Differential power of placebo across major psychiatric disorders: a preliminary meta-analysis and machine learning study

Cao, Bo; Liu, Yang S.; Selvitella, Alessandro; Librenza-Garcia, Diego; Passos, Ives Cavalcante; Sawalha, Jeffrey; Ballester, Pedro; Chen, Jianshan; Dong, Shimiao; Wang, Fei; Kapczinski, Flávio; Dursun, Serdar; Li, Xinmin; Greiner, Russell; Greenshaw, Andrew J.

doi:10.1038/s41598-021-99534-z

Cited by 4 publications

(7 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have also highlighted the potential of placebobased responses to provide therapeutic outcomes across many clinical conditions [37][38][39] and also to moderate oxytocin based effects [19]. Meta-analyses in the autism field have further supported the existence of placebo responses of a moderate effect size [40].…”

Section: Discussionmentioning

confidence: 96%

The effect of oxytocin nasal spray on social interaction in young children with autism: a randomized clinical trial

et al. 2022

View full text Add to dashboard Cite

Early supports to enhance social development in children with autism are widely promoted. While oxytocin has a crucial role in mammalian social development, its potential role as a medication to enhance social development in humans remains unclear. We investigated the efficacy, tolerability, and safety of intranasal oxytocin in young children with autism using a double-blind, randomized, placebo-controlled, clinical trial, following a placebo lead-in phase. A total of 87 children (aged between 3 and 12 years) with autism received 16 International Units (IU) of oxytocin (n = 45) or placebo (n = 42) nasal spray, morning and night (32 IU per day) for twelve weeks, following a 3-week placebo lead-in phase. Overall, there was no effect of oxytocin treatment over time on the caregiver-rated Social Responsiveness Scale (SRS-2) (p = 0.686). However, a significant interaction with age (p = 0.028) showed that for younger children, aged 3–5 years, there was some indication of a treatment effect. Younger children who received oxytocin showed improvement on caregiver-rated social responsiveness ( SRS-2). There was no other evidence of benefit in the sample as a whole, or in the younger age group, on the clinician-rated Clinical Global Improvement Scale (CGI-S), or any secondary measure. Importantly, placebo effects in the lead-in phase were evident and there was support for washout of the placebo response in the randomised phase. Oxytocin was well tolerated, with more adverse side effects reported in the placebo group. This study suggests the need for further clinical trials to test the benefits of oxytocin treatment in younger populations with autism.Trial registration www.anzctr.org.au (ACTRN12617000441314).

show abstract

Section: Discussionmentioning

confidence: 96%

The effect of oxytocin nasal spray on social interaction in young children with autism: a randomized clinical trial

et al. 2022

View full text Add to dashboard Cite

show abstract

“…The magnitude of placebo effect is larger in trials on depressive disorder, bipolar depression and mania, and smaller in trials on schizophrenia 38,39 . Nevertheless, placebo effect has been increasing not only in depression 38 but also in schizophrenia over the past 24 years 189 , and is a major obstacle for developing novel medications 32 .…”

Section: Trends Aimed To De‐risk Trial Programmes Of Novel Agentsmentioning

confidence: 99%

“…While the ingredients driving placebo effect can be studied and have the poten tial to identify safe therapeutic elements that can be exported into clinical care 35 , high placebo response is a plague that af fects RCTs across different mental disor ders 32,38,39 . In fact, it has been suggested that some major pharmaceutical compa nies have diminished their investment in developing medications for mental dis orders because of the challenges in signal detection due to higher than expected pla cebo responses.…”

Section: Placebo Response and Drug-placebo Differencementioning

confidence: 99%

“…Reasons for these failures may be related to the true inefficacy of a drug, its toxicity profile, insufficiently understood dose‐response relationships, unknown patient factors, but also the limited knowledge of the biological mechanisms underpinning mental disorders, which prevents the identification of potentially relevant subgroups. An additional factor involved is the increasing placebo response across multiple mental disorders, whose reasons remain insufficiently understood 32‐40 .…”

mentioning

confidence: 99%

See 1 more Smart Citation

The future of psychopharmacology: a critical appraisal of ongoing phase 2/3 trials, and of some current trends aiming to de‐risk trial programmes of novel agents

et al. 2023

View full text Add to dashboard Cite

Despite considerable progress in pharmacotherapy over the past seven decades, many mental disorders remain insufficiently treated. This situation is in part due to the limited knowledge of the pathophysiology of these disorders and the lack of biological markers to stratify and individualize patient selection, but also to a still restricted number of mechanisms of action being targeted in monotherapy or combination/augmentation treatment, as well as to a variety of challenges threatening the successful development and testing of new drugs. In this paper, we first provide an overview of the most promising drugs with innovative mechanisms of action that are undergoing phase 2 or 3 testing for schizophrenia, bipolar disorder, major depressive disorder, anxiety and trauma‐related disorders, substance use disorders, and dementia. Promising repurposing of established medications for new psychiatric indications, as well as variations in the modulation of dopamine, noradrenaline and serotonin receptor functioning, are also considered. We then critically discuss the clinical trial parameters that need to be considered in depth when developing and testing new pharmacological agents for the treatment of mental disorders. Hurdles and perils threatening success of new drug development and testing include inadequacy and imprecision of inclusion/exclusion criteria and ratings, sub‐optimally suited clinical trial participants, multiple factors contributing to a large/increasing placebo effect, and problems with statistical analyses. This information should be considered in order to de‐risk trial programmes of novel agents or known agents for novel psychiatric indications, increasing their chances of success.

show abstract

“…Khan and coauthors compared 6 disorders in a 2005 study, which is still the most comprehensive study to date, to our knowledge; however, significant conditions, like mania or social phobia, were not included. Other reviews have focused on depressive disorders or a few other diagnoses …”

Section: Introductionmentioning

confidence: 99%

Differential Outcomes of Placebo Treatment Across 9 Psychiatric Disorders

Bschor,

Nagel,

Unger

et al. 2024

JAMA Psychiatry

View full text Add to dashboard Cite

ImportancePlacebo is the only substance systematically evaluated across common psychiatric diagnoses, but comprehensive cross-diagnostic comparisons are lacking.ObjectiveTo compare changes in placebo groups in recent high-quality randomized clinical trials (RCTs) across a broad spectrum of psychiatric disorders in adult patients.Data SourcesMEDLINE and the Cochrane Database of Systematic Reviews were systematically searched in March 2022 for the latest systematic reviews meeting predetermined high-quality criteria for 9 major psychiatric diagnoses.Study SelectionUsing these reviews, the top 10 highest-quality (ie, lowest risk of bias, according to the Cochrane Risk of Bias tool) and most recent placebo-controlled RCTs per diagnosis (totaling 90 RCTs) were selected, adhering to predetermined inclusion and exclusion criteria.Data Extraction and SynthesisFollowing the Cochrane Handbook, 2 authors independently carried out the study search, selection, and data extraction. Cross-diagnosis comparisons were based on standardized pre-post effect sizes (mean change divided by its SD) for each placebo group. This study is reported following the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline.Main Outcome and MeasureThe primary outcome, pooled pre-post placebo effect sizes (dav) with 95% CIs per diagnosis, was determined using random-effects meta-analyses. A Q test assessed statistical significance of differences across diagnoses. Heterogeneity and small-study effects were evaluated as appropriate.ResultsA total of 90 RCTs with 9985 placebo-treated participants were included. Symptom severity improved with placebo in all diagnoses. Pooled pre-post placebo effect sizes differed across diagnoses (Q = 88.5; df = 8; P &lt; .001), with major depressive disorder (dav = 1.40; 95% CI, 1.24-1.56) and generalized anxiety disorder (dav = 1.23; 95% CI, 1.06-1.41) exhibiting the largest dav. Panic disorder, attention-deficit/hyperactivity disorder, posttraumatic stress disorder, social phobia, and mania showed dav between 0.68 and 0.92, followed by OCD (dav = 0.65; 95% CI, 0.51-0.78) and schizophrenia (dav = 0.59; 95% CI, 0.41-0.76).Conclusion and RelevanceThis systematic review and meta-analysis found that symptom improvement with placebo treatment was substantial in all conditions but varied across the 9 included diagnoses. These findings may help in assessing the necessity and ethical justification of placebo controls, in evaluating treatment effects in uncontrolled studies, and in guiding patients in treatment decisions. These findings likely encompass the true placebo effect, natural disease course, and nonspecific effects.

show abstract

Differential power of placebo across major psychiatric disorders: a preliminary meta-analysis and machine learning study

Cited by 4 publications

References 32 publications

The effect of oxytocin nasal spray on social interaction in young children with autism: a randomized clinical trial

The effect of oxytocin nasal spray on social interaction in young children with autism: a randomized clinical trial

The future of psychopharmacology: a critical appraisal of ongoing phase 2/3 trials, and of some current trends aiming to de‐risk trial programmes of novel agents

Differential Outcomes of Placebo Treatment Across 9 Psychiatric Disorders

Contact Info

Product

Resources

About