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Chronic hallucinatory psychosis is a disease that has long been considered in the French literature, but it is neglected by the current Anglo-Saxon classification systems, which generally relegate it among the atypical forms of Schizophrenia.

Schizophrenia is associated with a significant risk of suicide: 40-50% of schizophrenic patients report suicidal ideation at some point in their lives, and 4-13% eventually commit suicide. In order to be able to predict and prevent suicide in schizophrenic patients, it is necessary to investigate and characterise suicide victims who meet the criteria for psychotic disorders and risk factors.The aim of this retrospective study was to verify the associations between suicide attempts (SAs) and the demographic and clinical variables of 106 patients who met the DSM-IV-TR criteria for schizophrenia. The patients were divided into two groups on the basis of the presence/absence of lifetime suicide attempts, and their main demographic and clinical characteristics were analysed and compared.The patients with a history of SAs frequently had a duration of untreated psychosis (DUP) of ≥1 year (chi-squared test=9.984, df=1, p=0.0016). They also showed significant associations with the presence of a depressive dimension (chi-squared test=4.439, df=1, p=0.0351), hospitalisations before SAs (chi-squared test=25.515, df=1, p0.001), and a family history of psychiatric disorders (chi-squared test=12.668, df=2, p=0.0018) or suicidal behaviours (chi-squared test=18.241, df=2, p=0.0001). Finally, they were more frequently prescribed typical antipsychotic agents.The severity of psychiatric symptoms indicates a high risk of suicide in schizophrenic patients. Further prospective studies of larger samples should investigate the role of early interventions and atypical antipsychotic treatment in reducing the risk.

Cannabis, cocaine, amphetamines and derivative substances so as hallucinogens and other drugs with psychotomimetic properties has reached an extensive misuse often producing psychotic reactions similar to primary psychotic disease like schizophrenia. In particular cannabis and cocaine use by young people has been increased during these years, and the age of first use is dramatically decreased [1,2].

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.

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.

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) (P0.003, P0.02). 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 (P0.05). The SAPS and SANS responders had a significantly higher mean metabolic ratio [MR = (NCLZ/CLZ)] than the nonresponders (P0.01), 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.

A possible relationship between haematological adverse reactions and clozapine (CLZ) metabolism rate was studied. Sixteen chronic schizophrenic outpatients (mean age 34.62 years +/- 7.56 SD) were treated with CLZ, 75-600 mg/daily for 9 weeks. CLZ and norclozapine (NCLZ) plasma levels were determined weekly, contemporarily with blood cell counts. CLZ plasma levels ranged from 25 to 1270 ng/ml (mean 266.27 ng/ml +/- 197.44 SD), while NCLZ plasma levels ranged from 25 to 1280 ng/ml (mean 169.0 ng/ml +/- 127.94 SD). NCLZ/CLZ ratio ranged from 0.13 to 1.72 (mean 0.72 +/- 0.28 SD). Leukocyte count ranged from 5.2 to 18.8 10(9)/l (mean 9.37 10(9)/l +/- 2.94 SD) and neutrophil count ranged from 1.8 to 13.4 10(9)/l (mean 5.73 +/- 2.57 SD). No correlation was found between CLZ dosage and NCLZ plasma levels. Both CLZ and NCLZ plasma levels correlated positively with neutrophil count (CLZ: P = 0.001, r = 0.26; NCLZ: P = 0.01, r = 0.20). The correlation between NCLZ/CLZ plasma level ratio and neutrophil count was significantly negative (P = 0.002, r = 0.25). These preliminary data suggest that the NCLZ/CLZ ratio, as an index of CLZ metabolism, might be a possible risk factor associated with CLZ treatment.

Sulpiride is a substituted benzamide with a selective action on receptors of the dopamine D2-like family, and clinical and pharmacological data suggest that it could be considered to be an atypical antipsychotic. Sulpiride penetrates the blood-brain barrier poorly because of its low lipid solubility. It is mainly excreted unchanged in the urine, and accumulation of the drug could occur in patients with renal dysfunction and possibly in elderly patients with declining glomerular filtration rate. At low dosages (50 to 150 mg/day), sulpiride produces a disinhibiting and antidepressant effect, which is probably related to its action on D2 presynaptic autoreceptors, thus facilitating dopaminergic neurotransmission. Data have confirmed the efficacy of sulpiride in patients with acute or chronic schizophrenia during both short and long term treatment, but long term, placebo-controlled trials are still lacking. It is still doubtful whether sulpiride is more effective than typical antipsychotics for the treatment of negative symptoms. Data from clinical studies are controversial; the majority of authors indicate that sulpiride produces a better recovery rate from negative than from positive symptoms at low doses, but it shows a similar efficacy either on negative and positive symptoms at higher doses. The safety profile of sulpiride is similar to that of typical antipsychotics, although the frequency of adverse effects seems to be globally lower. Extrapyramidal reactions appear generally to be mild. Autonomic effects occur less frequently with sulpiride than with typical antipsychotics, showing no clinically relevant influence on cardiovascular parameters and, on the whole, good tolerability in elderly patients. Sulpiride is known to induce prolactin elevation in both serum and CSF, which may be associated with impotence in men and diminished gonadal function in women; these effects appear to be dosage-dependent. Sulpiride can be considered to be an atypical antipsychotic, considering its action on negative, defective symptoms, its partial activity against positive symptoms, and its low incidence of extrapyramidal adverse effects. Sulpiride could find its specific therapeutic role in elderly patients with schizophrenia, as it shows a good margin of safety between therapeutic dosages and toxic concentrations.

1. Clinical activity, tolerability and kinetic profile of L-sulpiride (200–300 mg/die p.o.) in relation to age, in 14 chronic schizophrenic in patients diagnosed according to DSM III-R, typed as negative forms, were studied. 2. The drug showed Its efficacy in negative forms of schizophrenia, without any significant difference between negative and positive symptoms even if productive symptom scores were quite low already in pre-treatment condition. 3. No more side effects (anticholinergic and extrapyramidal) in elderly patients compared to young/adult ones were reported. 4. No significant differences between young/adult and elderly patients for the various pharmacokinetic parameters (t 1 2 , AUC, Cmax, Tmax, Vd and CI), after acute and multiple dosing, were observed.

1. Clinical activity, extrapyramidal side-effects were evaluated in 22 schizophrenic out patients diagnosed according to DSM III and treated with haloperidol decanoate (50-300 mg i.m. monthly dose) for 12 months. 2. BPRS total scores did not show significant fluctuations showing a clinical stability of the patient population. 3. Patients with a duration of illness greater than 10 yrs (Group 2) showed significant (p less than 0.01) higher EPSE total scores compared to those with a duration of illness less than 10 yrs (Group 1). 4. A positive correlation was found between the administered dose and haloperidol plasma levels. 5. Patients from Group 2 reached the steady-state more slowly and showed a lower total L/D ratio compared to those from Group 1. 6. The pharmacokinetic approach seems desirable in order to adjust the dose and avoid schizophrenic relapses.

To evaluate clinical outcomes and the tolerability of 2 weeks' quetiapine (QTP) treatment for hospitalised patients in a naturalistic setting.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.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; p0.05). The improvement in PANSS significantly correlated with plasma levels and dose/kg in each diagnostic category (Spearman's coefficient was 0.75 [p0.01] for schizophrenia and borderline personality disorder, and was 0.68 [p0.05] for drug-induced psychosis).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.

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.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.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.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.

Acute psychotic episodes represent critical situations during the course of schizophrenia. Olanzapine (OLZ), a second-generation antipsychotic, is efficacious in acute settings at dosages of 5 to 20 mg/d, and it can be considered a first-line treatment for patients with an acute episode of schizophrenia. The aim of this study was to evaluate the efficacy and tolerability of OLZ at a starting dose of 5 mg versus 20 mg in acute schizophrenic patients and to compare titration versus nontitration.Fifty-one schizophrenic inpatients were randomly assigned to receive OLZ at 5 mg/d (26 patients, group 1) or 20 mg/d (25 patients, group 2) as a starting dosage during an exacerbation phase. In group 1, the OLZ dosage was increased to a mean dosage of 10.55 (+/- 4.00) mg/d. Group 2 received OLZ at a fixed dose of 20 mg throughout the hospitalization period. Olanzapine was significantly and clinically effective on Brief Psychiatric Rating Scale (BPRS), Positive and Negative Syndrome Scale, PANSS positive symptoms, and Hamilton Rating Scale for Depression in both groups. There were no significant differences between groups 1 and 2 in the percent improvement in BPRS, Positive and Negative Syndrome Scale, PANSS positive symptoms, PANSS negative symptoms, or Hamilton Rating Scale for Depression; but group 2 was significantly superior in the mean percent improvement in the BPRS items of anxiety (P < 0.001) and suspiciousness (P < 0.05). In conclusion, the higher doses evidence more efficacy on anxiety and suspiciousness, so it seems to be useful to begin therapy with a full dose of the drug to obtain the maximum effect without any significant side effects.

1. 1. A prevalence of depressive symptomatology, ranging from 25% to 80% has been reported during the course of schizophrenia. 2. 2. Depressive symptoms were assessed in 144 schizophrenic patients (DSM IV) during an acute exacerbation phase. 3. 3. Depressive symptoms showed a prevalence ranging from 5. 5% (severe clinical pictures) to 54. 8 % (mild clinical pictures). 4. 4. The authors did not find a correlation between depressive symptoms per se and the presence of negative psychotic symptoms. Depression may be linked not so much to negative symptoms but to the psychotic state itself. 5. 5. Depressive symptomatology concurrently occured with schizophrenic relapses and improved together with the psychotic clinical picture, independently of the neuroleptic drug employed. Haloperidol, haloperidol decanoate and fluphenazine decanoate all showed a similar improvement of depressive symptoms. 6. 6. L-sulpiride showed a trend to be most effective on depressive symptomatology in comparison to the other neuroleptics.

Cholecystokinin (CCK), β-endorphin (BE), and vasoactive intestinal peptide (VIP) in peripheral blood mononuclear cells from 30 drug-naive schizophrenics compared to 22 healthy controls were studied. Patients were evaluated with the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of the Negative Symptoms (SANS) at baseline (T0), and after four weeks (T4) in nine patients who were subsequently treated with haloperidol (HL). Neuropeptide concentrations in peripheral blood mononuclear cells (PBMC) were measured at T0 and, for the treated patients, at T4. There was a negative correlation between CCK and SANS baseline scores and a trend for patients who responded poorly to HL (i.e. patients with a prevalence of negative symptomatology) to have lower CCK basal values.

Several studies suggest a high comorbidity of substance abuse and schizophrenia, associated with higher frequency of relapse, more positive symptoms and depression, cognitive impairment, poorer outcome and treatment response. A high incidence of substance abuse is also observed in first-episode patients. Among patients with substance abuse, the onset precedes the onset of psychosis of several years in most cases. All the patients with a first episode of schizophrenia, at first admission to the Psychiatric Service of Diagnosis and Treatment of Ospedale Maggiore of Milan during the years 1990 to 2004, have been included in our study. The clinical evaluation has been obtained considering the following items of Brief Psychiatric Rating Scale (BPRS): conceptual disorganization, depressed mood, hostility, hallucinations, unusual content of thought. The results showed that 34.7% of first-episode schizophrenic patients had a lifetime history of substance abuse. The age of onset of schizophrenia is significantly lower for drug abusers than for patients without any type of abuse and for alcohol abusers (p < 0.005). In multi drug abusers, cannabis resulted the most frequently used (49%), followed by alcohol (13%), and cocaine (4%). Substance abusers have obtained a significant higher score in "thought disturbance" item (p < 0.005) and in "hostility" item (p < 0.005) compared to non substance abusers. Non drug abusers showed lower mean scores of "hostility" item compared to cocaine abusers and multi drug abusers (p < 0.005). Our findings seem to indicate that substance abuse in the early course of illness determines an earlier onset of schizophrenia and increases severity of some psychotic symptoms like "hallucination" and "unusual content of thought". Therefore persons incurring a risk of schizophrenia may be warned of the possible relation between substances and psychosis and have to be counselled against the use of them.

Epidemiological knowledge of parasuicides and drug self-poisoning is still limited by a lack of data. A number of preliminary studies, which require further analysis, evidenced that parasuicidal acts occur more often among females, that the peak rate is generally recorded between the ages of 15 and 34 years and psychotropic medications seems to be the most frequently used. The aim of this study was to describe the demographic and clinical variables of a sample of subjects admitted to the Posisoning Treatment Centre (CAV), Niguarda General Hospital, Milan, following drug self-poisoning. Furthermore, this study is aimed to identify the risk factors associated to parasuicidal gestures, with special care for the used drugs, the presence of psychiatric or organic disorders, alcoholism and drug addiction.The study included the 201 patients attending the CAV in 1999 and 2000 who satisfied the criteria of self-poisoning attempts: 106 cases in 1999 and 95 in 2000.The sample had a prevalence of females (64%). The peak rates of parasuicides from drug self-poisoning were reached between 21 and 30 years among the females, and 31 and 40 years among the males. 81.6% of the patients used one or more psychoactive drugs, the most frequent being the benzodiazepines (58.7%), classic neuroleptics (16.9%) and new-generation antidepressants (SSRIs, SNRIs, NARIs) (12.9%). The prevalence of mood disorders was higher among females (64% vs 42%), whereas schizophrenia was more frequently diagnosed in males (22% vs 10%). 61% (33%) had a history of previous attempted suicides. The presence of clinically relevant organic diseases was observed in 24.9% of the sample.

1. The possible influence of haloperidol and its metabolite plasma levels on clinical outcome in schizophrenic patients was evaluated. 2. 18 schizophrenic inpatients diagnosed according to DSM III, were treated with conventional haloperidol p.o. for four weeks. 3. Plasma levels of haloperidol and its reduced metabolite were measured by mass-spectrometry assay. Clinical outcome was evaluated by BPRS. 4. Cluster analysis only considering BPRS improvement and reduced haloperidol/haloperidol ratio was able to discriminate two groups of patients: one of non responders and the other of responders. The former group presented higher ratios than the latter. 5. Reduced haloperidol/haloperidol ratio could be considered as a good marker for prediction of the clinical outcome.

Clonazepam (CLN), a benzodiazepine originally used as an anti-epileptic, was tested in schizophrenia in a double blind comparison in combination with haloperidol (HL). Twenty-four schizophrenic inpatients, diagnosed according to DSM III were treated with HL and CLN (Group 1) or HL and placebo (Group 2) for 4 weeks. The Brief Psychiatric Rating Scale (BPRS) and the Extrapyramidal Side Effect Scale (EPSE) were used for assessing psychopathological features and extrapyramidal side-effects before treatment and then weekly. No differences in specific schizophrenic symptoms were detected between the two groups, but in Group 1 an early significant BPRS amelioration was noticed compared to Group 2. Moreover, the excitement item improved significantly in Group 1 only, from the second week. Less severe EPSE scores were observed in Group 1 in comparison to Group 2. In conclusion the combination of CLN and HL seems to be preferred to HL alone in cases of psychotic excitement and in order to reduce the severity of extrapyramidal side-effects.

1. The knowledge of the pharmacokinetic profile of fluphenazine decanoate (FPZ-D) suggested it was suitable for treatment of schizophrenic patients not just during the maintenance phase of the disease but also during acute relapses. 2. 27 acute schizophrenic in-patients (diagnosed according to the DSM III) were treated with FPZ-D, 25 mg i.m. with repeated administrations (after 2, 4, 30 days). 3. FPZ-D proved effective in all cases, already after the second day and particularly on Brief Psychiatric Rating Scale items such as delusion, hallucinations, hostility. 4. Extrapyramidal side-effects, appeared in about 40% of the patients. 5. The use of the drug both in the acute phase and maintenance schizophrenia therapy is envisaged, overcoming the problems deriving from the rejection by patients of any therapeutic tool and consequently the therapeutic "milieu".