A cluster-analytical approach toward real-world outcome in outpatients with stable schizophrenia.

BACKGROUND: This study aims to empirically identify profiles of functioning, and the correlates of those profiles in a sample of patients with stable schizophrenia in a real-world setting. The second aim was to assess factors associated with best profile membership. METHODS: Three hundred and twenty-three outpatients were enrolled in a cross-sectional study. A two-step cluster analysis was used to define groups of patients by using baseline values for the Heinrichs-Carpenter Quality of Life Scale (QLS) total score. Logistic regression was used to construct models of class membership. RESULTS: Our study identified three distinct clusters: 50.4% of patients were classified in the "moderate" cluster, 27.9% in the "poor" cluster, 21.7% in the "good" cluster. Membership in the "good" cluster versus the "poor" cluster was characterized by less severe negative (OR=.832) and depressive symptoms (OR=.848), being employed (OR=2.414), having a long-term relationship (OR=.256), and treatment with second-generation antipsychotics (SGAs) (OR=3.831). Nagelkerke R(2) for this model was .777. CONCLUSIONS: Understanding which factors are associated with better outcomes may direct specific and additional therapeutic interventions, such as treatment with SGAs and supported employment, in order to enhance benefits for patients, as well as to improve the delivery of care in the community.

A randomized, single-blind, comparison of duloxetine with bupropion in the treatment of SSRI-resistant major depression.

INTRODUCTION: For patients who continue to experience depressive symptoms despite an adequate antidepressant SSRI trial, across-class switch is considered one of the best treatment options. The goal of the present work was to compare in terms of efficacy two different dual-action compounds, duloxetine and bupropion, in patients who failed to respond in two consecutive antidepressant trials with SSRIs. METHODS: The patients were allocated randomly to duloxetine (120 mg daily) or bupropion extended release (300 mg daily). The intended medication period was 6 weeks. The primary measure of efficacy was depressive symptoms severity. RESULTS: A total of 49 participants were randomly assigned to duloxetine 120 mg (n=27) or bupropion 300 mg (n=22). The ITT efficacy patient sample consisted of 46 patients. Relatively high response and remission rates in treatment groups were found: from 60 to 70% of patients responded to treatment, and approximately 30 to 40% were in remission by the endpoint (week 6). No statistically significant difference emerged between the two groups at any post-baseline assessment, neither on mean scores of rating scales nor on qualitative efficacy measures. LIMITS: Limitations of the study are the lack of a placebo arm, difficult to include owing to ethical reasons, and the relatively small size of the sample. CONCLUSIONS: These preliminary results seem to support the hypothesis that in patients unresponsive to SSRIs the administration of antidepressants with different mechanisms of action is an effective switching strategy. Further studies are needed in light of the challenge posed by resistant depression.

Pharmacotherapy of borderline personality disorder: a systematic review for publication purpose.

Borderline Personality Disorder (BPD) is a common disorder in psychiatric practice and drugs are widely used in its treatment, targeting symptom clusters, such as affective dysregulation, impulsive-behavioural dyscontrol, and cognitive-perceptual symptoms. In last period, a growing number of studies on pharmacological treatment of BPD have been performed, but different proposals of treatment guidelines are not completely in accordance on drug indications for BPD patients. This article reviews double-blind randomized controlled trials comparing active drugs versus placebo and drugs versus drugs, published between 1990 and 2010 and focused on the treatment of borderline personality disorder. Different classes of psychoactive agents, such as antipsychotics, mood stabilizers, antidepressants, and dietary supplementation were tested in BPD patients. More recent evidences suggest that mood stabilizers (topiramate, valproate and lamotrigine), second generation antipsychotics (olanzapine and aripiprazole) and omega-3 fatty acids can be useful to treat affective symptoms and impulsive-behavioural dyscontrol in BPD patients. Moreover, antipsychotics significantly improve cognitive symptoms in patients with BPD. SSRIs were found effective in decreasing severity of depressed mood, anxiety and anger, mainly in subjects with a concomitant affective disorder. Effects of antidepressants on impulsive behaviours are uncertain. Further studies are needed to improve methods of trials and confirm these findings.

Outcome and length of stay in psychiatric hospitalization, the experience of the University Clinic of Turin.

BACKGROUND: Given the current tendency to shorten psychiatric hospitalization and change its organization, an issue could be raised regarding its outcomes. PURPOSE: To analyze features related to length of stay in a short-term inpatient treatment, to study outcomes and to evaluate the diagnosis-specific effects of hospitalization. METHOD: A sample of 310 consecutive hospitalized patients, with psychotic disorder, depressive disorder and bipolar disorder (DSM IV-TR), was recruited at the University Psychiatric Clinic, Service for Cognitive Disorders, Department of Neuroscience, University of Turin. Severity of illness was rated using the brief psychiatry rating scale (BPRS). We evaluated relations between length of stay and clinical and socio-demographic features (linear regression) and possible differences confronting BPRS scores at admission and discharge in the different diagnostic subgroups (ANOVA for repeated measures). RESULTS: All the sample of patients showed a significant improvement in symptomatology during hospitalization. Worse symptomatology in anxiety-depression domain of BPRS at admission in the whole sample was positively correlated with length of stay. A longer length of stay was also shown in patients with diagnosis of depressive disorder. Finally, a different pattern of improvement of BPRS (total score and domains) was shown between the different diagnostic groups. CONCLUSION: Brief hospitalization in our service was shown to be highly effective. Different diagnostic groups had different response to hospitalization, showing faster improvement in characteristic symptomatology, but the anxiety-depression domain showed the highest percentage of change for all the diagnostic groups. We therefore suppose that hospitalization has two effects: a specific (due to tailored therapies) and a non-specific one (due to non-specific therapy and to a placebo-like effect).

Efficacy and tolerability of duloxetine in the treatment of patients with borderline personality disorder: a pilot study.

Guidelines of the American Psychiatric Association for borderline personality disorder (BPD) indicate selective serotonin reuptake inhibitors and the serotonin and noradrenaline reuptake inhibitor (SNRI) venlafaxine for treating affective dysregulation and impulsive behavioural dyscontrol symptoms. The SNRI duloxetine has been studied in patients with major depression, generalized anxiety disorder and fibromyalgia, showing particular efficacy on somatic complaints. This study investigates duloxetine in the treatment of patients with BPD. Eighteen outpatients with a DSM-IV-TR diagnosis of BPD were treated with open-label duloxetine, 60 mg/day, for 12 weeks. Patients were assessed at baseline, week 4 and 12 with the CGI Severity item, the BPRS, the HAM-D, the HAM-A, the SOFAS, the BPD Severity Index (BPDSI) and the HSCL-90-Somatization Subscale (HSCL-90 SOM). Adverse effects were evaluated using the Dosage Record Treatment Emergent Symptom Scale. Statistics were performed with the analysis of variance. Significant P values were

Emergency psychiatry.

Up to 15% of people that are visited in the Emergency Department of a Hospital have a mental disorder and/or a psychiatric symptom: often this is not recognized or not properly treated. The reasons for this are more than one and involve: the emergency physicians that are not always prepared and sensible to face this kind of disorders; the psychiatrists that are not always well tuned with the language and the clinic of the emergency; and the patients, that can ignore or deny the psychiatric nature of their problems. After an initial definitions of the most important terms and concepts (Psychiatric Emergency and Urgency, Behavioral Emergency, Acute Presentations of Mental Disorders, and Crisis) the Medical and Psychiatric Assessment are discussed with different Clinical Presentations and Classifications, Psychosocial Evaluation and Risk Assessment. Finally the Clinical Management and the Pharmacological Treatment are presented with special attention to the underlying medical causes and to the use of new drugs, especially second generation antipsychotics, alone or combined with benzodiazepines.

The effect of gender on planning: An fMRI study using the Tower of London task.

Since the introduction of brain mapping, evidences of functional gender differences have been corroborating previous behavioral and neuropsychological results showing a sex-specific brain organization. We investigated gender differences in brain activation during the performance of the Tower of London (TOL) task which is a standardized test to assess executive functions. Eighteen healthy subjects (9 females and 9 males) underwent fMRI scanning while solving a series of TOL problems with different levels of difficulty. Data were analyzed by modeling both genders and difficulty task load. Task-elicited brain activations comprised a bilateral fronto-parietal network, common to both genders; within this network, females activated more than males in dorsolateral prefrontal cortex (DLPFC) and right parietal cortex, whereas males showed higher activity in precuneus. A prominent parietal activity was found at low level of difficulty while, with heavier task demand, several frontal regions and subcortical structures were recruited. Our results suggest peculiar gender strategies, with males relying more on visuospatial abilities and females on executive processing.

Psychometric comparison of students in medicine and other faculties: social factors and psychologic symptoms.

Few studies have investigated personality and psychopathological profiles associated to the choice of university education. Our study examined students from four faculties of Turin University, in Turin, Italy (Medicine, Engineering, Education, Law), comparing sociodemographic features, personality characteristics and psychiatric symptoms. A heterogeneous group of 1,323 students were assessed using a semistructured interview, the Personality Diagnostic Questionnaire-Revised (PDQ-R), and the Symptoms Checklist 90 (SCL-90). Statistical analysis included four logistic regression models, each fitted for one faculty, considering the other three as a control group. Associations were found in Medical and Engineering students concerning type of high school, school final score, and father?s socioeducational level. Factors associated with students of Law and Education included socioeducational characteristics, but stronger correlations were seen with PDQ-R personality scales and SCL-90 symptom clusters. In conclusion, four different profiles were identified. Medicine was not significantly related to personality and psychiatric factors. Engineering was related to male gender, choice of technical high school and father?s social level. Law was related to female gender and narcissistic personality profile. These data may be useful for counseling activities addressed to high school and university students.

Management of treatment resistant obsessive-compulsive disorder. Algorithms for pharmacotherapy.

Treatment resistant OCD subjects, defined as those patients who undergo an adequate trial of SRI (clomipramine or SSRI) and do not respond or show unsatisfactory results, account for 40-50% of all patients. Once the appropriateness of the trial has been assessed, several options exist for the clinicians. If clomipramine or citalopram have been used, an appropriate strategy consists in giving the same drug intravenously. Double-blind studies exist on the efficacy of clomipramine IV, while data are missing for citalopram. Another option that should be considered first, although data are scarce, is the addition of a cognitive behavioral therapy, when available, in the forms of exposure and response prevention. When such options are not suitable or available, augmentation of the ongoing SRI with another compound represents the preferable strategy. Double-blind, placebo-controlled studies have shown the efficacy of adding pindolol (7.5 mg/d), risperidone (2 mg/d) and olanzapine (5-10 mg/d). Other agents have been proposed, but data emerging from double-blind studies were negative or contradictory. Another option available is switching from CMI to SSRI, or vice versa, or from SSRI to SSRI. Data regarding such treatment strategy, however, are highly preliminary, based on a couple of open label reports and on studies performed in treatment resistant depression. An unresolved question is whether augmentation should be preferred to switching. No data exist in OCD; a practical approach would suggest augmentation first, considering that response should be obtained faster than by switching compound. When all the available and effective strategies prove uneffective, clinicians should consider switching the patient to other compounds in monotherapy, such as venlafaxine, sumatriptan, inositol, although research is strongly needed before conclusions on the efficacy of such compounds can be drawn.

Bulimia nervosa with and without obsessive-compulsive syndromes.

The present study was performed in a group of bulimic (BN) females (1) to assess prevalence rates of comorbid obsessive-compulsive phenomena; (2) to investigate whether BN patients display a characteristic cluster of obsessive-compulsive symptoms; and (3) to determine whether obsessive-compulsive symptoms influence the clinical picture of BN. Thirty-eight DSM-IV BN females were interviewed by means of the Structured Clinical Interview for DSM-III-R (SCID) to assess the prevalence rate of obsessive compulsive disorder (OCD); the Yale-Brown Obsessive-Compulsive Symptom Scale (Y-BOCS) Symptom Check-List was also used to evaluate the presence of obsessive-compulsive symptoms. The phenomenology of BN females with obsessive-compulsive syndromes (OCS) as detected by the Y-BOCS was compared to that shown by a "control" group of nonbulimic OCD females. Finally, the eating-related psychopathology of BN women with and without OCS was compared. The current prevalence rates of OCD and of subthreshold obsessive-compulsive syndrome (sOCS) in our sample were 10.5% and 15.8%, respectively. Thus, a total of 26.3% of BN females had a current OCS that comprised both clinical disorders and subthreshold syndromes. No differences were detected between obsessive-compulsive symptoms of these females and those of the control group of nonbulimic OCD females. BN females with OCS had higher ratings on the Eating Disorder Inventory (EDI) total score and on the "drive for thinness" and the "bulimia" items of the scale, as compared to BN females without OCS. In conclusion, it appears that a considerable proportion of BN females display OCS, which sometimes are not severe enough to fulfill diagnostic criteria for OCD. Moreover, in these patients, obsessive-compulsive symptoms are undistinguishable from those of OCD females, and exert a negative influence on the clinical picture of the bulimic disorder.

Clinical features of dysthymia and age: a clinical investigation.

A few authors have described the clinical picture of dysthymia in groups of elderly patients and pointed out differences from literature reports of dysthymia in younger adults. The present study, an attempt to analyze age effects on clinical characteristics of dysthymia throughout a lifetime, was performed in a sample of 106 patients, all aged > or =18 years, who were diagnosed according to DSM-IV. The patients were evaluated using: (1) a semistructured interview to assess clinical features, family history and previous treatments; (2) the Hamilton Depression Rating Scale; (3) the Interview for Recent Life Events; and (4) the Structured Clinical Interview for DSM-IV Disorders. Statistical analysis with stepwise logistic regression revealed that age was positively related to concomitant medical illnesses and to the total score of recent life events, but negatively related to the presence of avoidant or dependent personality disorders. The data suggested different etiologic pathways in older and younger patients. Dysthymia appeared to be associated in younger adults with abnormalities of personality; in the elderly, with a history of health problems and life losses.

Dysthymic disorder: clinical characteristics in relation to age at onset.

BACKGROUND: The variability in the clinical presentation of dysthymia has given rise to a rich debate in literature, and various hypotheses have been proposed. One is that the clinical presentation differs in relation to age at onset. The aim of the study was to evaluate differences in socio-demographic and clinical characteristics in a sample of patients with dysthymia (DSM-IV), in relation to age at onset. METHOD: 84 consecutive outpatients with a diagnosis of dysthymia (DSM-IV) were studied. All subjects were evaluated by a semistructured clinical interview and the following rating scales: HAM-A, HAM-D, MADRS, Paykel's Interview for Recent Life Events. RESULTS: 23.8% of the sample had early-onset (<21 yrs) dysthymia. Patients with early-onset disorder were significantly younger at the observation, more frequently female and single. They had a significantly longer duration of illness and in a significantly higher percentage had already received a specialist treatment before admission in the present trial. No differences in the frequency of symptoms were observed. A significantly higher percentage of patients with late-onset disease reported at least one stressful event in the year preceding the onset of dysthymia. A positive history of major depression was significantly more common among the early-onset group; social phobia, panic disorder and conversive disorder were also more frequent in this group. The late-onset patients frequently presented generalized anxiety disorder, substance abuse and somatization disorder. LIMITATION: The study is retrospective and enrolls a limited number of cases. CONCLUSIONS: The present study agrees with other reports on the differences in clinical presentation of dysthymia according to age at onset. Although they are not actually related to age at onset, some interesting findings emerged in the symptomatological characterization of the disorder, referring to the diagnostic criteria proposed in DSM-IV.

[Post-partum as a specific risk factor for the onset of obsessive-compulsive disorder: clinical-controlled study]. / Il post partum come fattore di rischio specifico per l'esordio del disturbo ossessivo-compulsivo: studio clinico controllato.

OBJECTIVE: The aim of this study is to evaluate the presence of triggering life-events for the onset of Obsessive-Compulsive Disorder in women (OCD). DESIGN: Clinical controlled study. SETTING: Service for depressive and anxiety disorders; Department of Neuroscience, Psychiatric Unit, University of Turin. METHODS: The study compares twenty-nine women with OCD (DSM-IV criteria) with twenty-nine healthy control women matched for demographic features and with twenty-nine women with Bulimia Nervosa (DSM-IV criteria) matched for age, age at onset, education and marital status. All patients were assessed with the Clinical Structured Interview for DSMIII-R (SCID) and with the Interview for Recent Life Event by Paykel. Moreover, OCD patients were assessed with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and bulimic patients with the Eating Disorder Inventory (EDI). RESULTS: The study demonstrates that the only specific life event that is significantly associated with the onset of OCD is "having a new born child" No significant differences in frequency and severity of stressing life events were found in the three groups. CONCLUSIONS: The results confirms the findings of our previous study: post partum is the only risk factor for the onset of OCD in female population, compared to healthy control. Furthermore, this research points-out the importance and the specificity of this association showing that post partum is not a risk factor in all psychiatric disorders.

Occurrence and clinical correlates of psychiatric co-morbidity in delusional disorder.

The present study investigated the occurrence and the clinical correlates of psychiatric co-morbidity in a sample of 64 patients with delusional disorder (DD). Subjects were evaluated with a semi-structured interview for the collection of demographic and clinical features of the disorder; co-morbid axis 1 disorders were determined according to the clinical interview using DSM-IV by Othmer and Othmer. Delusional disorder subjects with and without co-morbid diagnoses were compared to investigate whether the presence of another psychiatric disorder influenced the clinical features of the illness.Seventy-two percent of the subjects had at least one additional lifetime psychiatric diagnosis. High lifetime co-morbidity was found with affective disorders, whose onset generally had been subsequent to the onset of DD. Patients with at least one co-morbid disorder (N = 46) had an earlier age at onset, presented for the first psychiatric consultation at an earlier age, and were younger at index evaluation for this study with respect to patients without co-morbidity (N = 18). Types of DD differed significantly according to the presence/absence of lifetime co-morbid disorders: DD patients with co-morbidity were in most cases persecutory type (54.4%) while DD patients without co-morbidity were mixed type (66.7%). Our data indicate that there is a considerable proportion of patients whose DDr is strictly connected with other co-occurring psychiatric disorders (mainly affective disorders), which exert an influence on the phenomenology of the illness.

The cAMP-dependent protein kinase substrate Rap1 in platelets from patients with obsessive compulsive disorder or schizophrenia.

Previous studies have reported that the cAMP-dependent protein kinase and one of its substrates, namely Rap1, are altered in patients with affective disorders. Abnormalities in the cAMP-dependent protein kinase have also been reported in platelets of patients with obsessive compulsive disorder and schizophrenia. However, it remains to be determined whether abnormalities in Rap1 are specifically related to affective disorders or may also be present in schizophrenia and obsessive compulsive disorder. Thus, we investigated Rap1 in platelets from 12 drug-free patients with obsessive compulsive disorder, ten drug-free patients with schizophrenia, and 20 healthy subjects. While no difference was observed in the levels of Rap1 between groups, the phosphorylation state of Rap1 was significantly lower in patients with obsessive compulsive disorder than in schizophrenic patients and controls. These data further support the idea that abnormalities of cAMP signalling pathway could be associated, albeit in a somewhat different way, with several psychiatric disorders.

Gender-related distribution of personality disorders in a sample of patients with panic disorder.

OBJECTIVE: We examined gender differences in the frequency of DSM-IV personality disorder diagnoses in a sample of patients with a diagnosis of panic disorder (PD). METHOD: One hundred and eighty-four outpatients with a principal diagnosis of PD (DSM-IV) were enrolled. All patients were evaluated with a semi-structured interview to collect demographic and clinical data and to generate Axis I and Axis II diagnoses in accordance with DSM-IV criteria. RESULTS: Males were significantly more likely than females to meet diagnoses for schizoid and borderline personality disorder. Compared to males, females predominated in histrionic and cluster C diagnoses, particularly dependent personality disorder diagnoses. A significant interaction was found between female sex and agoraphobia on personality disorder (PD) distribution. CONCLUSIONS: Male PD patients seem to be characterized by more severe personality disorders, while female PD patients, particularly with co-morbid agoraphobia, have higher co-morbidity rates with personality disorders belonging to the 'anxious-fearful cluster'.

Gender-related differences in the onset of panic disorder.

OBJECTIVE: To investigate gender-related differences in premorbid conditions and in the role of triggering events in the onset of panic disorder (PD). METHOD: One hundred and eighty-four out-patients with a principal diagnosis of PD (DSM-IV) were evaluated with a semi-structured interview to generate Axis I and Axis II diagnoses according to DSM-IV, to collect family history of psychiatric disorders and life events. The statistical analysis was performed comparing men and women. RESULTS: Men and women showed similar age at onset of PD. A family history of mood disorders characterized females. Men had higher rates of cyclothymia, body dysmorphic disorder and depersonalization disorder preceding PD, while women had higher rates of bulimia nervosa. Dependent and histrionic PDs were more common among women, while borderline and schizoid PDs were more common among men. Life events showed a significant role in precipitating PD onset in women. CONCLUSION: Premorbid clinical conditions of PD seem to differentiate between males and females in the role of precipitating events.

Relapses after discontinuation of drug associated with increased resistance to treatment in obsessive-compulsive disorder.

The aim of the present study was to determine whether obsessive-compulsive disorder (OCD) patients whose symptoms recur after drug discontinuation respond again when the same drug at the same daily dosage is reinstituted. Eighty-one patients who were responders to a previous 6-month, open-label, noncomparative, acute treatment phase with fixed doses of selective reuptake inhibitors (SRIs) and who relapsed within 6 months of drug discontinuation had the drug to which they responded in the acute phase reinstated at the same daily dose. The reinstitution trial lasted 24 weeks with monthly evaluations (Yale-Brown Obsessive-Compulsive Scale and Clinical Global Improvement). Data obtained in the reinstitution phase were analysed using Pearson's chi-squared test or Fisher's exact test when appropriate. The cumulative percentages of patients who responded in the second trial were compared to those of patients who responded in the acute treatment phase (for each treatment and for all SRIs together) across all evaluation times. When considering all patients together, a lower percentage of responders resulted when SRIs were reinstated: the difference in the cumulative percentage of responders appeared at month 4 and increased at months 5 and 6 (Pearson chi-squared, P = 0.028, P = 0.009 and P < 0.001, respectively). When considering the patients separately according to the SRI used, no differences in the percentages of responders were found at any time. Our results indicate that patients whose symptoms recur after drug discontinuation respond again when the same drug used previously (at the same dosage used in the acute phase) is reinstated, but at a lower degree with respect to the acute treatment. Findings from our study, together with literature data indicating high relapse rates when discontinuing the treatment after the acute phase, support the idea of continuing the treatment in OCD over the long term.

Olanzapine augmentation of fluvoxamine-refractory obsessive-compulsive disorder (OCD): a 12-week open trial.

A few studies have tried antipsychotic augmentation in obsessive-compulsive disorder (OCD) patients who are non-responders to selective serotonin reuptake inhibitors. The aim of this study was to investigate the efficacy and tolerability of olanzapine addition to fluvoxamine-refractory OCD patients and to assess if a comorbid chronic tic disorder or a concomitant schizotypal personality disorder was associated with response. Twenty-three OCD non-responders to a 6-month, open-label trial with fluvoxamine (300 mg/day) entered a 3-month open-label trial of augmentation with olanzapine (5 mg/day). OC symptom change was measured with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the Clinical Global Impression (CGI) scale. Differences between responders and non-responders were assessed with regard to age, sex, duration of illness, baseline Y-BOCS score, and comorbidity with chronic tic disorders or schizotypal personality disorder. A significant decrease of mean Y-BOCS score between pre- and post-treatment (26. 8+/-3.0 vs. 18.9+/-5.9) was found at endpoint. Ten patients (43.5%) were rated as responders. The most common side effects were mild to moderate weight gain and sedation. In our sample, three patients (13. 04%) had a chronic motor tic disorder, and four (17.39%) had a codiagnosis of schizotypal personality disorder. Concomitant schizotypal personality disorder was the only factor significantly associated with response. It appears that augmentation of olanzapine in fluvoxamine-refractory OCD may be effective in a large number of patients, including those with comorbid schizotypal personality disorder.

Lymphocyte peripheral benzodiazepine receptor mRNA decreases in obsessive-compulsive disorder.

The relative content of peripheral benzodiazepine receptor (pBR) mRNA was examined by reverse transcriptase-polymerase chain reaction in lymphocytes of obsessive-compulsive disorder (OCD) patients, according to their clinical course of illness. pBR mRNA significantly decreased only in chronic OCD patients (n=8) as compared to controls (n=10), whereas no significant changes were observed in episodic OCD patients (n=7). We suggest that modulation of pBR gene expression might delineate a clinical heterogeneity in OCD.