Atypical antipsychotics are used in large scale in reason of their few side effects, as extrapyramidal symptoms. Dispite of this safety they can cause severe dystonia as Pisa Syndrome.

This case brings an example of Pisa Syndrome induced by the use of Ziprasidone.

A thirty five year old female, diagnosed with Bipolar disorder was treated in a psychiatry ambulatory with lithium 1200mg and haloperidol 10mg. As the psycosis persisted it was necessary to change the antipsychotic and ziprasidone was chosen.

Three months after the introduction of ziprasidone, the patient began to present severe dystonia symptoms. In the occasion could be noticed sustained involuntary flexion of the body and head to one side as well as slight rotation of the trunk.

In reason of the extrapyramidal symptoms, ziprasidone was suspended.

The case was treated with anticholinergic drugs. Prometazine and biperidene were tried but neither was effective.

Two months after the suspension of Ziprasidone the patient recovered completely and did not present any signs of dystonia.

Pisa Syndrome can be caused by atypical neuroleptics as ziprasidone.

The treatment is difficult and anticholinergics are not effective.

In some situations Pisa Syndrome can be definitive.

The use of atypical antipsychotics requires knowledgment and experience from the psychiatrist. The potencial of atypical antipsychotics to cause extrapyramidal symptoms as Pisa Syndrome can not be forgotten.

The pathophysiology of extrapyramidal side effects of typical antipsychotic drugs and the role of gender as a risk factor is poorly understood.

To elucidate the role of gender and the oestrogen hypothesis in extrapyramidal side effect severity.

To investigate gender differences in side effects of antipsychotic drugs and explore the role of oestrogen levels in side effect severity.

25 women and 23 men with a diagnosis of schizophrenia were examined for side effects using the Extrapyramidal Side Effects Rating Scale (ESRS), the Simpson Angus Rating Scale for Extrapyramidal Side Effects and the Abnormal Involuntary Movements Scale (AIMS).

Higher antipsychotic doses and use of anticholinergics were noted in males.Women had higher ESRS scores and Simpson Angus scores. Men had higher mean scores for AIMS and the Barnes Akathisia Rating Scale. Age was significantly correlated with scores on ESRS, AIMS and Simpson Angus Rating Scale. There was a highly significant correlation between ESRS score and absence of a regular menstrual cycle. No association with age or antipsychotic dose was found between the groups. Women without a regular cycle scored significantly higher on Simpson Angus Rating Scale. Women with regular cycles scored significantly higher on Barnes Akathisia Rating Scale. There was no difference in AIMS score between the groups. No significant difference was found on any measure between women who were in the high and low oestrogen phases of the cycle.

Gender, age and the presence of a menstrual cycle should be considered when prescribing antipsychotic medication.

Mr. Y is a 36 year old male patient diagnosed with simple schizophrenia that has complained of insomnia since the age of sixteen. During the last three years the treatment that the patient was following was stable and consisted of 100 mg of diazepam, 300 mg of levomepromazine and 120 mg of clotiapine every night. During the last year 60 mg of duloxetine were added to treat a moderate depression. His mood improved with the prescribed treatment, but eleven months later it worsened. In an attempt to simultaneously treat the mood and the sleep disorder, during a period of 4 days, a dosis of 12.5 mg of aglomelatin at dinner was introduced while the morning dose of duloxetine was reduced to 30mg. On the fifth day, agomelatine was increased to 25 mg at dinner while duloxetine was suspended. The antipsychotic treatment was kept stable while the patient was instructed to reduce 10 mg of diazepam every week until next appointment one month later. In the next appointment the patient had completely suspended diazepam one week before the appointment. The patient referred improved sleep quality and no rebound insomnia.

Agomelatine may be a valid treatment of insomnia in schizophrenia.

Paroxetine is a SSRI, widely used nowadays for treating diverse psychiatric pathologies, such as anxiety disorders, affective disorders… It is well known by clinician that paroxetine used is doses between 10-50 mg has evident benefits in the therapeutic process.

Different adverse effects are commonly expected when using paroxetine, and some other side effects are considered rare, meaning that are shown in 1 or more every 10.000 patients but less than 1/1000.

Comprehensive review of the scientific literature (Medline, Psychoinfo, Medex) on hyperprolactinemia secondary to SSRI treatments published over the last years.

This is a case report of a 32 year-old- female treated with paroxetine, suffering from panick attacks frequently in the context of an anxiety disorders. After 2 years she quited consuming cocaine in 2007.

The patient after a couple of months being treated with paroxetine observes lactation, galactorrhea, and amenorrea.

Analysis were done, in the beginning an increase in prolactine levels was found, after changing the treatment although prolactine levels were lowering the galactorrhea persisted in time.

Before considering paroxetine as a factor, she started to be studied in a fertilization program, where she still is.

Galactorrhea cases with tricyclic antidepressants, as well as with selective serotonin reuptake inhibitors are rarely reported. The observed lactation is presumed to be secondary to a drugmediated increase in prolactine levels. This is the report of a case of hyperprolactinemia and galactorrhea following treatment with paroxetine in a young female with an anxiety disorder.

There is increasing concern about the use of multiple medications in psychiatric patients.Older adults make up 15% of the population yet they account for 30% of the prescribed medications. There is increased risk of falls, confusion and consequent functional decline as a result of potential interactions and adverse drug events.

To document the extent of polypharmacy and potential drug interactions in elderly inpatient population at the point of discharge.

25 consecutive discharge summaries from an elderly mixed (organic and functional) inpatient unit were evaluated.

out of 25 (15 female and 10 male) patients with age range of 59-97 years, an average of 6.5 drugs (Range:2-17; Median:6) were prescribed. An average of 3.1 pair of interactions (Range:0-15; Median:3) were noted. Potentially hazardous interactions (Average 0.68; Range:0-4) was a worrying trend in this patient group.

Polypharmacy is commonplace in elderly patients and is worrisome. Different strategies like in-house pharmacist may offer some safeguards though further research is needed.

To determine how informed psychiatric outpatients are about the role of anticholinergic drugs in their treatment.

Using a clinician-administered questionnaire designed by the authors; socio-demographic data and views about the role of Benzhexol in their treatments were obtained from all patients whose case records showed that they were currently prescribed Benzhexol.

98 patients met inclusion criteria, mostly males (n=54; 55.1%). The respondents were predominantly in the age range 25 - 44years (n=67; 68.4%) and single (n=52; 53%). Two-thirds had no more than secondary education. Though more than half of respondents reported having being on their current combination of drugs for more than 1 year, 34% could not give the names of any of their medications. A third reported not knowing the role of Benzhexol in their treatment and of those who claimed to know, 64% (n=42) gave responses that reflected no understanding. Majority (n=31; 74%) of such responses were adjudged to have potentially deleterious implications on their health and outcome. There was no statistically significant association between educational status and knowledge of the role of Benzhexol in patients’ treatment. Only 18% reported ever being educated about the role of Benzhexol in their treatment.

The study provides evidence that majority of the patients may not be well informed about important aspects of their treatment and that health workers may have neglected to educate them. It further calls for an urgent need to improve the patient-information aspects of service delivery in our clinics.

Concomitant antipsychotic prescription is common in clinical psychiatry, although it is not an evidence-based practice. The aim of the study was to describe the prescription of antipsychotics in inpatients with schizophrenia and identify which are the factors associated with this tendency.

We reviewed retrospectively the psychotropic drugs prescribed at the time of discharge of 177 inpatients who met criteria for schizophrenia [DSM-IV-TR] on an acute psychiatry unit from 2007 to 2008.

One hundred and two patients (57.6%) were male. Mean age (SD) was 38.1 (14.6) years. The percentage of patients discharged on treatment with two or more antipsychotics was 43.5%. Although in the strict sense we should not consider it as polipharmacy, the most frequent combination was long acting injectable risperidone with oral risperidone (21.5%), followed by long acting injectable typical antipsychotic with oral risperidone (3.4%). There was a significant association between the number of prescribed antipsychotics and the total number of previous hospitalizations and the number of hospitalizations during the previous year (ANOVA p=0.001 and p< 0.001 respectively). No correlation was found between polypharmacy and age. There was a significant association between the number of antipsychotics prescribed and the use of anticholinergic treatment (t-test p=0.005).

Our polypharmacy rates are comparable with prior European data (30-76%). Despite of the clinical guidelines, antipsychotic polipharmacy is an extended therapeutic strategy not necessarily related with resistant schizophrenia. Most of the antipsychotic associations identified are not evidenced-based practice. More clinical trials are needed to determine the efficacy of different combinations.

Olanzapine is a novel antipsychotic agent. It has a pleotrophic pharmacology and affects dopaminergic, serotonergic, muscarinic and adrenergic activities. The therapeutic advantage of recent antipsychotics (so-called atypical antipsychotics) has been attributed to alpha-2 adrenergic antagonist effects.

The aim of this study was to evaluated effectiveness of Olanzapine in patients with schizophrenia.

Study was designed for 8-week, observational study. 40 patients, both genders, aged 20-65 years, with diagnosed various types of schizophrenia were enrolled in the study as outpatient and inpatient setting. The patients had to have a total score ≥40 on Positive and Negative scale - two parts of the Positive and Negative Syndrome Scale (PANSS). The efficacy parameter was the percent of score difference between baseline and week 8 of therapy on two above-mentioned PANSS subscales. The difference was considered as significant improvement if decrease from the baseline was 20% or more.

All 40 enrolled patients completed the study. After the 8 weeks of treatment, 32/40 patients (80%) had clinically significant improvement of 20% or more decreased total PANSS score (Positive and Negative subscale). In 8/40 patients (20%) clinical improvement was also reported with < 20% decreased total PANSS score.

In this observational study olanzapine appears to be very good effectiveness in patients with schizophrenia.

The poor compliance to antipsychotic medication is a major problem in ambulatory treatment of patients with psychotic symptoms, leading to an increased risk of exacerbation and inpatient readmission.

Our objective is to clarify if the administration of prolonged release antipsychotics (PRAP) is a relevant factor in the decrease of inpatients readmissions.

Through a retrospective study, we assessed the socio-demographic and psychopathological features of a sample of patients with diagnostic of Schizophrenia and Schizoaffective disorder (DSM-IVTR), who were admitted to a psychiatric inpatient unit, in the period of two years (January 2007 to December 2008). This sample was divided in two groups (with readmissions/without readmissions), considering as having readmissions the patients that were readmitted in the nine months after the first medical discharge. We compared the use of PRAP versus oral antipsychotics (OAP) at the time of the first medical discharge, assessing if these differences had any impact in the readmissions.

Sample of 88 patients, 55,68% (n=49) male, 53,41% (n=47) unemployed, 64,77% (n=57) single. The most frequent diagnostic was Paranoid schizophrenia (73,86%, n= 65), followed by Schizoaffective disorder (17.05%, n= 15). Of the patients that had readmissions (n=15; 17,05%), 40,00% were medicated with PRAP (n=6) compared with 49,32% (n=36) of the patients with no readmissions (n=73). These differences had no statistic significance.

Taking in consideration the small sample of patients, the frequency of readmissions was low. About 50% of the patients were medicated with PRAP+OAP, with no evidence that this decision had reduced the readmissions.

Schizophrenia is a debilitating and cronic disease for which full recovery is typically not considered to be a realistic treatment endpoint. Symptomatic remission, however, may be an objectively attainable treatment goal.

We wanted to assess remission rates over 52 weeks in patients with schizophrenia treated with ziprasidone

Remission rates were calculated using data from a 52 week study in which patients diagnosed with acute schizophrenia were stabilized with ziprasidone (n=30, dose 120-140mg/day) For this analysis, remission was operationalized according to the consensus-based symptomatic remission criteria established by the Remission in Schizophrenia Working Group. Accordingly, patients were required to achievescores Syndrome Scale (PANSS) items (delusions, unusual thought content, hallucinatory behavior, conceptual disorganization, mannerisms/posturing, blunted affect, social withdrawal, lack of spontaneity) and to maintainthe item score threshold for at least 6 consecutive months.

Thirty-seven percent of ziprasidone treated patients satisfied the criteria for symptomatic remission within the 52-week trial period. Approximately 7% of patientslost their remission status prior to the end of thetrial, with mean time in remission of 6.5 months. Forty-six percent of patients never met the PANSS item threshold. During the 52-week study, few patients discontinued due to adverse events other than worsening of symptoms(7%) or received concomitant medication for EPS (18%)

Nearly one third of the patients treated with ziprasidone achieved remission status within 6 months. Most patients who achieved remission remained in remission for more than 9 months until trial termination. Overall CGI-Is of these patients were significantly better than for patients without remission.

To explore the relationship between symptomatic and functional outcomes in adults (age 18-65 years) with ADHD during open label treatment with PR OROS MPH.

Post hoc analyses of a 7-week open-label extension (OLE) (N=370) of a 5 week, placebo controlled double-blind study (DB) which explored safety, efficacy, functional and quality of life outcomes in subjects with a diagnosis of ADHD (DSM-IV). Medication was flexibly dosed (18-90 mg/day) and adjusted individually to best effect during OLE. Regression analyses were performed on the change from DB baseline at OL endpoint in functionality and quality of life as measured by the Sheehan Disability Scale (SDS) and Quality of Life (Q-LES-Q). Baseline score, country, randomization group, sex, change from baseline in CAARS Hyperactivity / Impulsivity, CAARS Inattention and CGI-S at DB endpoint were included as covariates in the analyses.

337 / 370 patients completed the 7-week open label treatment. Improvement on CAARS Hyperactivity / Impulsivity at DB endpoint was significantly related with improvement in SDS “work”, “social life”, “family life” (at least p< 0.005) and “total score” as well as quality of life (p< 0.05) at the end of open label treatment. Change in CGI-S and CAARS Inattention at DB endpoint vs. DB baseline were not related with improvements in any of the functional or quality of life scales at OL endpoint (p>0.05).

These results indicate that improvement in daily functioning and QOL under active treatment may be particularly related to improvement in hyperactivity symptoms.

Sexual dysfunction (SD) is an important underestimated adverse effect of antidepressant drugs. Patients, in fact, if not directly questioned, tend to scarcely report them. The aim of the present meta-analysis was to quantify SD caused by antidepressants on the basis of studies where sexual functioning was purposely investigated through direct inquiry and specific questionnaires.

A literature search was conducted using MEDLINE, ISI Web of Knowledge, and references of selected articles. Selected studies performed on patients without previous SD were entered in the Cochrane Collaboration Review Manager (RevMan version 4.2). Our primary outcome measure was the rate of total treatment-emergent SD. Our secondary outcome measures were the rates of treatment-emergent desire, arousal, and orgasm dysfunction.

Our analyses indicated a significantly higher rate of total and phase-specific treatment-emergent SD compared with placebo for the following drugs in decreasing order of impact: sertraline, venlafaxine, citalopram, paroxetine, fluoxetine, imipramine, phenelzine, duloxetine, escitalopram, and fluvoxamine, with SD ranging from 25.8% to 80.3% of patients. No significant difference with placebo was found for the following antidepressants: agomelatine, amineptine, bupropion, moclobemide, mirtazapine, and nefazodone.

Treatment-emergent SD caused by antidepressants is a considerable issue with a large variation across compounds. Some assumptions, such as the inclusion of open-label studies or differences in scales used to assess SD, could reduce the significance of our findings. However, treatment-emergent SD is a frequent adverse effect that should be considered in clinical activity for the choice of the prescribed drug.

Olanzapine plasma concentration ≥ 23, 2 ng/ml have been identified as a predictor of clinical response in acutely ill patients with schizophrenia. Aim was to determine relation between plasma concentration of olanzapine in a sample of inpatients or outpatients with acute mania by defining a plasma threshold (above which a better clinical response was obtained).

Open label, longitudinal, multicentric study including patients with acute mania and treated by olanzapine for 6 weeks; plasma concentration of olanzapine was measured at 3 and 6 weeks by high-performance liquid chromatography. Patients were considered “responsive” if they showed at least a 50% reduction in Young Mania Rating Scale score and a Clinical Global Impression Severity scale score of ≤ 3.

Twenty patients were including (13 men and 7 women), mean age 57.4 yr. The mean olanzapine dosage was 11.46 mg/day (SD=2.49) at the same dosage for 16.8 days (SD=6.5). Receiver operating characteristic curve analysis determined a plasma threshold to be 15, 9 ng/ml.

It's the first time that a threshold of Olanzapine is determined in bipolar mania into a consequent population. This result could be considered as additional tools to adjust posology for improve cares, when manic patients are resistant.

There are no large scale studies on Epilepsy in populations with Learning disability in Ireland. As many as one fifth of these clients have epilepsy. Aggressive treatment may lead to diminishing returns in terms of symptomatic control, while causing unwanted effects.

1. 1. We aimed to quantify rates of epilepsy, aetiology and anti- epileptic drug (AED) use in our population.

2. 2. To look at degree of disability and correlation with AED use.

3. 3. To look at management/ quality of life issues using a validated instrument.

:

1. 1. Medline review using search terms Intellectual OR Learning difficult* OR Mental Retard* AND Epilepsy.

2. 2. Simple questionnaire used to identify all clients with Epilepsy. Database analysed using SPSS analysis.

3. 3. 11 cases selected for review looking at qualitative aspects, using Semi structured interview and GEOS scale.

1. · 210 patients found to have a history of epilepsy (42% of clients).

2. · Multiple Aetiologies identified. Commonest known Aetiology: Trisomy 21.

3. · Polypharmacy is common. Most commonly used AED: Sodium Valproate. Mean AED use: 1.595 (SD+- 1.077).

4. · Clients with Trisomy 21 aged less than 40 tended to be on more medication (2.05, SD= +-1.38) than those over 40 years (1.43, SD= +- 0.89)

5. · Greater concerns on qualitative measures regarding clients with refractory epilepsy or where epilepsy changed over time.

Our study highlights previously recognised changing patterns in aetiology of Learning Disability and also the changes over time in these clients. More study is required.

We examined the course of patients admitted for the first time in the Acute mental health ward of a Psychiatric Clinic in a Psychiatric Hospital within a ten-year hiatus. During this time the sociodemographic characteristics of the population were altered due to migration from former Eastern Europe countries, the transition from typical to atypical antipsychotic medication was completed and attempts were made to promote community psychiatry.

We compared two groups of 77 and 87 patients admitted for the first time during 1997 and 2007 respectively. Prescribed medication when given an exit diagnosis was calculated to haloperidol equivalency, following guidelines described in Kane et al.

Results indicate that the groups were comparable as to size, sex, age, entry diagnosis and length of stay. The groups differed significantly as to origin, with the 2007 group having significantly more migrants but also patients originating from more distant provinces within Greece. There was a significant increase in involuntary admissions. While there was an increase in the use of atypical antipsychotics there was no significant difference in treatment potency.

Introduction of atypical antipsychotics enabled the clinician to provide treatment of similar antipsychotic potency with better tolerance profile, but failed to reduce length of stay. The increase in involuntary admissions and number of admissions from more remote regions raises doubts on the efficiency of the psychiatric reforms attempted during that time in order to promote community psychiatry.

Serotonin Syndrome (SS) is an adverse drug reaction that drives mental-status changes, autonomic hyperactivity and neuromuscular abnormalities.

Neuroleptic Malignant Syndrome (NMS) is an idiopathic reaction to dopamine-antagonist that consists of extra-pyramidal symptoms, autonomic dysfunction, hyperthermia, diaphoresis and fluctuating consciousness.

Differential diagnosis is sometimes difficult for their overlapping clinical features. Potentially lethal, both require heightened clinical awareness for prevention, recognition and prompt treatment.

Caucasian 59 years-old woman with Catatonic profile (Scored: severity-17points/ 5 screening in Bush-Francis Catatonia-Rating-Scale).

1. - Hypothyroidism

2. - Bipolar Disorder type-2 (25 years of evolution)

15 days before hospitalization, anafranil and fluoxetine treatment was replaced by Trazodone 200 mg/day and venlafaxine 150mg/day. She was also on valpromida and lorazepam 15 mg/day.

Mutism, negativism. No reaction to painful stimuli, stuporous. Diaphoresis, pallor, tremor, axial rigidity without pyramidalism (>lower limbs), high fever (40°C), tachycardia (>100lpm), rhabdomyolysis (CPK reached 17.000, 48 hours after the admission), leukocytosis, upper transaminasas, hiponatremia with hiperpotasemia.

1. - NMS: Intensity, duration and high CPK are suggestive (Sternbach). This syndrome has been described due to Venlafaxine.

2. - SS: Combination of Venlafaxine and Trazodone favors but she doesn't have acatisia, hiperreflexia, diarrhea and it wasn't resolved after 96 hours.

Drugs were removed and Lorazepam on high doses (5mg/day) was prescribed. One month later the patient was totally recovered of the episode.

If unsure diagnoses it's priority to remove the causing drugs and supportive care. Afterwards, it can be used benzodiacepines, also dantroleno in SNM.

Neuroleptic Malignant Syndrome (NMS) is a rare and potentially lethal adverse reaction generally associated with typical antipsychotics. Cardinal features include muscle rigidity, hyperthermia, mental status changes, elevated CPK levels.

We report on a patient receiving olanzapine, an atypical antipsychotic, who developed NMS.

A 31 year-old male with a 5 year history of paranoid psychosis, was successfully treated with olanzapine 15 mg per day. He was also receiving oxcarbazepine for epilepsy (1200 mg/ day) and also suffered from spastic congenital paraparesis. He was almost asymptomatic for 4 years. At some point there was a recurrence of his illness with restlessness and aggressive behaviour. The patient decided to receive additionally 5 mg of olanzapine,without consulting psychiatrist. Soon he developed hyperthermia, hypertonia and confusion. He was initially admitted in a general hospital with leukocytosis and elevated CPK levels (1999 U/L). Other laboratory examinations were within normal limits. He was treated with ceftriaxone and parenteric fluids. After 48 hours he was improved and olanzapine was reinitiated (10 mg/day), and a few hours later he developed fever (40' C), hypertonia, dysphagia, confusion, CGS: 7/15 and elevated CPK levels (4900 U/LT). He was then transferred to the Intensive Care Unit and received treatment for NMS with bromocryptine and dantrolene sodium. His temperature returned to normal in two days and in 6 days he was physically stable. Twenty days later he received treatment for psychosis with low dose quetiapine.

NMS characterized by muscular rigidity and fever may rarely occur with atypical neuroleptics, such as olanzapine.

To assess the impact of lisdexamfetamine dimesylate (LDX; Vyvanse®, Shire US Inc.), which is the first long-acting prodrug stimulant indicated for treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adults in the United States, on performance and quality of life (QOL) in adults with ADHD.

Subjects (n=142; aged 18 to 55 years) with ADHD entered a 4-week open-label dose-optimisation phase, then a 2-week, double-blind crossover phase. The primary efficacy measure was the average postdose total score on the Permanent Product Measure of Performance (PERMP) math test given predose and 2, 4, 8, 10, 12, and 14 hours postdose. The Adult ADHD Impact Module (AIM-A) was self-administered during the dose-optimisation phase. Safety was assessed by monitoring adverse events (AEs).

In the intention-to-treat population (n=105), postdose average PERMP least squares mean (SE) scores were higher (P< .0001) for LDX (312.9 [8.59]) vs placebo (289.5 [8.59]) and at every postdose time point ≥14 hours (P≤.0017 for each). Mean change from baseline scores on AIM-A subscales (n=127) showed improvement (P< .001) with LDX in 6 measured QOL domains (living with ADHD; general wellbeing; work, home, and school performance and daily functioning; relationships and communication; interference with life; and concern caused by symptoms). Treatment-emergent AEs (≥10%) in the dose-optimisation phase were decreased appetite (36.6%), dry mouth (30.3%), headache (19.7%), and insomnia (18.3%).

LDX improved QOL and performance (up to 14 hours) and demonstrated a safety profile consistent with long-acting stimulant use.

Supported by funding from Shire Development Inc., Wayne, PA, US.

Cardiovascular side effects of antipsychotics are been studied both in typical and atypical antipsychotics but, in particular, with clozapine few systematic studies of these effects have been performed. In this study, we reviewed electrocardiographic (ECG) data from patients treated with clozapine.

Observational, retrospective study in our Clozapine Day Clinic from 2000 to 2008. We recluted 197 patients (70% men) with mean age 31,75 ± 9,0 years who began treatment with clozapine. All of them had an electrocardiogram taken before starting treatment and after 18 weeks of follow-up. None suffered from heart diseases. QTc was evaluated by Bazett formula (QT/ (R-R’)1/2). Treatment prescribed was taken down and drug serum levels were detected. Statistical analysis was executed by SPSS 17.0.

There was significant correlation between doses prescribed and levels of clozapine and norclozapine (r=.304, p=.023; r=.354 p=.007), between levels of clozapine, norclozapine and QTc enlargement (r=.348, p=.008; r=.268 p=.046) and between levels of clozapine, norclozapine and heart rate (r=.390, p=.003; r=.326 p=.014). There were no differences between QTc and treatment with clozapine or other antipsychotic (p=0.902), between sex or if polypharmacy existed. ECG alterations were a case of supraventricular extrasystoles, another of Wolf-Parkinson -White Syndrome and other inespecific alterations like repolarizations or left hypertrophy.

We did not find either major incidence on cardiological effects or significative QTc enlargement during treatment with clozapine in contrast to other antipsychotic previously prescribed. Therefore clozapine may be in the same cardiologic safety rank than other antipsychotics.

To develop consensus-based clinical diagnostic criteria for neuroleptic malignant syndrome (NMS).

A 17-member international expert panel of psychiatrists, neurologists, anesthesiologists and emergency medicine specialists was asked to identify clinical features that are most important or valuable in diagnosing NMS; when the feature was quantitative in nature, they were also asked to provide the corresponding critical value. The Delphi technique is a formal consensus procedure that employs a postal survey method to solicit opinions from each panel member, and to feed this information back to the entire panel in the form of anonymous, statistically aggregated data. This iterative process of information exchanges (opinions collected, group responses analyzed, feedback given to panel), or “rounds”, continues until consensus has been reached. In the present study, the predetermined consensus criterion was a round-round mean change of 10% or less for any survey item, and 5% or less across all items.

The expert panel reached consensus on the following diagnostic criteria in five iterations:

1. (1) exposure to a dopamine antagonist, or dopamine agonist withdrawal, within past 72 hours;

2. (2) hyperthermia;

3. (3) rigidity;

4. (4) mental status alteration;

5. (5) creatine phosphokinase elevation;

6. (6) sympathetic nervous system lability (2 or more of blood pressure elevation, blood pressure fluctuation, diaphoresis, urinary incontinence);

7. (7) tachycardia and tachypnea; and

8. (8) negative work-up for infectious, toxic, metabolic and neurological causes.

These are the first consensus-based diagnostic criteria for NMS, and may be preferred to previous ad hoc approaches to diagnosing this disorder.