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.

Augmentation strategies in partial responder and/or treatment-resistant schizophrenia patients treated with clozapine.

INTRODUCTION: Although clozapine (CLZ) is considered the best evidence-based therapeutic option for treatment of resistant schizophrenia patients, a significant proportion of CLZ-treated patients show a partial or inadequate response to treatment, leading to increased healthcare cost and poor quality of life for affected individuals. AREAS COVERED: This paper comprises a review of main research in CLZ augmentation strategies for treatment-refractory schizophrenia, with a focus on research conducted between 1990 and 2014. Databases that were searched include: PubMed, CINAHL, EMBASE PsychINFO, AgeLine and Cochrane Database of Systematic Reviews. Primary search terms were 'clozapine augmentation', 'clozapine and add-on' and 'treatment-resistant schizophrenia', with cross reference to specific agents covered in this article. We reviewed the available evidence on CLZ augmentation with antipsychotics, antidepressants, mood stabilizers and other agents. EXPERT OPINION: Many drugs have been evaluated as CLZ add-on therapies without demonstrating convincing efficacy in treating refractory schizophrenia symptoms. More research is needed to better define outcomes in schizophrenia, the topic of treatment-resistance and more well-designed trials are required to establish true efficacy and safety of CLZ augmentation strategies.

Anger in health, benign breast disease and breast cancer: a prospective case-control study.

BACKGROUND: The State-Trait Anger Expression Inventory 2 (STAXI-2) is a psychometric instrument measuring anger experience and expression. Associations between the STAXI-2 and risk of breast cancer (BC) are rarely considered together in a prospective study. PATIENTS AND METHODS: A total of 117 women with breast symptoms referred for breast examination were selected and assessed before any diagnostic procedures. RESULTS: Twenty-four patients with BC, 44 with benign breast disease (BBD) and 49 healthy individuals (HHS) were included. Scores for parameters state anger/feel like expressing anger physically (SANGP) were significantly higher in the HHS group (HHS vs. BBD: p=0.027; HHS vs. BC: p=0.025). BC patients showed a trend to lower scores in almost all scales of STAXI-2, except for the scales trait anger/angry temperament (TANGT), anger expression-in (AX-I), and anger control-out (AC-O), that were higher than the two other groups' scores. CONCLUSION: The results of this study do not support a specific link between STAXI-2 and breast cancer risk.

Reboxetine adjuvant therapy in patients with schizophrenia showing a suboptimal response to clozapine: a 12-week, open-label, pilot study.

The present 12-week open-label uncontrolled trial was aimed to explore the efficacy of reboxetine add-on pharmacotherapy on clinical symptoms and cognitive functioning in 15 patients with schizophrenia with suboptimal response (mean [SD] Brief Psychiatric Rating Scale baseline total score, 32.2 [5.4]) despite receiving clozapine monotherapy at the highest tolerated dosage. The results obtained evidenced that reboxetine at a dosage of 4 mg/d mildly reduced only depressive symptoms (Calgary Depression Scale for Schizophrenia: P = 0.035, Cohen d = 0.7), whereas worsening of performances on phonemic fluency (P = 0.012, Cohen d = 0.5) was observed. After Bonferroni correction, changes at the Calgary Depression Scale for Schizophrenia and at the Verbal Fluency Task were not further confirmed.The results obtained indicate that reboxetine seemed to be scarcely effective for reducing clinical symptoms in patients with schizophrenia who have had an incomplete clinical response to clozapine. Regarding cognitive functioning, in our sample, a trend to experience cognitive impairment in the examined domains was observed, as confirmed by a mild worsening of performances on cognitive tasks.Schizophrenia is a heterogeneous disorder with regard to pathophysiology; therefore, data reflecting the mean response of a sample of patients may fail to reveal therapeutic effects. More research is needed to better identify subgroups of patients with peculiar features, which may account for responsivity to experimental medications and augmentation strategies.

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.

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.

Executive functions and basic symptoms in adolescent antisocial behavior: a cross-sectional study on an Italian sample of late-onset offenders.

Executive cognitive functions (ECFs) and other cognitive impairments, such as lower IQ and verbal deficits, have been associated with the pattern of antisocial and delinquent behavior starting in childhood (early-onset), but not with late-onset antisocial behavior. Beyond objective measures of ECF, basic symptoms are prodromal, subjectively experienced cognitive, perceptual, affective, and social disturbances, associated with a range of psychiatric disorders, mainly with psychosis. The goal of the present study was to examine ECF and basic symptoms in a sample of late-onset juvenile delinquents. Two-hundred nine male adolescents (aged 15-20 years) characterized by a pattern of late-onset delinquent behavior with no antecedents of Conduct Disorder, were consecutively recruited from the Social Services of the Department of Juvenile Justice of the city of Messina (Italy), and compared with nonantisocial controls matched for age, educational level, and socio-demographic features on measures for ECF dysfunction and basic symptoms. Significant differences between late-onset offenders (completers=147) and control group (n=150) were found on ECF and basic symptoms measures. Chi-square analysis showed that a significantly greater number of late-onset offending participants scored in the clinical range on several ECF measures. Executive cognitive impairment, even subtle and subclinical, along with subjective symptoms of cognitive dysfunction (basic symptom), may be contributing factor in the development and persistence of antisocial behaviors displayed by late-onset adolescent delinquents. The findings also suggest the need for additional research aimed to assess a broader range of cognitive abilities and specific vulnerability and risk factors for late-onset adolescent offenders.

Augmentation of clozapine with ziprasidone in refractory schizophrenia: a double-blind, placebo-controlled study.

The present 16-week double-blind, randomized, placebo-controlled trial was aimed to explore the efficacy of ziprasidone add-on pharmacotherapy on clinical symptoms and cognitive functioning in 40 schizophrenic patients (active group, n = 20; placebo group, n = 20) with residual symptoms (Brief Psychiatric Rating Scale mean [SD] baseline total score in active group vs placebo, 40.4 [5.9] vs 37.9 [6.8]) despite receiving clozapine monotherapy at the highest tolerated dosage. The results obtained evidenced that ziprasidone augmentation of clozapine significantly reduced Positive and Negative Syndrome Scale "Negative" (P = 0.006, mean change [SD] in active group vs placebo, -2.7 [2.3] vs 1.1 [2.1], Cohen d = 1.7) and "General Psychopathology" (P = 0.009, mean change [SD] in active group vs placebo, -5.3 [3.8] vs -0.7 [2.0], Cohen d = 1.5). Regarding cognitive domains, ziprasidone was more effective than placebo in improving semantic fluency (P < 0.0001, mean change [SD] in active group vs placebo, 4.4 [3.5] vs -0.1 [4.1], Cohen d = 1.2). Ziprasidone had only a small effect on prolongation of heart-rate corrected QT interval (QTc) of the electrocardiogram, not significantly different from placebo (QTc milliseconds, mean [SD], week 16 in active group vs placebo, 408.17 [20.85] vs 405.45 [17.11], P = 0.321); within-group comparison revealed that QTc prolongation induced by ziprasidone was statistically significant (baseline vs week 16, P = 0.002). Ziprasidone added to clozapine was effective on negative and cognitive symptoms, although it may be proposed as a helpful treatment in schizophrenia, mainly for those patients who partially respond to clozapine monotherapy.

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.

Effect of aripiprazole augmentation of clozapine in schizophrenia: a double-blind, placebo-controlled study.

The simultaneous prescription of two or more antipsychotic drugs in combination is a common treatment strategy for those patients who have demonstrated a suboptimal response to clozapine; nevertheless, evidence suggesting potential advantages of combination treatment with clozapine plus one antipsychotic in terms of efficacy and tolerability are still sparse. The present 24-week double-blind, randomized, placebo-controlled trial of adjunctive aripiprazole to clozapine therapy in schizophrenia was aimed to explore the efficacy of aripiprazole add-on pharmacotherapy on clinical symptomatology and cognitive functioning in a sample of patients with treatment-resistant schizophrenia receiving clozapine. After clinical and neurocognitive assessments patients were randomly allocated to receive, in a double-blind design, either up to 15 mg/day of aripiprazole or a placebo. A final sample of thirty-one patients completed the study. The results obtained indicate that aripiprazole added to stable clozapine treatment showed a beneficial effect on the positive and general psychopathological symptomatology in a sample of treatment-resistant schizophrenia patients. Regarding executive cognitive functions, aripiprazole augmentation of clozapine had no significant effects. The findings provide evidence that aripiprazole augmentation of clozapine treatment is well-tolerated and may be of benefit for patients who are partially responsive to clozapine monotherapy; further double-blind, placebo-controlled trials in a larger number of patients are required to evaluate the therapeutic potential of aripiprazole augmentation of clozapine.

Emerging treatments in the management of schizophrenia - focus on sertindole.

The antipsychotic treatment of schizophrenia is still marked by poor compliance, and drug discontinuation; the development of more effective and safer drugs still remains a challenge. Sertindole is a second-generation antipsychotic with high affinity for dopamine D(2), serotonin 5-HT(2A), 5-HT(2C), and α(1)-adrenergic receptors, and low affinity for other receptors. Sertindole undergoes extensive hepatic metabolism by the cytochrome P450 isoenzymes CYP2D6 and CYP3A4 and has an elimination half-life of approximately three days. In controlled clinical trials sertindole was more effective than placebo in reducing positive and negative symptoms, whereas it was as effective as haloperidol and risperidone against the positive symptoms of schizophrenia. The effective dose-range of sertindole is 12-20 mg, administered orally once daily. The most common adverse events are headache, insomnia, rhinitis/nasal congestion, male sexual dysfunction, and moderate weight gain, with few extrapyramidal symptoms and metabolic changes. Sertindole is associated with corrected QT interval prolongation, with subsequent risk of serious arrythmias. Due to cardiovascular safety concerns, sertindole is available as a second-line choice for patients intolerant to at least one other antipsychotic agent. Further clinical studies, mainly direct "head-to-head" comparisons with other second-generation antipsychotic agents, are needed to define the role of sertindole in the treatment of schizophrenia.

Depression, anxiety and anger in subtypes of irritable bowel syndrome patients.

The present study aimed to elucidate the differences in depression, anxiety, anger, and quality of life in a sample of non-psychiatric IBS patients, starting from the hypothesis that IBS subtypes may have different symptomatic expressions of negative emotions with different outcomes on quality of life measures. Forty-two constipation-predominant IBS (C-IBS) subjects and 44 diarrhea-predominant IBS (D-IBS) subjects, after an examination by a gastroenterologist and a total colonoscopy, underwent a clinical interview and psychometric examination for the assessment of depression, anxiety, anger and quality of life. IBS subtypes showed different symptomatic profiles in depression, anxiety and anger, with C-IBS patients more psychologically distressed than D-IBS subjects. Affective and emotional symptoms should be considered as specific and integral to the syndrome, and recognizing the differences between IBS subtypes may have relevant implications for treatment options and clinical outcome.