To assess the prevalence of metabolic syndrome (MS) and the coronary heart disease (CHD) risk in patients with schizoaffective disorder treated with antipsychotics.

Schizoaffective patients from a multicentre cross-sectional study, in which 117 psychiatrists recruited consecutive outpatients meeting DSM-IV criteria for schizophrenia, schizophreniform or schizoaffective disorder and receiving antipsychotic treatment in monotherapy for at least 12 weeks. MS was defined as fulfilment of at least 3 of the following components (NCEP-ATP-III definition): waist circumference >102(men)/>88(women) cm; triglycerides >=150mg/dL; HDL-cholesterol < 40mg/dL(men)/< 50mg/dL(women); blood pressure >=130/85; fasting glucose >=110mg/dL. CHD risk was assessed by SCORE (10-year CV death) and Framingham (10-year all CV events) functions.

268 valuable patients with schizoaffective disorder (127 men, 48.1%), 41.9±12.3 years (mean±SD) were examined. MS was presented in 26.5% (95%CI:21.2-31.8) of subjects [26.8% in men (19.1-34.5), 27.0% (19.6-34.4) in women (p=0.966)]. the overall 10-year CV risks (CV death or any event) were 0.8±1.6 (SCORE) and 6.5±6.8 (Framingham), respectively. the 8.4% (95%CI:5.0-11.8) and 20.1% (95%CI:15.2-24.9) of patients showed high/very-high risk according to SCORE (≥3%) and Framingham (≥10%), respectively. A high/very-high risk of any CV event (Framingham≥10%) was associated with age above 40(men)/45(women) years [OR: 32.44 (9.59-109.71, p< 0.001)], and CGI-S=3-4; [OR: 4.32 (1.15-16.26, p=0.03)]. Women showed lower risk of any CV event [OR: 0.30 (0.14-0.65, p=0.002)].

MS prevalence and CHD risk were high among patients with schizoaffective disorder treated with antipsychotics. Gender, age and poor disease control could be associated with CHD risk.

*On behalf of the CLAMORS Collaborative Group.

In elderly schizophrenia patients remission is difficult to determine due to long disease duration, exposure to differing treatments, long-standing side-effects, non-adherence, cognitive decline and physical co-morbidity.

Retrospective chart review of elderly (60+ years) schizophrenia patients admitted to a university affiliated tertiary psychiatric center. Patients were experiencing an exacerbation at admission. Remission criteria were as defined by the APA's “Remission in Schizophrenia Working Group”. Clinical status and improvement were quantified using the Clinical Global Impression scale.

During 2006 forty-eight elderly schizophrenia patients were admitted to our center. of these, 25 patients were treated with long-acting risperidone (LAR), 18 women and 7 men, mean age 72 years (range: 62-81), mean disease duration 30.4 years (range:14-42) and mean number of previous hospitalizations 8.9 (range:1-21). Co-morbid physical illness was present in 12 patients (hypertension, diabetes, CHF and hypothyroidism). of 25 patients treated with LAR, 19 (76%) continued uninterrupted treatment for 6 months or longer. in 6 patients treatment was discontinued due to insufficient response. All patient's (N=25) clinical severity ratings with the CGI-S were in the range of 5 to 7 prior to treatment. Following 6 months of LAR treatment, mean dose 36.0 mg/2 weeks (range: 25-50), 18 patients were rated as “improved” or “very much improved” on the CGI-I scale. in 15/25 patients (60%) symptomatic remission was achieved.

LAR may be effective in achieving remission among elderly schizophrenia patients. Tolerability was high and adherence rates improved. the inherent bias in a retrospective analysis need temper our observations.

Risperidone (RISP) may induce both elevated prolactin (PRL) levels and weight gain. the aim of this study was to evaluate body weight and mass index (BMI), and PRL modifications in schizophrenic patients treated for 1 year with long-acting risperidone (LAR).

Body weight and BMI (calculated as weight in kilograms divide by height in meter squared) were determined at baseline and at endpoint in 19 schizophrenic patients (9 men and 10 women; mean[SEM] age 33.4[2.9] years). PRL levels were determined at baseline, after oral risperidone treatment (mean length of treatment: 79[30] days; mean dose: 5.8[0.5] mg daily) and during a 12 month treatment with LAR (mean dose: 50[10] mg every 2 weeks; PRL levels were measured before each injection).

At endpoint, a significant weight gain (Δweight: 8,1[1,4] kg) and BMI (ΔBMI: 2,9[0,5] kg/m²) was observed (both p< 0.0002). Compared with baseline, PRL levels were significantly increased (p< 0.0007; mean ΔPRL: 33[8] ng/ml). There was an association between ΔBMI>1,5 kg/m² and ΔPRL>40 ng/ ml (p< 0.04). Moreover ΔBMI was linked to the length of treatment (rho=0.47; n=19; p< 0.05).

Our results suggest a link between weight gain and long term hyperprolactinemia in patients treated with LAR. It has been hypothesized that PRL may have a role in the regulation of food intake by increasing leptin synthesis and secretion.

Risperidone is the first atypical antipsychotic available in a long-acting injection formulation. in United Kingdom, it is licensed for use in treatment of psychosis in patients tolerant of oral Risperidone. the Summary of Product Characteristics clearly defines the methods of initiation and titration.

We performed a naturalistic observational study of 61 patients suffering with psychosis. the cohort comprised patients being prescribed Risperidone long-acting Injection (RLAI) within various Community Mental Health Teams and Assertive Outreach Team of the Trust. the data was collected related to three broad areas: reasons for choice of RLAI, initiation and titration of RLAI, continuation of RLAI.

• • 35/61 patients have been prescribed oral atypical antipsychotic (including 16/61 being prescribed oral Risperidone) prior to the injectable formulation and 3/61 had received Clozapine.

• • In 12/61 non-compliance was suspected and only 11/25 patients stated a preference for an injectable formulation.

• • 33/61 received oral supplementation during initiation.

• • 29/61 were initiated on dose of RLAI commensurate with the current dose of oral Risperidone

• • In 35/61, dose was changed in less than 4 weeks intervals.

• • 43/61 continued to receive RLAI. 18/61 discontinued due to patient refusal (6/18), patient not tolerated (3/18), not effective (2/18), patient non-attendance (1/18), patient moved area (1/18), other reasons (2/18), no reasons specified (3/18).

Prescribing of RLAI did not follow recommendation from manufacturers during initiation and titration. Non-Compliance with previous medication was main reason for use of RLAI. However, discontinuation with RLAI was primarily related to refusal/intolerance of treatment.

Delirium occur frequently in hospitalized patients. High-potency antipsychotic drugs have been used for the treatment of delirium; however, there is a risk of acute side effects. Therefore, atypical antipsychotic drugs could be used to the treatment of delirium.

The present study aimed to provide comparison of intramuscular injection of olanzapine and intramuscular injection of haloperidol for patients with delirium was conducted with a randomized, open prospective study.

Sixty-two patients admitted at the Catholic University of Korea Kangnam St. Mary's hospital, Seoul, South Korea were enrolled in this study. They were diagnosed as delirium by two independent psychiatrists using DSM-IV-TR. the Delirium Rating Scale-revised-98(DRS-R-98) and clinical global impression-severity (CGI-S) were checked daily. the Simpson-Angus Rating Scale, the Barnes Akathisia Rating Scale and the Abnormal Involuntary Movement Scale were used for the assessment of side effects.

The DRS-R-98 and CGI-S scores were significantly decreased over time in both treatment groups without any significant group difference and time by the group interaction effect (F=28.35, P< 0.0001). Adverse events occurred lower in olanzapine group. both treatments were well tolerated and there were no serious adverse events occurred by intramuscular olanzapine or haloperidol.

This study showed that either intramuscular olanzapine or intramuscular haloperidol would be effective and tolerable for treating delirium, however, olanzapine showed lower side effects than haloperidol. Adequately powered studies will be mandatory to draw any definite conclusion.

Quetiapine induced hypothyroidism is a rare side effect requiring either drug discontinuation or initiation of thyroid replacement therapy. We highlight the potential reversibility of quetiapine induced hypothyroidism in two such cases.

Two case reports.

Case 1.Quetiapine (200mg/day) was initiated to a psychotic female patient due to exaggeration of positive symptomatology. Although her thyroid function tests (TFTs) upon admission were normal after a month significant decreases in T3 and T4 level and an elevation in TSH was observed. 45 days later the TFT returned to normal, although she remained on quetiapine. Case 2. Quetiapine (300mg/daily) was prescribed to a bipolar male patient due to a mixed affective episode with a very good response. Despite his normal admission TFTs, three weeks later a decrease in total T4 and a marked increase in TSH was observed .45 days later, although no measures were taken, TFTs returned within reference range.

These are the first cases reporting reversibility of quetiapine induced hypothyroidism. TFTs alterations are dose related, relatively slight and linked to a positive history of thyroid abnormality. Our patients did not fulfil any of these criteria. Besides, hypothyroidism resolved although the antipsychotic therapy was continued and no thyroid replacement therapy was given. We suggest a careful thyroid monitoring for patients initiating quetiapine. However, physicians should wait in cases of thyroid dysfunction, since thyroid dysregulation may soon be resolved.

Recently, there is an interest on the possible association between quetiapine and hypothyroidism. the aim of this study is to critically review all the reported cases in the international literature.

A Medline search for all studies dealing with quetiapine induced hypothyroidism was carried out from January 1997 to June 2008.

Published literature on quetiapine's impact on thyroid function consists of 1 double-blind study, 1 observational study, 2 open studies, 3 case reports and data from the product monograph. A study on elderly psychotic patients revealed only small decreases in T4 levels, while another one in adolescents show trends for decrease in T4 and a marked increase in TSH. an observational study of thyroid function in patients treated with quetiapine and other antipsychotics, found a decrease in T4 with no changes in TSH and T3 and another one only slight increases in TSH. in the case reports all patients excibited clinical hypothyroidism. in one case there was a positive history for hypothyroidism, while in another one the patient had experienced lithium induced hypothyroidism in the past. According to quetiapine manufacturer 0.4% of the patients experienced TSH increases with half of them requiring thyroid replacement treatment. in studies, where quetiapine was adjunct to lithium or divalproate, 12% of patients had elevated TSH levels.

We suggest a careful thyroid monitoring for patients initiating quetiapine, since hypothyroidism may emerge and masquerade psychopathologic manifestations. However, there is an open question whether thyroid dysfunction is a permanent or reversible condition.

Long-acting depot antipsychotic medication is associated with extrapyramidal side effects (EPS). This may reduce adherence to medication, and precipitate relapse (1). Clearly, EPS is a major drawback and early detection is essential. However, in an earlier review of patients’ medical notes, we identified only one patient with an examination that recorded the presence of EPS. Despite the fact that a number of rating scales are available. We proposed that the application of these rating scales, would allow us to improve the assessment of EPS.

All patients prescribed a depot antipsychotic or long-acting risperidone injection, were identified. the Barnes Akathisia Scale (2) was chosen to rate akathisia, a modified Simpson-Angus scale (3) was chosen to rate parkinsonism and the Abnormal Involuntary Movement Scale (4) was chosen to rate tardive dyskinesia.

A total of 43 patients were evaluated. 23 (53%) patients showed drug induced EPS. the total number of positive cases of akathisia was 12 (28%), and 10 (23%) patients were found to have tardive dyskinesia. 13 (30%) patients were found to have drug induced parkinsonism.

Our screening programme has identified high rates of previously undiscovered drug induced EPS.

Clozapine remains the gold standard of treatment for schizophrenic patients with treatment-resistant symptoms. Sometimes patients develop unusual hematological reactions with increased mostly red blood cells, which rises differential diagnostic issues: is it a side effect of clozapine treatment or is it a primary medical condition?

To elucidate the etiology of the hematological disturbances in order both to control psychotic symptoms as well as to maintain an optimal somatic profile of the patient.

41 years female with a long history of schizophrenia became refractory of treatment, so clozapine was instituted as treatment of first choice. by monitoring paraclinical parameters we found progressive increased of the blood cells, mainly red blood cells, which has un unpredictable risk for somatic complications. We approached this case by interdisciplinary management-psychiatric and hematological to find the etiology of this peculiar comorbid condition.

The evaluations performed led us to the conclusion that there are two different nosologic entities, treatment of the psychiatric condition revealing polycythemia vera. This conclusion required reducing clozapine dose and adding another atypical antipsychotic. All subsequent evaluations demonstrated the efficiency in managing the psychiatric disorder and even an improvement in hematological condition.

Treatment-resistant schizophrenia remains a challenge for psychiatrists, clozapine treatment requiring for an active monitoring because it can be a trigger for an unusual somatic disease-polycythemia vera.

Data pertaining to changes in weight during long-term treatment with quetiapine (QTP) have been published previously (1).

Pooled data are presented from 26 short-term clinical studies (up to 12 weeks) of QTP or quetiapine extended-release (QTP XR)-as monotherapy or adjunct therapy-conducted by AstraZeneca up to November 2007. Studies were conducted in adult patients (18-65 years) across a number of psychiatric diagnoses. Variables were analyzed irrespective of fasting status with similar analyses planned in the fasting subset. LSM changes from baseline for the difference between QTP and placebo are presented.

Approximately 10000 patients were included in the analyses, 70% of whom were treated with QTP or QTP XR. Across the entire short-term dataset, the difference in LSM change in weight for QTP vs. placebo was 1.07 kg. Corresponding differences in glucose regulation parameters were 1.39 mg/dL for glucose and 0.04% units for HbA1C. the overall difference in total cholesterol was 5.48 mg/dL, with differences in HDL and LDL cholesterol of -0.62 mg/dL and 1.69 mg/dL. the difference in LSM change in triglycerides was 22.62 mg/dL.

Within the context of balancing potential risks against the acknowledged benefits of atypical antipsychotics, the degree and significance of variations in metabolic parameters is an area of continued interest. This analysis helps clinicians to better understand changes in important metabolic parameters across trials with QTP and QTP XR, and the size and uniqueness of the dataset permits further analyses within this important area.

Supported by funding from AstraZeneca Pharmaceuticals LP.

Prolongation of myocardial repolarization, i.e. lengthening of the QTc interval on surface electrocardiogram, with increased risk of cardiac arrhythmias, has been recognized as a side effect of many drugs. Most conventional and atypical antipsychotic drugs can cause dose-related prolongation of QTc, although there are important differences in the potency of individual agents. Antipsychotic polipharmacy increases the risk for sever cardiac side effects.

In this prospective clinical investigation, we analyzed ECGs in 46 patients suffering from schizophrenic disorder who were treated with different antipsychotic drugs one week after the admission to the psychiatric hospital. Hearth rate, QT interval and QTc interval were assessed. the average daily dose of prescribed antipsychotic drugs was calculated and transformed to chlorpromazine units.

Average QTc interval in patients undergoing our clinical investigation was 417 msec, only 3 out of 46 (6,5%) patients had QTc over 450 msec and only one patient (2,2%) had QTc over 500 msec.

We found no differences in QTc interval between patients who were treated either with conventional or atypical antipsychotic or with combination of both, and no gender differences for QTc interval were found.

Our results raise the question of the clinical relevance of a single ECG for diagnostics of cardiac complications in schizophrenia patients and suggest the need to conduct ECG monitoring in patients with high risk for cardiac complications during antipsychotic treatment.

Antipsychotic medications are registered for the use in psychosis, mania and agitation. the aim of our study was to assess the off-label use of atypical antipsychotics (AA) at the Crisis Intervention Unit (CIU).

Hospital records of 280 patients that were treated at the CIU in year 2007 were included to the observational study. Patients were screened for diagnosis (ICD-10), gender, age, suicidal behaviour and for prescribed psychotropic medications. Off-label use of atypical antipsychotics for diagnoses other than psychosis was evaluated.

Most hospitalised patients suffered for stress related disorders: adjustment disorder F43.2 (34%), acute stress disorder F 43.0 (2%), mixed anxiety-depression disorder F41.2 (19%), depression (24%), anxiety disorders (4%) and other disorders (17%). Patients were treated with antidepressants (92%), benzodiazepines (55%), hypnotics (44%) and mood stabilising drugs (9%) during their stay at the CIU. at discharge from hospital benzodiazepines (31%) and hypnotics (12%) were prescribed in lower percentages. 51% of patients received AA at least once during their stay at the CIU, 49% received AA for off-label use and it was prescribed for most of the hospital stay (for 87% of the time). Average daily CPU at admission to the hospital was 107.52 and at the discharge it was 100.33. No significant differences were noted among the different diagnoses for off-label AA use.

Atypical antipsychotics are widely used for indications other than psychosis, even though the long-term effects of their use are not yet known and safety issues remain to be examined further.

To assess frequency and baseline factors associated with adherence with antipsychotic medication during long-term treatment in outpatients with schizophrenia.

SOHO is a 3-year, prospective, observational study that included 10 972 patients changing or starting a new antipsychotic medication Treatment adherence during 4 weeks prior to the visit was assessed at each visit by participating psychiatrists as:

• • the patient has not been prescribed medication;

• • the patient almost always adheres;

• • the patient adheres half of the time; and

• • the patient never adheres to antipsychotic medication.

6731 patients with at most one missing visit were analysed. Data from the missing visit were imputed from the previous visit; 71.2% were considered to be adherent and 28.8% non-adherent over the 3-year follow-up period. the strongest predictor of medication adherence during follow-up was adherence at baseline (OR = 4.01, 95% CI: 3.46-4.64). other baseline predictors of adherence included not using antipsychotics in the previous 4 weeks, receiving treatment for first time, being socially active, and a higher body mass index. Baseline predictors of non-adherence were alcohol dependence, substance abuse, hospitalisation in previous 6 months, living independently housing and having hostile behaviours.

Alcohol dependence, substance abuse and living independently were associated with non-adherence. Previous adherence, being socially active and receiving medication for the first time was associated with better adherence. Limitation: medication adherence was assessed by the psychiatrist through a single item question.

To evaluate dyslipidaemia risk among patients with schizophrenia treated with aripiprazole or olanzapine.

Pooled analysis of the aripiprazole clinical database, including studies of ≥7 days with at least an oral aripiprazole monotherapy arm. Mean changes from baseline to endpoint and shifts from normal to abnormal lipid levels were calculated.

Seventeen placebo- and five olanzapine-controlled studies (3 weeks->3 years) of adult patients (≥18 years) were included. Mean changes (LOCF) in lipids were similar between aripiprazole and placebo for all lipid parameters; aripiprazole showed significant improvements versus olanzapine (p≤0.01). the incidence (OC) of switching to abnormal lipid levels from baseline normal was similar between placebo and aripiprazole, and significantly lower with aripiprazole than olanzapine for most measures.

Despite limitations inherent to pooled analyses, these findings lend further support to the differential profile of atypicals, with aripiprazole showing effects on lipids comparable with placebo.

Clozapine is the drug of choice for patients with treatment-resistant schizophrenia. However a minority of them have been unable to continue with Clozapine due to side-effects, for example rash. This report looks at the use of graded desensitization in a patient who developed cutaneous reactions to Clozapine.

This report describes the management of a patient with treatment resistant-schizophrenia, mild learning disabilities and epilepsy, following a cutaneous reaction to Clozapine. Having been maintained on Clopixol depot until 4 years ago, he required a change in antipsychotics following a relapse of psychotic symptoms. He was then treated unsuccessfully with various anti-psychotics, before starting Clozapine, to which he showed a good response. Unfortunately he developed an eczematous rash on two separate occasions when the drug was introduced. Again he was tried on other anti-psychotics, to which he also developed a rash. He was then put on a graded desensitization regimen of liquid Clozapine.

Graded desensitization, using incremental increases in drug dose, allowed maintenance treatment with therapeutic doses of Clozapine to be achieved in the absence of cutaneous hypersensitivity reactions. the patient's previously treatment-resistant psychotic symptoms were improved by this method.

We should be aware of possibilities for the management of both the common and uncommon side-effects associated with Clozapine, as the result might vastly improve the patients’ quality of life. Desensitisation regimens can be an effective means of overcoming drug hypersensitivity but should be used with great caution, especially when patients exhibit delayed-type hypersensitivity reactions.

The ConstaTRE study was designed to compare long-term relapse in stable patients treated with risperidone long-acting injectable (RLAI) or the oral atypical antipsychotic quetiapine.

This was a randomized, open-label, prospective, active-controlled, multicenter, 2-year trial in symptomatically stable patients with schizophrenia or related disorder who were switched from stable treatment with oral risperidone, olanzapine, or oral conventional antipsychotic to RLAI or quetiapine. Primary efficacy measure was time-to-relapse. Positive and Negative Syndrome Scale (PANSS) scores and safety (adverse events [AEs] and Extrapyramidal Symptom Rating Scale [ESRS]) evaluations were reported.

710 patients were randomized (n=355 per group), with 666 patients (n=329 RLAI and n=337 quetiapine) being evaluable. Mean doses were 32.8±8.0 mg every-two-weeks for RLAI and 396.8±141.9 mg/day for quetiapine. Kaplan-Meier analysis indicated a significantly longer relapse-free period with RLAI treatment (log rank: p< 0.0001). Relapse occurred in 16.5% of RLAI and 31.3% of quetiapine patients. Mean duration of treatment was 483.8±277.8 and 400.7±290.6 days for RLAI and quetiapine, respectively. Total PANSS scores improved significantly from baseline to endpoint for the RLAI-treated group (p< 0.001). the endpoint difference favors RLAI over quetiapine (p< 0.001). Treatment-emergent AEs were similar between groups. ESRS total scores decreased for both groups. Possibly prolactin-related AEs occurred more often with RLAI than quetiapine (4.6% versus 1.5%, respectively). Somnolence was reported less often with RLAI than quetiapine (1.8% versus 11.3%, respectively).

Time-to-relapse was significantly longer and relapse rates were significantly lower for RLAI compared with quetiapine. both treatments were well tolerated.