Differential cerebral metabolic changes with paroxetine treatment of obsessive-compulsive disorder vs major depression

Background: Serotonin reuptake inhibitors (SRIs) effectively treat both major depressive disorder (MDD) and obsessive-compulsive disorder (OCD). We compared and contrasted the functional neuroanatomical effects of SRIs in OCD and MDD as these 2 disorders occurred separately and concurrently by measuring pretreatment to posttreatment cerebral glucose metabolic changes in OCD vs MDD vs concurrent OCD +MDD. Methods: We obtained [F-18] fluorodeoxyglucose positron emission tomography (PET) brain scans on 25 subjects with OCD, 25 with MDD, and 16 with concurrent OCD+MDD before and after 8 to 12 weeks of treatment with paroxetine hydrochloride. Controls (n = 16) were scanned 10 to 12 weeks apart without treatment. Treatment response was defined as a more than 25% decline in OCD symptom severity, a more than 50% decline in MDD severity, and "much improved" clinical global impression. Results: Although all patient groups received the same paroxetine dose for the same duration, regional metabolic changes differed significantly among diagnostic. groups. Subjects with OCD alone showed significant metabolic decreases in the right caudate nucleus, right ventrolateral prefrontal cortex (VLPFC), bilateral orbito-frontal cortex, and thalamus that were not seen in any other group. Both the MDD and concurrent OCD+MDD groups showed metabolic decreases in the left VLPFC and increases in the right striatum. Treatment response was associated with a decrease in striatal metabolism in non-depressed OCD patients but with an increase in striatal activity in patients with OCD+MDD. Conclusions: Brain metabolic responses to SRIs are both disorder-specific and response-specific. They vary according to the underlying pathophysiology of the patient and the degree of symptomatic improvement.