Nocebo effect in multiple system atrophy: systematic review and meta-analysis of placebo-controlled clinical trials

Abstract

Background Nocebo effect is prevalent among neurological diseases, resulting in low adherence and treatment outcome. We sought to examine the nocebo effect in randomized controlled trials (RCTs) in multiple system atrophy (MSA). Methods We searched RCTs in MSA from Medline since September, 2021. RCTs for drug treatment conducted in adult MSA patients with more than 5 cases in each treatment arm were included. We assessed the number of dropout due to placebo intolerance. We also did a symptomatic/disease-modifying subgroup analysis based on two different treatment purposes. The STATA software was used for statistical analysis. Overall heterogeneity was assessed using the Cochran Q and I2. Results Data were extracted from 11 RCTs fulfilling our search criteria. Of 540 placebo-treated patients, 64.2% reported at least one adverse event (AE) and 7.5% reported dropout because of AEs. The chance of dropping out because of an AE and experiencing at least one AE did not differ between placebo and active drug treatment arms. Besides, the pooled nocebo dropout rate in the symptomatic subgroup was similar to that of the disease-modifying subgroup. Conclusion In MSA RCTs, nocebo dropout rate was not at a low level among neurological disorders. Nocebo effect was an important reason of dropout because of AE in placebo and active drug treatment arms. Different treatment purposes may not influence nocebo effect.

The nocebo effect across health outcomes: A systematic review and meta-analysis.

“…To date there has been no systematic, quantitative investigation of the processes involved in nocebo effects across health outcomes. There have of course been a number of meta-analyses examining nocebo responses within placebo groups of RCTs for specific conditions, such as restless leg syndrome (Silva et al, 2017), attention deficit hyperactivity disorder (Faraone et al, 2022), multiple system atrophy (Wang, Zhang, et al, 2022), Parkinson's disease (Leal Rato et al, 2019), epilepsy (Zis et al, 2017), and fibromyalgia (Häuser et al, 2011), among others. Critically, however, findings based on placebo arms of RCTs cannot quantify the nocebo effect because there is no control comparator (Petersen et al, 2014).…”

The Use of Authorized Concealment to Minimize Nocebo Side Effects: A Survey of US Public Attitudes

“…Closely related, but distinct from nocebo effects, is the less frequently studied tendency to misattribute common cooccurring symptoms, such as fatigue and headache, to taking a drug that also may increase side-effect reports [6,7]. Nocebo effects and misattribution of common symptoms, along with recognized reporting and methodological factors [8,9], are likely causes of the often substantial and comparable prevalence of symptoms and discontinuation rates among placebo and active medication groups in randomized placebo-controlled clinical trials [10][11][12][13][14][15][16]. These factors can account for many selfreported side effects from medications, such as erectile dysfunction and depression associated with β-blockers [17][18][19], myalgias and fatigue with statins [20][21][22][23], dry mouth, constipation, and drowsiness with selective serotonin reuptake inhibitors and tricyclic antidepressants [24][25][26].…”

The Nacebo Effect and its Application in Dentistry

“…A negative influence, due to nacebo effects, intrudes with the medical and dental treatment's outcome. 3 For this, there should be advanced strategies for preventing or even overcoming their influence that would optimize treatment outcomes. Even if the treatment is carried out perfectly keeping all SOPs and steps of that concerned treatment in mind, the patient's negative expectations about the treatment may interfere psychologically with the outcome.…”