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Abstract
It is often assumed that beta-blockers, e.g. metoprolol (METO), induce erectile dysfunction (ED) in men. However, cardiovascular diseases can also induce ED and there is also the possibility that psychological factors, such as fear of the disease and side effects of the prescribed drug, may also induce ED. Thus, it is often assumed that beta-blockers induce ED in a large percentage of men, but this statement is not well validated and the role of the pharmacologic effect of METO per se on the occurrence of ED is largely unknown. To get an answer we selected 114 men (age 57 +/- 4.7 years) without ED but with newly diagnosed arterial hypertension, and who could be treated with METO.
METO (100 mg/day) was given as a retard formulation. The hypertensive men were randomized into 3 groups. In group 1 patients were fully informed (they knew that the drug was METO and that it might induce ED). In group 2 patients were partially informed (they knew that the drug was METO, but were not informed that it might induce ED). In group 3 patients were not informed either about the drug used or about the possible occurrence of ED. The first phase of the study lasted 60 days. After 60 days the incidence of ED was 32% in group 1, 13% in group 2, and 8% in group 3 (p < 0.01). All patients with ED entered the second, cross-over, double-blind phase of the study. METO was continued at unchanged dosage, and tadalafil (20 mg) and a placebo were given to treat ED.
Both treatments were equally effective.
Prejudice about the possible occurrence, i.e. the Hawthorne effect, of ED with METO facilitates the occurrence of this side effect in hypertensive men. Since the etiology of this ED is largely psychological, it is not surprising that placebo is as effective as tadalafil in reversing this side effect.
... In a study by Cocco (2009) male participants were randomized to receive different levels of information about metoprolol and its ability to induce erectile dysfunction (ED). Participants were either fully informed about the drug and that it might induce ED, partly informed of the drug but not that it can induce ED, or not informed at all (Cocco, 2009). ...
... In a study by Cocco (2009) male participants were randomized to receive different levels of information about metoprolol and its ability to induce erectile dysfunction (ED). Participants were either fully informed about the drug and that it might induce ED, partly informed of the drug but not that it can induce ED, or not informed at all (Cocco, 2009). After 60 days, men who were fully informed reported significantly more problems with erectile dysfunction (32%) than those partly informed (13%) or not informed at all (8%). ...
Symptoms guide lifesaving health behaviors, play an integral part in healthcare encounters, and the processing of symptoms has a major role in almost all somatic diseases. However, the psychological processes involved in symptom perception and interpretation are yet to be fully understood. This article explores popular theories and psychological factors that explain how individuals notice symptoms and considers implications related to misinterpretation, such as delays in seeking healthcare. A focus is also provided on the impact of information technology on symptom appraisal. Finally, reassurance as a clinical intervention is reviewed, and suggestions are provided for future research.
... The effects of information provision on the nocebo effect are also demonstrated by two studies which explored the influence of information about the side effects of active medications (Cocco, 2009;Mondaini et al., 2007). Cocco (2009) randomly assigned patients into three groups, all treated with metoprolol. ...
... The effects of information provision on the nocebo effect are also demonstrated by two studies which explored the influence of information about the side effects of active medications (Cocco, 2009;Mondaini et al., 2007). Cocco (2009) randomly assigned patients into three groups, all treated with metoprolol. Group 1 were fully informed of their medicine and the side effect of sexual dysfunction; group 2 were informed about the medication, but not about side effects; group 3 were not informed of either the type of medicine or side effects. ...
The nocebo effect is a potentially powerful phenomenon that can result in harmful or unpleasant treatment outcomes caused by negative expectations, past experience, and other aspects of the treatment context. These aversive outcomes can cause patients to discontinue an otherwise beneficial treatment—resulting in suboptimal health outcomes, added burden of illness, reduced quality of life, and unnecessary hospitalisations, medical consultations, and increased cost for both the patient and the health care system. Much research to date has focused on the role of negative expectations in nocebo effects; this review also emphasises the more overlooked mechanisms of anxiety and classical conditioning, and how these might be usefully targeted to reduce nocebo effects. The evidence for each of these mechanisms, and their potential interactions, is reviewed. Regardless of how they develop, nocebo effects can contribute substantially to the overall burden of treatment side effects, and an overview of evidence‐based interventions to reduce nocebo effects by targeting each of the underlying mechanisms is presented. Currently, no strategies are systematically applied to reduce nocebo effects, and most interventions have yet to be translated from experimental laboratory research into applied clinical settings. Future work should focus on developing and testing theoretically‐based interventions to reduce nocebo effects, and on translating findings from lab‐based studies into clinical practice and healthcare policy.
... Практически аналогичным был дизайн исследования, проведенного G. Cocco (2009) с целью оценить риск развития ЭД при применении метопролола. В исследование были включены 114 мужчин в возрасте 57±4,7 года с АГ без ЭД, которые были рандомизированы в группы лечения в зависимости от получения информации о препарате. ...
... Вероятно, поэтому исходные показатели ЭД в этом исследовании существенно превышали такие в общей популяции и среди больных АГ. К существенным ограничениям исследования авторы отнесли то, что в заключительный анализ не вошли данные 30% первоначально включенных пациентов, отсутствие контрольной группы пациентов, которые не получали блокаторы β-адренорецептов, а также невозможность исключить эффект Хоторна, описанный ранее в исследованиях в области изучения ЭФ (Silvestri A. et al., 2003;Cocco G., 2009). ...
... Evidence indicates that the informed consent process is likely to contribute to the formation of nocebo effects. Simply alerting patients to the possibility that they might experience a particular side effect or set of side effects makes these symptoms substantially more likely to occur [13][14][15][16][17]. However, the principles of respect for patient autonomy and non-maleficence in medical ethics conflict here: although informing patients about possible side effects can increase the nocebo effect, it is ethically unacceptable to simply not provide information about potential adverse treatment effects [18]. ...
... The nocebo effect at this time point was also specific to the symptoms that were listed as treatment side effects. This finding is in line with previous research that indicates that the informed consent process itself can generate nocebo effects [13][14][15]. The current findings add to previous research by demonstrating a true nocebo effect [30], that is, sham-treated participants experienced heightened symptoms that had been listed as side effects compared to participants in the no treatment control group. ...
Background
One contributing factor to the development of nocebo effects is information provided about possible side effects. However, nondisclosure of information can be problematic.
Purpose
We assessed whether positively framed side effect information (highlighting likelihood of not experiencing side effects) can reduce nocebo effects compared to negatively framed information (highlighting likelihood of experiencing side effects).
Methods
One hundred twelve participants took part in research ostensibly assessing the influence of benzodiazepines (actually sham capsules) on anxiety. Participants were randomized to receive a sham capsule with positively or negatively framed information about four side effects, or a no-treatment control condition. Side effect expectations were assessed after information provision. Framed side effects and other unmentioned symptoms were assessed during the session and 24-hr follow-up.
Results
Nocebo effects occurred in symptoms presented as side effects (regardless of framing) during the study session and follow-up (ps < .003). At follow-up, there was also a nocebo effect in other unmentioned symptoms (p = .018). Positive framing reduced side effect symptoms compared with negative framing during the study session (p = .037), but this effect was no longer present at follow-up (p = .53). Side effect expectations did not differ between the framing conditions (p = .14).
Conclusions
Positive framing reduced side effects short-term, but not at follow-up. Expectations did not differ between negative and positive framing. Nocebo effects appeared to generalize to other unmentioned symptoms over a 24-hr period. Further research is needed to determine whether the initial impact of positive framing can be maintained over time.
... This is known as the nocebo effect and is an important but relatively neglected phenomenon compared to the placebo effect. However, we know that the act of informing patients about the possible side effects of a treatment alone can significantly increase the numbers of patients who report those side effects (Cocco 2009) and intensify worry and concern (Barsky 2017). ...
... The centers that listed gastrointestinal side effects had six times the withdrawals for gastrointestinal symptoms than the center that did not list this side effect. Similarly, among patients who were being treated with beta blockers, those warned of sexual dysfunction side effects reported these side effects three to four times more frequently than a control group who did not receive this information (Cocco 2009). ...
Placebo effects constitute a major part of treatment success in medical interventions. The nocebo effect also has a major impact, as it accounts for a significant proportion of the reported side effects for many treatments. Historically, clinical trials have aimed to reduce placebo effects; however, currently, there is interest in optimizing placebo effects to improve existing treatments and in examining ways to minimize nocebo effects to improve clinical outcome. To achieve these aims, a better understanding of the psychological and neurobiological mechanisms of the placebo and nocebo response is required. This review discusses the impact of the placebo and nocebo response in health care. We also examine the mechanisms involved in the placebo and nocebo effects, including the central mechanism of expectations. Finally, we examine ways to enhance placebo effects and reduce the impact of the nocebo response in clinical practice and suggest areas for future research. Expected final online publication date for the Annual Review of Psychology Volume 70 is January 4, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
... These results are in line with previous studies which have found that the awareness of specific potential medication side effects can increase the reporting of those side effects. [26][27][28] Finally, it is also probable that the media coverage of the Eltroxin formulation change increased the likelihood that patients themselves would make adverse event reports, and that health professionals would also enquire about or notice these symptoms in their patients, attribute them to the medication and report these symptoms as adverse drug reactions. Media coverage has previously been shown to increase reports of adverse drug reactions. ...
... with previous studies which have found that the awareness of specific potential medication side effects can increase the reporting of those side effects.[26][27][28] These findings invite consideration of current health media coverage, which in the case of Eltroxin was often based around dramatic stories told by individual patients about their experiences of extremely unpleasant adverse events following the medication formulation change. ...
... Moreover, previous studies have used different questionnaires to assess erectile function, making clinical trials for ED somewhat heterogeneous. Finally, patients' perceptions of drugs on potential adverse events bias can lead to the Hawthorne effect, which can further exacerbate sexual dysfunction (8) and exaggerate the incidence of drug side effects (9). ...
Background
The causal relationship between hypertension, antihypertensive drugs and the risk of erectile dysfunction is still uncertain. We performed a univariable and multivariable Mendelian randomization study to investigate whether they are causally related to erectile dysfunction.
Methods
Genetic variants associated with blood pressure were derived from the genome-wide association study meta-analysis of the UK Biobank and International Consortium of Blood Pressure (N = 757,601). Summary association data for hypertension were obtained from the UK Biobank (N = 463,010) and the FinnGen study (N = 356,077). The summary statistics of erectile dysfunction were obtained from the European ancestry with 223,805 subjects. The SNP instruments used to assess the effect of the protein targets of antihypertensive drugs on erectile dysfunction were obtained from previous studys. Causal effects were estimated using the univariate Mendelian randomization method (inverse variance weighted, MR-Egger, weighted median, MR-PRESSO and Wald ratios) and the multivariate Mendelian randomization method. Sensitivity analyses were implemented with the Cochran's Q-test, MR-Egger intercept test, MR-PRESSO, and leave-one-out analysis.
Results
Univariate MR found that elevated diastolic blood pressure may increase the occurrence of erectile dysfunction (odds ratio [OR] = 1.012; 95% confidence interval [CI]: 1.000–1.024; P = 0.047). Genetically predicted hypertension is also associated with ED (For the FinnGen, OR = 1.106; 95% CI: 1.027–1.191; P = 0.008. For the UK Biobank, OR = 3.832; 95% CI: 1.410–10.414; P = 0.008). However, after adjusting for systolic blood pressure, diastolic blood pressure and hypertension using multivariate Mendelian randomization, only hypertension was causally associated with ED occurrence (For the FinnGen, OR = 1.103; 95% CI: 1.018–1.195; P = 0.017. For the UK Biobank, OR = 5.037; 95% CI: 1.601–15.846; P = 0.006). We found no evidence that the use of angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers, and thiazide diuretic increased the risk of erectile dysfunction.
Conclusions
Genetically predicted hypertension increases the risk of erectile dysfunction, but we found no causal relationship between elevated systolic/diastolic blood pressure and erectile dysfunction. We speculate that the relationship between elevated blood pressure and erectile dysfunction risk may be nonlinear. We found little evidence that antihypertensive drugs increase the risk of erectile dysfunction.
... This is consistent with the results from a Cross-National Survey on Men's Health Issues in which up to 20% of men reported to experience erectile dysfunction after being treated with β-blockers [118]. In addition, two controlled trials identified erectile dysfunction as a side effect of metoprolol [23,46], although there is some controversy about the interpretation of these study results [32]. The underlying mechanism could involve effects of the blood flow to the penis [51]. ...
Background:
Although Post-SSRI Sexual Dysfunction (PSSD) has finally been recognized by the European Medicines Agency as a medical condition that can outlast discontinuation of SSRI and SNRI antidepressants, this condition is still largely unknown by patients, doctors, and researchers, and hence, poorly understood, underdiagnosed, and undertreated.
Objective:
Becoming familiar with the symptomatology of PSSD and understanding the underlying mechanisms and treatment options.
Method:
We applied a design thinking approach to innovation to 1) provide insights into the medical condition as well as the personal needs and pains of a targeted patient; and 2) generate ideas for new solutions from the perspective of this particular patient. These insights and ideas informed a literature search on the potential pathophysiological mechanisms that could underlie the patient's symptoms.
Results:
The 55-year-old male patient developed symptoms of low libido, delayed ejaculation, erectile dysfunction, 'brain zaps', overactive bladder and urinary inconsistency after discontinuation of the SNRI venlafaxine. In many of these symptoms a dysregulation in serotonergic activity has been implicated, with an important role of 5-HT1A receptor downregulation and possible downstream effects on neurosteroid and oxytocin systems.
Conclusions:
The clinical presentation and development of symptoms are suggestive of PSSD but need further clinical elaboration. Further knowledge of post-treatment changes in serotonergic - and possibly noradrenergic - mechanisms is required to improve our understanding of the clinical complaints and to inform appropriate treatment regimes.
... Nocebo responses can also occur after intake of an active drug, which may be facilitated through misattribution of symptoms or patient expectations. Several studies have shown that patients report more AEs when they are informed about potential AEs [14][15][16]. However, many of the AEs from verum drugs are not attributable to pharmacological effects [7]. ...
Background
Adverse events of chemotherapy may be caused by pharmacodynamics or psychological factors such as negative expectations, which constitute nocebo effects. In a randomized controlled trial, we examined whether educating patients about the nocebo effect is efficacious in reducing the intensity of self-reported adverse events.
Methods
In this proof-of-concept study, N = 100 outpatients (mean age: 60.2 years, 65% male, 54% UICC tumour stage IV) starting first-line, de novo chemotherapy for gastrointestinal cancers were randomized 1:1 to a nocebo education (n = 49) or an attention control group (n = 51). Our primary outcome was patient-rated intensity of four chemotherapy-specific and three non-specific adverse events (rated on 11-point Likert scales) at 10-days and 12-weeks after the first course of chemotherapy. Secondary outcomes included perceived control of adverse events and tendency to misattribute symptoms.
Results
General linear models indicated that intensity of adverse events differed at 12-weeks after the first course of chemotherapy (mean difference: 4.04, 95% CI [0.72, 7.36], p = .02, d = 0.48), with lower levels in the nocebo education group. This was attributable to less non-specific adverse events (mean difference: 0.39, 95% CI [0.04, 0.73], p = .03, d = 0.44) and a trend towards less specific adverse events in the nocebo education group (mean difference: 0.36, 95% CI [− 0.02, 0.74], p = .07, d = 0.37). We found no difference in adverse events at 10-days follow-up, perceived control of adverse events, or tendency to misattribute non-specific symptoms to the chemotherapy.
Conclusions
This study provides first proof-of-concept evidence for the efficacy of a brief information session in preventing adverse events of chemotherapy. However, results regarding patient-reported outcomes cannot rule out response biases. Informing patients about the nocebo effect may be an innovative and clinically feasible intervention for reducing the burden of adverse events.
Trial registration
Retrospectively registered on March 27, 2018 to the German Clinical Trial Register (ID: DRKS00009501).
... For example, nocebo responses can occur when expectations of adverse outcomes of medical treatments or agents produce negative or worsening health symptoms Mitsikostas et al., 2020). Beliefs about risks, expectations of specific symptoms and anxiety are known to increase nocebo responses Cocco, 2009;Colloca and Miller, 2011;Daniali and Flaten, 2021), and information about adverse effects can trigger nocebo responses (Bagarić et al., 2021). For example, negative messaging by health professionals about side-effects increases reports of cognitive problems in people receiving chemotherapy (Jacobs et al., 2017), and media reports about WiFi radiation can increase reports of somatic symptoms (Bräscher et al., 2017). ...
Drug recalls and lawsuits against pharmaceutical manufacturers are accompanied by announcements emphasizing harmful drug side-effects. Those with elevated health anxiety may be more reactive to such announcements. We evaluated whether health anxiety and financial incentives affect subjective symptom endorsement, and objective outcomes of cognitive and physiological functioning during a mock drug recall. Hundred and sixty-one participants reported use of over-the-counter pain medications and presented with a fictitious medication recall via a mock Food and Drug Administration (FDA) website. The opportunity to join a class-action lawsuit was manipulated. We assessed health anxiety, recalled drug usage, blood pressure, heart rate, and performance on a computerized Trail Making Test (TMT). Symptom endorsement was strongly predicted by health anxiety. When combined, three health anxiety measures explained 28.5% variance (Cohen’s d = 1.26). These effects remain strong after controlling for depression and anxiety. Litigation condition did not predict symptom endorsement. Blood pressure and heart rate were modestly predicted by health anxiety, but not by litigation condition. TMT performance was consistently predicted by health anxiety, with higher scores associated with poorer performance. Although there were no main effects for litigation, interactions consistently emerged for the TMT, with generally poorer performance for those with higher health anxiety in the non-litigation condition; whereas health anxiety was unrelated to performance for the litigation condition. All but one participant joined the litigation when given the opportunity, despite a healthy sample and minimal use of pain medication. Subsequent data from 67 individuals with no mention of the FDA scenario or litigation showed that health anxiety still significantly predicts symptom endorsement (12.6% variance), but the explained variance is less than half that obtained in the FDA scenario. The findings suggest that health anxiety plays a significant role in adverse symptom reporting, beyond anxiety or depression, and this effect is independent of the presence of the FDA recall. The lack of differences for health anxiety and symptom endorsement between litigation and non-litigation conditions rules out malingering. Although it is general practice in drug recalls to list potential adverse side effects caused by medications, this may elicit unintended symptom experiences and health anxious individuals may be more susceptible.
... Prior studies have documented that expecting symptoms may lead to experiencing them. Cocco [19] showed that individuals who were fully informed about the sexual side effects of a treatment reported similar symptoms three times more than those in the control group who were not informed about the sexual side effects. It is not known, however, whether the association of certainty and symptoms was due to the participants attributing their bodily symptoms as related to COVID-19. ...
Background
A nocebo effect occurs when inactive factors lead to worsening of symptoms or reduce treatment outcomes. Believing that one is or has been infected with COVID-19 may act as a nocebo. However, not much is known about potential nocebo effects associated with the reporting of COVID-19 symptoms.
Aim
An online survey investigated whether certainty of being infected with COVID-19, age, sex, cognitive, emotional and personality factors were associated with perceived severity of COVID-19 symptoms.
Methods
Participants ( N=375) filled out an online survey containing 57 questions asking about symptoms resembling COVID-19, certainty of being infected with COVID-19, anxiety, stress and personality dimensions.
Results
Certainty of being infected with COVID-19 and anxiety predicted 27% of the variance in reporting of COVID-like symptoms. The mediation analysis showed that both higher certainty of being infected and anxiety independently predicted increased reports of COVID-like symptom. Females had higher anxiety and stress levels, and reported more COVID-like symptoms than males did. Older age was not associated with reporting COVID-like symptoms.
Conclusions
Believing to be infected with COVID-19, along with anxiety, can enhance the severity of COVID-like symptoms. Thus, the nocebo effect was due to both cognitive and emotional factors and was higher in females.
... Patients' perception on the adverse events related potential of drugs is important for medication adherence in the setting of arterial hypertension [53]. It has been postulated that being prejudiced for potential adverse events causes the so-called Hawthorne effect that further inhibits sexual function [54,55]. Upon adverse events development, like ED, which cannot be objectively and extensively assessed by physicians, the presence of such side effects is often exaggerated [56]. ...
PurposeTo determine the effect of major antihypertensive classes on erectile function (EF) in patients with or at high risk of cardiovascular disease.Methods
We performed a systematic review and frequentist network meta-analysis of randomized controlled trials assessing the effect of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, calcium channel blockers, and thiazide diuretics on EF compared to each other and to placebo (PROSPERO: CRD42020189529). Similarly, we performed a network meta-analysis to explore the effect of different β-blockers on erectile function (nebivolol, other vasodilating and non-vasodilating β-blockers, placebo). Records were identified through search of PubMed, Cochrane Library, and Scopus databases and sources of grey literature until September 2020.ResultsWe included 25 studies (7784 patients) in the qualitative and 16 studies in the quantitative synthesis. The risk of bias was concerning or high in the majority of studies, and inconsistency was also high. No significant differences in EF were demonstrated in the pairwise comparisons between major antihypertensive classes. Similarly, when placebo was set as the reference treatment group, no treatment strategy yielded significant effects on EF. In the β-blockers analysis, nebivolol contributed a beneficial effect on EF only when compared to non-vasodilatory β-blockers (OR 2.92, 95%CI 1.3–6.5) and not when compared to placebo (OR 2.87, 95%CI 0.75–11.04) or to other vasodilatory β-blockers (OR 2.15, 95%CI 0.6–7.77).Conclusion
All antihypertensive medication classes seem to exert neutral or insignificant effects on EF. Further high-quality studies are needed to better explore the effects of antihypertensive medication on EF.
... Patients' perception on the adverse events related potential of drugs is important for medication adherence in the setting of arterial hypertension [53]. It has been postulated that being prejudiced for potential adverse events causes the so-called Hawthorne effect that further inhibits sexual function [54,55]. Upon adverse events development, like ED, which cannot be objectively and extensively assessed by physicians, the presence of such side effects is often exaggerated [56]. ...
Aims
Major antihypertensive medication classes are suggested to exert diverse effects on erectile function (EF). Guideline recommendations suggest that thiazide diuretics and β-blockers possess the worst profile regarding erectile function (EF), while angiotensin receptor blockers and nebivolol the best profile. We aimed to determine the comparative effect of major antihypertensive classes on EF in patients with or at high risk of cardiovascular disease.
Methods
We performed a systematic review and frequentist network meta-analysis of randomized controlled trials assessing the effect of antihypertensive agents on EF (PROSPERO: CRD42020189529). Records were identified through search of PubMed, Cochrane Library and Scopus databases and sources of grey literature until September 2020.
Results
We included 25 studies (7784 patients) in the qualitative and 16 studies in the quantitative synthesis. The risk of bias was concerning or high in the majority of studies and inconsistency was also high. No significant differences in EF were demonstrated in the pairwise comparisons between major antihypertensive classes. Similarly, when placebo was set as the reference treatment group, no treatment strategy yielded significant effects on EF. In the β-blockers analysis, nebivolol contributed a beneficial effect on EF only when compared to non-vasodilatory β-blockers (OR 2.92, 95% CI 1.3–6.5) and not when compared to placebo (OR 2.87, 95% CI 0.75–11.04) or to other vasodilatory β-blockers (OR 2.15, 95% CI 0.6–7.77).
Conclusion
All antihypertensive medication classes seem to exert neutral or insignificant effects on EF. Further high-quality studies are needed to better explore the effects of antihypertensive medication on EF.
... Doctors should value the trust of the patients in them, but health care providers can use our knowledge of placebo mechanism to reduce the patient's anxieties and improve positive expectations. Through enhancing the psychosocial context and a supportive clinical environment with a good patient-doctor relationship, physicians can garner the placebo effect to the patient's benefit [24]. ...
The history of medicine and the history of placebo are closely intertwined. To understand placebo and its effects this article gives a brief overview about its history, the possible mechanisms of action and its counterpart, nocebo.
The Catholic Church used placebo around the sixteenth century for the separation from real and incorrect exorcisms, but it needed Henry Beecher during World War II to quantify the placebo effect as control arm in well-designed studies.
Until today the different mechanisms of action of placebo remain poorly researched. Understanding them would allow its effect to be modulated to better serve in research and clinical settings. Expectation, psychosocial context and conditioning play a significant role in the effect size and amplitude.
The counterpart, nocebo, is even less investigated, even it is commonly observed as adverse effects during medical treatments.
Conclusion: Placebo and nocebo are both underestimated and underresearched in their value. Through further investigation doctors could strengthen the placebo response and prevent adverse effects to help their patients at low cost. These techniques would benefit the patient-doctor relationship, which is the alter of a trust-based successful therapy.
... The proposed study could be of short duration (3 months are an adequate time period) and should have erectile dysfunction as primary endpoint, in order to uncover the effects of monotherapy, potential between-class and within-class differences (e.g. nebivolol versus other beta blockers), and shed light on the beta blocker debate, that is, whether the detrimental effects of beta blockers on erectile function are real or perceived as suggested by two studies [234][235][236]. ...
: Sexual health is an integral part of overall health, and an active and healthy sexual life is an essential aspect of a good life quality. Cardiovascular disease and sexual health share common risk factors (arterial hypertension, diabetes mellitus, dyslipidemia, obesity, and smoking) and common mediating mechanisms (endothelial dysfunction, subclinical inflammation, and atherosclerosis). This generated a shift of thinking about the pathophysiology and subsequently the management of sexual dysfunction. The introduction of phosphodiesterase type 5 inhibitors revolutionized the management of sexual dysfunction in men. This article will focus on erectile dysfunction and its association with arterial hypertension. This update of the position paper was created by the Working Group on Sexual Dysfunction and Arterial Hypertension of the European Society of Hypertension. This working group has been very active during the last years in promoting the familiarization of hypertension specialists and related physicians with erectile dysfunction, through numerous lectures in national and international meetings, a position paper, newsletters, guidelines, and a book specifically addressing erectile dysfunction in hypertensive patients. It was noted that erectile dysfunction precedes the development of coronary artery disease. The artery size hypothesis has been proposed as a potential explanation for this observation. This hypothesis seeks to explain the differing manifestation of the same vascular condition, based on the size of the vessels. Clinical presentations of the atherosclerotic and/or endothelium disease in the penile arteries might precede the corresponding manifestations from larger arteries. Treated hypertensive patients are more likely to have sexual dysfunction compared with untreated ones, suggesting a detrimental role of antihypertensive treatment on erectile function. The occurrence of erectile dysfunction seems to be related to undesirable effects of antihypertensive drugs on the penile tissue. Available information points toward divergent effects of antihypertensive drugs on erectile function, with diuretics and beta-blockers possessing the worst profile and angiotensin receptor blockers and nebivolol the best profile.
... incidence of erectile dysfunction, depending on the fact if they were or were not informed on the potential side effect of erectile dysfunction, respectively ("… it may cause erectile dysfunction; but, it is uncommon") [12]. These findings were confirmed in an independent study with similar design involving the use of metoprolol [13]. ...
Since tobacco remains a leading cause of global morbidity and mortality, emphasis needs to be given to preventive approaches to tobacco consumption. Environmental and policy strategies with fear appeals are important contributors to reductions in smoking prevalence. Fear appeals are persuasive messages-often using graphic and emotionally evocative imagery and language-that attempt to scare their audiences into tobacco cessation. While the intentions of fear appeals are benign, their effects are not necessarily so; here, we argue that some fear appeals carry a significant risk of backfiring by eliciting nocebo effects among its viewers. In this context, it is important to recognize that there is currently no justification for disregarding potential nocebo effects. Therefore, we should improve our understanding of nocebo effects in the field of preventive medicine, as well as the impact of strategies aimed at mitigating their negative health effects.
... Previous studies have shown that information about likely side effects from medication can result in a significant increase in reports of those specific effects. Patients who were told about sexual side effects when starting finasteride or beta-blocker medication were significantly more likely to report these symptoms than patients who were not told of these side effects (Cocco, 2009;Mondaini et al., 2007). Similarly, in the context of a clinical trial, those patients warned of gastrointestinal side effects in one research site were more likely to complain of this as a side effect and withdraw from the study due to these complaints (Myers, Cairns, & Singer, 1987). ...
Background: In 2017, patients on a generic or branded antidepressant venlafaxine were switched to a new generic formulation (Enlafax). In February and April 2018, two major NZ media outlets ran stories about the new generic being less effective and causing specific side effects. This study aimed to examine the effect of the media coverage on drug side effects reported to the national Centre for Adverse Reactions Monitoring (CARM) and whether the specific symptoms reported in the media increased compared to side effects not reported in the media.
Method: We analysed monthly adverse reaction reports for Enlafax to CARM from October 2017 to June 2018 and compared adverse reports, complaints of decreased therapeutic effect and specific symptom reports before and after the media coverage using an interrupted time series analysis.
Results: We found the number of side effects and complaints of reduced therapeutic effect increased significantly following the media stories (interruption effect = 41.83, 95% CI [25.25, 58.41], p = .003; interruption effect = 15.49, 95% CI [7.01, 23.98], p = .012, respectively). The specific side effects mentioned in the media coverage, including suicidal thoughts, also increased significantly compared to other side effects not mentioned in the media.
Conclusions: In the context of a drug switch, media reports of side effects appear to cause a strong nocebo response by increasing both the overall rate of side effect reporting and an increase in the specific side effects mentioned in the media coverage, including reduced drug efficacy and heightened suicidal thoughts.
Keywords
media, nocebo effect, venlafaxine, side effects, generic medicines
... In these studies, patients received the same treatment yet different side effect information. Some studies showed that, the more information patients received, the more side effects they reported (16)(17)(18)(19), while others studies found no difference (20)(21)(22). Although it cannot be concluded whether informing about side effects is disadvantageous in general, strategies to prevent nocebo side effects may be useful for clinicians, especially when treating patients who are at risk of developing nocebo effects. ...
Relevance. Informing patients about potential adverse events as part of the informed consent may facilitate the development of nocebo-driven drug adverse events (nocebo side effects).
Objective. To investigate whether informing about the nocebo effect using a short information sheet can reduce nocebo side effects.
Methods. A total of N = 44 participants with weekly headaches for at least 6 months were recruited by using the cover story of a clinical trial for a headache medication. In reality, all participants took a placebo pill and were randomized to the nocebo information group or the standard leaflet group. Participants were instructed to read the bogus medication leaflet entailing side effects information shortly before pill intake. The nocebo group additionally received an explanation about the nocebo effect as part of the leaflet. Questionnaires were completed at baseline, 2 minutes, and 4 days after the pill intake. We conducted general linear models with bootstrap sampling. Baseline symptoms were included as a covariate.
Results. Most participants (70.5%) reported nocebo side effects at 2 minutes. Participants who received the nocebo information (n = 24) reported less nocebo symptoms than the control group (n = 20) (estimated difference: 3.3, BCa 95% CI [1.14; 5.15], p = .01, Cohen’s d = 0.59). Baseline symptoms, perceived sensitivity to medicine, and side effect expectations each moderated the group effect (estimated difference in slope: 0.47, BCa 95% CI [0.19; 0.73], p = .001, d = 0.75; 1.07 [0.27; 1.61], p = .006, d = 0.73; 1.57 [0.38; 2.76], p = .02, d = 0.58). No group differences were found at 4-day follow-up. After revealing the actual aim of the study, 86% of the participants evaluated the nocebo information to be helpful in general.
Conclusions. Results provide the first evidence that informing about the nocebo effect can reduce nocebo side effects.
... Participants reported more numerous AEs compared to the control information suggesting that the positive information about side effects has led to hypervigilance. The quantity and contents of information about side effects can play a critical role in side effect reporting and attribution [4,39,40]. In our case, both groups received an equal amount of information. ...
Side effects are frequent in pharmacological pain management, potentially preceding analgesia and limiting drug tolerability. Discussing side effects is part of informed consent, yet can favor nocebo effects. This study aimed to test whether a positive suggestion regarding side effects, which could act as reminders of the medication having been absorbed, might favor analgesia in a clinical interaction model. Sixty-six healthy males participated in a study “to validate pupillometry as an objective measure of analgesia”. Participants were unknowingly randomized double-blind to positive vs control information about side effects embedded in a video regarding the study drugs. Sequences of moderately painful heat stimuli applied before and after treatment with diclofenac and atropine served to evaluate analgesia. Atropine was deceptively presented as a co-analgesic, but used to induce side effects. Adverse events (AE) were collected with the General Assessment of Side Effects (GASE) questionnaire prior to the second induced pain sequence. Debriefing fully informed participants regarding the purpose of the study and showed them the two videos.The combination of medication led to significant analgesia, without a between-group difference. Positive information about side effects increased the attribution of AE to the treatment compared to the control information. The total GASE score was correlated with analgesia, i.e., the more AEs reported, the stronger the analgesia. Interestingly, there was a significant between-groups difference on this correlation: the GASE score and analgesia correlated only in the positive information group. This provides evidence for a selective link between AEs and pain relief in the group who received the suggestion that AEs could be taken as a sign “that help was on the way”. During debriefing, 65% of participants said they would prefer to receive the positive message in a clinical context. Although the present results cannot be translated immediately to clinical pain conditions, they do indicate the importance of testing this type of modulation in a clinical context.
... Several medications commonly used in HF treatment have been shown to either cause or worsen ED. 33 Unfortunately, there are conflicting data on many medications, and studies are limited by the inability to withdraw medications necessary for HF treatment. ...
Background:
Sexual activity is an important indicator of quality of life and is significantly impaired in patients with heart failure(HF). Cardiac resynchronization therapy (CRT) has positive effects on cardiac dysfunction and endothelial dysfunction that lead to erectile dysfunction. We aimed to evaluate that CRT may improve sexual activity in HF patients.
Methods:
136 patients (mean age 61.8 ± 12.8) were evaluated for the study. All patients filled out the Sexual Health Inventory for Men (SHIM) questionnaire for evaluating the erectile functions of patients before the CRT implantation. 180 days after CRT implantation, SHIM questionnaire were re-evaluated.
Results:
In the whole study population SHIM test scores were significantly increased after CRT therapy (12.99 ± 3.22 vs. 18.03 ± 5.00; p<0.001). Patients were divided into two groups according to the CRT response. Increase in SHIM test scores were significantly more in response (-) group then response (+) group [In response (-) group 0.81 ± 1.77; p=0.465 vs. in response (+) group 6.94 ± 3.36; p<0.001]. Positive crt response was found as an independent predictor of SHIM score (p<0.001).
Conclusion:
Our study showed that CRT therapy had positive effects on HF patients wityh erectile dysfunction.
... 24 Another study showed that hypertensive rats treated with amlodipine recovered impaired neurogenic relaxation of their corpora cavernosa. 25 An early placebo-controlled, cross-over study showed that nifedipine caused some subjective decrease in masturbatory erectile firmness, with no other significant consequences on erectile function. 26 In a separate study that same year, researchers determined that nifedipine (and dihydropyridine diltiazem) seemed to improve sexual function, especially when compared with hydrochlorothiazide. 27 Overall, CCBs do not seem to be associated with ED and are likely to have a neutral effect. ...
Erectile dysfunction (ED) affects about 50% of men in the USA and is primarily attributed to physiological (organic) and psychological causes. However, a substantial portion of men suffer from ED due to iatrogenic causes. Common medications such as antihypertensives, non-steroidal anti-inflammatory drugs and antacids may cause ED. Physicians should be aware of the various prescription medications that may cause ED to properly screen and counsel patients on an issue that many may feel too uncomfortable to discuss. In this review, we discuss the physiology, data and alternative therapies for the ED caused by medications.
... Whatever thelegitimacy of those-claims, in this-study, the-effect was observed, leaving little-doubt that subjects can, and do, change-their-behavior, when under investigation. This-effect is one of the-hardest inbuilt unavoidable-biases, toeliminate, or factor, into the-design of an-experiment, and hence, evaluation of the-Hawthorne-effect continues, in the-present-day (Levitt & List, 2011;Menezes et al., 2011;Cocco, 2009;Kohli et al., 2009;Leonard, 2008). Some of the-studies are Randomized-Controlled-Trials (McCambridge et al., 2012;Evans 2010); Quasi-Experimental-Studies (Fernald et al., 2012;Ertem et al., 2001); and Observational-Studies (Fox et al., 2008;Maury et al., 2006;Eckmanns et al.,2006;Mangione-Smith et al., 2002), vast-majority of studies, however, is in medical-fields. ...
Improving operations-efficiency is an ongoing need , for all-industries, including textile-manufacturing. Time-study is essential, for-both; planning and control, of industrial-operations. This-research used Time-study, of observational-design-type, and of element-scope-level. Classical-stopwatch-technique was-used, to-ascertain the-standard-time, for the-printing-operaton, on the Octrooi-Aangevraagd Rotary-Screen printing-machine, for 3 cycles. Performance-rating was obtained using the-speed-rating-technique. The-machine-operation was-divided into 4 distinct and repetitive machine-elements: machine setup ; color-impression; drying; and pickup. This-time-study established Standard-Second-Value of 18, 725.41, giving machine-utilization of 65%. The-most time-consuming elements, requiring constant-operators' attention, were found to-be color-impression, and pick-up/curing. Hawthorne-Effect was also-observed, where machine-operators noticeably-changed their-behavior, when they know that their-work being-measured. The-study made several-recommendations for future-more broader and deeper-research.
... der könnte als seltene Nebenwirkung Erektionsstörungen zur Folge haben", waren es 31 bzw. 32 %, zehnmal so viele, allein abhängig von der Art der Ankündigung [5,29]. Eine systematische Übersichtsarbeit mit Metaanalyse fand eine robuste Assoziation zwischen der Erwartung und dem Auftreten von Übelkeit nach Chemotherapie [6]. ...
Erwartungen des Patienten erhöhen die Wahrscheinlichkeit ihres Eintretens und sind so Hauptauslöser von Placebo- und Noceboeffekten. Starke Placeboeffekte sind nicht nur regelmäßig bei medikamentöser oder nichtmedikamentöser Scheinbehandlung in placebokontrollierten Studien nachweisbar, sondern tragen zu jeder echten Behandlung wesentlich bei. Für die maximale Wirksamkeit von Medikamenten und anderen Behandlungen sind daher begleitende Worte notwendig, mit positiven Ausdrücken und nicht mit Negationen. Diese Verstärkung durch Placeboeffekte ist wichtiger als die durchaus verbreitete Anwendung von Placebos, die wegen der Aufklärungs- und Therapiepflicht und der ebenfalls inhärent induzierten Nebenwirkungen problematisch bleibt. Jedes falsche Sprechen über Symptome oder Nebenwirkungen kann diese verstärken oder auslösen. Noceboeffekte sind nicht eingebildet, sondern echte Symptome, die durchaus gefährlich sein können und einen beträchtlichen Teil behandelter Nebenwirkungen ausmachen. Sie sollten durch mehr Bewusstsein und Kenntnisse darüber vermieden oder neutralisiert werden. Dies gelingt bei der Risikoaufklärung durch Kombination mit Positivem, wie dem erwarteten Nutzen der Behandlung oder der Prophylaxe und Therapierbarkeit von Nebenwirkungen. Vorhandene Negativerwartungen werden durchbrochen, indem andere Möglichkeiten wieder in das Blickfeld gerückt und Negativerfahrungen in der Vergangenheit belassen werden. Placebo- und Noceboeffekte wirken im Kontext, das heißt in Abhängigkeit von den individuellen Patientenerfahrungen und -vorstellungen sowie der Arzt-Patienten-Beziehung, die den besten Schutz vor Aufklärungsschäden darstellen kann. Die Erwartung und ihre Effekte werden außerdem stark von der Erwartung des Arztes und von Mitpatienten, Medien und Gesellschaft beeinflusst.
... Some of these studies were specifically designed in a randomized fashion to assess the effect of beta-blockers on erectile function and proposed that beta-blockers were worse than placebo [113][114][115]. However, a few studies support that betablocker-related ED is attributed to the knowledge of the po-tential side effects of the drugs and not to the drugs per se [126,127]. Despite the substantial amount of data supporting an unfavorable role of this class of drugs on erectile function, the placebo effect cannot be excluded as a potential explanation. ...
Background:
Sexual dysfunction affects millions of people with an increasing prevalence, worldwide. The pathophysiology of the disease shares several similarities with cardiovascular disease (CVD), including atherosclerosis, endothelial dysfunction, structural vascular damage and subclinical inflammation. Erectile dysfunction (ED) and female sexual dysfunction are common among patients with CVD and risk factors such as hypertension, diabetes, obesity and metabolic syndrome. Given the common pathogenesis of the diseases, ED is an independent prognostic factor of future ED events. Patients with overt ED or risk factors are usually treated with several drugs for the management of these conditions. Several of these drugs have been evaluated for their effect on sexual activity.
Results and conclusion:
Among the antihypertensive drugs, diuretics and beta-blockers seem to exert a detrimental impact on sexual function, with nebivolol being the only beta-blocker with favorable properties through an increase in nitric oxide bioavailability. In contrast, renin-angiotensin system inhibitors and calcium-channel blockers have a neutral effect on sexual activity. Hypoglycemic drugs have been less evaluated in the ED setting, with metformin, pioglitazone and liraglutide presenting favorable results. Statins on the other hand have not provided consistent results with observational studies suggesting a detrimental role in sexual activity and a few randomized studies indicating a neutral or even beneficial effect on erectile function.
... The effect of pills, real and placebo, is another testament to the power of the mind in producing reality (Barsky, Saintfort, Rogers, & Borus, 2002;Cocco, 2009). The meaning of "placebo effects" is widely known, whereas its counterpart" nocebo effects" is less acknowledged. ...
Medical procedures and tests become a challenge when anxiety and pain make it difficult for the patient to cooperate or remain still when needed. Fortunately, a short intervention with hypnoidal language at the onset of a procedure induces a positive and sustained change in the way pain and anxiety are processed. Although anesthesia may appear to be a simple solution to eliminate pain, the adverse effects of preanesthesia anxiety on postoperative behavior and recovery are often not fully appreciated. This article discusses options for self-hypnotic relaxation that are applicable to interactions with children. The high suggestibility of children makes it relatively easy to engage them in make-believe scenarios. Avoidance of negative suggestions is key in avoiding nocebo effects that may be difficult to overcome later. Once a child is immersed in his or her preferred scenario or hobby/activity of choice, environmental and procedural stimuli can be easily integrated in the imagery. Ego-strengthening metaphors that tie in features of strength, confidence, or resilience are particularly empowering. Even when children are fully under general anesthesia, they may still have recall of what is said in the room, and therefore, caution in word choice should be maintained.
... Group 3 patients knew neither the drug name nor a possible ED side effect. After 60 days the ED incidence according to the IIEF questionnaire was 32% in group 1, 13% in group 2, and 8% in group 3 (p < 0.01) [Cocco, 2009]. In another study with the same design, 96 men with newly diagnosed cardiovascular disease were treated with atenolol 50 mg daily for three months. ...
Erectile dysfunction (ED) impacts over 100 million men worldwide and occurs at a higher incidence in men with hypertension. Beta blockers are one of several antihypertensive drug classes associated with ED. Nebivolol is a beta blocker with vasodilating properties mediated through endothelial release of nitric oxide which facilitates penile erection. Thus, nebivolol may offer an advantage over other beta blockers in the patient with hypertension and ED. A literature search comparing nebivolol with other beta blockers identified four European studies of limited duration, with the longest study being 28 weeks. Survey scores for erectile function showed significant improvement in erectile function with nebivolol in two of the studies, while the other two studies showed erectile function did not significantly worsen with nebivolol as compared with other beta blocker agents. One study showed improved erectile function scores, possibly due to the presence of a Hawthorne effect. Based on this small sample of studies, nebivolol may be of use in the patient with or at risk of developing ED, when a practitioner specifically wants to use a beta blocker as add-on antihypertensive treatment.
... In a face-to-face clinic visit, physicians can often misinterpret what patients are saying, or patients might report inaccurate symptoms for a variety of reasons. [23][24][25][26] Social media can provide plastic surgeons insight into their patients' expectations, concerns, and queries as reported by patients in an unsolicited environment. Such feedback might be extremely difficult or costly to obtain otherwise. ...
Background
Social media have been used to study many aspects of health and human behavior. Although social media present a unique opportunity to obtain unsolicited patient-reported outcomes, its use has been limited in plastic and reconstructive surgical procedures, including migraine nerve surgery. The goal of this study was to utilize the most popular social media site, Facebook, to evaluate patients’ experience with migraine surgery.
Methods
Six months of data regarding nerve surgery, nerve stimulators, and radiofrequency nerve ablation were collected from posts and comments written by members of 2 Facebook groups. Outcomes were classified by degree of resolution of symptoms.
Results
A total of 639 posts related to migraine surgery. Of 304 posts commenting on postoperative success of nerve surgery, 16% reported elimination of headaches and 65% significant improvement (81% with complete or significant improvement), 5% partial improvement, 11% no change, and 3% worsening symptoms. Nerve surgery had a higher success rate than nerve stimulators and radiofrequency ablation. Nerve surgery was recommended by 90% of users.
Conclusions
The 81% rate of complete or significant improvement of symptoms in this study is close to the 79% to 84% shown in current literature. Similar to the findings of a recent systematic review, surgery is more efficacious compared with nerve stimulators and ablation. This study adds to evidence favoring migraine surgery by removing evaluator bias and demonstrates that surgical outcomes and satisfaction data may be obtained from social media.
... 3,4 To understand the potential impact of negative consumer responses to RNC cigarettes, it is essential to evaluate the role of expectancies (ie, expectations about consequences of use 16 ); for example, prior work documents that negative drug treatment expectancies (eg, expecting negative side effects or poor treatment outcomes) significantly (and independently) increase the likelihood of their occurrence. [17][18][19][20][21] To simulate real-world conditions reflecting a nicotine reduction policy, several studies have employed open-label designs in which smokers knew study-supplied cigarettes contained reduced nicotine. As such, it is unclear if negative responses to these cigarettes resulted from product design features (eg, RNC cigarettes objectively tasted worse) or participants' expectancies (eg, associating nicotine with taste caused smokers to expect and consequently report poorer taste). ...
Objectives: We sought to determine if negative responses to reduced nicotine content (RNC) cigarettes during open-label trials result from smokers’ (negative) expectancies. We examined the effects of nicotine content description – independent of actual nicotine content – on subjective responses (craving reduction, withdrawal suppression, mood changes, and sensory ratings) and smoking behaviors (topography measures and carbon monoxide [CO] boost).
Methods: Thirty-six 12-hour-abstinent daily smokers completed a 3-session crossover trial. During each session, participants smoked their preferred brand cigarette – blinded and described as containing “usual,” “low,” and “very low” nicotine content – through a topography device and completed CO and subjective response assessments.
Results: Although nicotine content was identical, compared to the “usual” content cigarette, participants experienced less craving reduction after smoking the “very low” nicotine cigarette, and rated its smoke as weaker (p < .05). Participants took shallower puffs of the “low” nicotine cigarette (p < .05), and rated the “low” and “very low” nicotine cigarettes as weaker and too mild (p < .01).
Conclusions: Negative responses to RNC cigarettes may be due, in part, to negative expectancies about using cigarettes containing less nicotine. In this context, RNC cigarette marketing and labeling are likely important considerations if a federal nicotine reduction policy is initiated.
To alleviate anti-cancer treatment burden in advanced breast cancer, patient-clinician communication strategies based on nocebo-effect mechanisms are promising. We assessed distinct/combined effects on psychological outcomes (e.g. anxiety; main outcome) and side-effect expectations of (1) nocebo information about the (non)pharmacological origin of side effects, and (2) clinician-expressed empathy through reassurance of continuing support. Furthermore, we explored whether information and empathy effects on side-effect expectations were mediated by decreased anxiety. In a two-by-two experimental video-vignette design, 160 cancer patients/survivors and healthy women watched one of four videos differing in level of nocebo information (±) and empathy (±). Regression and mediation analysis were used to determine effects of information/empathy and explore anxiety’s mediating role. Anxiety was not influenced by empathy or information (Stai-state: p = 0.295; p = 0.390, VAS p = 0.399; p = 0.823). Information improved (specific) side-effect coping expectations (p < 0.01). Empathy improved side-effect intensity expectations (p < 0.01 = specific; p < 0.05 = non-specific/partial) and specific side-effect probability expectations (p < 0.01), and increased satisfaction, trust, and self-efficacy (p < 0.001). No mediating effects were found of anxiety on expectations. Mainly empathy, but also nocebo information improved psychological outcomes and—mainly specific—side-effect expectations. Exploring the power of these communication elements in clinical practice is essential to diminish the anti-cancer treatment burden in advanced breast cancer.
Our aims were to provide updated information on placebo/nocebo effect and the potential use of placebo in clinical practice. This article can only provide a rough overview on the placebo and nocebo effect and is intended to serve as a starting point for the reader to go deeper into the corresponding literature. The placebo effect has been observed in multiple medical conditions, after oral administration, with manual therapies as well as with surgery and invasive procedures. The use of placebo in clinical trials is fundamental, although the ethics of its use is under discussion. The placebo may behave like a drug from the pharmacokinetic and pharmacodynamic point of view and can also be associated with adverse events (nocebo effect). Placebo can modify treatment by increasing or decreasing the effects of drugs. The factors associated with the occurrence of placebo effect are multiple, but in addition to those that depend on the placebo itself, the doctor-patient relationship would be the most important. As a result of findings that were published in the last two decades, the psycho-neurobiological basis of placebo is becoming better understood, although further studies are needed. In conclusion, the placebo effect in the clinic exhibits weak to moderate intensity. Placebo, in addition to its use in the clinical trial, should be considered another therapeutic remedy either as stand alone or in association with treatment, and could be useful in certain circumstances. The use of placebo should be regulated by the European health authorities through a guide in clinical practice that will improve patient care.
Zusammenfassung Als Placebo-Effekte gelten die positiven Wirkungen einer Scheinsubstanz oder Scheinbehandlung. Ein Placebo versucht die positiven Wirkungen eines Arzneimittels oder einer Intervention nachzuahmen, ohne aber dabei das spezifische Arzneimittel oder die spezifische Behandlungsmethode zu beinhalten. Als Hauptmechanismen haben sich die Erwartungen auf das Behandlungsergebnis durch den Patienten, assoziative Lernprozesse sowie die Qualität der Beziehung zwischen Patienten und Behandler herausgestellt. Placebo-Effekte können aber auch vom Behandler oder Versuchsleiter ausgehen. Die Erwartungen eines Arztes oder Versuchsleiters auf den Ausgang einer Behandlung können die wahrgenommene Wirksamkeit des Patienten und somit die Ergebnisse der Intervention beeinflussen. Ähnliche Einflüsse auf den Ausgang eines Experimentes durch die Erwartungen des Experimentators sind in der Psychologie aus der Priming-Forschung bekannt. Begründungen, warum die Erwartungen eines Versuchsleiters das Experiment selbst beeinflussen, lassen sich in der Psychologie und der Quantenphysik finden. In dieser Arbeit werden die unterschiedlichen Wirkfaktoren des Placebo-Effekts aufgezeigt und in einem Online-Experiment nachgestellt. Der Einfluss der Erwartungen eines Versuchsleiters wird herausgearbeitet und mit verschiedenen Theorien aus der Psychologie und der Quantenphysik begründet. Die Ergebnisse der vorliegenden Arbeit geben einen Hinweis auf die Objektivität von wissenschaftlichen Studien und Experimenten. Diese scheint nicht immer gegeben zu sein, da auch die Erwartungen des Versuchsleiters einen Einfluss auf die Resultate haben. Das wäre auch eine Erklärung dafür, dass viele Replikationsstudien andere Ergebnisse liefern als die Originalstudien. Abstract The positive effects of a sham substance or treatment are considered placebo effects. A placebo tries to mimic the positive effects of a drug or an intervention, but does not include the specific drug or treatment. The main mechanisms that have emerged are expectations of the patient's treatment outcome, associative learning processes and the quality of the relationship between patient and practitioner. Placebo effects can, however, also originate from the practitioner or test director. A doctor's or investigator's expectations of the outcome of a treatment can affect the perceived effectiveness of the patient and thus the results of the intervention. Similar influences on the outcome of an experiment due to the expectations of the experimenter are known in psychology from priming research. Reasons why the experimenter's expectations influence the experiment itself can be found in psychology and quantum physics. In this work, the different active factors of the placebo effect are shown and simulated in an online experiment. The influence of the examiners' expectations is worked out and justified with various theories from psychology and quantum physics. The results of the present work give an indication of the objectivity of scientific studies and experiments. This does not always seem to be the case, as the investigator's expectations also have an influence on the results. That would also explain why many replication studies give different results than the original studies.
Body sensations can negatively impact human health-related behavior in two major ways. First, symptoms of top-down origin, e.g., evoked by patient information leaflets describing possible medication side effects or bombastic media stories, can cause severe suffering and decrease patients’ adherence to the treatment. This is called nocebo response; it can be activated by conscious and nonconscious expectations, conditioning (personal or vicarious), social contagion, or certain aspects of the doctor–patient relationship. Nocebo reactions can be explained as side effects of the predictive way our brain works thus cannot be completely eliminated. Second, the lack of unpleasant body sensations in asymptomatic diseases might also negatively impact patients’ adherence to treatment. For both cases, knowledge of these phenomena and voluntary effort based on logical reasoning are required to overcome strong primary experience.
Let us leave the conceptual problems aside for a while and keep the phrase placebo effect. Even then there is a multitude of issues to be examined: Do placebo effects exist after all? If they do exist, what is their nature in relation to the human mind and body? How and why have they evolved? Are there placebo effects outside medicine? Is there a certain kind of personality that is prone to placebo effects? Can placebo effects be seen in children and non-human animals? I will begin with the question concerning the existence of placebo effects.
Erectile dysfunction is a common problem which is seen
among hypertensive patients. It is thought that medications used in
treatment of hypertension may contribute this problem as well. Contrary
to common belief, new generation drugs doesn’t produce adverse
effect on erectile function. Phosphodiesterase 5 inhibitors can be used
safely in treatment of erectile dysfunction in hypertensive patients.
Introduction: Although statins have a satisfactory safety profile and are well tolerated, many statin-treated patients report muscle symptoms in clinical practice which contribute to drug discontinuation and, consequently, adverse cardiovascular outcomes.
Areas covered: This narrative review will cover the definition and prevalence of statin intolerance, the clinical spectrum of statin-associated muscle symptoms (SAMS) with special focus on patients with only mild myalgias, the complexity of statin muscle intolerance diagnosis and provide an overview on the nocebo effect of particular importance for physicians.
Expert opinion: Many patients are unable to tolerate statin therapy, with SAMS being the most common cause of statin intolerance. The reported incidence of SAMS was consistently lower in randomized placebo-controlled trials than in observational studies. These results strongly suggested that SAMS were not always due to by the pharmacologic effects of statin therapy. Convincing patients that their muscle symptoms might be due to causes other than statin treatment is sometimes difficult. Furthermore, clinicians should not prematurely discontinue statin therapy before considering other possible causes, including the nocebo effect.
Background: Nocebo effects contribute to a large proportion of the non-specific side-effects attributed to medications and are mainly generated through negative expectations. Previous reviews show that interventions designed to change participants' expectations have a small effect on pain experience. They are also effective in reducing side-effects caused by exposure to sham medications. To date, there has been no review of the influence of such interventions on symptoms attributed to real medicinal treatments.
Objective: To review studies using a randomized controlled design testing the effect of brief psychological interventions compared to usual practice on the side-effect experience to medicinal treatments in healthy volunteers and patients.
Methods: We searched Web of Science, Scopus, Medline, PsycINFO, PsycARTICLES, and Cochrane CENTRAL using search terms for randomized controlled trials along with “nocebo,” “placebo effect,” “medication,” “side-effects,” and associated terms. Studies were eligible if they studied a human population, used an active medicine, delivered a brief psychological intervention intended to influence side-effect reporting compared to usual care or no intervention, and used a randomized controlled design. Because of the heterogeneity of the literature we used a narrative synthesis and assessed evidence quality using the GRADE approach.
Results: Our database search and supplementary search of the reference sections of included studies retrieved 50,140 citations. After screening, full text review and manual reference searches, 27 studies were included. The quality of the studies and evidence was judged to be low. The strongest and most consistent effect came from omitting side-effect information, although surprisingly de-emphasizing side-effects did not affect side-effect reporting. Other techniques, including priming, distraction, and altering the perception of branding, produced mixed results.
Conclusion: Brief psychological interventions can influence side-effect reporting to active medications. Research is currently investigating new ways to de-emphasize side-effects whilst still upholding informed consent, but larger confirmatory trials with suitable control groups are needed. The literature in this area would be improved by more detailed reporting of studies.
In diesem Kapitel wird die Krankheit realistisch angeschaut – geradeaus ins Gesicht, sozusagen von Auge zu Auge –, dissoziiert, d. h. abgespalten, und mit Zuversicht, Vertrauen und Mut nur als Teil des Gesamtproblems Selbstheilung verstanden und erlebt. Sie lernen, die Krankheit zu entmystifizieren, sie weniger wichtig, weniger bedeutsam als Ihre Gesundheit zu machen: den Nocebo-Effekt zu reduzieren bis hin zu eliminieren. Dieses unterscheidet die Methode der sechs dramaturgischen Elemente (SDE-Methode) maßgebend von den meisten anderen geführten Vorstellungsmethoden, die in der Regel ausschließlich ressourcenorientiert arbeiten und den Gegenspieler zur Gesundheit, die Krankheit, wenn überhaupt, höchstens indirekt einbeziehen.
Background Pharmacovigilance, as it is carried out primarily by healthcare professionals is more focused on being very objective in nature. Acknowledging the importance of the subjective experience of patients in pharmacovigilance was underpinned by its unique ability to bring about a more holistic understanding through the deep information unraveled by the patients. Medication safety-related information has to be shared with patients to allow them to be actively involved in their therapy and pharmacovigilance. Despite the advantages of sharing information, it stands to reasons whether sharing information related to possible side effects would negatively affect patients and impinge upon their treatment plan and process. Aim of the Review The purpose of this systematic review was to critically assess the potential negative impact of informing patients about medication side effects by written and/or oral information on medication compliance, occurrence/development of suspected side effects and clinical outcomes. Method A comprehensive search was conducted in PubMed, and Cochrane library to identify potential records between the year 1975 and 2017; then titles, abstracts, and full texts were screened using the inclusion criteria to filter out irrelevant studies. The data extraction, and the results were narratively synthesized and presented in tables. Results A total of 2012 articles were screened for inclusion, 32 full-text articles were assessed for eligibility and finally resulting in the inclusion of 17 randomized control studies which met the set criteria. Findings unraveled that the educational intervention did not result in increased occurrence/reporting of side effects in most of the evaluated studies; except 4 studies, and no significant impact on compliance to medications and negative clinical outcome was observed. Apprehension of negative events to medications were observed in two of the four studies which evaluated these parameters. Conclusion The present review did not find enough evidence to support the over concerns on the potential negative impact of sharing of information on the adverse effects to patients, though the influence could manifest as nocebo-effect. The various components and methods employed for this information sharing process can influence the potential impact of this activity. These concerns about the undesirable effects should not deter the active involvement of patients in pharmacovigilance activities. There is a definite need to have more studies in this area, where much of concern still does exist among the various stakeholders of drug safety information.
Many studies have shown that educating patients about the potential adverse effects of a drug can increase the chances that those adverse effects will be experienced. Studies have further shown that how such information is communicated can also impact this nocebo risk. Additionally, information provided through patient education can influence treatment efficacy, perhaps by moderating the placebo response. There is therefore a need to optimize the manner in which patients are educated about their medications so that placebo-related benefits are enhanced and nocebo-related harm is minimized. This article provides suggestions on the subject for clinical practice as well as research. Nonspecific factors in psychopharmacology are important and should not be neglected.
Hypertension and its related disorders have a high mortality as well as morbidity and require strict adherence to medications in order to mitigate these consequences. Sexual dysfunction is prevalent among patients with hypertension and can either be attributed to the disease progression or as a result of antihypertensive medications. Most patients report the symptoms after initiation therapy and sometimes leads to a spurious association with antihypertensive drugs. However, most drugs in the antihypertensive classes have been associated with sexual dysfunction in both men and women. The most implicated drugs are diuretics, beta-blockers, and centrally acting agents while angiotensin modulating drugs have proved to improve upon erectile dysfunction. The older generation of antihypertensive medications tends to have a negative impact on sexual performance. Females experience sexual dysfunction associated with hypertension and its treatment, but this is grossly under-reported compared to their male counterparts. The incidence in females is higher compared to men and it is sometimes erroneously considered as part of the post-menopausal period rather than hypertension. The impact of medications on sexual dysfunction has somewhat produced contrasting results with some studies showing an association with medications and others proving otherwise. Clinicians need to be aware of the impact of sexual dysfunction among hypertensive patients in order to make an informed decision regarding dosage and choice of medications while keeping target blood pressure in mind.
Some of the information that physicians convey to their patients can inadvertently amplify patients’ symptoms and become a source of heightened somatic distress, an effect that must be understood by physicians to ensure optimal management of patient care. This effect illustrates the iatrogenic potential of information, as opposed to the iatrogenic potential of drugs and procedures.
Sexual function is an important component of quality of life. The present chapter examines issues concerning sex and implantable electronic devices, including sexual dysfunction and safety concerns. Performing sex involves a 3–5 metabolic equivalent effort, a gradual increase in catecholamines with a modest and short increase in heart rate and blood pressure. Overall sexual activity is safe, especially if response to moderate physical activity tested normal. Pathology based research suggests a mild increased in the incidence of myocardial infarction, specifically in men performing extra-marital sex. However, significant arrhythmia that may lead to activation of an implanted defibrillator is extremely rare. Sexual dysfunction is prevalent in patients with a cardiovascular disease including those with implantable devices. Patients with pacemakers may have sexual dysfunctions which seem attributable to older age, and not to the device. Heart failure patients implanted with a resynchronization device may benefit from improved sexual function and consequently better quality of life. Despite these low risks, “sexual avoidance” is prevalent among patients with implanted defibrillators and has several causes such as fear, anxiety and altered body image. Sex and sexuality should be actively addressed during medical consultation to relieve unjustified fears and provide patients with adequate information and treatment.
In der Medizin wirken nicht nur Medikamente und Operationen, sondern auch der Therapeut und seine Worte, und wie immer sind beide Richtungen möglich. Jedes Symptom einer Krankheit, jede Nebenwirkung oder Komplikation kann durch ein falsches Sprechen darüber induziert werden. Suggestionen beeinflussen nicht nur psychische Funktionen wie Angst und Schmerz, sondern auch körperliche. Starke, bildhafte Worte, Doppeldeutigkeiten, Missverständnisse, unbedachte Gespräche, Fachjargon und Risikoaufklärung bilden mannigfaltige Negativsuggestionen. Nicht die medizinische Aufklärung, sondern die Art der Aufklärung gehört auf den Prüfstand. Durch Kenntnis von Nocebo-Effekten und Negativ-Suggestionen können diese besser erkannt und vermieden werden. Diese Negativeinflüsse wirken im Kontext, d. h. in Abhängigkeit von individueller Vorgeschichte und Ängsten des Patienten sowie von dem entstandenen Vertrauensverhältnis. Der beste Schutz vor Schäden durch Aufklärung und Negativ-Suggestionen ist eine tragfähige therapeutische Beziehung. Kenntnisse aus der Hypnotherapie können hier die medizinische Kommunikation wesentlich verbessern.
The supposed superiority of randomized over non-randomized studies is used to justify claims about therapeutic effectiveness of medical interventions and also inclusion criteria for many systematic reviews of therapeutic interventions. However, the view that randomized trials provide better evidence has been challenged by philosophers of science. In addition, empirical evidence for average differences between randomized trials and observational studies (which we would expect if one method were superior) has proven difficult to find. This chapter reviews the controversy surrounding the relative merits of randomized trials and observational studies. It is concluded that while (well-conducted) observational can often provide the same level of evidential support as randomized trials, merits of (well-conducted) randomized trials warrant claims about their superiority, especially where results from the two methods are contradictory.
Background: In April 2009, the NHS Institute for Innovation and Improvement released four Better Care Better Value (BCBV) prescribing indicators. One indicator targeted renin–angiotensin–aldosterone system (RAAS) drugs, i.e., angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), to improve their prescribing efficiency. The indicator affects the proportion of items written for ACEIs as a percentage of the total number of prescriptions for RAAS drugs. A proportion of 80% ACEIs has been proposed and considered as an achievable target based on the small proportion (2–10%) of patients who cannot tolerate the ACEIs-related side effects, mostly dry cough. However, neither the impact of the BCBV indicator on the utilisation of ACEIs/ARBs nor its cost-saving implication is yet known. The BCBV indicator involves switching established ARBs users to ACEIs, where appropriate. However, no previous studies have specifically investigated the clinical and economic impact of the switch of ARBs and hence it is unclear whether the switch from ARBs to ACEIs, promoted by the BCBV indicator, would be associated with any clinical or economic issues. Without any financial incentives or legislation enforcement, uptake of the BCBV policy is predicted to be low, especially as evidence suggests that single measures are ineffective in altering GPs’ prescribing behaviour. However, the uptake and implementation of the BCBV indicator has not yet been explored. Aims: This thesis aimed to evaluate the impact of the BCBV indicator for ACEIs/ARBs on the utilisation of ACEIs/ARBs in treating hypertension (HT) and any associated cost savings. The effects of switching patients from ARBs to ACEIs on clinical outcomes (adherence, blood pressure [BP] level and HT-related complications), healthcare resources and costs were also investigated. Prior to this, patients’ adherence and persistence patterns (discontinuation and switching), and potential associated factors were studied. Finally, the uptake and implementation of the BCBV indicator in real practice was explored. Methods:This research used an explanatory sequential mixed-method approach. Firstly, an interrupted time series analysis was used on data extracted from the Clinical Practice Research Datalink (CPRD), from April 2006 to March 2012, to examine the impact of the BCBV indicator on the repeated cross-sectional monthly ACEIs/ARBs prescriptions and costs in patients with primary hypertension, which was validated using national dispensing datasets. Secondly, a retrospective cohort study was conducted using prescription records extracted from CPRD for patients with primary hypertension who were prescribed antihypertensive drugs from April 2006 to March 2013. Patients’ adherence and persistence patterns (including switching) to antihypertensive drug classes were quantified and their association with patients’ characteristics tested, using Generalised Linear Models and survival analysis. Thirdly, a retrospective cohort study was conducted on patients who switched their index drug class from ARBs to ACEIs to evaluate the clinical outcomes and resources used associated with ARBs switching, using data from CPRD in linkage with Hospital Episode Statistics, and applying multilevel regression for data analysis. Finally, semi-structured interviews were conducted with 16 general practitioners, to explore their views about ACEIs/ARBs prescribing and the BCBV policy to understand the reasons underpinning the effectiveness/ineffectiveness of the BCBV indicator. The interviews were recorded, transcribed verbatim and analysed using a thematic approach. Results:Impact of the BCBV indicator on ACEIs/ARBs utilisation and cost saving. The ACEIs prescription proportion declined from 71.2% in April 2006 to 70.7% in March 2012. The policy initially resulted in a sudden reduction of 0.3% (95%CI: –0.44, –0.16) in the level of ACEIs prescription proportion; however, it was thereafter associated with a sustained, significant increase of 0.013% (95%CI: 0.0007, 0.02). The failure to achieve the 80% target by the end of the study period resulted in missing a potential cost saving of 23.9% of the total ACEIs/ARBs cost. In June 2014, a potential cost saving of ~£1 million was predicted, had the 80% target been achieved; this substantial saving was several years after the availability of several low-cost generic ARBs. Adherence and persistence to antihypertensive drug classes: Among the 176,835 patients with primary hypertension included in this analysis, 38.4% and 20% were non-adherent (proportion of days covered [PDC]<80%) to their antihypertensive drug class and therapy, respectively. The discontinuation rate of antihypertensive drug class (56.1%) and therapy (35.5%) was relatively high by the end of six-year follow-up period. Using ARBs as the index drug class, prevalent hypertensive patients, prevalent antihypertensive drug users and increasing age were associated with higher PDC to antihypertensive drug class and therapy but a lower risk of drug discontinuation; whereas a higher deprivation level, comorbidity score and switching of antihypertensive drug class were associated with lower PDC to antihypertensive drug therapy but a higher risk of discontinuation. Overall, 26% of the included patients switched their antihypertensive drug class. Using ARBs, higher deprivation, higher comorbidity and prevalent antihypertensive drug users were protective factors against switching; whereas female gender, prevalent hypertensive patients, higher BP level and increasing age were associated with a higher risk of switching. Clinical and economic implications of switching patients from ARBs to ACEIs: Of the 46,193 patients who switched their antihypertensive drug therapy, only 470 patients switched from ARBs to ACEIs – they were included in this study. Based on whether the patient combined ACEIs with other antihypertensive drug classes in the post-switching period, 369 patients were classified into ACEIs-combined group and 101 patients into ACEIs-monotherapy group. Compared with the pre-switching period, the proportion of non-adherent patients (PDC<80%) in the post-switching period increased significantly (17% vs. 27%); however, this significant increase was observed only in the ACEIs-combined group (17.3% vs. 29%). The switching of ARBs was associated with a significant reduction in both systolic and diastolic BP (144.2 vs. 141.9 mmHg, p<0.001) and (84.6 vs. 82.6 mmHg, p<0.001), respectively; however, this effect was found only in the ACEIs-combined group. The incidence of all HT-related complications was comparable in both pre- and post-switching periods, except for the incidence of MI, which reduced significantly only in the ACEIs-combined group (OR=0.1, 95%CI: 0.04, 0.6). Importantly, the switching of ARBs to ACEIs was associated with a significant reduction in the total medical costs (mean cost difference: –£329.2, 95%CI: –534.6, –205.7). Uptake and implementation of the BCBV indicator: Potential barriers suggested for the poor uptake of the BCBV policy, included a lack of GP awareness of the policy, GPs’ negative attitudes toward the policy and a lack of financial incentives. Among other reasons, the current high proportion of ARBs users appeared to be related to an over-switching of ACEIs to ARBs in anticipation of an ACEIs-related dry cough. Suggested measures for increasing the policy uptake included effective dissemination strategies, linking the policy to financial incentives and providing guidance on performing the switching. Furthermore, strategies to address the over-switching of ACEIs to ARBs were considered essential for the BCBV policy to achieve its 80% ACEIs target. Conclusions:The BCBV indicator was ineffective and failed to achieve the 80% ACEIs target. The association of achieving the 80% target with a remarkable cost-saving opportunity and the lack of any negative clinical consequences following the switching of ARBs to ACEIs indicate the ongoing necessity to reconsider and reinforce this policy through multiple initiatives to increase its future effectiveness, building on the study’s identified barriers and suggested solutions. This thesis represents a case study of a failed and an ineffective prescribing policy, attributed primarily to inappropriate policy implementation. It provides key lessons for policy makers and healthcare authorities on the importance of effective implementation strategies as an integral component to any successful policy.
The placebo effect refers to a therapeutic benefit arising as a rule from the expectation of benefit itself, not from the actual composition of a treatment. Thus patients who are told they are receiving a painkiller but actually get saline solution can still enjoy an analgesic effect owing to the evocative power of the medical ritual. Note that this model doesn’t entail that the benefit of the treatment is illusory. On the contrary, placebos can stimulate the release of the body’s opioids, an effect that can be blocked by the opioid antagonist, naloxone. Correspondingly, the nocebo effect refers to a harm arising from the expectation of harm, as when people led to believe they have suffered a toxic exposure fall ill. While the nocebo effect is ethically difficult to study and much of the knowledge about it derives from observation and accidental findings rather than experiment, both the placebo and nocebo effect appear to operate largely through the power of suggestive messages, enhanced in many cases by theatrical effects. Among the messages capable of springing to life in our minds and bodies are those that propel the process of medicalization. “Telling people they are sick undoubtedly has a strong negative placebo effect.”1
The supposed superiority of randomized over non-randomized studies is used to justify claims about therapeutic effectiveness of medical interventions and also inclusion criteria for many systematic reviews of therapeutic interventions. However, the view that randomized trials provide better evidence has been challenged by philosophers of science. In addition, empirical evidence for average differences between randomized trials and observational studies (which we would expect if one method were superior) has proven difficult to find. This chapter reviews the controversy surrounding the relative merits of random-ized trials and observational studies. It is concluded that while (well-conducted) observational can often provide the same level of evidential support as randomized trials, merits of (well-conducted) randomized trials warrant claims about their superiority, especially where results from the two methods are contradictory.
We prospectively evaluated erectile function (EF) using the Sexual Health Inventory for Men (SHIM) and the erectile hardness score (EHS) as well as urinary statuses using the International Prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS) before and 3, 6, and 12 months after a daily treatment with 0.5 mg dutasteride (DUT). Significant improvements were observed in IPSS and OABSS in 98 patients with the DUT treatment, and the effects were similar between 28 patients with potency with baseline SHIM of 8 or greater and 70 severe erectile dysfunction (ED) patients at baseline. In the 28 patients with potency, significant decreases were observed in SHIM and EHS after 3, 6, and 12 months of the DUT treatment, with the severity of ED according to SHIM deteriorating in half of these patients after 12 months of the DUT treatment. Eighteen out of 28 patients (64.3%) with potency at baseline had awareness of the occurrence of ED before the DUT treatment, were younger, and had higher SHIM and EHS just before the DUT treatment than their counterparts. Regular assessments of EF may be needed, especially in younger patients and those with higher levels of EF before the administration of DUT.
The present investigation elucidates the deleterious effects of three prototypical antihypertensive drugs namely, propranolol, clonidine and captopril on the erectile physiology. In order to delineate the direct drug effects from vascular insufficiency inherent in hypertensive states, the study was conducted on a normotensive animal model. The adverse effects of these drugs were estimated as changes in sexual behaviour and intracavernous pressure response of electrical stimulation in the treated rats compared to normal age-matched controls (n = 10, each group). Copulation studies indicated significant impairment of sexual function in the groups on propranolol and clonidine. The cavernous pressure response to nerve stimulation at the end of sixteen weeks further reinforced the gross compromise on sexual function in these two treated groups. In contrast, the captopril administration produced only marginal alterations to the responses recorded. The results from this study clearly indicate that propranolol and clonidine interfere with sexual behaviour and nerve mediated response to erection whereas captopril which is devoid of significant effects on these parameters, may be a better therapeutic option.
Erectile dysfunction (ED) is common affecting over 50% of men aged 40–70 years.1 It increases with age so that men over 70 years (with a prevalence of 70%) have three times the incidence of men in their 40s. It is an important cause of relationships breaking down with the man losing self-esteem, feeling a failure, and the partner feeling rejected so that the man's problem becomes a couple's frustration and concern. With the development of the phosphodiesterase type 5 inhibitors has come a greater understanding of the mechanisms responsible and the important role of endothelial dysfunction, and hence vascular disease, as the major cause of ED.2 Though the commonest cause is now recognized to be organic, psychological consequences will result and both aspects need to be addressed.
With the recognition that endothelial dysfunction is the common denominator linking vascular disease to ED came the realization that ED may not just be a consequence of vascular disease, especially coronary disease, but a harbinger of silent coronary disease—‘a sentinel’.3 The smaller penile arteries (1–2 mm in diameter) potentially suffer …
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Widely distributed throughout the body, cyclic nucleotide phosphodiesterases (PDEs) are functionally heterogeneous enzymes with potential roles in a number of physiological actions. Among these enzymes, PDE type 5 has received particular attention because of the widespread use of the PDE5 inhibitor sildenafil citrate as an oral therapy for erectile dysfunction. Within the corpus cavernosum of the penis, PDE5 catalyzes the enzymatic degradation (inactivation) of cyclic 3′,5′-guanosine monophosphate, which is a second messenger and key mediator of vascular and trabecular erectile tissue smooth muscle relaxation. By amplifying the nitric oxide-cyclic nucleotide signalling pathway, PDE5 inhibitors serve as ‘contingent agonists’ of the physiological response to sexual arousal. In experimental models, tadalafil increased the sensitivity of penile resistance arteries and erectile tissues to three stimuli of smooth muscle relaxation, namely electrical field stimulation, sodium nitroprusside, and acetylcholine. In randomized, double-blind, placebo-controlled trials, sildenafil and the investigational agents tadalafil and vardenafil significantly enhanced erectile function in the majority of patients and were well tolerated.
Antihypertensive drugs are commonly associated with adverse side effects in both clinical and laboratory studies. We investigated the sexual sequelae of several major classes of antihypertensive drugs (e.g., beta blockers, central alpha agonists, diuretics) in normal males and in hypertensive patients. We compared the effects of four widely used agents (methyldopa, propranolol, atenolol, hydrochlorothiazide-triamterene) and placebo, in a selected sample of 21 sexually dysfunctional male hypertensives, 13 of whom completed all five phases of the study. Each study drug was administered for a 1-month treatment period, followed by a 2-week, single-blind washout phase, according to a randomized, Latin square crossover design. Dependent variables for the study included a broad range of hormonal, NPT, and self-report measures of sexual response. Results indicated a lack of consistent drug effects on measures of sexual response, although more frequent sexual and nonsexual side effects were observed with methyldopa and propranolol. As in our previous studies, age was negatively correlated with both hormonal and NPT measures, whereas changes in blood pressure were not significantly related to sexual function scores. Results do not support the hypothesis that sexually dysfunctional males are at greater risk for adverse sexual sequelae when treated with centrally active agents or diuretics.
Erectile dysfunction (ED) is the most common sexual problem in men, after premature ejaculation, affecting up to 30 million in the United States. In a society in which sexuality is widely promoted, ED impacts on feelings of self-worth and self-confidence and may impair the quality of life of affected men and their partners. Damage to personal relationships can ensue; and the anger, depression, and anxiety engendered spill over into all aspects of life. Patients are often embarrassed or reluctant to discuss the matter with their primary care practitioners. Unfortunately, many physicians fail to take the opportunity to promote open discussion of sexual dysfunction. They too, may avoid the topic through personal embarrassment. Since the National Institutes of Health (NIH) Consensus Conference on Impotence in 1992, the inadequate level of public and professional understanding of ED has begun to be addressed. As a first step in breaking down the communication barriers between patients and practitioners, it is important that physicians have a thorough understanding of the wide variety of conditions associated with ED and how the different risk factors for ED may be readily identified. This review addresses the diagnosis of ED and identifies diagnostic tests that can be used by primary care physicians to determine the patients most at risk and the treatments most suited to meet the patients' and their partners' goal for therapy.
Erectile dysfunction is a highly prevalent medical problem affecting a significant proportion of men. It is important for a number of reasons, causing impairment of quality of life and, if related to drug therapy, leading to non-compliance. Drug therapy accounts for erectile dysfunction in approximately 25% of cases and is mostly readily reversible when the offending agent is stopped, or a suitable alternative is substituted. Many classes of drug may be responsible, interfering with the normal physiological processes leading to penile erection in a dose-related fashion, and in ways which can usually be predicted from their pharmacology. The most commonly implicated classes of drug include antihypertensives such as thiazide diuretics and beta-adrenoceptor antagonists and psychotherapeutic drugs, especially selective serotonin reuptake inhibitor (SSRI) antidepressants. We review the agents which can cause erectile dysfunction, the evidence for this adverse effect and the physiological mechanisms involved. We present an approach to the management of the patient with erectile dysfunction in whom concomitant drug therapy may be responsible. We recommend that drug therapy should always be considered as a possible cause of erectile dysfunction before specific investigation and therapy is considered.
In a prospective trial assessing the effects of beta-blockers on sexual function men with coronary heart disease were randomized to a 4 month treatment with sustained release metoprolol 95 mg or placebo. A standardized and validated self-report questionnaire (KEED = Kölner Erhebungsbogen der Erektilen Dysfunktion) dealing with several aspects of sexual performance in men had to be answered at the beginning and at the end of the study. Based on 65 patients completing the study, sex life seemed unaffected by metoprolol treatment.
Patients with cardiovascular diseases frequently complain of erectile dysfunction especially when treated with beta-blockers. In order to assess whether the effect of beta-blockers on erectile dysfunction is in part related to patient knowledge of the drug side effects, 96 patients (all males, age 52+/-7 years) with newly diagnosed cardiovascular disease and not suffering from erectile dysfunction entered a two phase, single cross over study.
During the first phase of the study patients received atenolol 50mg o.d. (A), 32 patients were blinded on the drug given (group A), 32 were informed on the drug given but not on its side effects (group B) and 32 took A after being informed on its side effects on erectile function (group C). After 3 months the incidence of erectile dysfunction was 3.1% in the group A, 15.6% in group B and 31.2% in group C (P<0.01). All patients reporting ED entered the second phase of the study and were randomised to receive Sildenafil 50mg and placebo in a cross over study. Sildenafil citrate and placebo were equally effective in reversing erectile dysfunction in all but one patient reporting ED with Atenolol.
Our results show that the knowledge and prejudice about side effects of beta-blockers can produce anxiety, that may cause erectile function.
Sexual sequelae of antihypertensive drugs: treat-ment effects of self-report and physiological measures in middle-aged male hyperten-sives Effects of beta-blockers on sexual performance in men with coronary heart disease. A prospec-tive, randomized and double blinded study
- Rc Rosen
- Jb Kostis
- A Jekelis
18: 5–24. 5 Rosen RC, Kostis JB, Jekelis A, et al: Sexual sequelae of antihypertensive drugs: treat-ment effects of self-report and physiological measures in middle-aged male hyperten-sives. Arch Sex Behav 1994; 6 Franzen D, Metha A, Seifert N, et al: Effects of beta-blockers on sexual performance in men with coronary heart disease. A prospec-tive, randomized and double blinded study