-
The Cochrane Database of Systematic... Apr 2018Depression is common in the postnatal period and can lead to adverse effects on the infant and wider family, in addition to the morbidity for the mother. It is not clear... (Review)
Review
BACKGROUND
Depression is common in the postnatal period and can lead to adverse effects on the infant and wider family, in addition to the morbidity for the mother. It is not clear whether antidepressants are effective for the prevention of postnatal depression and little is known about possible adverse effects for the mother and infant, particularly during breastfeeding. This is an update of a Cochrane Review last published in 2005.
OBJECTIVES
To assess the effectiveness of antidepressant medication for the prevention of postnatal depression, in comparison with any other treatment, placebo or standard care.
SEARCH METHODS
We searched the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR ‒ both Studies and References), CENTRAL (Wiley), MEDLINE (OVID), Embase (OVID), PsycINFO (OVID), on 13 February 2018. We also searched the World Health Organization (WHO) trials portal (ICTRP) and ClinicalTrials.gov on 13 February 2018 to identify any additional unpublished or ongoing studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of initiation of antidepressants (alone or in combination with another treatment), compared with any other treatment, placebo or standard care for the prevention of postnatal depression among women who were either pregnant or had given birth in the previous six weeks and were not currently depressed at baseline.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. We requested missing information from investigators wherever possible and sought data to allow intention-to-treat analyses.
MAIN RESULTS
Two trials including a total of 81 participants fulfilled the inclusion criteria for this review. All participants in both studies had a history of postnatal depression and were not taking antidepressant medication at baseline. Both trials were conducted by the same research group. Risk of bias was low or unclear in most domains for both studies. We were unable to perform a meta-analysis due to the small number of studies.One study compared nortriptyline with placebo and did not find any evidence that nortriptyline was effective in preventing postnatal depression. In this study, 23% (6/26) of women who took nortriptyline and 24% (6/25) of women who took placebo experienced postnatal depression (RR 0.96, 95% CI 0.36 to 2.59, very low quality evidence) in the first 17 weeks postpartum. One woman taking nortriptyline developed mania; and one side effect, constipation, was more common among women taking nortriptyline than those taking placebo.The second study compared sertraline with placebo. In this study, 7% (1/14) of women who took sertraline developed postnatal depression in the first 17 weeks postpartum compared with 50% (4/8) of women who took placebo. It is uncertain whether sertraline reduces the risk of postnatal depression (RR 0.14, 95% CI 0.02 to 1.07, very low quality evidence). One woman taking sertraline had a hypomanic episode. Two side effects (dizziness and drowsiness) were more common among women taking sertraline than women taking placebo.Conclusions are limited by the small number of studies, small sample sizes and incomplete outcome data due to study drop-out which may have led to bias in the results. We have assessed the certainty of the evidence as very low, based on the GRADE system. No data were available on secondary outcomes of interest including child development, the mother‒infant relationship, breastfeeding, maternal daily functioning, family relationships or maternal satisfaction.
AUTHORS' CONCLUSIONS
Due to the limitations of the current evidence base, such as the low statistical power of the included studies, it is not possible to draw any clear conclusions about the effectiveness of antidepressants for the prevention of postnatal depression. It is striking that no new eligible trials have been completed in the period of over a decade since the last published version of this review. Larger trials are needed which include comparisons of antidepressant drugs with other prophylactic treatments (e.g. psychological interventions), and examine adverse effects for the fetus or infant. Future reviews in this area may benefit from broadening their focus to examine the effectiveness of antidepressants for the prevention of perinatal (i.e. antenatal or postnatal) depression, which could include studies comparing antidepressant discontinuation with continuation for the prevention of relapse of depression during pregnancy and the postnatal period.
Topics: Antidepressive Agents; Depression, Postpartum; Female; Humans; Nortriptyline; Placebos; Randomized Controlled Trials as Topic; Sertraline
PubMed: 29669175
DOI: 10.1002/14651858.CD004363.pub3 -
Proceedings of the National Academy of... May 2018Placebo effect refers to beneficial changes induced by the use of inert treatment, such as placebo-induced relief of physical pain and attenuation of negative affect. To... (Randomized Controlled Trial)
Randomized Controlled Trial
Placebo effect refers to beneficial changes induced by the use of inert treatment, such as placebo-induced relief of physical pain and attenuation of negative affect. To date, we know little about whether placebo treatment could facilitate social functioning, a crucial aspect for well-being of a social species. In the present study, we develop and validate a paradigm to induce placebo effects on social trust and approach behavior (social placebo effect), and show robust evidence that placebo treatment promotes trust in others and increases preference for a closer interpersonal distance. We further examine placebo effects in real-life social interaction and show that placebo treatment makes single, but not pair-bonded, males keep closer to an attractive first-met female and perceive less social anxiety in the female. Finally, we show evidence that the effects of placebo treatment on social trust and approach behavior can be as strong as the effect of intranasal administration of oxytocin, a neuropeptide known for its function in facilitating social cognition and behavior. The finding of the social placebo effect extends our understanding of placebo effects on improvement of physical, mental, and social well-being and suggests clinical potentials in the treatment of social dysfunction.
Topics: Adult; Choice Behavior; Female; Humans; Interpersonal Relations; Male; Oxytocin; Placebo Effect; Placebos; Social Behavior; Trust; Young Adult
PubMed: 29760054
DOI: 10.1073/pnas.1800779115 -
Neuron Jul 2008In modern medicine, the placebo response or placebo effect has often been regarded as a nuisance in basic research and particularly in clinical research. The latest... (Review)
Review
In modern medicine, the placebo response or placebo effect has often been regarded as a nuisance in basic research and particularly in clinical research. The latest scientific evidence has demonstrated, however, that the placebo effect and the nocebo effect, the negative effects of placebo, stem from highly active processes in the brain that are mediated by psychological mechanisms such as expectation and conditioning. These processes have been described in some detail for many diseases and treatments, and we now know that they can represent both strength and vulnerability in the course of a disease as well as in the response to a therapy. However, recent research and current knowledge raise several issues that we shall address in this review. We will discuss current neurobiological models like expectation-induced activation of the brain reward circuitry, Pavlovian conditioning, and anxiety mechanisms of the nocebo response. We will further explore the nature of the placebo responses in clinical trials and address major questions for future research such as the relationship between expectations and conditioning in placebo effects, the existence of a consistent brain network for all placebo effects, the role of gender in placebo effects, and the impact of getting drug-like effects without drugs.
Topics: Animals; Brain; Clinical Trials as Topic; Conditioning, Psychological; Humans; Nerve Net; Placebo Effect; Placebos; Psychomotor Performance; Reward
PubMed: 18667148
DOI: 10.1016/j.neuron.2008.06.030 -
JAMA Apr 2021Although effective agents are available to prevent painful vaso-occlusive episodes of sickle cell disease (SCD), there are no disease-modifying therapies for ongoing... (Comparative Study)
Comparative Study Randomized Controlled Trial
IMPORTANCE
Although effective agents are available to prevent painful vaso-occlusive episodes of sickle cell disease (SCD), there are no disease-modifying therapies for ongoing painful vaso-occlusive episodes; treatment remains supportive. A previous phase 3 trial of poloxamer 188 reported shortened duration of painful vaso-occlusive episodes in SCD, particularly in children and participants treated with hydroxyurea.
OBJECTIVE
To reassess the efficacy of poloxamer 188 for vaso-occlusive episodes.
DESIGN, SETTING, AND PARTICIPANTS
Phase 3, randomized, double-blind, placebo-controlled, multicenter, international trial conducted from May 2013 to February 2016 that included 66 hospitals in 12 countries and 60 cities; 388 individuals with SCD (hemoglobin SS, SC, S-β0 thalassemia, or S-β+ thalassemia disease) aged 4 to 65 years with acute moderate to severe pain typical of painful vaso-occlusive episodes requiring hospitalization were included.
INTERVENTIONS
A 1-hour 100-mg/kg loading dose of poloxamer 188 intravenously followed by a 12-hour to 48-hour 30-mg/kg/h continuous infusion (n = 194) or placebo (n = 194).
MAIN OUTCOMES AND MEASURES
Time in hours from randomization to the last dose of parenteral opioids among all participants and among those younger than 16 years as a separate subgroup.
RESULTS
Of 437 participants assessed for eligibility, 388 were randomized (mean age, 15.2 years; 176 [45.4%] female), the primary outcome was available for 384 (99.0%), 15-day follow-up contacts were available for 357 (92.0%), and 30-day follow-up contacts were available for 368 (94.8%). There was no significant difference between the groups for the mean time to last dose of parenteral opioids (81.8 h for the poloxamer 188 group vs 77.8 h for the placebo group; difference, 4.0 h [95% CI, -7.8 to 15.7]; geometric mean ratio, 1.2 [95% CI, 1.0-1.5]; P = .09). Based on a significant interaction of age and treatment (P = .01), there was a treatment difference in time from randomization to last administration of parenteral opioids for participants younger than 16 years (88.7 h in the poloxamer 188 group vs 71.9 h in the placebo group; difference, 16.8 h [95% CI, 1.7-32.0]; geometric mean ratio, 1.4 [95% CI, 1.1-1.8]; P = .008). Adverse events that were more common in the poloxamer 188 group than the placebo group included hyperbilirubinemia (12.7% vs 5.2%); those more common in the placebo group included hypoxia (12.0% vs 5.3%).
CONCLUSIONS AND RELEVANCE
Among children and adults with SCD, poloxamer 188 did not significantly shorten time to last dose of parenteral opioids during vaso-occlusive episodes. These findings do not support the use of poloxamer 188 for vaso-occlusive episodes.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT01737814.
Topics: Adolescent; Adult; Analgesics, Opioid; Anemia, Sickle Cell; Child; Double-Blind Method; Female; Humans; Male; Pain; Placebos; Poloxamer; Vasodilator Agents; Young Adult
PubMed: 33877274
DOI: 10.1001/jama.2021.3414 -
PloS One 2013Placebos are widely used in clinical practice in spite of ethical restrictions. Whether such use is justified depends in part on the relative benefit of placebos... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Placebos are widely used in clinical practice in spite of ethical restrictions. Whether such use is justified depends in part on the relative benefit of placebos compared to 'active' treatments. A direct test for differences between placebo and 'active' treatment effects has not been conducted.
OBJECTIVES
We aimed to test for differences between treatment and placebo effects within similar trial populations.
DATA SOURCES
A Cochrane Review compared placebos with no treatment in three-armed trials (no treatment, placebo, and treatment). We added an analysis of treatment and placebo differences within the same trials. SYNTHESIS METHODS: For continuous outcomes we compared mean differences between placebo and no treatment with mean differences between treatment and placebo. For binary outcomes we compared the risk ratio for treatment benefit (versus placebo) with the risk ratio for placebo benefit (versus no treatment). We conducted several preplanned subgroup analyses: objective versus subjective outcomes, conditions tested in three or more trials, and trials with varying degrees of bias.
RESULTS
In trials with continuous outcomes (n = 115) we found no difference between treatment and placebo effects (MD = -0.29, 95% CI -0.62 to 0.05, P = 0.10). In trials with binary outcomes (n = 37) treatments were significantly more effective than placebos (RRR = 0.72, 95%CI = 0.61 to 0.86, P = 0.0003). Treatment and placebo effects were not different in 22 out of 28 predefined subgroup analyses. Of the six subgroups with differences treatments were more effective than placebos in five. However when all criteria for reducing bias were ruled out (continuous outcomes) placebos were more effective than treatments (MD = 1.59, 95% CI = 0.40 to 2.77, P = 0.009).
CONCLUSIONS AND IMPLICATIONS
Placebos and treatments often have similar effect sizes. Placebos with comparatively powerful effects can benefit patients either alone or as part of a therapeutic regime, and trials involving such placebos must be adequately blinded.
Topics: Evidence-Based Medicine; Humans; Placebo Effect; Placebos
PubMed: 23690944
DOI: 10.1371/journal.pone.0062599 -
BMC Medicine Feb 2010The use of placebo interventions outside clinical trials is ethically, professionally and legally controversial. Little is known about the frequency and circumstances of... (Review)
Review
BACKGROUND
The use of placebo interventions outside clinical trials is ethically, professionally and legally controversial. Little is known about the frequency and circumstances of placebo use in clinical practice. Our aim was to summarize the available empirical studies addressing these issues.
METHODS
We searched PubMed and EMBASE from inception to July 2009 in order to identify cross-sectional surveys, qualitative or longitudinal studies among health care professionals, students or patients which investigated at least one of the following issues--frequency of placebo use or attitudes to, or motivations for, the use of placebo interventions. At least two reviewers extracted information on the study methods, participants and findings. Descriptive summaries were prepared in an iterative process by at least two reviewers per study.
RESULTS
Twenty-two studies from 12 different countries met the inclusion criteria. Most studies had relevant shortcomings. The proportion of respondents reporting that they had applied 'pure' placebos (for example, saline injection) during their professional life varied between 17% and 80% among physicians and between 51% and 100% among nurses, but it seems that the actual frequency of such use seems to be rare. The use of 'impure' or 'active' placebos (for example, antibiotics for viral infections) is likely to be much more frequent. However, it is impossible to make a reliable estimation because there is no agreement of what an impure placebo might be. Studies using qualitative methods or asking participants to judge case examples suggest that motivations and attitudes towards placebo use are complex and health care providers are often faced with a dilemma.
CONCLUSIONS
Although the available evidence is incomplete and confusing at times there can be little doubt that the prevalence of placebo use outside of clinical trials is not negligible and that views and attitudes on placebos use differ considerably among individuals, both health care professionals and patients. Further research is needed to clarify these issues.
Topics: Bioethics; Clinical Trials as Topic; Empirical Research; Health Knowledge, Attitudes, Practice; Health Personnel; Humans; Placebos; Surveys and Questionnaires
PubMed: 20178561
DOI: 10.1186/1741-7015-8-15 -
The Journal of Neuroscience : the... Nov 2011There is accumulating evidence from different methodological approaches that the placebo effect is a neurobiological phenomenon. Behavioral, psychophysiological, and... (Review)
Review
There is accumulating evidence from different methodological approaches that the placebo effect is a neurobiological phenomenon. Behavioral, psychophysiological, and neuroimaging results have largely contributed to accepting the placebo response as real. A major aspect of recent and future advances in placebo research is to demonstrate linkages between behavior, brain, and bodily responses. This article provides an overview of the processes involved in the formation of placebo responses by combining research findings from behavioral, psychophysiological, and neuroimaging methods. The integration of these different methodological approaches is a key objective, motivating our scientific pursuits toward a placebo research that can inform and guide important future scientific knowledge.
Topics: Autonomic Nervous System; Brain; Clinical Trials as Topic; Humans; Nervous System Diseases; Neuroimaging; Placebo Effect; Placebos; Psychophysiology
PubMed: 22072664
DOI: 10.1523/JNEUROSCI.4099-11.2011 -
The Israel Journal of Psychiatry and... 2014Prior to the development of the pharmaceutical industry and the advocacy of evidence based medicine in the late 20th century, placebo treatments were commonly used by... (Review)
Review
Prior to the development of the pharmaceutical industry and the advocacy of evidence based medicine in the late 20th century, placebo treatments were commonly used by physicians. In current clinical practice, neither a physician's confidence in the efficacy of a specific treatment nor his personal ethical norms are any longer sufficient to initiate a given therapy. We will discuss whether placebo treatments can be ethically used in clinical practice as an alternative to standard therapy, and propose an innovative conceptualization of the factors involved in the exclusion of placebo treatments from the clinical setting. Patient-related ethical and interpersonal arguments and physician-related legal and ideological arguments concerning placebo usage are presented. We describe current use of placebo treatments in the healthcare system and suggest that placebo therapy thrives and that its therapeutic efficacy is widely acknowledged. There is currently "underground" use of placebo medication, open label placebo trials, and innovative approaches to informed consent to facilitate ethical prescription of placebo therapy. Finally, using the specific example of treatment for depression, we demonstrate how the arguments against placebo use might be undermined, to retrieve the legitimacy of placebo therapy.
Topics: Humans; Mental Disorders; Placebos
PubMed: 25618281
DOI: No ID Found -
PLoS Biology Feb 2017
-
Osteoarthritis and Cartilage Oct 2009Many observations support a major biological effect from the way in which people interpret the meaning of each component of their medical experience and the context in... (Review)
Review
Many observations support a major biological effect from the way in which people interpret the meaning of each component of their medical experience and the context in which this occurs. A recent systematic review of randomised controlled trials in osteoarthritis has demonstrated that the effect size of "placebo" is substantial and is usually greater than that obtained from the specific effect of an individual treatment. In the context of a randomised controlled trial, such a large placebo or "meaning" response is considered a nuisance, but in the context of clinical practice the optimisation of such meaning and contextual responses, through enhanced "care", could greatly benefit people who suffer from osteoarthritis.
Topics: Humans; Osteoarthritis; Pain; Physician-Patient Relations; Placebo Effect; Placebos; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 19410027
DOI: 10.1016/j.joca.2009.03.023