Emergency department admission and mortality rate for suicidal behavior. A follow-up study on attempted suicides referred to the ED between January 2004 and December 2010.

BACKGROUND: The international literature reports that for every completed suicide there are between 8 and 22 visits to an Emergency Department (ED) for attempted suicide/suicidal behavior. AIMS: To describe the characteristics of admission to emergency departments (EDs) for suicide-related presenting complaints in the metropolitan area of Bologna; to estimate the risk for all-cause mortality and for suicide; to identify the profiles of subjects most at risk. METHOD: Follow-up of patients admitted to the EDs of the metropolitan area of Bologna between January 2004 and December 2010 for attempted suicide. A Cox model was used to evaluate the association between sociodemographic variables and the general mortality risk. RESULTS: We identified 505 cases of attempted suicide, which were more frequent for female subjects, over the weekend, and at night (8:00 p.m./8:00 a.m.). The most used suicide methods were psychotropic drugs, sharp or blunt objects, and jumping from high places. In this cohort, 3.6% of subjects completed suicide (4.5% of males vs. 2.9% of females), 2.3% within 1 year of the start of follow-up. The most common causes of death were drug use and hanging. In the multivariate analysis, those who used illicit drugs 24 hr prior to admission to the ED (hazard ratio [HR] = 3.46, 95% CI = 1.23-9.73) and patients who refused the treatment (HR = 6.74, 95% CI = 1.86-24.40) showed an increased mortality risk for suicide. CONCLUSION: Deliberate self-harm patients presenting to the ED who refuse treatment represent a specific target group for setting up dedicated prevention schemes.

Analysis of risperidone and 9-hydroxyrisperidone in human plasma, urine and saliva by MEPS-LC-UV.

Risperidone is currently one of the most frequently prescribed atypical antipsychotic drugs; its main active metabolite 9-hydroxyrisperidone contributes significantly to the therapeutic effects observed. An original analytical method is presented for the simultaneous analysis of risperidone and the metabolite in plasma, urine and saliva by high-performance liquid chromatography coupled to an original sample pre-treatment procedure based on micro-extraction by packed sorbent (MEPS). The assays were carried out using a C8 reversed-phase column and a mobile phase composed of 73% (v/v) acidic phosphate buffer (30 mM, pH 3.0) containing 0.23% triethylamine and 27% (v/v) acetonitrile. The UV detector was set at 238 nm and diphenhydramine was used as the internal standard. The sample pre-treatment by MEPS was carried out on a C8 sorbent. The extraction yields values were higher than 92% for risperidone and 90% for 9-hydroxyrisperidone, with RSD for precision always lower than 7.9% for both analytes. Limit of quantification values in the different matrices were 4 ng/mL or lower for risperidone and 6 ng/mL or lower for the metabolite. The method was successfully applied to plasma, urine and saliva samples from psychotic patients undergoing therapy with risperidone, with satisfactory accuracy results (recovery>89%) and no interference from other drugs. Thus, the method seems to be suitable for the therapeutic drug monitoring of schizophrenic patients using the three different biological matrices plasma, urine and saliva.

Analysis of risperidone and its metabolite in plasma and saliva by LC with coulometric detection and a novel MEPS procedure.

A new analytical method, based on the use of liquid chromatography with coulometric detection, has been developed and applied to quantify risperidone and its main active metabolite 9-hydroxyrisperidone in human plasma and saliva. The analytes were separated on a reversed phase C18 column, using a mobile phase composed of acetonitrile (26%) and a pH 6.5 phosphate buffer (74%). Pipamperone was used as the internal standard. A high sensitivity coulometric detection analytical cell containing two flow-through working electrodes was used: electrode 1 was set at +0.500V and electrode 2 at +0.700V. The detector response was linear over a plasma and saliva concentration range of 0.5-50.0ngmL(-1) for risperidone and 0.5-100.0ngmL(-1) for 9-hydroxyrisperidone. The limit of quantitation and the limit of detection for risperidone and 9-hydroxyrisperidone were 0.5ngmL(-1) and 0.17ngmL(-1), respectively. A novel clean-up procedure of biological samples was developed using the microextraction by packed sorbent technique, which gave good extraction yield for both the analytes, with absolute recovery values higher than 90.1%. The intra-day and the inter-day precision results, expressed by relative standard deviation values, were lower than 5.8%. Accuracy and selectivity assays were also satisfactory. The validated method has been successfully applied to the analysis of risperidone and 9-hydroxyrisperidone in plasma and saliva of psychiatric patients undergoing therapy with risperidone.

Simultaneous HPLC determination of 14 tricyclic antidepressants and metabolites in human plasma.

A HPLC method has been developed for the simultaneous determination of seven tricyclic antidepressants (TCAs) and seven metabolites in human plasma. The analyte separation was obtained using a C8 reversed phase column and a mobile phase composed of 68% aqueous phosphate buffer at pH 3.0 and 32% ACN. The UV detector was set at 220 nm and loxapine was used as the internal standard. A careful pre-treatment procedure for plasma samples was developed, using SPE on C2 cartridges, which gives satisfactory extraction yields (>80%) and good sample purification. The LOQs were always lower than 9.1 ng/mL and the LODs always lower than 3.1 ng/mL for all analytes. The method was successfully applied to plasma samples from depressed patients undergoing therapy with one or more TCA drugs. Precision data (RSD <8.1%), as well as accuracy results (recovery >80%), were satisfactory and no interference from other drugs was found. Hence the method seems to be suitable for the therapeutic drug monitoring of patients treated with TCAs under monotherapy or polypharmacy regimens.

Analysis of the recent antipsychotic aripiprazole in human plasma by capillary electrophoresis and high-performance liquid chromatography with diode array detection.

Two methods, based on the use of capillary electrophoresis (CE) and high-performance liquid chromatography (HPLC), respectively, were developed for the analysis of the atypical antipsychotic aripiprazole in plasma of schizophrenic patients for therapeutic drug monitoring purposes. Good analytical performances were obtained with the CE method, using uncoated fused silica capillaries and a background electrolyte composed of 50mM phosphate buffer at pH 2.5. With 20 kV voltage, aripiprazole was detectable at 214 nm within 5 min. The second analytical method, based on HPLC with diode array detection, employed a C8 reversed-phase column and a mixture of a 12.5mM phosphate buffer, pH 3.5, containing triethylamine and acetonitrile as the mobile phase. Aripiprazole was detected at 254 nm and a complete chromatographic run lasted about 10 min. For both analytical methods loxapine was used as the internal standard and the same plasma sample pre-treatment by means of solid-phase extraction on cyano cartridges was carried out, with extraction yield values always higher than 91.3%. Linear responses for aripiprazole were obtained between 70 and 700 ng mL(-1) and precision assays (expressed as relative standard deviation values) were lower than 7.0%. After validation, both methods were successfully applied to human plasma samples drawn from schizophrenic patients undergoing therapy with Abilify tablets. Accuracy was satisfactory, with recovery value higher than 91.0%.

Clinical features and therapeutic management of patients admitted to Italian acute hospital psychiatric units: the PERSEO (psychiatric emergency study and epidemiology) survey.

BACKGROUND: The PERSEO study (psychiatric emergency study and epidemiology) is a naturalistic, observational clinical survey in Italian acute hospital psychiatric units, called SPDCs (Servizio Psichiatrico Diagnosi e Cura; in English, the psychiatric service for diagnosis and management). The aims of this paper are: (i) to describe the epidemiological and clinical characteristics of patients, including sociodemographic features, risk factors, life habits and psychiatric diagnoses; and (ii) to assess the clinical management, subjective wellbeing and attitudes toward medications. METHODS: A total of 62 SPDCs distributed throughout Italy participated in the study and 2521 patients were enrolled over the 5-month study period. RESULTS: Almost half of patients (46%) showed an aggressive behaviour at admission to ward, but they engaged more commonly in verbal aggression (38%), than in aggression toward other people (20%). A total of 78% of patients had a psychiatric diagnosis at admission, most frequently schizophrenia (36%), followed by depression (16%) and personality disorders (14%), and no relevant changes in the diagnoses pattern were observed during hospital stay. Benzodiazepines were the most commonly prescribed drugs, regardless of diagnosis, at all time points. Overall, up to 83% of patients were treated with neuroleptic drugs and up to 27% received more than one neuroleptic either during hospital stay or at discharge. Atypical and conventional antipsychotics were equally prescribed for schizophrenia (59 vs 65% during stay and 59 vs 60% at discharge), while atypical drugs were preferred in schizoaffective psychoses (72 vs 49% during stay and 70 vs 46% at discharge) and depression (41 vs 32% during stay and 44 vs 25% at discharge). Atypical neuroleptics were slightly preferred to conventional ones at hospital discharge (52 vs 44%). Polypharmacy was in general widely used. Patient attitudes toward medications were on average positive and self-reported compliance increased during hospital stay. CONCLUSION: Results confirm the widespread use of antipsychotics and the increasing trend in atypical drugs prescription, in both psychiatric in- and outpatients.

Determination of the antidepressant paroxetine and its three main metabolites in human plasma by liquid chromatography with fluorescence detection.

A high-performance liquid chromatographic method has been developed for the determination in human plasma of the specific serotonin reuptake inhibitor (SSRI) antidepressant paroxetine and its three main metabolites (M1, M2, M3). Fluorescence detection was used, exciting at lambda = 294 nm and monitoring emission at lambda = 330 nm for paroxetine (lambda(exc) = 280 nm, lambda(em) = 330 nm for M1 and M2; lambda(exc) = 268 nm, lambda(em) = 290 nm for M3). Separation was obtained on a reversed-phase C18 column using a mobile phase composed of 66.7% aqueous phosphate at pH 2.5 and 33.3% acetonitrile. Imipramine (lambda(exc) = 252 nm, lambda(em) = 390 nm) was used as the internal standard. A careful pre-treatment of plasma samples was developed, using solid-phase extraction with C8 cartridges (50 mg, 1 mL). The calibration curves were linear over a working range of 2.5-100 ng mL(-1) for paroxetine and of 5-100 ng mL(-1) for all metabolites. The limit of detection (LOD) was 1.2 ng mL(-1) for PRX and 2.0 ng mL(-1) for the metabolites. The method was applied with success to plasma samples from depressed patients undergoing treatment with paroxetine. Hence, the method seems to be suitable for the therapeutic drug monitoring of paroxetine and its main metabolites in depressed patients' plasma.

Simultaneous analysis of classical neuroleptics, atypical antipsychotics and their metabolites in human plasma.

A high-performance liquid chromatographic method has been developed for the simultaneous determination of classical neuroleptics (chlorpromazine, haloperidol, loxapine and clotiapine), atypical antipsychotics (clozapine, quetiapine and risperidone) and their active metabolites (N-desmethylclozapine, clozapine N-oxide and 9-hydroxyrisperidone) in human plasma. Separation was obtained by using a C8 reversed-phase column and a mobile phase composed of 70% aqueous phosphate buffer containing triethylamine at pH 3.0 and 30% acetonitrile. The UV detector was set at 238 nm and amitriptyline was used as the internal standard. A careful pre-treatment procedure of plasma samples was developed, using solid-phase extraction with cyanopropyl cartridges, which gives high extraction yields (>or=93%). The limits of quantitation (LOQ) were always lower than 2.6 ng mL-1 and the limits of detection (LOD) were always lower than 0.9 ng mL-1 for all analytes. The method was applied with success to plasma samples from schizophrenic patients undergoing polypharmacy with two or more different antipsychotics. Precision data and accuracy results were satisfactory and no interference from other central nervous system (CNS) drugs was found. Hence the method is suitable for the therapeutic drug monitoring (TDM) of the analytes in psychotic patients' plasma.

Main clinical features in patients at their first psychiatric admission to Italian acute hospital psychiatric wards. The PERSEO study.

BACKGROUND: Few data are available on subjects presenting to acute wards for the first time with psychotic symptoms. The aims of this paper are (i) to describe the epidemiological and clinical characteristics of patients at their first psychiatric admission (FPA), including socio-demographic features, risk factors, life habits, modalities of onset, psychiatric diagnoses and treatments before admission; (ii) to assess the aggressive behavior and the clinical management of FPA patients in Italian acute hospital psychiatric wards, called SPDCs (Servizio Psichiatrico Diagnosi e Cura = psychiatric service for diagnosis and management). METHOD: Cross-sectional observational multi-center study involving 62 Italian SPDCs (PERSEO--Psychiatric EmeRgency Study and EpidemiOlogy). RESULTS: 253 FPA aged < or = 40 were identified among 2521 patients admitted to Italian SPDCs over the 5-month study period. About half of FPA patients showed an aggressive behavior as defined by a Modified Overt Aggression Scale (MOAS) score greater than 0 Vs 46% of non-FPA patients (p = 0.3651). The most common was verbal aggression, while about 20% of FPA patients actually engaged in physical aggression against other people. 74% of FPA patients had no diagnosis at admission, while 40% had received a previous psychopharmacological treatment, mainly benzodiazepines and antidepressants. During SPDC stay, diagnosis was established in 96% of FPA patients and a pharmacological therapy was prescribed to 95% of them, mainly benzodiazepines, antipsychotics and mood stabilizers. CONCLUSION: Subjects presenting at their first psychiatric ward admission have often not undergone previous adequate psychiatric assessment and diagnostic procedures. The first hospital admission allows diagnosis and psychopharmacological treatment to be established. In our population, aggressive behaviors were rather frequent, although most commonly verbal. Psychiatric symptoms, as evaluated by psychiatrists and patients, improved significantly from admission to discharge both for FPA and non-FPA patients.

An observational study in psychiatric acute patients admitted to General Hospital Psychiatric Wards in Italy.

OBJECTIVES: this Italian observational study was aimed at collecting data of psychiatric patients with acute episodes entering General Hospital Psychiatric Wards (GHPWs). Information was focused on diagnosis (DSM-IV), reasons of hospitalisation, prescribed treatment, outcome of aggressive episodes, evolution of the acute episode. METHODS: assessments were performed at admission and discharge. Used psychometric scales were the Brief Psychiatric Rating Scale (BPRS), the Modified Overt Aggression Scale (MOAS) and the Nurses' Observation Scale for Inpatient Evaluation (NOSIE-30). RESULTS: 864 adult patients were enrolled in 15 GHPWs: 728 (320 M; mean age 43.6 yrs) completed both admission and discharge visits. A severe psychotic episode with (19.1%) or without (47.7%) aggressive behaviour was the main reason of admission. Schizophrenia (42.8% at admission and 40.1% at discharge) and depression (12.9% at admission and 14.7% at discharge) were the predominant diagnoses. The mean hospital stay was 12 days. The mean (+/- SD) total score of MOAS at admission, day 7 and discharge was, respectively, 2.53 +/- 5.1, 0.38 +/- 2.2, and 0.21 +/- 1.5. Forty-four (6.0%) patients had episodes of aggressiveness at admission and 8 (1.7%) at day 7. A progressive improvement in each domain/item vs. admission was observed for MOAS and BPRS, while NOSIE-30 did not change from day 4 onwards. The number of patients with al least one psychotic drug taken at admission, in the first 7 days of hospitalisation, and prescribed at discharge, was, respectively: 472 (64.8%), 686 (94.2%) and 676 (92.9%). The respective most frequently psychotic drugs were: BDZs (60.6%, 85.7%, 69.5%), typical anti-psychotics (48.3%, 57.0%, 49.6%), atypical anti-psychotics (35.6%, 41.8%, 39.8%) and antidepressants (40.9%, 48.8%, 43.2%). Rates of patients with one, two or > 2 psychotic drugs taken at admission and day 7, and prescribed at discharge, were, respectively: 24.8%, 8.2% and 13.5% in mono-therapy; 22.0%, 20.6% and 26.6% with two drugs, and 53.2%, 57.8% and 59.0% with > two drugs. Benzodiazepines were the most common drugs both at admission (60.0%) and during hospitalisation (85.7%), and 69.5% were prescribed at discharge. CONCLUSION: patients with psychiatric diseases in acute phase experienced a satisfactory outcome following intensified therapeutic interventions during hospitalisation.

Simultaneous determination of the antipsychotic drugs levomepromazine and clozapine and their main metabolites in human plasma by a HPLC-UV method with solid-phase extraction.

A HPLC method with UV detection has been developed for the simultaneous determination of levomepromazine, clozapine and their main metabolites: N-desmethyl-levomepromazine, levomepromazine sulphoxide, O-desmethyl-levomepromazine, N-desmethylclozapine and clozapine N-oxide. The analytes were separated on a C8 reversed-phase column using a mobile phase composed of acetonitrile and a pH 2.0, 34 mM phosphate buffer containing 0.3% triethylamine (29:71, v/v). Loxapine was used as the internal standard. A reliable biological sample pre-treatment procedure by means of solid-phase extraction on C1 cartridges was implemented, which allows to obtain good extraction yields (>91%) for all analytes and appropriate sample purification from endogenous interference. The method was validated in terms of extraction yield, precision and accuracy. These assays gave RSD% values for precision always lower than 4.9% and mean accuracy values higher than 92%. The method is suitable for the therapeutic drug monitoring (TDM) of patients undergoing polypharmacy with levomepromazine and clozapine.

Possible levomepromazine-clozapine interaction: two case reports.

OBJECTIVE: To report and comment upon two cases of suspected pharmacological interaction between the "classical" neuroleptic levomepromazine (LMP) and the "atypical" antipsychotic clozapine (CLZ). CASE SUMMARY: The patients who simultaneously took the two drugs had unusually low plasma levels of CLZ and its metabolites, even though they took high doses of CLZ. The patients were considered "non-responders" to the treatment by the psychiatrist. When LMP was withdrawn from the therapy, plasma concentrations of CLZ returned to therapeutic levels and one of the two patients experienced the anticipated therapeutic response. DISCUSSION: No information can be found in the literature regarding possible interactions between LMP and CLZ. However, the results of the two cases reported herein point out to a possible lack of therapeutic efficacy of CLZ therapy during this kind of polypharmacy. CONCLUSION: While two cases are too few to draw any conclusion, it would be prudent on the part of psychiatrists to consider a possible drug interaction in patients receiving both CLZ and LMP who fail to respond to the therapy.