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An Olfactory Reference Syndrome Successfully Treated by Aripiprazole Augmentation of Antidepressant Therapy

Muffatti, Riccardo MD; Scarone, Silvio MD; Gambini, Orsola MD

Cognitive & Behavioral Neurology: December 2008 - Volume 21 - Issue 4 - pp 258-260
doi: 10.1097/WNN.0b013e318185e6bd
Case Reports

Objective: To describe a case of a 65-year-old woman with persistent olfactory hallucination and delusional self-reference, successfully treated by aripiprazole augmentation of antidepressant therapy.

Background: Olfactory reference syndrome is a nosologic entity, which has been assimilated to various Diagnostic and Statistical Manual of Mental Disorder-IV-text revision codified diseases and several pharmacologic treatments have been proposed without a constant clinical response.

Method: Psychiatric, neurologic, neuropsychologic, imaging, and electroencephalogram data are reported.

Results: The patient showed a significant improvement with aripiprazole.

Conclusions: We propose a pathophysiologic model of olfactory reference syndrome to explain the good response of our patient to aripiprazole. We hypothesize a disruption in the top-down regulation of the orbitofrontal cortex on the primary olfactory cortex and the olfactory bulb at the basis of the illness. Aripiprazole acting as a partial agonist of dopamine D2 receptors in the olfactory bulb compensates for the lack of modulation in this site, restoring the correct processing of olfactory information.

Department of Psychiatry, University of Milan Medical School and San Paolo Hospital, Italy

Reprints: Riccardo Muffatti, MD, Department of Psychiatry, University of Milan Medical School and San Paolo Hospital, Via di Rudinì 8, Milan, Italy (e-mail:

Received for publication August 10, 2007; accepted July 2, 2008

© 2008 Lippincott Williams & Wilkins, Inc.