Send Orders for Reprints to reprints@benthamscience.net 710 Current Neuropharmacology, 2019, 17, 710-736 REVIEW ARTICLE 1570-159X/19 $58.00+.00 ©2019 Bentham Science Publishers Psychopharmacological Treatment of Obsessive-Compulsive Disorder (OCD) Antonio Del Casale 1,* , Serena Sorice 2 , Alessio Padovano 2 , Maurizio Simmaco 1 , Stefano Ferracuti 3 , Dorian A. Lamis 4 , Chiara Rapinesi 1 , Gabriele Sani 1 , Paolo Girardi 1 , Georgios D. Kotzalidis 1 and Maurizio Pompili 1 1 Department of Neuroscience, Mental Health, and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University, Unit of Psychiatry, Sant’Andrea University Hospital, Rome, Italy; 2 Residency School in Psychiatry, Faculty of Medicine and Psychology, Sapienza University, Unit of Psychiatry, Sant’Andrea University Hospital, Rome, Italy; 3 Department of Human Neuroscience, Sapienza University, Rome, Italy; 4 Department of Psychiatry and Behav- ioral Sciences, Emory University School of Medicine, Atlanta, GA, USA Abstract: Background: Obsessive-compulsive disorder (OCD) is associated with affective and cognitive symptoms causing personal distress and reduced global functioning. These have consider- able societal costs due to healthcare service utilization. Objective: Our aim was to assess the efficacy of pharmacological interventions in OCD and clinical guidelines, providing a comprehensive overview of this field. Methods: We searched the PubMed database for papers dealing with drug treatment of OCD, with a specific focus on clinical guidelines, treatments with antidepressants, antipsychotics, mood stabiliz- ers, off-label medications, and pharmacogenomics. Results: Prolonged administration of selective serotonin reuptake inhibitors (SSRIs) is most effec- tive. Better results can be obtained with a SSRI combined with cognitive behavioral therapy (CBT) or the similarly oriented exposure and response prevention (ERP). Refractory OCD could be treated with different strategies, including a switch to another SSRI or clomipramine, or augmentation with an atypical antipsychotic. The addition of medications other than antipsychotics or intravenous antidepressant administration needs further investigation, as the evidence is inconsistent. Pharma- cogenomics and personalization of therapy could reduce treatment resistance. Conclusions: SSRI/clomipramine in combination with CBT/ERP is associated with the optimal response compared to each treatment alone or to other treatments. New strategies for refractory OCD are needed. The role of pharmacogenomics could become preponderant in the coming years. Keywords: Obsessive compulsive disorder, psychopharmacology, pharmacogenomics, selective serotonin reuptake inhibitors, atypical antipsychotics, off-label treatments. 1. INTRODUCTION Obsessive-Compulsive Disorder (OCD) is a psychiatric disorder included in the DSM-5 Obsessive-Compulsive Spectrum Disorders. The main symptoms include intrusive thoughts (obsessions), and ritualistic behavior (compulsions) [1]. OCD affects more than 1% of the population worldwide [2, 3], with lifetime prevalence of 2-3% in the general popu- lation [4], and no difference in gender distribution, although *Address correspondence to this author at the Department of Neuroscience, Mental Health, and Sensory Organs (NESMOS), Sant’Andrea Hospital, Via di Grottarossa 1035-1039, 00189 Rome, Italy; Tel: +39-0633775951; Fax: +39-0633775342; E-mail: antonio.delcasale@uniroma1.it juvenile-onset OCD is more often familial and more preva- lent in boys than in girls [5, 6]. Age at OCD onset is bi- modal, with the first peak in late childhood or early adoles- cence, and the second in early adulthood (i.e., 20-29 years) [7, 8]. Onset is usually gradual and its clinical presentation in child-onset and adult-onset forms is generally similar [1]. However, these differ in associated comorbidities [5]. Illness course has a chronic but fluctuating pattern, which often re- lates to stressful life events [9, 10]. The life of patients with OCD is characterized by more years of disability than that of patients with multiple sclero- sis and Parkinson disease combined [11, 12]. Despite the illness burden, it is often unrecognized or misrecognized in A R T I C L E H I S T O R Y Received: March 14, 2018 Revised: July 06, 2018 Accepted: August 12, 2018 DOI: 10.2174/1570159X16666180813155017