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.

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.

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.

Alexithymia, negative emotions, and sexual behavior in heterosexual university students from Italy.

Alexithymia is a construct which denotes thought characterized by pragmatic content, an inability to recognize and verbally express emotion, a difficulty in distinguishing between feelings and bodily sensations, and a limitation in fantasy life. Research has revealed a role for alexithymia in different kinds of sexual dysfunctions; it was also associated with reduced frequency of penile-vaginal intercourse but not with sexual behaviors-like masturbation-which do not include an emotional interaction in normal individuals. The aim of this research was to further investigate the association between alexithymia scores and sexual behavior in a sample of normal individuals, taking into account the role of gender differences and the possible effect of negative emotions (depression, anxiety, and anger). Participants were 300 university students (142 men and 158 women); sexual behavior was measured by the Sex and the Average Woman (or Man) Scale while alexithymia was measured with the Toronto Alexithymia Scale. The findings of the study showed that higher alexithymia scores were associated with lower levels of sexual satisfaction and higher levels of sexual detachment for females, and with sexual shyness and sexual nervousness for both genders. Results also suggested that the correlations between alexithymia scores and sexual behavior are partially influenced by the effect of negative emotions. Overall, it seems that the same detachment which denotes the alexithymic interpersonal style also characterizes sexual behavior.

Drugs and sexual behavior.

This study investigated the association between drugs and sexual behavior in a sample of polydrug substance abusers recruited from several Italian therapeutic communities; participants were 90 polydrug substance abusers (opiates, cocaine, amphetamine, inhalants, marijuana/sedatives or hallucinogens abusers) who were compared with 90 nonsubstance-abusing individuals. Sexual behavior was measured by the Italian version of the Sex and the Average Woman (or Man; SAWM), a questionnaire that assesses different kind of sexual attitudes. Results showed that drug-abusing individuals are particularly inclined to search for sexual intercourse and are open to different kinds of sexual experiences; however, they have difficulties in establishing committed and deep relationships with their partners, showing signs of inhibition, affective detachment or anger. Their sexual lives are also surrounded by negative emotions, disturbing thoughts and maladjusted behaviors. The importance of integrating sexual problems into therapeutic strategies is discussed.

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.

The relationship between anger and heterosexual behavior. An investigation in a nonclinical sample of urban Italian undergraduates.

INTRODUCTION: The relationship between anger and sexual behavior has never been thoroughly addressed, although it may deserve special attention because of its theoretical and practical consequences. AIM: We were interested in determining the extent in which trait anger was associated with dysfunctional sexual behavior, taking into account possible gender differences. METHOD: In this correlational study, 410 volunteers (199 men and 211 women) recruited from the students of the University of Messina, Italy, participated in the study. Median age of participants was 24 years. Men and women did not differ significantly in age (U = 18996, P = 0.606). MAIN OUTCOME MEASURES: The individuals' sexual behavior was assessed using the Sex and the Average Woman (or Man) questionnaire. RESULTS: We found no association between trait anger and either measure of sexual motivation: sexual excitement, r (396) = 0.11, P = 0.016, and sexual fulfillment, r (396) = -0.06, P = 0.134. Also, gender had no effect on either of these two variables. Trait anger had a positive significant correlation with neurotic sex, r (396) = 0.29, P < 0.002, impersonal sex, r (396) = 0.20, P < 0.002, and aggressive sex, r (396) = 0.28, P < 0.002. As we predicted, the associations between trait anger and these last three variables were stronger for men than for women (although only aggressive sex had a significant result). In multivariate analyses, impersonal sex ceased to be a significant correlate of trait anger. CONCLUSIONS: Trait anger has a negative effect on sexual behavior. It seems to exert its worst effects on the nature of sexual interpersonal behavior rather than on sexual motivation. We found no effect of gender on sexual motivation. However, the positive correlation between anger and relational sexual behavior was stronger for men than for women.

Morphometrical and morphological analysis of lateral ventricles in schizophrenia patients versus healthy controls.

The goal of this report was to highlight lateral ventricle morphology and volume differences between schizophrenia patients and matched controls. Subjects identified as suitable for analysis comprised 15 schizophrenia patients and 15 healthy subjects. The method applied is three-dimensional (3D) volume rendering starting from structural magnetic resonance imaging (MRI) studies of selected ventricular regions. Differences between groups relative to the global ventricular system and its subdivisions were found. Total lateral ventricle volume, right ventricle volume and left ventricle volume were all higher in schizophrenia patients than in controls; unilateral differences between the two groups were also outlined (right ventricle volume>left ventricle volume in schizophrenia patients vs. healthy subjects). Furthermore, occipital and frontal horn enlargement was found in schizophrenia patients compared with normal controls, but the difference in the temporal horn was not statistically significant. A substantial difference was noted in lateral ventricle morphology between the two groups. Our findings were consistent with the literature and may shed light on some of the discrepancies in previous reports on differences in lateral ventricle volume enlargement.

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.

Defense mechanisms in a sample of non-psychiatric obese subjects.

The aim was to assess the prevalent defense mechanisms in a sample of obese subjects; since specific defensive styles may interfere with the management of stressors and emotions, they may also influence the onset, the severity, and the maintenance of obesity. 70 obese subjects and 70 healthy normal-weight volunteers were assessed using the Defense Mechanisms Inventory -- DMI. Significant differences between groups have emerged at Turning Against Object (t=-5.30; p<0.0001), Projection (t=-5.55; p<0.0001), Turning Against Self (t=-4.87; p<0.0001) and Reversal (t=-3.61; p<0.0001) variables. Within the obese group, significant differences have been found at Turning Against Object (U=264; p=.001) and Projection (U=359; p=.042) scales, both higher in males. No significant differences on DMI scores in relation to the severity of obesity have been observed. An inadequate defensive structure might represent a vulnerability to emotional states and stressful life events. The assessment of defense mechanisms may provide a valid tool for long-term treatments of obesity.

The relationship between personality and sexual motivation: an investigation based on Cloninger's model in nonclinical Italian subjects.

BACKGROUND: The aim of this study was to investigate the relationship between personality and sexual motivation according to Cloninger's psychobiological model of the personality. METHODS: Three hundred and ten volunteers recruited among the students of the University of Messina, Italy, participated in the study. All subjects underwent a psychometric examination with the following instruments: Temperament and Character Inventory (TCI) and Sex and the Average Woman (or Man; SAWM). RESULTS: The best negative predictor of Sexual Excitement and Satisfaction was the temperamental dimension Harm Avoidance; as it regards character dimensions, Cooperativeness was the best negative predictor of Sexual Excitement, while Self-Directedness was the best positive predictor of Sexual Satisfaction. CONCLUSIONS: Overall, inhibitory aspects of the personality have deeper effects on sexual motivation than excitatory ones. The results of this research suggest the importance of studying the relationship between personality and sexual behavior. An integrative psychobiological approach to the study of sexual excitement and satisfaction may give a fundamental contribution to the assessment and psychological treatment of predisposing personality factors (like avoidant tendencies) involved in the development and persistence of sexual dysfunction.

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.

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.

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.

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.

Effect of adjunctive lamotrigine treatment on the plasma concentrations of clozapine, risperidone and olanzapine in patients with schizophrenia or bipolar disorder.

The effect of lamotrigine on the steady-state plasma concentrations of the atypical antipsychotics clozapine, olanzapine, and risperidone was investigated in patients with schizophrenia or bipolar disorder stabilized on chronic treatment with clozapine (200-500 mg/day; n = 11), risperidone (3-6 mg/day; n = 10) or olanzapine (10-20 mg/day; n = 14)). Lamotrigine was titrated up to a final dosage of 200 mg/day over 8 weeks, and pharmacokinetic assessments were made at baseline and during treatment weeks 6 and 10, at lamotrigine dosages of 100 and 200 mg/day respectively. The plasma concentrations of clozapine, norclozapine, risperidone, and 9-hydroxy-risperidone did not change significantly during treatment with lamotrigine. The mean plasma concentrations of olanzapine were 31 +/- 7 ng/mL at baseline, 32 +/- 7 ng/mL at week 6, and 36 +/- 9 ng/mL at week 10, the difference between week 10 and baseline being statistically significant (P < 0.05). Adjunctive lamotrigine therapy was well tolerated in all groups. These findings indicate that lamotrigine, at the dosages recommended for use as a mood stabilizer, does not affect the plasma levels of clozapine, risperidone, and their active metabolites. The modest elevation in plasma olanzapine concentration, possibly due to inhibition of UGT1A4-mediated olanzapine glucuronidation, is unlikely to be of clinical significance.