Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2023 Jul;68(7):479-494.
doi: 10.1177/07067437221115029. Epub 2022 Jul 25.

Systematic Review and Meta-Analysis of the Placebo Effect and its Correlates in Obsessive Compulsive Disorder

Safoura Mohamadi  1 , Masoud Ahmadzad-Asl  2 , Seyed Aria Nejadghaderi  3 , Roxana Jabbarinejad  4 , Seyed Hamidreza Mirbehbahani  3 , Mark Sinyor  2 , Margaret A Richter  2   5 , Farnoush Davoudi  6
Affiliations
Meta-Analysis

Systematic Review and Meta-Analysis of the Placebo Effect and its Correlates in Obsessive Compulsive Disorder

Safoura Mohamadi et al. Can J Psychiatry. 2023 Jul.

Abstract
in English, French

Background: Obsessive-compulsive disorder (OCD) is a major mental health condition with a lifetime prevalence rate of 1.3% among adults. While placebo effects are well described for conditions such as depressive and anxiety disorders, they have not been systematically characterized in OCD.

Objectives: We aimed to determine the impact of placebos in improving different symptom domains in patients with OCD.

Methods: We systematically searched PubMed, EMBASE, Scopus, Web of Science, Ovid, the Cochrane Library, and Google Scholar databases/search engine from inception to January 2021 for randomized controlled trials of treatments for OCD with a placebo arm. A modified Cohen's effect size (ES) was calculated using change in baseline to endpoint scores for different measurement scales within placebo arms to estimate placebo effects and to investigate their correlates by random-effects model meta-analyses.

Results: Forty-nine clinical trials (placebo group n = 1993), reporting 80 OCD specific (153 measures in general) were included in the analysis. Overall placebo ES (95% confidence interval [CI]) was 0.32 (0.22-0.41) on OCD symptoms, with substantial heterogeneity (I-square = 96.1%). Among secondary outcomes, general scales, ES: 0.27 (95%CI: 0.14-0.41), demonstrated higher ES than anxiety and depression scales, ES: 0.14 (95%CI: -0.4 to 0.32) and 0.05 (95%CI: -0.05 to 0.14), respectively. Clinician-rated scales, ES: 0.27(95%CI: 0.20-0.34), had a higher ES than self-reported scales, ES: 0.07 (95%CI: -0.08 to 0.22). More recent publication year, larger placebo group sample size, shorter follow-up duration, and younger age of participants were all associated with larger placebo ES. Egger's test reflected possible small-study effect publication bias (P = 0.029).

Conclusion: Placebo effects are modest in OCD trials and are larger in clinician ratings, for younger patients, and early in the treatment course. These findings underscore the need for clinicians and scientists to be mindful of placebo effects when formulating treatments or research trials for OCD.

Systematic review registration number: PROSPERO CRD42019125979.

Contexte: Le trouble obsessionnel-compulsif (TOC) est un grand problème de santé mentale dont le taux de prévalence de durée de vie est de 1,3% chez les adultes. Bien que les effets des placebos soient bien décrits pour des conditions comme les troubles dépressifs et anxieux, ils n’ont pas été systématiquement caractérisés dans le TOC.

Objectifs: Nous visions à déterminer l’effet des placebos pour améliorer différents domaines de symptômes chez des patients souffrant du TOC.

Méthodes: Nous avons systématiquement cherché dans les bases de données et moteurs de recherche PubMed, EMBASE, Scopus, Web of Science, Ovid, the Cochrane Library, et Google Scholar du début à janvier 2021 des essais randomisés contrôlés de traitements du TOC avec un bras placebo. La taille de l’effet (TE) de Cohen modifiée a été calculée à l’aide du changement au départ vers les scores de points finaux pour différentes échelles de mesure au sein des bras placebos afin d’estimer les effets placebos et d’investiguer leurs corrélats par des méta-analyses d’un modèle à effets aléatoires.

Résultats: Quarante-neuf essais cliniques (groupe placebo n = 1993), déclarant 80 cas spécifiques du TOC (153 mesures en général) ont été inclus dans l’analyse. En général, la TE du placebo (intervalle de confiance IC à 95% était 0,32 (0,22 à 0,41) sur les symptômes du TOC, avec une hétérogénéité substantielle (I-carré = 96,1%). Parmi les résultats secondaires, les échelles générales, TE : 0,27 (IC à 95% 0,14 à 0,41), démontraient une TE plus élevée que les échelles d’anxiété et de dépression, TE : 0,14 (IC à 95% −0,4 à −0,32) et 0,05 (IC à 95% −0,05 à −0,14), respectivement. Les échelles d’évaluation clinique, TE : 0,27 (IC à 95% 0,20 à 0,34) avaient une TE plus élevée que les échelles auto-rapportées. TE : 0,07 (IC à 95% −0,08 à −0,22). L’année de publication plus récente, la plus grande taille de l’échantillon du groupe placebo, la durée plus courte du suivi, et l’âge plus jeune des participants étaient tous associés à une plus grande TE du placebo. Le test d’Egger a reflété un possible biais de publication d’effet d’étude modeste (P = 0,029).

Conclusion: Les effets placebos sont modestes dans les essais du TOC et sont plus élevés dans les évaluations des cliniciens, pour les patients plus jeunes, et tôt dans le cours du traitement. Ces résultats soulignent le besoin pour les cliniciens et les scientifiques de tenir compte des effets placebos quand ils formulent des traitements et/ou des essais de recherche pour le TOC.

Keywords: OCD; Obsessive compulsive disorder; meta-analysis; placebo; placebo effect; systematic review.

PubMed Disclaimer

Conflict of interest statement

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article. M. Sinyor receives salary support from Academic Scholars Awards from the Departments of Psychiatry at Sunnybrook Health Sciences Centre and the University of Toronto.

Figures

Figure 1.
Figure 1.
Study selection process. OCD = obsessive compulsive disorder; RCT = randomized controlled trial.
Figure 2.
Figure 2.
Characteristics and calculated OCD-specific placebo effect sizes for the included RCTs (n  =  1945, using 80 measurements) in patients with OCD. Age = in placebo group, years; CBT = cognitive behavioral therapy; CI = confidence interval; CR = controlled release; F/U = duration of follow-up in weeks; HR = high risk; ITT = intention-to-treat; LR = low risk; male (%) = in placebo group; measurements# = number of outcome measurements during the study; N = placebo group sample size; NAC = N-acetyl cysteine; OCT = obsessive compulsive disorder; PP = per-protocol analysis; quality = study quality for risk of bias, based on Cochrane tool for assessing risk of bias in randomized trials (RoB 2); RCT = randomized controlled trials; rTMS = repetitive transcranial magnetic stimulation; SC = some concerns; Tools# = number of different tools for outcome measurement in each study; Tx-Resistant = treatment-resistant OCD as the target of the study.
Figure 3.
Figure 3.
Forest plot of the effect sizes of placebo effect by measurement tools. *The effect size for intervention group has been presented only for the purpose of comparing with the placebo effect size, and it does not reflect the efficacy of interventions in OCD due to heterogenous and diverse group of intervention types. **Sample size in placebo group. The sum of sample sizes outnumbers total sample size of studies as some studies have used more than one measurement tools. BAI = Beck Anxiety Inventory; CASS = Covi Anxiety Scale Schedule; CDI = children's depression inventory; CGAS = Children's Global Assessment Scale; CGI = clinical global impression; CPRS = comprehensive psychopathological rating scale - OCD subscale; GSI = General Symptom Index; HAM-A = Hamilton Anxiety Scale; HAM-D = Hamilton Depression Scale; LOI-CV = Leyton Obsessional Inventory-Child Version Symptom/Resistance/interference; MDRS = Montgomery-Asberg Depression Rating Scale; MOCI = Maudsley Obsessional Compulsive Inventory; NIMH-Anxiety = National Institute of Mental Health-Anxiety Scale; NIMH-Depression = National Institute of Mental Health-Depression Scale; NIMH-GI = National Institute of Mental Health-Global Impairment. NIMH-OC = National Institute of Mental Health-Obsessive-Compulsive Scale; OCD = Obsessive-Compulsive disorder; OCI = Obsessional Compulsive Index; OCR = obsessive-compulsive (OC) rating scale; BDI = Beck Depression Inventory; PGI = Patient Global Impression; PSCL = Physical Symptom Checklist; R = test–retest Reliability of each tool (used in calculation of modified effect size); RCMAS = Revised Children's Manifest Anxiety Scale; SAR-SR = Social Adjustment Scale-Self Rating; SCL-90 = 90-items Symptom Checklist (SCL −90 includes the whole scale and/or GSI/OCI subscales); SDS = Self-rating Depression Scale/Zung; STAI = State-Trait Anxiety Inventory; Studies No. = Number of studies using each tool/measurement; YBOCS = Yale-Brown Obsessive-Compulsive Scale.
Figure 4.
Figure 4.
(a) The OCD-specific placebo effect in patients with OCD based on outcome measurement type, analysis protocol, placebo type, and participants’ characteristics. Age = studies on only 17 + year-old subjects have been categorized as adult; CI = confidence interval; ITT = intention-to-treat analysis or last observation carried forward (LOCF); K = number of measurements in each group; PP = per-protocol analysis; Tx-resistant = only Treatment-resistant OCD subjects were included in the study; based on the study's definition. (b) The all-measure placebo effect in patients with OCD based on outcome measurement types, analysis protocol, placebo type, and participants’ characteristics. K = number of measurements in each group; CI = confidence interval; ITT = intention-to-treat analysis or last observation carried forward (LOCF); OCD = obsessive-compulsive disorder; PP = per-protocol analysis; age = studies on only 17 + year-old subjects have been categorized as adult. Tx-resistant = only treatment-resistant OCD subjects were included in the study, based on the study's definition.
Figure 5.
Figure 5.
Meta-regression analyses on placebo effects in OCD based on: (a) publication year, (b) follow-up duration (weeks), (c) placebo group mean age (years), and (d) placebo group sample size. OCD = obsessive-compulsive disorder; r = regression coefficient; SE = standard error of r; CI = confidence interval; bubble's size correlated with the weight of each measurement based on inverse-variance.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Fawcett EJ, Power H, Fawcett JM. Women are at greater risk of OCD than men: a meta-analytic review of OCD prevalence worldwide. J Clin Psychiatry. 2020;81(4). doi:10.4088/JCP.19r13085. - DOI - PubMed
    1. Ruscio AM, Stein DJ, Chiu WT, Kessler RC. The epidemiology of obsessive-compulsive disorder in the national comorbidity survey replication. Mol Psychiatry. 2010;15(1):53–63. doi:10.1038/mp.2008.94. - DOI - PMC - PubMed
    1. Mathes BM, Morabito DM, Schmidt NB. Epidemiological and clinical gender differences in OCD. Curr Psychiatry Rep. 2019;21(5):36. doi:10.1007/s11920-019-1015-2. - DOI - PubMed
    1. Fontenelle LF, Barbosa IG, Luna JV, de Sousa LP, Abreu MN, Teixeira AL. A cytokine study of adult patients with obsessive-compulsive disorder. Compr Psychiatry. 2012;53(6):797–804. doi:10.1016/j.comppsych.2011.12.007. - DOI - PubMed
    1. Pauls DL, Abramovitch A, Rauch SL, Geller DA. Obsessive–compulsive disorder: an integrative genetic and neurobiological perspective. Nat Rev Neurosci. 2014;15(6):410–424. doi:10.1038/nrn3746. - DOI - PubMed

MeSH terms