Treatment strategies for serotonin reuptake inhibitor-resistant obsessive-compulsive disorder: A network meta-analysis of randomised controlled trials

Abstract

Objectives

Treatment-resistant obsessive-compulsive disorder is a chronic debilitating illness. We conducted a network meta-analysis [NMA] to compare the efficacy of all interventions in SRI-resistant OCD from published Randomised controlled trials [RCT].

Methods

We performed an NMA of RCTs in SRI resistant OCD from all modalities of treatments; pharmacological, psychological, neuromodulation, neurosurgery including deep brain stimulation. The design-by-treatment interaction inconsistency model within the frequentist framework was adopted with a change in Yale-Brown Obsessive-Compulsive Scale score as the primary outcome. We conducted sensitivity analyses excluding studies examining neurosurgical interventions, deep brain stimulation, studies in the paediatric population, and studies from a single geographical region. We also conducted analyses of interventions categorised into treatment groups.

Results

55 RCTs examining 19 treatments or placebo involving 2011 participants were included in the NMA. Ondansetron [Standardised mean difference −2.01 (95% CI: −3.19, −0.83)], deep TMS [– 1.95 (−3.25, −0.65)], therapist administered Cognitive Behavioural Therapy [CBT-TA] [−1.46 (−2.93, 0.01)] and aripiprazole [−1.36 (−2.56, −0.17)] were ranked as the best four treatments on using the Surface Under the Cumulative Ranking [SUCRA] percentage values (85.4%, 83.2%, 80.3%, 67.9% respectively). While all four interventions had large effect sizes, CBT[TA] narrowly missed statistical significance in our analysis. In sensitivity analyses, deep TMS was ranked as the best treatment strategy for SRI-resistant OCD. The small number of subjects in individual studies, higher confidence interval limits, and wider prediction interval for most agents warrant a cautious interpretation.

Conclusions

Considering the principal analysis and sensitivity analyses together, deep TMS, ondansetron, CBT[TA], and aripiprazole may be considered a first-line intervention for SRI-resistant OCD in adults.

Other

This work was not funded. The NMA has been registered with PROSPERO, [Registration number: CRD42020173589]

Keywords:

• OCD
• obsessive compulsive disorder
• resistant
• augmentation

Acknowledgements

The author acknowledges the contribution of Dr. Manjushree Malkonahalli with data entry.

Author contribution

NPR, S.S. conceptualised the study. NPR, V.K., B.B. and YCJR were involved in the study design. S.S., PKM, TGI, NKC, V.K., NPR were involved in data collection. PKM and B.B. conducted the data analysis. S.S., PKM, V.K., YCJR and NPR were involved in the interpretation of the results. S.S., PKM wrote the first draft of the manuscript which was edited by V.K. and NPR. All authors contributed to revisions. All authors have approved the final manuscript.

Disclosure statement

The authors report no conflict of interest.

Additional information

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.