Fluvoxamine Treatment and D2 Receptors: a Pet Study on OCD Drug-Naïve Patients

Abstract

Changes in D 2 receptors during antidepressant therapy have been reported in patients with major depressive disorder using PET/SPET. The aim of this study was to evaluate modifications in D 2 receptors that might occur in patients affected by obsessive-compulsive disorder (OCD) during serotonin reuptake sites inhibitors (SSRIs). To this purpose, we measured the in vivo binding of [ 11 C]raclopride ([ 11 C]Rac)in the brain of a group of OCD naïve patients before and after the repeated administration of the inhibitor SSRI fluvoxamine. Eight patients with a Diagnostic and Statistical Manual of Mental Disorders IVth edition diagnosis of OCD completed the study undergoing a PET scan and a complete clinical evaluation before and during treatment with fluvoxamine. Patients have been compared also with a group of nine age-matched normal volunteers. Fluvoxamine treatment significantly improved clinical symptoms and increased [ 11 C]Rac binding potential (BP) in the basal ganglia of OCD patients (7.575.2, 6.976.9, and 9.979.3% in dorsal caudate, dorsal putamen, and ventral basal ganglia, respectively; po0.01) to values closer to those observed in the group of normal subjects. Chronic treatment with fluvoxamine induces a slight but significant increase in striatal [ 11 C]Rac BP of previously drug-naïve OCD patients. The modifications in D 2 receptor availability might be secondary to fluvoxamine effects on serotoninergic activity.

Meta-analytic investigations of common and distinct grey matter alterations in youths and adults with obsessive-compulsive disorder

“…Greater GMV in the right striatum of children with OCD after exposure to SSRIs was also reported in a longitudinal VBM study when a less stringent threshold was adopted for statistical analysis (Lazaro et al, 2009). Moreover, a PET study demonstrated that fluvoxamine treatment could significantly improve clinical symptoms and increase[(11)C] Rac binding potential in the dorsal putamen of OCD patients (Moresco et al, 2007). Given that greater striatal volume was not observed in drug-naive OCD-youths ( Figure 2C) in the current meta-analysis, we hypothesized that the volume enlargement of the putamen may be associated with drug therapy.…”

The application of deep brain stimulation in the treatment of psychiatric disorders

“…DBS studies show that serotonin levels in frontal areas increase following NAc-DBS (van Dijk, Klompmakers, Feenstra, & Denys, 2012), indicating that the therapeutic effects for OCD might be mediated by restoring prefrontal serotonergic neurotransmission. In addition, striatal dopamine was increased in patients with OCD following DBS targeted at the NAc (Moresco et al, 2007), which parallels increased dopamine release after successful treatment of OCD with SRIs . This association between dopamine increase and therapeutic DBS seems counterintuitive, given the hyperdopaminergic hypothesis of OCD.…”

Modulation of striatal dopamine release by 5-HT2A and 5-HT2C receptor antagonists: [11C]raclopride PET studies in the rat

“…As pharmacological manipulation of these serotonergic inputs may provide a useful avenue in treatment of schizophrenia, substance abuse, and obsessive compulsive and affective disorders (Kapur and Remington 1996;Moresco et al 2007;Rothman and Baumann 2006), interaction between 5-HT and DA systems is an important area for translational research. Although influences of serotonergic systems on striatal DA release have been comprehensively determined in experimental animals using invasive techniques (e.g., microdialysis), the extent to which these findings may be investigated non-invasively in man is unclear.…”