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| Author(s): |
Daniel Lucas da Conceição Costa
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) |
| Defense date: | 2016-09-28 |
| Examining board members: |
Roseli Gedanke Shavitt;
Albina Rodrigues Torres
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| Advisor: | Roseli Gedanke Shavitt |
| Abstract | |
INTRODUCTION: Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder with a lifetime prevalence of 2-3%. Treatment guidelines recommend serotonin reuptake inhibitors (SRIs) as the first-line pharmacological treatment for OCD. However, approximately half of patients treated with an adequate trial of SRIs fail to fully respond to treatment. OCD is associated with hyperactivity in cortical-striatum-thalamus-cortical (CSTC) circuits. Cortico-striatal and thalamo-striatal afferents use the excitatory neurotransmitter glutamate, and there is evidence suggesting abnormal glutamate levels and/or homeostasis in OCD patients. Researchers have been testing glutamate-modulating medications in OCD, with some evidence for efficacy. N-Acetylcysteine (NAC), a glutamate-modulating agent, is being considered as an add-on strategy for treatment-resistant OCD. The main objective of this study was to determine if NAC is effective in treatment-resistant OCD patients after 16 weeks of SRI augmentation. METHODS: We conducted a randomized, double blind, placebo-controlled, 16-week trial in an OCD-specialized outpatient clinic at a tertiary hospital (May 2012-October 2014). Inclusion criteria: age between 18-65 years; DSM-IV primary diagnosis of OCD; failure to respond to at least one previous adequate pharmacological treatment for OCD; baseline Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) global score >= 16 or >= 10 if only compulsions are present; OCD symptoms of at least moderate severity on the Clinical Global Impression-Severity subscale. Medications in use at randomization were maintained at the same dose. Assessments were conducted at baseline and end of the study. The primary outcome measure was the Y-BOCS scores. To evaluate the variables group, time, and interaction effects for Y-BOCS scores at all time points, we used nonparametric analysis of variance (ANOVA) with repeated measures. The secondary outcomes were the mean reduction of the baseline Beck Anxiety and Depression Inventories, Dimensional Yale-Brown Obsessive-Compulsive Scale and Brown Assessment of Beliefs Scale scores. Trial registration: clinicaltrials.gov identifier NCT01555970. RESULTS: We assessed 145 patients for eligibility, 129 were eligible, 40 were randomized (NAC up to 3000 mg/day, n= 18; placebo, n= 22), 39 initiated the intervention and 35 completed the trial. Dropout did not significantly differ by treatment group (NAC: 1 of 17 [5.9%]; placebo: 3 of 22 [13.6%]; ?2 = .63; P= .43). Both groups significantly improved over the 16 weeks, as indicated by the reduction of baseline Y-BOCS scores, but there were no significant differences between groups (NAC: 25.6 [SD= 4.4] to 21.3 [DP= 8.1]; placebo: 24.8 [SD= 3.8] to 21.8 [SD= 6.0]; F= .33; P = .92). Adding NAC to SRI was superior to placebo in improving anxiety symptoms, as measured by the reduction of baseline Beck Anxiety Inventory score (mean [SD]: NAC= 7.8 [11.7]; placebo: -.55 [7.9]; U= 89; P= .02). There were no significant differences between groups in regards to the improvement of depressive symptoms, different dimensions of OCD symptoms and insight level. CONCLUSIONS: NAC augmentation of SRI was more effective than placebo in reducing the severity of anxiety symptoms in this sample of treatment-resistant OCD individuals. However, it was not better than placebo in reducing OCD severity (AU) | |
| FAPESP's process: | 12/14070-8 - Serotonin reuptake inhibitor augmentation with N-acetylcysteine in resistant obsessive-compulsive disorder: a double-blind, randomized and controlled study |
| Grantee: | Daniel Lucas da Conceição Costa |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |