Aggressiveness and violence in psychiatric patients: a clinical or social paradigm?

OBJECTIVE: Psychiatric disorders are often considered the leading cause of violence. This may be due to a stereotype created by media and general opinion. METHOD: The Modified Overt Aggression Scale (MOAS) was used to evaluate the severity of aggressive and violent behaviors in 400 patients who attended a post-acute psychiatric service in Milan from 2014 to 2016 and suffered from different psychiatric disorders. The psychopathological clinical picture was evaluated by Clinical Global Impression (CGI). The study also assessed the possible correlation between epidemiologic and sociodemographic factors, clinical variables, and aggression and violence. RESULTS: Of the total number of subjects, 21.50% showed a MOAS score >0, 11.50% presented mild aggression (0-10 MOAS weighted score), 9% moderate aggression (11-20), and 1% severe aggression (MOAS >20). With respect to violent behaviors, 16% of patients showed a score >0 in one MOAS subscale other than verbal aggression according to violence definition. The severity of clinical picture seemed to be related to higher weighted MOAS score. Multivariate testing of different sociodemographic and clinical variables showed that violence was related to unemployment status, and significantly correlated to compulsory admission (TSO), suicide attempts (TS), and personality disorders, while the severity of clinical psychiatric picture seemed to play a secondary role. CONCLUSION: Results have shown that personality disorders and sociodemographic factors, including economic factors, seem to be major determinants of violence among patients diagnosed with mental disorders.

Intraindividual and Interindividual Variability of Olanzapine Trough Concentrations in Patients Treated With the Long-Acting Injectable Formulation.

BACKGROUND: A long-acting injectable (LAI) formulation of olanzapine has been developed as an alternative to oral regimens. A therapeutic range of 20 to 80 ng/mL for oral olanzapine trough concentrations has been proposed. Here, we sought to investigate the intraindividual and interindividual variability of olanzapine concentrations with time in patients on maintenance therapy with the LAI formulation carried out in the routine clinical practice. METHODS: To address this issue, we carried out a retrospective analysis of therapeutic drug monitoring of olanzapine concentrations in 21 schizophrenic patients on maintenance LAI olanzapine. Drug concentrations were correlated with LAI olanzapine doses, duration of treatment, and main clinical characteristics. RESULTS: Fifty percent of the patients had olanzapine trough concentrations lower than 20 ng/mL. Only drug doses significantly correlated with olanzapine exposure. Mean interindividual and intraindividual coefficients of variations of olanzapine concentrations were 56% (range, 21%-97%) and 34% (range, 15%-69%), respectively. CONCLUSIONS: We have documented that, in a real-life setting, a large proportion of patients treated with olanzapine LAI had drug trough concentrations of less than 20 ng/mL; wide intraindividual and interindividual variability of olanzapine concentrations has been also observed. Our results could provide the rationale for the design of larger prospective, concentration-controlled clinical trials specifically designed with the goal to identify ad hoc therapeutic ranges of drug concentrations for olanzapine LAI.

Effect of N-Desalkylquetiapine/Quetiapine Plasma Level Ratio on Anxiety and Depression in Bipolar Disorder: A Prospective Observational Study.

BACKGROUND: The aim of this study was to analyze the relationships between quetiapine and N-desalkylquetiapine plasma levels and clinical improvement, particularly, in regard to depressive and anxious symptoms and to hostility. METHODS: This was a prospective observational study that involved 37 outpatients diagnosed as having bipolar disorder I or II. All the patients were observed during a clinical acute and postacute phase. Patients were prescribed 50-800 mg of quetiapine. Patients were evaluated at baseline, after 15 days and after 3 months using the Brief Psychiatry Rating Scale with particular reference to the dimensions of depression, anxiety, and hostility. The plasma concentrations of quetiapine and N-desalkylquetiapine were determined after 3 months using blood samples taken at steady state. RESULTS: There was a significant relationship between the N-desalkylquetiapine/quetiapine ratio and the improvement in the depression dimension, and there was not a significant relationship between the N-desalkylquetiapine/quetiapine ratio and anxiety and hostility improvement. Quetiapine treatment was well tolerated, and there were no extrapyramidal, anticholinergic, or other side effects to note. There was no relationship between plasma quetiapine or N-desalkylquetiapine concentrations and side effects. CONCLUSIONS: Our findings confirm the efficacy of quetiapine on depressive symptoms, and the available data support that quetiapine's antidepressant activity is mediated by the active metabolite norquetiapine, and it exemplifies the case of an active metabolite that can make a drug like quetiapine originally introduced as an antipsychotic a useful antidepressant agent.

"Long-acting" olanzapine in maintenance therapy of schizophrenia: A study with plasma levels.

INTRODUCTION: This prospective study was performed to evaluate clinical efficacy and tolerability of olanzapine long-acting injection (OLZ-LAI) and the relation between OLZ plasma level (PL) and the clinical outcome in maintenance therapy of schizophrenia. MATERIAL AND METHODS: Twenty-five chronic schizophrenic outpatients with age ranging from 18 to 65 years were included in this 9-month study. Patients were given a dosage of either 210 or 300 or 405 mg of OLZ-LAI every 28 days. Patients were evaluated at baseline and every four weeks by Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Symptom Scale (PANSS); at the same time, PL of OLZ was determined. The metabolic profile (aspartate aminotransferase, alanine aminotransferase, high-density lipoprotein, low-density lipoprotein, total cholesterol, and glucose levels) was analyzed every two months. RESULTS: BPRS and total PANSS showed a statistically significant improvement from T2 with a clinical stabilization of psychopathological picture. PL ranged from 4.0 to 78.9 ng/ml (mean 20.59 ng/ml ± 14.66 standard deviation). The coefficient of variation of PLs was related to clinical stabilization. No post-injection delirium sedation syndrome occurred. CONCLUSIONS: Our data reveal the efficacy of OLZ-LAI in maintenance treatment of schizophrenia at lower dosages also in comparison with that of oral therapy. OLZ-LAI seems to be useful for guaranteeing constant PL of the drug. A lesser variation of PL was the most predictable factor associated with maintenance of clinical benefit.

Brain metabolism in substance-induced psychosis and schizophrenia: a preliminary PET study.

INTRODUCTION: The relation between schizophrenia and cannabis abuse has been widely discussed from etiopathogenetic, psychopathological and neurometabolic points of view. Relatively little has been written about the differences between schizophrenia with co-occurrent cannabis abuse and substance-induced psychotic disorder (SIPD). Given these premises, our study aims to investigate the psychopathological and neurometabolic features of these clinical entities. METHODS: We enrolled patients experiencing an acute psychotic episode, affected either by schizophrenia with or without cannabis abuse (SCZ +/- CA; n = 5 and n = 5, respectively) with recent onset (<5 years of illness) or by SIPD (n = 6), as diagnosed by the Structured Clinical Interview for DSM-IV Axis I. Patients affected by SIPD were all cannabis abusers. All patients were assessed with the PANSS (Positive and Negative Scale for Schizophrenia), urinary toxicological tests and brain 18-FDG-PET scanning in resting condition. Statistical analysis (ANOVA) was performed with Statistical Parametric Mapping SPM8 and Scenium software. RESULTS: Bilateral hypermetabolism in the posterior cingulum and the precuneus (p < 0.001) was observed in SIPD patients compared to patients with schizophrenia, with or without cannabis abuse. CONCLUSIONS: Our preliminary PET findings suggest that substance abuse may cause increased brain metabolism in patients with induced psychosis but not in those with schizophrenia. These differences in brain metabolism were found in the posterior cingulum and precuneus, which are two core regions of the default mode network in humans.

Depression in schizophrenia: comparison of first- and second-generation antipsychotic drugs.

The aim of this study was to compare the effects of different antipsychotics on depressive symptoms in schizophrenic patients. The data were drawn from a retrospective, naturalistic, observational study in which 222 subjects diagnosed as being affected by schizophrenia during a re-exacerbation phase received 6 weeks of monotherapy with fluphenazine decanoate, haloperidol decanoate, haloperidol, clozapine, olanzapine, quetiapine, risperidone or l-sulpiride. The Brief Psychiatric Rating Scale (BPRS), Extrapyramidal Side Effects Rating Scale (EPSE) and Anticholinergic Rating Scale (ACS) were administered at baseline and six weeks after the beginning of the study; depressive symptoms were evaluated using the BPRS items "depressive mood" and "guilt feelings". All of the antipsychotic drugs led to improvements in the depressive dimension, but this was statistically significant only in the case of fluphenazine decanoate, haloperidol, olanzapine, risperidone and l-sulpiride. A clinical improvement in the depressive dimension significantly correlated with the severity of the psychotic picture and its amelioration. Female patients were significantly more likely to show an improvement in depressive symptoms. In conclusion, our findings suggest that atypical antipsychotics as a class do not seem to be more effective on the depressive dimension during the course of schizophrenia than typical ones, at least as far as the collected BPRS data are concerned. The only factor that seemed to influence the improvement in depressive symptoms during our study was gender, as females were significantly more likely to improve although there were no between-gender differences in the baseline severity of the clinical picture.

Hallucinatory disorder, an original clinical picture? Clinical and imaging data.

OBJECTIVE: The aim of this study was to verify the existence of areas of clinical and neurofunctional homogeneity in a group of patients with auditory verbal hallucinations (AVHs) as an isolated symptom, attributable to what we have called "Hallucinatory Disorder" (HD) in an attempt to propose a clinical picture that is distinct from Schizophrenia. METHOD: Nine patients clinically characterised by chronic AVHs were compared with nine schizophrenic patients using the Structured Clinical Interview for DSM-III-R, BPRS, PANSS, SAPS, SANS, HRS-A, HRS-D, CDSS, MMSE, CGI and PSYRATS. Both groups of patients and nine healthy subjects underwent EEG and SPECT examinations. RESULTS: Considering the psychopathological dimensions of Schizophrenia, in the HD patients clinical evaluations revealed a mono-dimensional clinical profile, whereas all these dimensions contributed to the clinical picture of the schizophrenic patients. The SPECT data showed that the schizophrenic patients had a reduced rCBF in some areas of the right frontal lobe, while the HD patients did not show any area of hypoperfusion. The SPECT hyperperfusion data showed an activation pattern in the HD patients that was characterised by the involvement of various cortical and subcortical cerebral areas, similar to those found in studies of inner speech and auditory verbal imagery. CONCLUSIONS: The two groups of patients present significant differences that seem capable of supporting the proposed hypothesis that HD may be an independent nosographical entity.

Perfectionism in depression, obsessive-compulsive disorder and eating disorders.

High levels of perfectionism have been observed in major depression, anxiety disorders and eating disorders. Though few studies have compared levels of perfectionism across these disorders, there is reason to believe that different dimensions of perfectionism may be involved in eating disorders than in depression or anxiety [Bardone-Cone, A. M. et al. (2007). Perfectionism and eating disorders: Current status and future directions. Clinical Psychology Review, 27, 84-405]. The present study compared patients with major depression, obsessive-compulsive disorder, and eating disorders on dimensions of perfectionism. Concern over Mistakes was elevated in each of the patient groups while Pure Personal Standards was only elevated in the eating disorder sample. Doubts about Actions was elevated in both patients with obsessive-compulsive disorder and eating disorders, but not in depressed patients. Analyses of covariance indicated that Concern over Mistakes accounted for most of the variance in the relationship of perfectionism to these forms of psychopathology.

Clinical pharmacokinetics of atypical antipsychotics: a critical review of the relationship between plasma concentrations and clinical response.

In the past, the information about the dose-clinical effectiveness of typical antipsychotics was not complete and this led to the risk of extrapyramidal adverse effects. This, together with the intention of improving patients' quality of life and therapeutic compliance, resulted in the development of atypical or second-generation antipsychotics (SGAs). This review will concentrate on the pharmacokinetics and metabolism of clozapine, risperidone, olanzapine, quetiapine, amisulpride, ziprasidone, aripiprazole and sertindole, and will discuss the main aspects of their pharmacodynamics. In psychopharmacology, therapeutic drug monitoring studies have generally concentrated on controlling compliance and avoiding adverse effects by keeping long-term exposure to the minimal effective blood concentration. The rationale for using therapeutic drug monitoring in relation to SGAs is still a matter of debate, but there is growing evidence that it can improve efficacy, especially when patients do not respond to therapeutic doses or when they develop adverse effects. Here, we review the literature concerning the relationships between plasma concentrations of SGAs and clinical responses by dividing the studies on the basis of the length of their observation periods. Studies with clozapine evidenced a positive relationship between plasma concentrations and clinical response, with a threshold of 350-420 ng/mL associated with good clinical response. The usefulness of therapeutic drug monitoring is well established because high plasma concentrations of clozapine can increase the risk of epileptic seizures. Plasma clozapine concentrations seem to be influenced by many factors such as altered cytochrome P450 1A4 activity, age, sex and smoking. The pharmacological effects of risperidone depend on the sum of the plasma concentrations of risperidone and its 9-hydroxyrisperidone metabolite, so monitoring the plasma concentrations of the parent compound alone can lead to erroneous interpretations. Despite a large variability in plasma drug concentrations, the lack of studies using fixed dosages, and discrepancies in the results, it seems that monitoring the plasma concentrations of the active moiety may be useful. However, no therapeutic plasma concentration range for risperidone has yet been clearly established. A plasma threshold concentration for parkinsonian side effects has been found to be 74 ng/mL. Moreover, therapeutic drug monitoring may be particularly useful in the switch between the oral and the long-acting injectable form. The reviewed studies on olanzapine strongly indicate a relationship between clinical outcomes and plasma concentrations. Olanzapine therapeutic drug monitoring can be considered very useful in assessing therapeutic efficacy and controlling adverse events. A therapeutic range of 20-50 ng/mL has been found. There is little evidence in favour of the existence of a relationship between plasma quetiapine concentrations and clinical responses, and an optimal therapeutic range has not been identified. Positron emission tomography studies of receptor blockade indicated a discrepancy between the time course of receptor occupancy and plasma quetiapine concentrations. The value of quetiapine plasma concentration monitoring in clinical practice is still controversial. Preliminary data suggested that a therapeutic plasma amisulpride concentration of 367 ng/mL was associated with clinical improvement. A therapeutic range of 100-400 ng/mL is proposed from non-systematic clinical experience. There is no direct evidence concerning optimal plasma concentration ranges of ziprasidone, aripiprazole or sertindole.

Gray matter volumes may predict the clinical response to paliperidone palmitate long-acting in acute psychosis: A pilot longitudinal neuroimaging study.

In schizophrenia, paliperidone palmitate (PP) long acting injectable (LAI) has been reported to sustain plasma concentrations and improve clinical symptoms. Moreover, it has also been demonstrated the important role of total gray matter (GM) volumes in predicting the clinical outcome. However, no studies investigating the association between PP-LAI treatment and brain morphometry has been published so far. Therefore, the main aim of our 24 weeks prospective observational exploratory study was to investigate the relation between brain anatomy and clinical outcome in seven patients with acute psychosis treated with PP-LAI. At baseline and every month (from T0 to T6) patients were clinically evaluated with the Brief Psychiatric Rating Scale (BPRS). 3T Magnetic Resonance Imaging at baseline was acquired and total GM and intracranial volumes were extracted to explore their predictive values on BPRS scores. After 24 weeks of treatment with PP-LAI, patients showed statistically significant improvements in BPRS scores. Moreover, subjects with higher total GM volumes had a significantly higher BPRS improvement at 24 weeks compared to patients with lower total GM volumes. Our findings confirm the effectiveness of PP-LAI in treating acute psychosis and suggest that greater GM volumes predict drug response, potentially supporting a favorable prognosis.

Patterns of clinical use of antipsychotics in hospitalized psychiatric patients.

The ways of using antipsychotic drugs have greatly changed over the last 10 years. The aim of this study was to evaluate such changes in psychiatric patients admitted to the Psychiatric Department of Milan's Ospedale Maggiore in 1989 (n=350), 1999 (n=718) and 2002 (n=628). The medical records of the hospitalized patients were evaluated by analyzing the anamnestic and clinical data with particular reference to age, gender, diagnosis and medication use. In 2002, atypical antipsychotics were more frequently prescribed as monotherapy upon discharge than typical antipsychotics (32.64% vs. 30.10%). Combinations of two or more antipsychotic drugs were prescribed upon discharge for 20.63% of the patients in 1989, 31.24% in 1999 and 23.09% in 2002. The combinations of one typical and one atypical drug increased from 4.04% in 1999 to 13.06% in 2002. The mean (+/-S.D.) daily antipsychotic drug dose (expressed in chlorpromazine equivalents) was significantly higher in 2002 than in 1999 and 1989. The results of this study confirm the trend to use combinations of one typical and one atypical antipsychotic, and higher doses.

Efficacy and tolerability of paliperidone ER in patients with unsatisfactorily controlled schizophrenia by other antipsychotics: a flexible-dose approach.

This study evaluates the effectiveness of paliperidone ER in patients with symptomatic but not highly acute schizophrenia in terms of efficacy, safety, and patients' perception of their social functioning and well-being. This is a multicenter, open-label prospective study with a flexible-dose approach; 133 patients were enrolled and followed for 13 weeks after switching to paliperidone ER. Outcome efficacy measures were as follows: the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression-Severity (CGI-S) scale, and the Personal and Social Performance (PSP) scale; in addition, the Subjective Well-being under Neuroleptics (SWN-20) scale, the Drug Attitude Inventory (DAI-30), and the sleep evaluation scale were used. Symptom Rating Scale (ESRS), adverse events, and subjective side effects were recorded. 118/133(88.7%) patients completed the study. The mean PANSS score decreased (88.98 ± 10.09 to 66.52 ± 16.29; P < 0.001); 40.5% of the patients achieved improvement of at least 30%. PSP and CGI-S scores as well as DAI-30 and SWN-20 decreased (P < 0.001). ESRS (P < 0.001) decreased significantly from the baseline. Throughout the trial, no deaths occurred and only one serious adverse event was reported. Paliperidone ER has proved to be efficacious, safe, and well tolerated also with this approach more closely resembling actual clinical practice. Patient-relevant outcome parameters such as social functioning and quality of life improved, which is crucial for treatment adherence in clinical practice.

Clinical outcome and tolerability of sertraline in major depression: a study with plasma levels.

Sertraline (SRT) has been shown to be an effective antidepressant in extensive clinical trial programs but data on plasma concentrations regarding clinical outcome and tolerability are lacking. Twenty-one out-patients of both sexes, with mean age of 50.23 years (S.D. = 17.37), affected by major depressive disorder, recurrent (Diagnostic and Statistical Manual of Mental Disorder--IV, DSM-IV), were treated with 25-150 mg of SRT once a day (mean=66.26 mg, S.D.=30.50) for 30 days. Clinical evaluation was assessed at baseline (T0), after 15 days (T15), and then after 30 days (T30). Plasma samples for SRT level determination were collected at T30. Brief Psychiatric Rating Scale (BPRS), Hamilton Rating Scale for Depression (HRS-D), and Hamilton Rating Scale for Anxiety (HRS-A) showed a significant improvement during the study (P<.01 vs. T0). The most commonly reported side effects were nausea (19%), cephalalgia (9.5%), dry mouth (9.5%), decreased libido (9.5%), tremor (4.7%), and tachycardia (4.7%). SRT plasma levels ranged from 2.82 to 112.20 ng/ml (mean=40.42 ng/ml, S.D.=26.93). No correlation between SRT plasma levels and clinical improvement or side effects were observed. Drug plasma level determination does not seem be strictly necessary from a clinical point of view but further research seems advisable in patients at risk like elderly and during long-term studies.

Nutritional management of anorexic patients with and without fluoxetine: 1-year follow-up.

This study evaluated the efficacy of nutritional management with and without fluoxetine (FLX) in anorexia nervosa diagnosed according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. Twenty-one patients, with a mean body mass index (BMI) of 15.21+/-2.33 kg/m(2), were treated with nutritional management and FLX at a mean dosage of 30.00+/-9.35 mg (pharmacological group); seventy-four patients, with a mean BMI of 14.24+/-2.16 kg/m(2), were treated only with nutritional management (nutritional group). Clinical evaluation was carried out under single-blind conditions at basal time and after 3, 6, and 12 months by a structured clinical interview, the Eating Disorder Interview based on Longitudinal Interval Follow-Up Evaluation (EDI-LIFE) and using a self-reported questionnaire, the Eating Disorder Inventory (EDI). BMI significantly increased in both the two treatment groups. In addition, the increase shown by the pharmacological group appeared near the beginning of treatment (i.e., at T1) and it was significantly higher than the increase shown by the nutritional group. Physical exercise showed a significant decrease in the pharmacological treatment group. On the other hand, fear of fatness and the scores of the subscales of the EDI significantly decreased in the nutritional treatment group. In terms of weight, the pharmacological group presented the higher amount of therapeutic success.

Effect of quetiapine and norquetiapine on anxiety and depression in major psychoses using a pharmacokinetic approach: a prospective observational study.

BACKGROUND: Quetiapine apparently differs from other antipsychotic drugs in terms of its antidepressant activity and efficacy in bipolar depression. The mechanism of this activity is unknown although it may be mediated by its metabolite N-desalkylquetiapine (norquetiapine). OBJECTIVE: The aim of the study was to analyse the relationships between quetiapine and norquetiapine plasma concentrations and clinical improvement in depressive and anxious symptoms. METHODS: This was a prospective observational study. Recruited patients were evaluated during a clinical post-acute phase. Patients were recruited from patients hospitalized in the Psychiatric Department of Ospedale Maggiore Policlinico of Milan, Italy. After discharge they were followed-up as outpatients. The study involved 41 outpatients (23 males, 18 females; age >18 years) diagnosed as affected by schizophrenia (17 patients), borderline personality disorder (eight patients) or bipolar depression (16 patients) on the basis of the Diagnostic and Statistical Manual of Mental Disorders, fourth text revision (DSM-IV-TR) criteria. Patients were prescribed 50-800 mg of quetiapine (Seroquel®). Patients were evaluated after discharge from the psychiatric department (baseline, T0), after 15 days (T1) and after 3 months (T2) using the Brief Psychiatry Rating Scale (BPRS) with particular reference to the dimensions of depression (items 5, 9 and 13) and anxiety (items 1, 2 and 6). Plasma quetiapine and norquetiapine concentrations were determined by means of high-performance liquid chromatography at T2. RESULTS: There was a significant improvement in the mean BPRS total score, as well as in the dimensions of anxiety and depression. The bipolar patients only showed a significant curvilinear relationship described by a second-order polynomial model between the plasma norquetiapine/quetiapine concentration ratio and the improvement in depression at T2. There was a significant negative linear correlation between the norquetiapine/quetiapine ratio and anxiety in all of the patients. CONCLUSION: The results of this study confirm the efficacy of quetiapine on both anxious and depressive symptoms. Norquetiapine has a specific effect on anxiety and depressive symptoms, showing a correlation between plasma concentrations and clinical efficacy only in patients with bipolar depression.

Depressive dimension, clinical outcome, and duration of hospitalization in acute schizophrenia.

In the present study we extract clusters of symptoms in acute hospitalized patients affected by Schizophrenia, using factor analysis of BPRS-E. We aim to explore the relationship between symptom dimensions, duration of hospitalization, and clinical outcome, in order to test if the depressive dimension might contribute significantly to predict the outcome. The data were drawn from a prospective, naturalistic, observational study of schizophrenic patients consecutively admitted to a psychiatric ward (SPDC, Ospedale Maggiore Policlinico of Milan), during a re-exacerbation phase. General symptomatology was measured through BPRS-E at baseline (T0) and at discharge (T1). We found symptoms of acute schizophrenia to cluster together in four distinct domains, labelled "Depression", "Excitement", "Positive symptoms", and "Negative symptoms". The "Depression" cluster is significantly associated to a good clinical outcome, as measured by percentage of improvement in BPRS score, but not to duration of hospitalization.

Neuropsychological functions and metabolic aspects in subclinical hypothyroidism: the effects of L-thyroxine.

Thyroid hypofunction is a slowly progressing graded phenomenon [Vanderpump MP, Tunbridge WM, French JM, Appleton D, Bates D, Clark F, et al. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol (Oxf) 1995;43(1):55-68]; subclinical forms (SCH) often represent a laboratory diagnosis in apparently asymptomatic patients. In the absence of adequate parameters for thyroid hormone action in tissues, the level of TSH increase corresponding to negative effects remains unsettled. We studied a wide range of physiological processes in a strictly selected population of 38 female patients (56.4+/-12.6 years) with minor forms of SCH (TSH 6.6+/-1.8 mIU/L), after exclusion of neurological, psychiatric and somatic disorders or confounding conditions. The investigations, performed at admission and after 6 months of l-thyroxine (LT4) treatment, included metabolic evaluation, health status perception and an extensive battery of neuropsychological tests and psychological rating scales. Lipid metabolism improved after LT4 (total cholesterol: 231.9+/-49.6 mg/dl pre- vs 221.0+/-40.0 mg/dl post-treatment; LDL cholesterol: 183.1+/-62.9 vs 162.7+/-53.7 mg/dl; apolipoprotein A1: 183.5+/-64.5 vs 160.9+/-50.3 mg/dl; p<0.05 for all comparisons), while glucose metabolism was unchanged. Health status perception was favourably influenced by the treatment (total SF-36 score 97.8+/-18.4 pre- vs 108.5+/-14.8 post-, p<0.0001); in a matched control group with euthyroid goiter, tested to examine the effects of medical care in the absence of treatment, no significant differences were found in the SF-36 scores at admission and after 6 months (109.3+/-15.1 vs 109+/-14.2, p=0.9). Attention performance improved after LT4; HRSD and HRSA scores did not significantly change, but negative correlations were found between FT3 levels and affective scores at admission, and between the post-treatment changes of affective scores and of FT3. In our study subtle disturbances of health status perception, attention and lipid metabolism associated to SCH of mildest degrees were reverted by LT4 replacement, reinforcing reports of unfavourable consequences of marginal thyroid disease.

Two weeks' quetiapine treatment for schizophrenia, drug-induced psychosis and borderline personality disorder: a naturalistic study with drug plasma levels.

OBJECTIVE: To evaluate clinical outcomes and the tolerability of 2 weeks' quetiapine (QTP) treatment for hospitalised patients in a naturalistic setting. METHODS: Patients with schizophrenia (n = 18), drug-induced psychosis (n = 10; 3 cocaine, 4 hashish and marijuana, and 3 all three substances) or borderline personality disorder (n = 13), were diagnosed by two expert clinicians on the basis of an unstructured clinical interview, and were treated with QTP (250-1000 mg/day). The subjects were then clinically assessed at baseline, and after 7 and 15 days, using the Brief Psychiatric Rating Scale, the Positive and Negative Symptoms Scale (PANSS) and the Hamilton Rating Scale for Depression. At the end of the study, plasma QTP levels were determined and examined in relation to clinical outcome and tolerability. RESULTS: The mean scores of each rating scale were significantly lower at the end of the study in the population as a whole, and within each diagnostic group. The percentage improvement was significantly greater in the patients with drug-induced psychosis than in those with schizophrenia (42.4 +/- 9.1% versus 23.6 +/- 13.5%). QTP was well tolerated, and the incidence of extrapyramidal side effects was low. There was a linear correlation between plasma levels and dose/kg of QTP (r = 0.31; p < 0.05). The improvement in PANSS significantly correlated with plasma levels and dose/kg in each diagnostic category (Spearman's coefficient was 0.75 [p < 0.01] for schizophrenia and borderline personality disorder, and was 0.68 [p < 0.05] for drug-induced psychosis). CONCLUSION: The results suggest that 2 weeks' QTP treatment may improve the clinical outcome of psychotic re-exacerbation phases in different diagnostic categories and indicate that QTP improves clinical outcome in drug-induced psychosis, as QTP levels correlated with the clinical improvement measured by PANSS.

Hallucinatory disorder: preliminary data for a clinical diagnostic proposal.

INTRODUCTION: Chronic hallucinatory psychosis is a psychopathological profile reported in French literature but not included in the current Anglo-American psychiatric classifications. We compared a group of patients with a clinical picture related to this syndrome to a group of patients with schizophrenia in order to evaluate the possibility of characterising hallucinatory disorder as a diagnostic entity. METHODS: Nine patients with a clinical profile related to chronic hallucinatory psychosis were compared to a group of nine patients with schizophrenia. All of the patients were clinically evaluated using the measures: SCID-P, GAF, BPRS, PANSS, SAPS, SANS, HRS-A, HRS-D, CDSS, MMSE, and CGI. RESULTS: Analysis of the clinical rating scales characterised schizophrenia as comprising three dimensions (positive, negative, and disorganised symptoms), each of which contributes differently to the psychopathological profile of individual patients. However, the patients with hallucinatory disorder seemed to be mainly characterised by auditory verbal hallucinations, with relative sparing of the other functions typically altered in patients with schizophrenia. CONCLUSIONS: The significant differences between the patients in the two groups seem to support the hypothesis that hallucinatory disorder may be considered as being a separate nosographic entity, in which the clinical picture is dominated by the experience of auditory verbal hallucinations.

Predictors of clinical outcome in schizophrenic patients responding to clozapine.

Many of the patients who respond better to clozapine (CLZ) than to typical antipsychotics still have residual psychopathology, but CLZ drug resistance data are lacking. The aim of this study was to evaluate the possible predictive factors of a clinical response to CLZ in a group of 20 schizophrenic patients (DSM-IV: 13 males and 7 females with a mean age of 35.5 years +/- 7.1 SD) resistant to typical antipsychotics but CLZ responders as assessed by the Brief Psychiatric Rating Scale (BPRS) (>20% improvement). After a 1-week washout period, CLZ was started at a dose of 25 mg/d, which was increased by the third week up to a maximum of 600 mg/d (mean 365.00 +/- 129.88 mg/d SD) and remained unchanged until the end of the study (week 8). The patients showed a significant improvement in the mean scores of the rating scales for positive (SAPS) and negative symptoms of schizophrenia (Scale for the Assessment of Negative Symptoms, SANS) (P < 0.003, P < 0.02). All of the patients included in the study were BPRS responders; 65% were also SAPS and 75% SANS responders (>20% improvement). The improvement in the SANS score was significantly greater among the female patients (P < 0.05). The SAPS and SANS responders had a significantly higher mean metabolic ratio [MR = (NCLZ/CLZ)] than the nonresponders (P < 0.01), and the percentage of improvement significantly correlated with the increase in MR. This finding suggests that the individual pharmacogenetics indicated by metabolic capacity may be related to clinical response. All of the patients showed a reduction in white blood cell counts, but this was significantly less in the SANS responders than the SANS nonresponders (P = 0.047). The SAPS responders had significantly lower neutrophil counts than the nonresponders (P = 0.03). Our results seem to suggest the importance of pharmacodynamic, constitutional, and genetic data over strict pharmacokinetics in determining the clinical response to CLZ.