SynthesisDrug safety2009
Differences in adverse effect reporting in placebo groups in SSRI and tricyclic antidepressant trials: a systematic review and meta-analysis.
Synthesis in Drug safety, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 13 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
77 citing papers in PubMed, 13 syntheses or guidelines pooled it, 205 citations in OpenAlex.
- Pooled it
- Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials: A Systematic Review and Meta-analysis.JAMA network open · 2022Pooled it
- A systematic review of factors associated with side-effect expectations from medical interventions.Health expectations : an international journal of public participation in health care and health policy · 2020Pooled it
- Placebo response rates and potential modifiers in double-blind randomized controlled trials of second and newer generation antidepressants for major depressive disorder in children and adolescents: a systematic review and meta-regression analysis.European child & adolescent psychiatry · 2020Pooled it
- Adverse Events and Nocebo Effects in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Journal of Crohn's & colitis · 2019Pooled it
- Are Patients WithFrontiers in pharmacology · 2019Pooled it
- Pharmacological interventions for the treatment of depression in chronic obstructive pulmonary disease.The Cochrane database of systematic reviews · 2018Pooled it
- Incidence of Placebo Adverse Events in Randomized Clinical Trials of Targeted and Immunotherapy Cancer Drugs in the Adjuvant Setting: A Systematic Review and Meta-analysis.JAMA network open · 2018Pooled it
- Effects of empathic and positive communication in healthcare consultations: a systematic review and meta-analysis.Journal of the Royal Society of Medicine · 2018Pooled it
- Considering benefits and harms of duloxetine for treatment of stress urinary incontinence: a meta-analysis of clinical study reports.CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne · 2017Pooled it
- Impact of morphine, fentanyl, oxycodone or codeine on patient consciousness, appetite and thirst when used to treat cancer pain.The Cochrane database of systematic reviews · 2014Pooled it
- Nonspecific adverse events in knee osteoarthritis clinical trials: a systematic review.PloS one · 2014Pooled it
- Meta-analyses of adverse effects data derived from randomised controlled trials as compared to observational studies: methodological overview.PLoS medicine · 2011Pooled it
- Are They Side Effects? Extraintestinal Symptoms Reported During Clinical Trials of Irritable Bowel Syndrome May Be More Severe at Baseline.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2022Trial
- Validation of serotonin transporter mRNA as a quantitative biomarker of heavy drinking and its comparison to ethyl glucuronide/ethyl sulfate: A randomized, double-blind, crossover trial.Alcoholism, clinical and experimental research · 2022Trial
- Tripping on nothing: placebo psychedelics and contextual factors.Psychopharmacology · 2020Trial
- Alternative package leaflets improve people's understanding of drug side effects-A randomized controlled exploratory survey.PloS one · 2018Trial
- Participant-Reported Symptoms and Their Effect on Long-Term Adherence in the International Breast Cancer Intervention Study I (IBIS I).Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2017Trial
- Learning to experience side effects after antidepressant intake - Results from a randomized, controlled, double-blind study.Psychopharmacology · 2017Trial
- Homeopathic drug proving of Okoubaka aubrevillei: a randomised placebo-controlled trial.Trials · 2013Trial
17 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on byPlacebo harm.2010
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBiases in adverse effect reporting in randomized controlled trials (RCTs) [e.g. due to investigator expectations or assessment quality] can be quantified by studying the rates of adverse events reported in the placebo arms of such trials.
objectiveWe compared the rates of adverse effects reported in the placebo arms of tricyclic antidepressant (TCA) trials and placebo arms of selective serotonin reuptake inhibitor (SSRI) trials.
methodsWe conducted a literature search for RCTs across PUBMED, Scopus and the Cochrane Central Register of Controlled Trials (CENTRAL). Only studies allowing adverse effect analysis were included. Publication year ranged from 1981 to 2007.
resultsOur systematic review and meta-analysis included 143 placebocontrolled RCTs and data from 12,742 patients. Only 21% of studies used structured and systematic adverse effect ascertainment strategies. The way in which trials recorded adverse events influenced the rate of adverse effects substantially. Systematic assessment led to higher rates than less systematic assessment. Far more adverse effects were reported in TCA-placebo groups compared with SSRI-placebo groups, e.g. dry mouth (odds ratio [OR] = 3.5; 95% CI 2.9, 4.2); drowsiness (OR = 2.7; 95%CI 2.2, 3.4); constipation (OR= 2.7; 95%CI 2.1, 3.6); sexual problems (OR =2.3; 95%CI 1.5, 3.5). Regression analyses controlling for various influencing factors confirmed the results.
conclusionAdverse effect profiles reported in clinical trials are strongly influenced by expectations from investigators and patients. This difference cannot be attributed to ascertainment methods. Adverse effect patterns of the drug group are closely related to adverse effects of the placebo group. These results question the validity of the assumption that adverse effects in placebo groups reflect the 'drug-unspecific effects'.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.