Duloxetine in Psychiatric Disorders: Expansions Beyond Major Depression and Generalized Anxiety Disorder.

Background: Duloxetine hydrochloride (DUL) is an antidepressant included in the pharmacological class of serotonin-norepinephrine reuptake inhibitors approved for the treatment of major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain. The aim of this review was to elucidate current evidences on the use of DUL in the treatment of a variety of psychiatric disorders. Methods: This systematic review was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. PubMed database was searched from January 1, 2003, to September 30, 2018, using 11 key terms related to psychiatric disorders ("persistent depressive disorder," "dysthymic disorder," "bipolar disorder," "seasonal affective disorder," "obsessive-compulsive disorder," "social phobia," "panic disorder," "posttraumatic stress disorder," "schizophrenia," "eating disorders," "sexual disorders," "personality disorders") and one key term related to duloxetine ("duloxetine hydrochloride"). Article titles and abstracts were scanned to determine relevance to the topic. For additional studies, the authors also examined the reference lists of several of the included papers. Results: Duloxetine may be an effective treatment for mood spectrum disorders, panic disorder, several symptom clusters of borderline personality, and as add-on drug in schizophrenia. Modest or conflicting results have been found for the efficacy of duloxetine in obsessive-compulsive disorder, posttraumatic stress disorder, eating, and sexual disorders. Conclusion: Major limitations of the reviewed studies were short trial duration, small sample sizes, and the lack of control groups. Defining the potential role of DUL in the treatment of psychiatric disorders other than major depressive disorder and generalized anxiety disorder needs further randomized, placebo-controlled studies.

Focus on Disruptive Mood Dysregulation Disorder: A review of the literature.

The inclusion of the Disruptive Mood Dysregulation Disorder (DMDD) in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), under the category of depressive disorders, provides a diagnosis for those children and adolescents with severe persistent irritability and temper outbursts, once misdiagnosed as Bipolar Disorders. The main and constantly present features of DMDD are chronic, non-episodic and persistent irritability, and temper tantrums disproportionate with the trigger. DMDD is characterized by high rates of comorbidity with other psychiatric disorders. Its main clinical manifestations overlap with Oppositional Defiant Disorder, Conduct Disorder, and Attention-Deficit/Hyperactivity Disorder. For this diagnostic overlap and the increasing use of pharmacological treatments in children and adolescents, the inclusion of DMDD diagnosis has been subjected to many criticisms. Since it is a new diagnostic entity, literature on DMDD prevalence, epidemiology, risk factors, and treatment guidelines, is still sparse and unclear. The aim of this review is to collect and analyze the literature on DMDD diagnostic criteria and main hallmarks, with particular attention to comorbidities and treatment options.

Does Personality Matter? Temperament and Character Dimensions in Panic Subtypes.

INTRODUCTION: Symptomatic heterogeneity in the clinical presentation of Panic Disorder (PD) has lead to several attempts to identify PD subtypes; however, no studies investigated the association between temperament and character dimensions and PD subtypes. The study was aimed to verify whether personality traits were differentially related to distinct symptom dimensions. METHODS: Seventy-four patients with PD were assessed by the Mini-International Neuropsychiatric Interview (M.I.N.I.), and the Temperament and Character Inventory (T.C.I.). Thirteen panic symptoms from the M.I.N.I. were included in a factor analysis with varimax rotation. A correlation analysis (Pearson's correlation), a linear regression analysis, and a forward stepwise regression analysis between the identified factors and T.C.I. variables were performed for evaluating the association between panic subtypes and personality features. RESULTS: Three factors were obtained: "Somato-dissociative", "Respiratory", and "Cardiologic" explaining respectively 18.31%, 13.71%, and 12.78% of the total variance. Correlations analyses showed that only "Somato-dissociative" factor was significantly correlated with T.C.I. "Self-directedness" (p<0.0001) and "Cooperativeness" (p=0.009) variables. Results from the regression analysis indicate that the predictor models account for 33.3% and 24.7% of the total variance respectively in "Somatic-dissociative" (p<0.0001) and "Cardiologic" (p=0.007) factors, while they do not show statistically significant effects on "Respiratory" factor (p=0.222). After performing stepwise regression analysis, "Self-directedness" resulted the unique predictor of "Somato-dissociative" factor (R²=0.186; ß=-0.432; t=-4.061; p<0.0001). CONCLUSION: Current results, although preliminary, suggest the importance of assessing personality and temperament features that may be potentially related to poor treatment response for a better understanding and characterization of PD subtypes.

Association between cortisol levels and pain threshold in systemic sclerosis and major depression.

Pain perception and threshold show complex interactions with the inflammatory, psychiatric and neuroendocrine stimuli. This study aims to test whether lower serum cortisol levels are associated with lower pain thresholds and higher degree of depression in systemic sclerosis (SSc) and major depression with atypical features (MD-AF) patients compared to controls. 180 female subjects (SSc = 60, MD-AF = 60, healthy controls = 60) participated in this observational, cross-sectional, parallel group study. Pressure pain threshold (PPT) was assessed in three anatomical sites: nail bed (NB), metacarpophalangeal joint (MCP) and quadriceps muscle (QDR). Depressive symptoms were evaluated using the Beck Depression Inventory (BDI) scale and morning serum cortisol levels were collected. In SSc patients, quality of life was measured through the Health Assessment Questionnaire (HAQ-DI) and the scleroderma-specific visual analogue scales (scleroderma-VAS). Lower PPT scores (NB 4.42 ± 1.6; MCP 4.66 ± 1.4; QDR 4.79 ± 1.5) were observed in SSc patients compared to both MD-AF (NB 7.33 ± 2.2; MCP 6.01 ± 1.9; QDR 6.31 ± 1.6; p < 0.005) and controls (NB 9.57 ± 2; MCP 7.9 ± 2.1 and QDR 8.43 ± 2.1; p < 0.0001), while MD-AF patients had lower PPT scores compared to controls (p < 0.0001). SSc patients had also lower serum cortisol levels compared to MD-AF patients (8.78 vs 13.6 µg/dl; p < 0.05). A direct correlation was observed between serum cortisol and PPT scores both in SSc (r 2 for NB 0.29; for MCP 0.25; for QDR 0.27) and in MD-AF (r 2 for NB 0.34; for MCP 0.25; for QDR 0.47; p < 0.05), while depressive symptoms negatively correlated with serum cortisol (r 2 for NB 0.34; for MCP 0.17; for QDR 0.15) and in MD-AF (r 2 for NB 0.19; for MCP 0.31; for QDR 0.30; p < 0.05). Among SSc patients, those with serum cortisol levels below the normal range (n = 16) had higher BDI scores (15, 6-21 vs 9, 2-15; p < 0.005), lower PPTs (NB 4 ± 1.4 vs 4.9 ± 0.9; MCP 4.1 ± 0.8 vs 4.8 ± 0.9; QDR 4.1 ± 1.2 vs 5 ± 0.9; p < 0.005) and higher HAQ-DI (1.25, 0.25-2 vs 0.75, 0-1.25; p < 0.05) and scleroderma-VAS scores (VAS overall severity 7, 5.5-9.5 vs 4.5, 2.5-6; p < 0.05). The effect of cortisol serum levels upon pain mechanism, in chronic inflammatory conditions warrants longitudinal studies to detect treatable variations in pain thresholds, depressive symptoms and to improve quality of life.

Low-Dose of Bergamot-Derived Polyphenolic Fraction (BPF) Did Not Improve Metabolic Parameters in Second Generation Antipsychotics-Treated Patients: Results from a 60-days Open-Label Study.

Objectives: The nutraceutical approach to the management of metabolic syndrome (MetS) might be a promising strategy in the prevention of cardio-metabolic risk. Low-dose bergamot-derived polyphenolic fraction (BPF) has been proven effective in patients with MetS, as demonstrated by a concomitant improvement in lipemic and glycemic profiles. The present study was aimed to further explore, in a sample of subjects receiving second generation antipsychotics (SGAs), the effects on body weight and metabolic parameters of a low dose of BPF (500 mg/day) administered for 60 days. Methods: Twenty-eight outpatients treated with SGAs assumed BPF at single daily dose of 500 mg/day for 60 days. Body weight, BMI, fasting levels of glucose, total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol and triglycerides were determined; moreover, Brief Psychiatric Rating Scale (BPRS) was administered. Results: Low-dose BPF administration did not change clinical and metabolic parameters, as well as clinical symptoms in the study sample. At the end of the trial, among completers (n = 24) only nine patients (37.5%) reached an LDL reduction >0 but <50%. Conclusions: Our results demonstrate that patients treated with SGAs may need higher BPF doses for obtaining the positive effects on body weight and metabolic parameters previously found in the general population at lower doses.

Anger, Smoking Behavior, and the Mediator Effects of Gender: An Investigation of Heavy and Moderate Smokers.

BACKGROUND: The existing literature suggests the presence of a possible relationship between high anger levels and smoking behavior; however, there are no available data highlighting possible differences between moderate and heavy smokers and the putative effect of gender on smoking behavior. OBJECTIVES: The aims of the current study were to assess the relationship among anger, depression, and anxiety and smoking patterns taking into account the possible mediator role of gender. METHODS: 150 smokers and 50 nonsmokers volunteers were recruited from the staff of the University of Messina, Italy. The final sample consisted of 90 smokers, divided in 50 heavy smokers (HS: more than 40 cigarettes per day), 40 moderate smokers (MS: 10-30 cigarettes per day), and 42 nonsmokers (NS). All subjects were assessed by State-Trait Anger Expression Inventory-2, Self-Rating Depression Scale, and Self-Rating Anxiety Scale. RESULTS: On anger, depression, and anxiety measures the HS group scored higher than MS and NS groups. HS showed higher than expected levels of trait-anger, a greater tendency to control anger reactions and to access to anger-management techniques. A moderate consumption of cigarettes (10-30 cigarettes per day) was not associated with negative emotions, as MS only showed higher than expected levels of state-anger. Cigarettes consumption was related to gender-specific anger features. Conclusions/Importance: Our study highlighted the importance of anger in smoking behavior and its related gender differences. Recognizing the link among anger, gender differences and smoking behavior could improve the knowledge for future-focused interventions on smoking cessation.

Metabolic outcomes of bergamot polyphenolic fraction administration in patients treated with second-generation antipsychotics: a pilot study.

Second-generation antipsychotics (SGAs) are notoriously associated with a marked increase in body weight and with a wide range of metabolic adverse effects, and their chronic use is related with an increased risk for the development of metabolic syndrome (MS). Different adjunctive treatments have been proposed to reduce SGAs-induced weight gain and/or metabolic abnormalities with inconsistent or too limited evidence to support their regular clinical use, thus suggesting the need to find new possible treatments. Bergamot polyphenolic fraction (BPF) has been proven effective in patients with MS, as demonstrated by a concomitant improvement in lipemic and glycemic profiles. The present study was aimed to explore the efficacy and safety of BPF treatment on metabolic parameters in a sample of subjects receiving atypical antipsychotics. Fifteen outpatients treated with SGAs assumed BPF at the oral daily dose of 1000 mg/day for 30 days. Fasting levels of glucose, glycated hemoglobin, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglycerides were determined. BPF administration resulted in a statistically significant reduction of body weight (P=.004) and in a trend for body mass index decrease (P=.005). No significant differences in other and metabolic parameters were observed. Our findings suggest that BPF, at the daily dose of 1000 mg for 30 days, could be an effective and safe agent to prevent weight gain associated with atypical antipsychotic use. However, further clinical trials with adequately powered and well-designed methodology are needed to better explore the BPF effectiveness on the SGAs-induced weight gain and metabolic side effects.

Personality traits and emotional patterns in irritable bowel syndrome.

The review focuses on those personality traits (neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness), constructs (alexithymia and distressed - Type D personality) and emotional patterns (negative and positive) that are of particular concern in health psychology, with the aim to highlight their potential role on the pathogenesis, onset, symptom clusters, clinical course, and outcome of irritable bowel syndrome (IBS). Personality traits and emotional patterns play key roles in affecting autonomic, immune, inflammatory, and endocrine functions, thus contributing not only to IBS clinical expression and symptomatic burden, but also to disease physiopathology. In this sense, psychological treatments should address those personality traits and emotional features that are constitutive of, and integral to IBS. The biopsychosocial model of illness applied to IBS acknowledges the interaction between biological, psychological, environmental, and social factors in relation to pain and functional disability. A holistic approach to IBS should take into account the heterogeneous nature of the disorder, and differentiate treatments for different types of IBS, also considering the marked individual differences in prevalent personality traits and emotional patterns. Beyond medications, and lifestyle/dietary interventions, psychological and educational treatments may provide the optimal chance of addressing clinical symptoms, comorbid conditions, and quality of life in IBS patients.

Effect of Ziprasidone Augmentation of Serotonin Reuptake Inhibitors in Treatment-Resistant Obsessive-Compulsive Disorder: A 12-Week, Open-Label Uncontrolled Preliminary Study.

OBJECTIVES: The present 12-week, open-label uncontrolled trial was aimed to explore the efficacy of ziprasidone add-on pharmacotherapy on clinical symptoms and cognitive functioning in a sample of patients with treatment-resistant obsessive-compulsive disorder receiving serotonin reuptake inhibitors (SRIs). METHODS: After clinical (Yale-Brown Obsessive Compulsive Scale [Y-BOCS], Hamilton Rating Scale for Depression) and neurocognitive (Wisconsin Card Sorting Test, Stroop Colour-Word Test, Trail Making Test) assessments, patients received 80 mg/d of ziprasidone. RESULT: A final sample of 17 patients completed the study. The results obtained indicate that ziprasidone added to stable SRIs treatment appeared to be moderately effective for reducing compulsive symptoms, as evidenced by changes on Y-BOCS compulsion scale score (P = 0.005) at the end of the trial. Only 4 subjects (23.5% of the completers) had a partial response (reduction between 25% and 34% in Y-BOCS total score), whereas none of the patients had a full response (reduction ≥ 35% in Y-BOCS total score). Regarding cognitive performances, no significant differences were found during the study. CONCLUSIONS: The findings provide evidence that ziprasidone added to ongoing treatment appeared to be mildly effective to improve symptoms in patients with obsessive-compulsive disorder who have failed to respond sufficiently to SRIs.

Extrasensory Perception Experiences and Childhood Trauma: A Rorschach Investigation.

This study investigated whether people who report recurrent extrasensory perception (ESP) experiences (telepathy, clairvoyance, and precognition) have suffered more traumatic experiences and traumatic intrusions. Thirty-one nonclinical participants reporting recurrent ESP experiences were compared with a nonclinical sample of 31 individuals who did not report recurrent ESP phenomena. Past traumatic experiences were assessed via a self-report measure of trauma history (Childhood Trauma Questionnaire); traumatic intrusions were assessed via a performance-based personality measure (Rorschach Traumatic Content Index). Participants also completed the Anomalous Experience Inventory, the Minnesota Multiphasic Personality Inventory-2, the Dissociative Experience Scale, and the Revised Paranormal Belief Scale. The ESP group reported higher levels of emotional abuse, sexual abuse, emotional neglect, physical neglect, and traumatic intrusions. The association between ESP experiences and trauma was partly mediated by the effects of dissociation and emotional distress. Implications for health professionals are discussed. Results also showed the reliability of the twofold method of assessment of trauma.

Efficacy and safety of sertindole in schizophrenia: a clinical review.

Sertindole is an atypical antipsychotic reintroduced into the European market in 2005 after a reevaluation of its risks and benefits, under the agreement that close electrocardiographic screening would be conducted. It has a high affinity for dopamine D2, serotonin 5-HT2A and 5-HT2C, and α1 adrenergic receptors. Moreover, sertindole shows modest affinity for H1-histaminergic and muscarinic receptors. The pharmacological properties, clinical efficacy, safety, and tolerability of sertindole are covered in this article based on a literature review from 1990 to 2014. Given current available findings, sertindole is at least effective as haloperidol, risperidone, and olanzapine on schizophrenia symptoms. Regarding its efficacy on cognitive symptoms, sertindole effect is supported by both preclinical and clinical studies versus haloperidol and olanzapine; however, its role on cognition needs further clarification. Concerning safety and tolerability issues, sertindole is characterized by a low potential to cause sedation and extrapyramidal symptoms, and by an acceptable metabolic profile; nevertheless, cardiac safety remains a major concern, and the electrocardiographic monitoring should be carried out during treatment to substantially reduce cardiovascular risk. In conclusion, although it has an equivalent profile compared to other antipsychotic drugs, sertindole actually remains a second-line choice for schizophrenic patients intolerant to at least one other antipsychotic agent.

Role of negative affects in pathophysiology and clinical expression of irritable bowel syndrome.

Irritable bowel syndrome (IBS) is regarded as a multifactorial disease in which alterations in the brain-gut axis signaling play a major role. The biopsychosocial model applied to the understanding of IBS pathophysiology assumes that psychosocial factors, interacting with peripheral/central neuroendocrine and immune changes, may induce symptoms of IBS, modulate symptom severity, influence illness experience and quality of life, and affect outcome. The present review focuses on the role of negative affects, including depression, anxiety, and anger, on pathogenesis and clinical expression of IBS. The potential role of the autonomic nervous system, stress-hormone system, and immune system in the pathophysiology of both negative affects and IBS are taken into account. Psychiatric comorbidity and subclinical variations in levels of depression, anxiety, and anger are further discussed in relation to the main pathophysiological and symptomatic correlates of IBS, such as sensorimotor functions, gut microbiota, inflammation/immunity, and symptom reporting.

Augmentation of clozapine with agomelatine in partial-responder schizophrenia: a 16-week, open-label, uncontrolled pilot study.

The present 16-week open-label uncontrolled trial was aimed to explore the efficacy of adjunctive agomelatine on clinical symptoms and cognitive functioning in 20 schizophrenia patients showing partial response (Brief Psychiatric Rating Scale, mean [SD] baseline total score = 37.5 [6.6]) to clozapine monotherapy at the highest tolerated dosage. The results obtained evidenced that agomelatine at a dosage of 50 mg/d was associated with score reduction in all Positive and Negative Syndrome Scale domains (positive, P = 0.011 and Cohen d = 0.7; negative, P < 0.0001 and Cohen d = 1.1; psychopathology, P = 0.001 and Cohen d = 0.9) and total score (P = 0.001, Cohen d = 1.2), depressive (Calgary Depression Scale for Schizophrenia, P = 0.013 and Cohen d = 0.6), and overall clinical symptoms (Brief Psychiatric Rating Scale, P = 0.001 and Cohen d = 0.6 ); moreover, improved performances on Stroop task (P = 0.006, Cohen d = 0.7) and Wisconsin Card Sorting Test "perseverative errors" (P = 0.033, Cohen d = 0.3) were observed. The favorable effect of agomelatine on clinical and cognitive symptoms was encouraging, and more research is needed to better identify subgroups of patients who are partially responsive to clozapine monotherapy in which agomelatine augmentation may be of benefit.

Aripiprazole plus topiramate in opioid-dependent patients with schizoaffective disorder: an 8-week, open-label, uncontrolled, preliminary study.

BACKGROUND: The aims of this study were to evaluate a combination of aripiprazole and topiramate in the treatment of opioid-dependent patients with schizoaffective disorder undergoing methadone maintenance therapy (MMT) and, further, to taper off patients from methadone treatment. METHODS: Twenty patients who met DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) criteria for opioid dependence and schizoaffective disorder receiving MMT (80 mg/day) were given aripiprazole (10 mg/day) plus topiramate (up to 200 mg/day) for 8 weeks. A methadone dose reduction of 3 mg/day until suspension at week 4 was established. RESULTS: Aripiprazole plus topiramate was effective in reducing clinical symptoms, and a rapid tapering off of MMT was achieved. CONCLUSIONS: Combining aripiprazole and topiramate may be effective in patients with a dual diagnosis of opioid dependency and schizoaffective disorder.

Agomelatine in the treatment of fibromyalgia: a 12-week, open-label, uncontrolled preliminary study.

Pharmacological therapy for fibromyalgia syndrome (FMS) is actually unsatisfactory; analgetic and nonsteroidal anti-inflammatory drugs are not very effective. On the other hand, it is opportune to underline that antidepressant drugs produce positive response on pain in patients with FMS. Furthermore, many studies showed that using variable doses of melatonin (3-6 mg/d) in subjects affected from FMS had significantly been effective on pain, sleep, daytime fatigue, and depression. This study was aimed to evaluate the efficacy of agomelatine on depression, anxiety, cognition, and pain in a sample of drug-free FMS patients. Agomelatine was administered at the single daily dose of 25 mg/d to 15 fibromyalgia "drug-free" female subjects during 12 weeks. Outcome measures included the Hamilton Rating Scale for Depression, the Hamilton Rating Scale for Anxiety, the Zung Self-Rating Depression Scale, the Zung Self-Rating Anxiety Scale, the Visual Analog Scale of Pain, the Quality of Life Index, the Wisconsin Card Sorting Test, the Verbal Fluency Task-Controlled Oral Word Association Test, and the Stroop Color-Word Test. Treatment with agomelatine significantly improved depression, anxiety, and pain in patients with FMS. Regarding executive/cognitive symptoms, treatment with agomelatine did not have a significant impact on the explored neuropsychological domains, although there was a trend toward the improvement of performances. The findings showed that agomelatine was effective and well tolerated in patients with FMS. Further research is needed to fully evaluate the role of agomelatine as a potential pharmacological strategy for the treatment of FMS.

Lamotrigine augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive-compulsive disorder: a double-blind, placebo-controlled study.

The present 16-week double-blind, randomized, placebo-controlled trial had the aim to explore the efficacy of lamotrigine add-on pharmacotherapy on clinical symptomatology and cognitive functioning in a sample of patients with treatment-resistant obsessive-compulsive disorder (OCD) receiving serotonin reuptake inhibitors (SRIs). After clinical and neurocognitive assessments, patients were randomly allocated to receive, in a double-blind design, 100 mg/day of lamotrigine or a placebo. A final sample of 33 patients completed the study. The results obtained indicate that lamotrigine added to stable SRI treatment substantially improved obsessive-compulsive (Yale-Brown Obsessive Compulsive Scale: obsessions, p < 0.0001; compulsions, p < 0.0001; total score, p < 0.0001), and affective symptoms (Hamilton Rating Scale for Depression p < 0.0001). Regarding cognitive functions, improvement was observed only in Semantic Fluency (p = 0.004). The findings provide evidence that lamotrigine augmentation of SRI treatment is well tolerated and may be proposed as an effective therapeutic strategy to improve outcome in treatment-resistant OCD.

Duloxetine as adjunctive treatment to clozapine in patients with schizophrenia: a randomized, placebo-controlled trial.

Antidepressant drugs have often been used as an augmentation strategy for those patients who have demonstrated a suboptimal response to clozapine. The present 16-week double-blind, randomized, placebo-controlled trial study aimed to explore the efficacy and tolerability of duloxetine add-on pharmacotherapy on clinical symptomatology and executive cognitive functioning in a sample of patients with treatment-resistant schizophrenia receiving clozapine. After clinical and neurocognitive assessments, the patients were randomly allocated to receive, in a double-blind design, at a dose of 60 mg per day of duloxetine or a placebo. A final sample of 33 patients completed the study. The results obtained indicate that duloxetine added to stable clozapine treatment showed a beneficial effect on the negative and general psychopathological symptomatology in a sample of treatment-resistant schizophrenic patients. With regard to executive cognitive functions, duloxetine augmentation of clozapine had no significant effects. The findings provide evidence that duloxetine augmentation of clozapine treatment is safe and well tolerated and may be of benefit for patients who are partially responsive to clozapine monotherapy.

Effect of aripiprazole augmentation of serotonin reuptake inhibitors or clomipramine in treatment-resistant obsessive-compulsive disorder: a double-blind, placebo-controlled study.

Based on the evidence that aripiprazole added to serotonin reuptake inhibitors (SRIs) or clomipramine in treatment-resistant obsessive-compulsive disorder (OCD) has reported promising results, the present 16-week, double-blind, randomized, placebo-controlled trial had the aim to explore the efficacy of aripiprazole add-on pharmacotherapy on clinical symptoms and cognitive functioning in a sample of treatment-resistant OCD patients receiving SRIs. After clinical and neurocognitive assessments, patients were randomly allocated to receive, in a double-blind design, 15 mg/d of aripiprazole or a placebo. A final sample of 30 patients completed the study. The results obtained indicate that aripiprazole added to stable SRI treatment substantially improved obsessive-compulsive symptoms as measured by changes on the Yale-Brown Obsessive Compulsive Scale total score and subscores (obsessions, P = 0.007; compulsions, P = 0.001; total score, P < 0.0001). Regarding cognitive functions, improvement was observed in some explored areas, such as attentional resistance to interference (Stroop score, P = 0.001) and executive functioning (perseverative errors, P = 0.015). The findings provide evidence that aripiprazole augmentation of SRIs/clomipramine treatment is well tolerated and may be proposed as an effective therapeutic strategy to improve outcome in treatment-resistant OCD.