The Phenomenology and Treatment of Obessive-Compulsive Disorder in Adults

Murphy, D L.

Abstract

Our studies conducted in the last year on obsessive-compulsive disorder (OCD) have had a primary focus on investigations of the mechanisms which may mediate successful treatment of the disorder by serotonergic (5-HT) agents including clomipramine, fluoxetine, and buspirone. Investigations conducted here and elsewhere have conclusively shown that clomipramine is more effective than structurally similar tricyclics such as desipramine, imipramine, and amitriptyline, all of which our less selective for serotonin. However, in a controlled comparison to clomipramine conducted here, the serotonin agonist buspirone was found to have similar efficacy in the treatment of OCD. In addition, our group conducted the first double-blind comparison of clomipramine versus fluoxetine in the treatment of OCD and demonstrated similar efficacy in both a randomized and non-randomized cohort of patients. This apparent preferential response to 5-HT selective agents in OCD is in contrast to the treatment response demonstrated In other anxiety and depressive disorders which fail to show a preferential response to serotonin-selective agents and represents further evidence of the importance of serotonergic pathways in OCD. In preliminary studies further evaluating possible serotonergic contributions to therapeutic effects in OCD, brief coadministration of the serotonin agonist, m-chlorophenylpiperazine (M-CPP), during chronic clomipramine and fluoxetine treatment led to a relative attenuation of the behavioral responses elicited by m-CPP prior to medication treatment in a group of OCD patients.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Mental Health (NIMH)
• Type: Intramural Research (Z01)
• Project #: 1Z01MH000336-11
• Application #: 3880832
• Support Year: 11
• Fiscal Year: 1990

Institution

• Name: U.S. National Institute of Mental Health
• Country: United States

Publications

Walitza, Susanne; Marinova, Zoya; Grünblatt, Edna et al. (2014) Trio study and meta-analysis support the association of genetic variation at the serotonin transporter with early-onset obsessive-compulsive disorder. Neurosci Lett 580:100-3

Wang, Y; Adamczyk, A; Shugart, Y Y et al. (2009) A screen of SLC1A1 for OCD-related alleles. Am J Med Genet B Neuropsychiatr Genet :

Shugart, Y Y; Wang, Y; Samuels, J F et al. (2009) A family-based association study of the glutamate transporter gene SLC1A1 in obsessive-compulsive disorder in 378 families. Am J Med Genet B Neuropsychiatr Genet 150B:886-92

Wheaton, Michael; Timpano, Kiara R; Lasalle-Ricci, V Holland et al. (2008) Characterizing the hoarding phenotype in individuals with OCD: associations with comorbidity, severity and gender. J Anxiety Disord 22:243-52

Murphy, Dennis L; Lesch, Klaus-Peter (2008) Targeting the murine serotonin transporter: insights into human neurobiology. Nat Rev Neurosci 9:85-96

Wendland, Jens R; Kruse, Matthew R; Cromer, Kiara R et al. (2007) A large case-control study of common functional SLC6A4 and BDNF variants in obsessive-compulsive disorder. Neuropsychopharmacology 32:2543-51

Lerner, A; Bagic, A; Boudreau, E A et al. (2007) Neuroimaging of neuronal circuits involved in tic generation in patients with Tourette syndrome. Neurology 68:1979-87

Cromer, Kiara R; Schmidt, Norman B; Murphy, Dennis L (2007) An investigation of traumatic life events and obsessive-compulsive disorder. Behav Res Ther 45:1683-91

Grados, M A; Samuels, J; Shugart, Y Y et al. (2007) Rare plus common SERT variants in obsessive-compulsive disorder. Mol Psychiatry 12:422-3

Cromer, Kiara R; Schmidt, Norman B; Murphy, Dennis L (2007) Do traumatic events influence the clinical expression of compulsive hoarding? Behav Res Ther 45:2581-92