The effects of deep-brain non-stimulation in severe obsessive-compulsive disorder: an individual patient data meta-analysis (original) (raw)

2019, Translational Psychiatry

Non-intervention-related effects have long been recognized in an array of medical interventions, to which surgical procedures like deep-brain stimulation are no exception. While the existence of placebo and micro-lesion effects has been convincingly demonstrated in DBS for major depression and Parkinson's disease, systematic investigations for obsessive-compulsive disorder (OCD) are currently lacking. We therefore undertook an individual patient data metaanalysis with the aim of quantifying the effect of DBS for severe, treatment-resistant OCD that is not due to the electrical stimulation of brain tissue. The MEDLINE/PubMed database was searched for double-blind, sham-controlled randomized clinical trials published in English between 1998 and 2018. Individual patient data was obtained from the original authors and combined in a meta-analysis. We assessed differences from baseline in obsessive-compulsive symptoms following sham treatment, as measured by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Four studies met the inclusion criteria, randomizing 49 patients to two periods of active or sham stimulation. To preclude confounding by period effects, our estimate was based only on data from those patients who underwent sham stimulation first (n = 24). We found that sham stimulation induced a significant change in the Y-BOCS score (t = −3.15, P < 0.005), lowering it by 4.9 ± 1.6 points [95% CI = (−8.0,-1.8)]. We conclude that non-stimulation-related effects of DBS exist also in OCD. The identification of the factors determining the magnitude and occurrence of these effects will help to design strategies that will ultimately lead to a betterment of future randomized clinical trials. Obsessive-compulsive disorder (OCD) is a highly debilitating neuropsychiatric disorder, affecting around 2% of the population. It is characterized by repeated intrusive thoughts, images or impulses (i.e., obsessions) that cause negative emotion (usually labeled as anxiety) and trigger behaviors aimed at reducing this negative affect (i.e., compulsions) 1. Effective treatment is available in the form of cognitive behavioral therapy (mainly exposure therapy) and pharmacological treatment (mainly with serotonin reuptake inhibitors (SSRIs) and clomipramine) 1. In spite of these treatment options, an estimated 10-20% of affected individuals remains resistant to all therapies, suffers from severe incapacitating symptoms and, consequently, maintains a very low quality of life 2. For this group of patients, the possibility of deep-brain stimulation was introduced in 1999, being regarded as an appealing "last resort option" mainly due to its adjustability and reversibility 3. By delivering electrical current to specific locations in the brain, DBS therapy can be tailored to the individual patient's level of complaints, and most stimulation-induced side effects can be minimized by adjusting stimulation parameters 2. The precise mechanism of action of DBS is only partially known, with evidence showing that DBS can exert its effect through both