conclusion

In the context of an acute psychiatric hospitalization, pilot data suggest that predictions of symptom control and metabolic risk correlated significantly with antipsychotic choice, but study psychiatrists were willing to assume relative degrees of metabolic risk in favor of effective symptom control. However, prescribing decisions were influenced by numerous patient and treatment factors. These findings support the potential utility of the ATCQ questionnaire in quantifying antipsychotic prescribing decisions. Further validation studies of the ATCQ questionnaire could enhance translation of research findings and application of treatment guidelines.     

The effects of cardiovascular exercise on human memory: A review with meta-analysis

We reviewed the evidence for the use of cardiovascular exercise to improve memory and explored potential mechanisms. Data from 29 and 21 studies including acute and long-term cardiovascular interventions were retrieved. Meta-analyses revealed that acute exercise had moderate (SMD = 0.26; 95% CI = 0.03, 0.49; p = 0.03; N = 22) whereas long-term had small (SMD = 0.15; 95% CI = 0.02, 0.27; p = 0.02; N = 37) effects on short-term memory. In contrast, acute exercise showed moderate to large (SMD = 0.52; 95% CI = 0.28, 0.75; p < 0.0001; N = 20) whereas long-term exercise had insignificant effects (SMD = 0.07; 95% CI = −0.13, 0.26; p = 0.51; N = 22) on long-term memory. We argue that acute and long-term cardiovascular exercise represent two distinct but complementary strategies to improve memory. Acute exercise improves memory in a time-dependent fashion by priming the molecular processes involved in the encoding and consolidation of newly acquired information. Long-term exercise, in contrast, has negligible effects on memory but provides the necessary stimuli to optimize the responses of the molecular machinery responsible for memory processing. Strategically combined, acute and long-term interventions could maximize the benefits of cardiovascular exercise on memory.     

Decreased serum BDNF levels in chronic institutionalized schizophrenia on long-term treatment with typical and atypical antipsychotics

Accumulating evidence showed that brain-derived neurotrophic factor (BDNF) may be involved in the pathophysiology of schizophrenia. Decreased BDNF levels have been found in the serum of schizophrenic patients with mixed results. In the present study, we assessed serum BDNF levels in a large group of 364 schizophrenic patients (157 on clozapine, 89 on risperidone and 118 on typical antipsychotics), compared to 323 healthy control subjects matched for age and gender. The schizophrenia symptomatology was assessed by the Positive and Negative Syndrome Scale (PANSS), and serum BDNF levels were measured by sandwich ELISA. The results showed that BDNF levels were significantly lower in chronic patients with schizophrenia than in healthy control subjects (9.9 ± 2.0 ng/ml vs.11.9 ± 2.3 ng/ml, p < 0.0001). Lower BDNF levels were observed in patients treated with risperidone (9.3 ± 2.3 ng/ml) compared to those with clozapine (10.2 ± 2.0 ng/ml, p < 0.001) and typical antipsychotics (10.0 ± 2.1 ng/ml, p < 0.01). Furthermore, a stepwise multiple regression analysis identified types of antipsychotic drugs (beta = − 0.37, t = − 3.15, p = 0.001) and BDNF levels (beta = − 0.26, t = − 2.51, p = 0.014) as the influencing factor for the positive symptom subscore of PANSS. In addition, there was a sex difference in BDNF levels in patients with schizophrenia (9.7 ± 1.9 ng/ml for males vs.10.4 ± 2.1 ng/ml for female, p < 0.005), but not in normal controls. Our findings indicated decreased BDNF serum levels in chronic patients with schizophrenia, which may be related to clinical phenotypes, including gender, antipsychotic treatment and the severity of psychotic symptoms.     

Gender differences in the effects of peroxisome proliferator-activated receptor γ2 gene polymorphisms on metabolic adversity in patients with schizophrenia or schizoaffective disorder

Objective

Metabolic syndrome (MS) is a major health problem in schizophrenic patients. Peroxisome proliferator-activated receptor γ2 (PPARγ2) is one of the candidate genes responsible for the liability to metabolic problems. In this study, we investigated the effect of the PPARγ2 gene Pro12Ala and C161T polymorphisms on metabolic adversities in patients with schizophrenia or schizoaffective disorder.

Methods

Metabolic profiles and PPARγ2 gene polymorphisms were determined in 600 patients (309 men and 291 women) with a clinical diagnosis of schizophrenia or schizoaffective disorder. Metabolic indices and components of MS were compared between patients with different Pro12Ala or C161T genotypes.

Results

In the whole population, the allele frequency of 12Ala and 161T was 4.4% and 24.7% respectively. Both polymorphisms had no significant effect on obesity or metabolic-related traits. However, following gender stratification of the data, we found female 12Ala allele carriers were at greater risk of developing abdominal obesity (OR = 4.0, 95% CI = 1.1-14.2, p = 0.04) and hypertension (OR = 2.9, 95% CI = 1.2-7.4, p = 0.02) than female 12Ala allele non-carriers. Male 161T allele carriers had lower insulin levels (p = 0.02) and lower high-density lipoprotein cholesterol (HDL-C) (p = 0.05) levels than male 161T allele non-carriers. Moreover, female 161T allele carriers had higher body weight (p = 0.04), waist circumference (p = 0.05), and systolic blood pressure (p = 0.01), and were at greater risk of developing hypertension (OR = 2.0, 95% CI = 1.1-3.5, p = 0.02). Haplotype analyses showed that PPARγ2 gene polymorphisms were significantly associated with HDL-C level in men and blood pressure in women.

Conclusions

We did not find an association of PPARγ2 gene polymorphisms with MS or obesity in our schizophrenia sample. But further analyses by gender stratification revealed gender-specific differences in the effect of different PPARγ2 genotypes on certain metabolic adversities in these patients.     

Abnormalities of rate-corrected QT intervals in Parkinson's disease-a comparison with multiple system atrophy and progressive supranuclear palsy

A number of patients with Parkinson's disease (PD) and multiple system atrophy (MSA), in whom sudden death does occur occasionally, have QT or rate-corrected QT (QTc) interval prolongation on electrocardiogram (ECG). Although these QT or QTc interval abnormalities are likely related to autonomic dysfunction, the pathophysiology remains unknown. The aim of this study was to compare the degree of QTc interval prolongation among akinetic-rigid syndromes, namely PD and related disorders, and to evaluate the relationship between QTc prolongation and severity of autonomic dysfunction. Thirty-four patients with PD, 22 with MSA, 11 with progressive supranuclear palsy (PSP) and 30 healthy controls underwent standard autonomic function tests, and electrocardiography variables (RR, QT and QTc intervals) were measured by an ECG recorder with an automated analyzer. The relationship between QTc interval and cardiovascular reflex tests were also analyzed. Orthostatic hypotension and decreased heart rate in response to respiratory stimuli were prominent in MSA, while these were relatively mild in PD. Unlike the RR and QT intervals, the QTc interval significantly differed among all groups (p<0.01). The QTc interval was significantly prolonged in PD (409+/-17 ms; p<0.001) and MSA (404+/-14 ms; p<0.05) compared with healthy controls (394+/-19 ms). Neither autonomic dysfunction nor QTc interval prolongation was evident in PSP. QTc intervals and cardiovascular reflexes did not correlate, except for Valsalva ratio. The QTc interval was obviously prolonged in PD patients to an extent that could not be accounted for simply by autonomic dysfunction levels. MSA patients showed slightly prolonged QTc intervals in spite of marked cardiovascular autonomic dysfunction. Abnormalities of the QTc may reflect the degeneration of cardioselective sympathetic and parasympathetic neurons that cannot be fully captured by cardiovascular autonomic function tests.     

Potentially traumatic events and serious life stressors are prospectively associated with frequency of doctor visits and overnight hospital visits

Objective

Cumulative lifetime exposure to potentially traumatic events and serious life stressors has been linked with both mental and physical health problems; however, less is known about the association between exposure to potentially traumatic events and serious life stressors with health care use. We investigated whether a higher number of potentially traumatic events and serious life stressors were prospectively associated with an increased number of doctor visits and nights spent in the hospital.

Methods

Participants were drawn from the Health and Retirement Study, a prospective and nationally representative study of adults aged 50 + in the United States (n = 7168). We analyzed the data using a generalized linear model with a gamma distribution and log link.

Results

A higher number of potentially traumatic events and serious life stressors were associated with an increased number of doctor visits and nights spent in the hospital. On a 10-point scale, each additional potentially traumatic event or serious life stressor was associated with an 8% increase in doctor visits after controlling for sociodemographic factors (RR = 1.08, 95% CI = 1.06–1.11; p < .001). Each additional potentially traumatic event or serious life stressor was also associated with an 18% increase in the number of nights spent in the hospital after controlling for sociodemographic factors (RR = 1.18, 95% CI = 1.10–1.27; p < .001).

Conclusion

Exposure to potentially traumatic events and serious life stressors is associated with increased doctor visits and nights spent in the hospital, which may have important implications for the current standard of care.     

Torsade de pointes in a patient with complex medical and psychiatric conditions receiving low-dose quetiapine

OBJECTIVE: Describe potential cardiac complications of low-dose quetiapine and other atypical antipsychotic drugs. METHOD: We present a case report of a 45-year-old Black woman with multiple medical and psychiatric problems taking low-dose quetiapine. RESULTS: Coincident with a generalized seizure, the patient developed 'ventricular fibrillation'. She was countershocked with restoration of normal sinus rhythm. The initial electrocardiogram showed QT interval prolongation. Shortly thereafter, classical torsade de pointes appeared, lasted 10 min, and resolved spontaneously. Hypomagnesemia was present. A cardiac electrophysiologist was concerned that the very slow shortening of the prolonged QTc interval after magnesium replacement implicated quetiapine as a risk factor for QTc interval prolongation and torsade de pointes. A psychosomatic medicine consultant asserted that the fragmented medical and psychiatric care almost certainly contributed to the patient's medical problems. We discuss other cases of QT interval prolongation by newer antipsychotic drugs and previous reports by our group concerning the association of psychotropic drugs, QT interval prolongation, and torsade de pointes. CONCLUSION: Atypical antipsychotic drug administration, when accompanied by risk factors, may contribute to cardiac arrhythmias including torsade de pointes.     

Circulating microparticles and risk of venous thromboembolism

Introduction

Circulating microparticles (MPs) may trigger a hypercoagulable state, leading to thrombotic complications. Data on their association with venous thromboembolism (VTE) are few and inconsistent.

Materials and methods

To investigate whether or not high levels of MPs are associated with an increased risk of VTE, we carried out a case-control study on 186 patients with a first, objectively diagnosed, episode of VTE and 418 healthy controls. Plasma levels of circulating MPs were measured by flow cytometry.

Results

Patients had higher median plasma levels of total MPs than controls (2184 per μL vs 1769 per μL, p < 0.0001). The risk of VTE increased progressively with increasing MPs, with a linear dose-response effect in the log odds. Individuals with MPs above the 90th percentile of the controls’ distribution (P₉₀ = 3263 per μL) had a 5-fold increased risk of VTE than those with MPs below the 10th percentile of controls (P₁₀ = 913 per μL), independently of sex, age, body mass index, thrombophilia, and plasma factor VIII levels [adjusted odds ratio: 5.30 (95%CI: 2.05-13.7)]. Using the 95th percentile of controls as cut-off (P₉₅ = 4120 per μL), the adjusted odds ratio was 2.20 (1.01-4.79) for individuals with MPs > P₉₅ compared with those having MPs ≤ P₉₅. After exclusion of individuals with antiphospholipid antibodies and hyperhomocysteinemia, the interaction between MPs > P₉₅ and thrombophilia increased the VTE risk from 1.63 (0.60-4.50) to 6.09 (1.03-36.1).

Conclusions

High levels of circulating MPs are a possible independent risk factor for VTE.     

抗精神病药致首发精神疾病QTc 间期变化的相关 因素分析

目的 调查抗精神病药致首发精神疾病QTc间期延长的影响因素.方法 对服用稳定剂量抗精神病药治疗1月的309例首发精神疾病患者进行回顾性调查,收集人口学资料、空腹血糖、血压、血脂等生化指标、心电图资料,以QTc≥440ms作为QTc间期延长的标准,分析QTc间期延长的状况及其相关因素.结果 QTc间期延长的发生率为10.6%.药物治疗组QTc间期均值大于基线期,差异有统计学意义(P<0.05);药物联合电休克治疗组以及药物联合脑电治疗组QTc间期与基线期相比,差异无统计学意义(P>0.05).单一抗精神病药治疗组QTc间期与基线期差异无统计学意义(P>0.05);而抗精神病药联用以及抗精神病药联用抗抑郁药/心境稳定剂组QTc间期均值大于基线期,差异有统计学意义(P<0.05).抗精神病药等效氯丙嗪剂量<1000mg/d组别QTc间期与基线期相比差异有统计学意义(P<0.05).抗精神病药剂量与QTc间期没有相关性.女性是QTc间期延长的风险因素(OR=3.26,95%CI=1.050~10.094),其他因素未进入回归方程.结论 首发精神疾病患者抗精神病药治疗期间QTc间期延长存在性别差异,女性发生QTc间期延长的风险是男性的3.26倍.药物联用延长的QTc间期并未达到异常值.抗精神病药剂量与QTc间期没有相关性.除了性别因素外,其他指标不是QTc间期延长的风险因素.     

Genetic Polymorphism of Glutathione <Emphasis Type="Italic">S</Emphasis>-transferase T1 (<Emphasis Type="Italic">GSTT1</Emphasis>) and QT-Interval in Schizophrenia Patients

Several antipsychotic agents are known to prolong the QT interval in a dose-dependent manner. The antipsychotic drugs are substrates of the phase I of biotransformation enzymes of cytochrome P450. In order to find the possible influence of polymorphism of GSTT1 (a member of class theta glutathione S-transferase) on rate-corrected QT interval (QTc) of schizophrenia patients, the present study was done. Forty-three schizophrenia in-patients participated in the study. The patients were diagnosed as chronic schizophrenia according to structured clinical interview using SCID-I (clinician version) to confirm and document DSM-IV diagnosis. Measurements of QT and RR intervals were recorded using a magnifying grid on lead II. The QTc was calculated according to Bazett’s formula. Polymerase chain reaction-based method was used in order to determine the GSTT1 genotypes. Based on the fitted model of multiple linear regression analysis, QTc decreased in persons with positive GSTT1 genotype in comparison with the null genotype (β = −0.328, t = −2.346, p = 0.024). Active genotype of GSTT1 decreased the QTc. Also, QTc was significantly associated with smoking status; it was decreased in smokers compared with nonsmokers (β = −0.372, t = −2.372, p = 0.014).     

A retrospective comparison of BMI changes and the potential risk factors among schizophrenic inpatients treated with aripiprazole, olanzapine, quetiapine or risperidone

The objective of this study was to evaluate weight gain and its potential risk factors among different second generation antipsychotics (SGAs). The study was conducted for Korean inpatients with schizophrenia in a university hospital in Seoul, between Jan 2000 and Dec 2007. Data were collected by reviewing the medical records of the patients, who were prescribed to one of the SGAs among aripiprazole, olanzapine, quetiapine or risperidone. The changes of weight and body mass index (BMI); risk of clinically significant weight gain (> 7% gain to initial weight) and their associations with various clinical characteristics of such patients were analyzed. Five hundred and eighty-eight (588) and 294 subjects treated with one of the four SGAs for a duration of 1 month and 2 months were included, respectively. Olanzapine showed significantly greater weight and BMI increase at month 1 (p = 0.028 for weight; p = 0.019 for BMI) and month 2 (p = 0.032 for weight; p = 0.029 for BMI) than others. Females showed greater BMI increase change (0.70 ± 0.91 kg/m², p = 0.008) and were also more likely to experience clinically significant weight gain (odd ratio = 1.846, 95% CI = 1.098 to 3.105, p = 0.021) at month 1.Younger patients (< 45 years old) had significantly greater weight and BMI increase at both months 1 and 2. Younger patients also showed greater risk for clinically significant weight gain at month 2 (odd odd ratio = 2.567, 95% CI = 1.196 to 5.508, p = 0.016). Low baseline BMI (< 25 kg/m²) was associated with greater weight gain at month 1 (1.92 ± 2.29 kg, p < 0.001) and month 2 (4.07 ± 3.56 kg, p < 0.001) and BMI increase at month 1 and month 2 (p < 0.001 for both). Patients with low baseline BMI showed higher risk of clinically significant weight gain at both months 1 and 2 (p< 0.001 for both). Olanzapine was shown to have higher metabolic risk than other SGAs in inpatients with schizophrenia. The individual's own clinical characteristics also exerted influence on weight gain effects of SGAs. Younger patients with lower baseline BMI were under greater risk of antipsychotic-induced weight gain. More studies are required to verify the role of gender on weight gain.     

Antipsychotic Polypharmacy and Corrected QT Interval: A Systematic Review

Objective:

It remains unclear whether antipsychotic polypharmacy, a common clinical practice, is related to an increased risk of corrected time between start of Q wave and end of T wave (QTc) interval prolongation. We conducted a systematic review of the literature to address this important issue.

Method:

A systematic literature search was conducted in October 2014, using MEDLINE, Embase, and PsycINFO. Studies and case reports were included if they reported QTc intervals or QTc interval changes before and after antipsychotic polypharmacy or QTc intervals in both antipsychotic polypharmacy and monotherapy groups.

Results:

A total of 21 articles (10 clinical trials, 4 observational studies, and 7 case reports) met inclusion criteria. The clinical trials have shown that a combination treatment with risperidone or pimozide is not obviously related to an increase in QTc interval, whereas ziprasidone or sertindole combined with clozapine may prolong QTc interval. Among the 4 observational studies, antipsychotic polypharmacy was not clearly associated with QTc prolongation in 3 studies, each cross-sectional. In contrast, one prospective study showed a significant increase in QTc interval following antipsychotic coadministration. The case reports indicated an increased risk of QTc prolongation in at least some patients receiving antipsychotic polypharmacy.

Conclusions:

Currently available evidence fails to confirm that antipsychotic polypharmacy worsens QTc prolongation in general, although the evidence is scarce and inconsistent. Clinicians are advised to remain conservative in resorting to antipsychotic polypharmacy, as a combination of some QTc-prolongation liable antipsychotics may further prolong QTc interval, and efficacy supporting the clinical benefits of antipsychotic polypharmacy is equivocal, at best.     

Botulinum toxin type A versus amitriptyline for the treatment of chronic daily migraine

Objective

To compare the effects of botulinum toxin type A with those of amitriptyline on the treatment of chronic daily migraines.

Methods

Chronic migraine sufferers were randomized into two groups and treated with 25 or 50 mg/day of amitriptyline or 250 U of botulinum toxin type A. A reduction of at least 50% in the number of pain episodes, in the intensity of pain, and in the number of drug doses for pain and reports of improvement by the patient or by the examiner were the main endpoints.

Results

Seventy-two subjects were enrolled in the study. A reduction of at least 50% in the number of days of pain was recorded in 67.8% of the patients in the BTX-A group and 72% (n = 23) of the patients in the AM group (p = 0.78; RR = 0.94; CI = 0.11–8). The reduction in the intensity of pain, as assessed using the visual analogical scale, was 50% in the BXT-A group and 55.6% in the AM group (p = 0.79; RR = 1.11; CI = 0.32–3.8). The reduction in the number of pain drug doses was 77% for the toxin group and 71% for the amitriptyline group (p = 0.76; RR = 0.92; CI = 0.45–1.88).

Conclusions

Botulinum toxin type A was as effective as amitriptyline for the prophylactic treatment of chronic daily migraines.     

Association of sleep disorders,chronic pain,and fatigue with survival in patients with chronic kidney disease: a meta-analysis of clinical trials

ObjectiveSleep disorders, chronic pain, and fatigue have been long-standing torments in most patients with chronic kidney disease (CKD). In this review, we attempted to explore whether these nontraditional cardiovascular risk factors are associated with increased mortality in patients with CKD.MethodElectronic searches were performed in MEDLINE (PubMed, 1966–2018), EMBASE (1974–2018), ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials databases. All prospective or retrospective studies were considered eligible if they were cohort or observational studies and the final outcome was all-cause death or mortality.ResultsWe ultimately included 18 studies (12 studies on sleep disorders, three studies on chronic pain, and three studies on fatigue) in our review. Pooled analysis of all studies indicated that patients with sleep disorders, chronic pain, and fatigue had increased risks of all-cause mortality (risk ratio [RR] = 1.47, 95% confidence interval [CI] = 1.30–1.66, p < 0.0001; RR = 1.29, 95% CI = 1.27–1.31, p < 0.0001; RR = 1.45, 95% CI = 1.23–1.70, p < 0.0001, respectively). Pooled results from four studies indicated that dialysis patients with sleep-disordered breathing had increased cardiovascular disease outcomes (RR = 2.45, 95% CI = 1.74–3.44, p < 0.0001).ConclusionSleep disorders, chronic pain, and fatigue are remarkably associated with increased all-cause mortality in patients with CKD. Large clinical randomized controlled trials are required to further confirm the results of our meta-analysis.