Most of the reported Olanzapine induced leukocytopenia cases are generally associated with elderly or other metabolic diseases. We present a 23 years old female diagnosed as obsessive compulsive disorder (OCD) in whom neutropenia developed due to Olanzapine.

The patient, who had diagnosis of OCD for three years and was treated with SSRIs previously, stopped drug intake few months ago. Symptoms of OCD exacerbated and additionally psychomotor agitation, irritability, rejection of treatment and persecutory thoughts started. She was hospitalized and Olanzapine 5 mg/d, Lorazepam 3mg/day were ordered. At the admission day the routine hematological and biochemical laboratory exams were in normal ranges. Olanzapine dosage was titrated up to 15mg/d in four days and psychotic features recovered on a large scale. Neutropenia was noticed at the sixth day of medication and Olanzapine was immediately stopped and Lorazepam was continued. No clinical signs of an infection occurred. After discontinuation of Olanzapine the blood cell counts started to increase at the first day and turned back to normal ranges at the sixth day. No special treatment was necessary. Psychiatric symptoms were remitted partially with Sertralin 200mg/g in 4 months.

Although the hematological effects of Olanzapine are still not clear exactly in this case the only probable agent to cause neutropenia is Olanzapine in young patient with no metabolic problems. Such a case would stress the importance of monitoring the patients while using antipsychotics whether they had a risk factor or not.

To assess the effects of clozapine, olanzapine and haloperidol on cholesterol triglycerides and glucose levels in aggressive schizophrenic patients. To determine whether changes in cholesterol are related to aggression.

100 physically aggressive schizophrenics were assigned to a randomized, double-blinded, parallel-group, 12-week treatment. There were 33, 34, and 33 subjects in the clozapine, olanzapine, and haloperidol groups, respectively. Fasting cholesterol, triglycerides and glucose were collected at baseline and at end of study. All aggressive events were recorded.

95 patients provided blood samples. There were differences among the three medications in weight change (F=7.6, df=2,93; p<.001), with greater weight gain for clozapine and olanzapine than haloperidol. There were significant differences among the 3 groups in changes in cholesterol (F=4.5, df=2,93; p=.01; greater increase for clozapine than for haloperidol, p <.01), triglycerides (F=5.5, df=2,93; p<.01; greater increase in clozapine than haloperidol, p <.01 and olanzapine p=.01) and glucose (F=3.9, df=2,93; p=.02; greater increase for clozapine than for haloperidol, p <.01 and than olanzapine, p=.05). We investigated the relationship to aggression, by dividing patients into high and low cholesterol groups through a median split. Patients in the low cholesterol group were more physically aggressive during the study than those in the high group (F=4.94, df=2,92, p=.03). A significantly higher percentage of the patients in the haloperidol group than in the clozapine group had values below the median.

Clozapine treatment is associated with increases in serum glucose, triglycerides and cholesterol. This increase in cholesterol may explain in part its antiaggressive effect.

Assess illness remission in patients with schizophrenia enrolled in the electronic-Schizophrenia Treatment Adherence Registry (e-STAR) in Czech Republic and Slovakia.

e-STAR is a secure web-based, ongoing, international, long-term observational study of patients with schizophrenia who initiate RLAI during routine clinical management. Data is collected retrospectively (1 year) and prospectively (2 years). Prospectively patients are evaluated for the following symptoms: delusions, conceptual disorganization, hallucinatory behaviour, mannerisms and posturing, unusual thought content, blunted affect, passive/apathetic social withdrawal, and lack of spontaneity and flow of conversation. Patients in whom all of these symptoms are absent, minimal or mild and within normal boundaries, stable, and do not interfere with thinking, social relations, and behaviour or functioning, were considered to be in cross-sectional remission and if this persisted for at least 6 months, they were considered to be in remission.

1,068 patients have been enrolled into e-STAR in Czech Republic and Slovakia; 280 patients have been followed for at least 12-months and were included. The majority were male (57.9%) with a diagnosis of schizophrenia or schizoaffective disorder (85.7%, 14.3% respectively) with a mean age of 37±12.1 years and a mean time since diagnosis of 9.2±9 years. The proportion of patients who met the criteria for cross-sectional remission increased from 2.4% at baseline to 37.9% at 12 months. After 12-months, 20.6% of patients met the criteria for illness remission.

Based on 12-month interim results, the proportion of patients who met the criteria for illness remission increased after initiating RLAI.

To assess changes in illness severity (Clinical Global Impression-Severity scale, CGI-S) and functioning (Global Assessment of Functioning, GAF) in patients initiated on risperidone long-acting injection (RLAI) during routine clinical practice and followed up for at least 12 months in the Netherlands.

e-STAR is an international, prospective, observational study of patients with schizophrenia who have been initiated with RLAI. Data are collected both retrospectively (1 year) and prospectively (2 years). Results presented in this report were based on data from patients with at least 12 months of available data in the Netherlands.

There are 190 patients currently enrolled in the Netherlands and 118 patients have at least 12 months of available data. Of the 118 patients, the majority were male (62.7%) with a mean age of 37.7±11.5 years and a mean time since schizophrenia diagnosis of 11.1±21.5 years. The main reasons for switching to RLAI were lack of compliance (42.4%), adverse events (25.4%) and lack of efficacy (24.6%) with previous therapy. At 12 months, 66.9% of patients were still on RLAI treatment. Of the patients who discontinued RLAI, the mean time to discontinuation was 157.8±76.5 days. Mean CGI-S score significantly improved from 4.05±1.14 at baseline to 3.15±1.38 at 12 months (p<0.001). Additionally, the mean GAF score significantly improved from 43.8±12.0 at baseline to 55.2±14.7 at 12 months (p<0.001).

These interim results showed that treatment with RLAI in patients with schizophrenia was associated with significant improvements in disease severity and functioning.

To evaluate patient and physician satisfaction with risperidone long-acting injection (RLAI) in patients with schizophrenia enrolled in the electronic Schizophrenia Treatment Adherence Registry (e-STAR) in Belgium.

e-STAR is an ongoing, international, prospective, observational study of patients with schizophrenia who start RLAI during their routine clinical management. Treatment satisfaction was assessed by the patient and physician on a 5-point scale from ‘very good’ to ‘very bad’.

135 patients with mean age 40.9±14 years and duration of illness 9.5±9.2 years initiated treatment with RLAI, followed-up for at least 18 months were included in this analysis. At baseline, only 29.2% of patients expressed “good” or “very good” satisfaction while 21.1% of them expressed “bad” or “very bad” with their previous treatment. Similarly at baseline, 38.2% of physicians reported “good” or “very good” level of satisfaction and 14.6% rated their satisfaction as “bad” or “very bad” at that time. After initiation of RLAI, both patient and physician satisfaction with treatment improved dramatically. At 18 months, 76.5% of patients were satisfied (‘good’ or ‘very good’) with RLAI treatment and only 2.4% felt ‘bad’ and none reported ‘very bad’. Physicians also expressed satisfaction with RLAI with 82.1% of them rated it as ‘good’ or ‘very good’. Only one physician reported satisfaction below ‘moderate’.

The low levels of patient and physician satisfaction with treatment prior to RLAI are likely to be a key decision driver to change therapy. After starting treatment with RLAI, both patient and physician satisfaction with the treatment substantially improved.

RGH-188 is an orally active, potent dopamine D3/D2 receptor antagonist/partial agonist atypical antipsychotic for the treatment of schizophrenia and bipolar mania.

RGH-188 displayed high affinity to human D3 receptors (Ki: 0.085 nM) and approximately six- and thirty-times less affinity to human D2, and 5-HT1A receptors. In various in vitro and in vivo assays RGH-188 behaved either as an antagonist or as a partial agonist on dopamine D3 and D2 receptors.

RGH-188 displayed potent antipsychotic activity (0.1-0.8 mg/kg) in rodent models such as apomorphine-induced climbing, amphetamine- and phencyclidine-induced hypermotility, conditioned avoidance response. It significantly improved the learning performance of rats (0.02-0.2 mg/kg) impaired by scopolamine in a water-labyrinth learning paradigm. RGH-188 showed no EPS liability as it produced no catalepsy up to 100-fold therapeutic range.

In a nonhuman primate positron emission tomography (PET) study using 11C-raclopride RGH-188 occupied striatal D2/D3 receptors in a dose dependent and saturable manner with an ED50 of 7 μg/kg iv. In healthy male subjects multiple administration of 1 mg RGH-188 resulted in over 70% D2/D3 receptor occupancy and the displacement showed correlation with RGH-188 and metabolites plasma levels.

After single administration to healthy volunteers, Tmax for RGH-188 was 3-4 hours and the terminal disposition half-life was 5-6 days. Over the dose range of 0.5-2.5 mg AUC of the parent drug was approximately dose-proportional. Systemic exposure to the pharmacologically active metabolites, desmethyl- and didesmethyl-RGH-188 was 20-30% and 50-200% of that to the parent, respectively.

To study the different effects of clozapine and its metabolites on the intracellular Ca2+ concentration([Ca2+]i) in cells of isolated rat islets.

Under low or high glucose (3.3 mmol/L or 16.7 mmol/L), the cells of isolated rat islets was treated with 1 mmol/L clozapine, desmethyl-clozapine and clozapine N-oxide respectively, blank control group was also set, [Ca2+]i represented by fluorescence intensity was measured by laser scanning confocal microscope after cells were loaded with calcium sensitive fluorecent indicator Fluo-4/AM.

Under low glucose, as compared with the blank control group, inhibitive effect on [Ca2+]i in cells was found in clozapine group and desmethyl-clozapine group respectively (P<0.01); As compared with the base line(0min), [Ca2+]i in cells was decreased according to the prolonging of time in clozapine group and desmethyl-clozapine group (P<0.05; 0.01), and the inhibitive effect of clozapine was more intensive than desmethyl-clozapine (P<0.01). Under high glucose, as compared with the blank control group, inhibitive effect on [Ca2+]i in β-cells was also found in clozapine group and desmethyl-clozapine group respectively (P<0.01); As compared with the base line(0min), [Ca2+]i in cells was also decreased according to the prolonging of time in clozapine group and desmethyl-clozapine group (P<0.05; 0.01), but the inhibitive effect of desmethyl-clozapine was more intensive than clozapine (P<0.01). However, no effect was found in clozapine N-oxide group under low or high glucose (P>0.05).

Clozapine and desmethyl-clozapine both inhibit [Ca2+]i in cells of isolated rat islets so that they can inhibit insulin secretion.

This study investigated the point prevalence of extrapyramidal movement disorders in patients with chronic schizophrenia and related disorders who are currently treated by Northland District Health Board (DHB) mental health services, New Zealand. The study also investigated evidence of variation in the point prevalence of these disorders based on the ethnicity of the patients (indigenous Māori patients and non-Māori).

151 patients, who had received antipsychotic medication for 3 months or more, were recruited as participants for the study using randomised computer software. Ethnicity was documented using self-identification. Akathisia was assessed using the Barnes Akathisia Rating Scale (BARS). The Abnormal Involuntary Movement Scale (AIMS) was used to assess tardive dyskinesia and extrapyramidal side effects (EPSE) were assessed by the Simpson-Angus Rating Scale (SAS).

9.3 % had akathisia using Barnes scale, 43% had Parkinsonian symptoms on SAS scale, and 18.5 % had tardive dyskinesia using AIMS scale. The analysis failed to show any statistically significant differences based on ethnicity (indigenous Māori and non-Māori). P = 0.284, 0.176, and 0.201 for Barnes, SAS and Aims respectively.

The findings suggest that the prevalence of neuroleptics-induced movement disorders in psychotic patients within Northland DHB (9%-43%), is similar to the documented international figures. These findings also indicate that there is no significant difference based on ethnicity between Māori and non-Māori in terms of movement disorders profile.

Venous thromboembolism (VTE) has been associated with the diagnosis of a psychiatric disease, as well as with the treatment with psychotropic drugs. Recent reports suggest an association between several atypical antipsychotics agents (eg. olanzapine) and an increased risk for VTE.

We prospectively analysed and consequently followed-up olanzapine users in a cohort of 138 consecutive patients under 60 years of age (male=72, mean age 45 years) suffering from objectively confirmed VTE over a three-year period (2004 - 2006). Data on known acquired or genetic risk factors for VTE were recorded for each patient.

Four Caucasian patients (one female, three males; mean age 49 years, range 37-55 years) with spontaneous VTE treated with olanzapine were registered. Two patients were obese. The hospitalization was extended in the female patient. We found coagulation abnormalities in all our subjects (elevated levels of factor VIII:C, mild hyperhomocysteinemia, FV Leiden and prothrombin gene G20210A mutations).

These cases indicate that VTE might be associated with the use of olanzapine, at least in the presence of several acquired or inherited risk factors such as immobilization, obesity and disorders of coagulation homeostasis including factor V Leiden, prothrombin gene G20210A mutations, high levels of factor VIII and hyperhomocysteinemia. Subjects treated with olanzapine should be monitored clinically for VTE. Interestingly, in three patients symptoms occurred in the first six months of olanzapine treatment.

We considered a sample of 35 epileptic patients (21 male and 14 female) with psychotic features, treated with specific antiepileptics and atypical antipsychotics (risperidone, olanzapine, quetiapine). It is well known that DA mediators partially inhibit motor seizures.

During one year, none of our patients related any increase of the frequency of seizures. Also, we did not highlight electroencephalographic changes in this period. Clinically, patients were assessed using PANSS scale.

Atypical antipsychotics can be safety utilized in patients with epilepsy, ascertaining a good control of psychotic features, without worsening neurological symptomatology.

The evaluation of the differential neuroprotective action of antipsychotics, objectivized through the alteration of hippocampal and prefrontal structures in an experimental study at Common Wistar rats. The neurobiological model of the glucorticoid aggression is validated on the animal model for stress.

We formed 10 study lots each constitued of 5 male adults rats, weighting 200-250 g, held through the study duration (10 days) in temperature, humidity, food and ambient stressless conditions. The studied substancies were administrated intraperitoneal, daily, for 10 days, saline solution equivalent to: olanzapine (0.15mg/kg/day) and ziprasidone (1.25mg/kg/day) single dose at 20:00 hours and haloperidole (0.20mg/kg/day), dexametasone (0.20mg/kg/day) and sulpiride (8mg/kg/day) in two equal doses, at a 12 hour interval (08:00 – 20:00).

The rats were sacrificed during the 10th day, at 6 hours after the last substance administration. The sample brain was histopathologically processed and studied with optical microscopy.

Frontal cortex and hippocamp were the most intensely affected to the haloperidole and dexametasone in contrast with atypical antipsychotics (sulpiride, ziprasidone, olanzapine), presented significant lesser structural changes in frontal cortex and hippocamp.

The lots treated with dexametasone and sulpiride and dexametasone and ziprasidone are lesser affected at the cerebral structure level than the dexametasone and olanzapine treated lot.

Haloperidole has a significant decrease in neuroprotection.

Atipical antipsychotics demonstrated an neuroprotective effect.

The dexametasone animal model of stress is similar to the clinical model of schizophrenia evolution with multiple relapses in wich neuroprotection seems to be significantly altered.

Clozapine is the first atypical antipsychotic with main indication in the treatment of refractory schizophrenia. The aim of this study was to explore clinical response to clozapine in patients with schizophrenia non-responsive to other antipsychotics and who also have symptoms of depression.

The descriptive retrospective study included 25 patients on clozapine followed up for 6 months period with clinical scales: BPRS and PANSS.

The achievments obtained and described in remission of symptomatology and improvement in quality of life. A significant reduction in rehospitalization is reported and also in the use of services of psychiatric emergencies.

This form of treatment is beneficial and most appropriate for patients with refractory schizophrenia and depressive symptoms.

The introduction of second generation antipsychotic (SGA) drugs represents a major advance in the treatment of schizophrenia. Concerns about the metabolic and cardiovascular adverse effects of the SGA, as opposed to first generation antipsychotic (FGA), have been disseminated. The benefits and risks of SGA have been studied with a focus on particular organ systems. Cardiovascular diseases are the leading cause for death in development countries. Weight gain and drug dependence are the risk factors for cardiovascular disease.

Concurrent comorbidity has become the rule among psychiatric inpatients. Unfortunately the majority of the clinical trials with SGA exclude the Dual Diagnosis patients (DDP). There is no evidence for examination of weight change during risperidone long-acting injectable (RLAI) treatment in DDP.

To compare the weight change in RLAI versus FGA-LAI treatment of DDP.

Twenty two DDP (21 (95.4%) males) meeting DSM-IV criteria for Schizophrenic spectrum disorders (median age=29 years [range, 21-39 years]).

BMI was determined by the dividing of weight by the square of height. The BMI was calculated for DDP who were treated by FGA-LAI or by RLAI treatment at baseline and after a period of 3 months.

There were no significant differences between the groups before the treatment (NS). There was no significant weight change as opposed to baseline in each of the groups (NS).

Treatment of DDPs with RLAI is safe and does not increase the middle-term risk of weight change.

Clozapine is still the drug of choice for patients with schizophrenia. However, there are still many patients not having a satisfied response to clozapine. In these patients clozapine is very often combined with other antipsychotics but the evidence for these combinations is poor. Due to the receptor profile of clozapine, the augmentation drug should be a non-sedating drug with no muscarinergic affinity and still have a low propensity to cause EPS. Sertindole has not been investigated as an augmentation drug to clozapine.

We present a 29 year old man with a treatment resistant schizophrenia. Currently he was treated with 400 mg of clozapine with a suboptimal response but was not able to tolerate a higher clozapine dose due to sedation. Sertindole 16 mg was instead added.

The baseline PANSS total score was 123 and after 12 weeks it was reduced to 90. No subjective or objective side-effects were seen.

Sertindole might be an ideal augmentation drug to clozapine due to the receptor profile but whether the combination is beneficial needs to be determined in a randomized double-blinded placebo trial.

Antipsychotic medications are used for the treatment of schizophrenia and other psychotic disorders. The aim of our study was to assess the off-label use of atypical antipsychotics (AA) in the Crisis Intervention Unit (CIU), Ljubljana, Slovenia.

Hospital records of 105 consecutive patients that were admitted to the CIU in the period of 4 months (June – September 2007) were included to the retrospective observational study. Patients were screened for diagnosis (ICD-10), gender, age, suicidal behavior and for prescribed psychotropic medications. Off-label use of atypical antipsychotics for diagnoses other than psychosis was evaluated. We noted which specific antipsychotics were prescribed for specific diagnoses with their daily dosages transformed to chlorpromazine units (CPU).

Most patients suffered for stress related disorders (48%), depression (32%), anxiety disorders (14%) and other disorders (6%). Gender ratio was in favour of women (77%). Average age of patients was 52,1 years. 27% of patients were admitted after the suicide attempt, 46% reported suicidal thoughts. Off-label use of AA was noted in 65% of patients who suffered from stress related disorders, in 36% of patients with depression and in 49% of patients with anxiety disorders.

Our results show that 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 compare the relative effectiveness and tolerability profile, in terms of Number Needed to Treat (NNT) for all causes of medication discontinuation and Number Needed to Harm (NNH) for 7% of increased of body weight of olanzapine, risperidone, typical (oral and depot) and other atypical antipsychotic medications (quetiapine and amisulpride) in previously untreated outpatients with schizophrenia during 36-month follow-up.

NNTs (NNHs) mean the number of patients needed to be treated with one antipsychotic instead of another to prevent (produce) one negative outcome.

Previously untreated patients with schizophrenia were defined as patients who i) had never received antipsychotic treatment for schizophrenia and ii) had not received antipsychotic treatment in the 6 months prior to study inclusion. Rate of medication discontinuation for any cause during the 36 months post initiation was calculated for olanzapine (28.9%), risperidone (36.2%), typicals (44.5%) and other aypicals) (34.7%). Cox and logistic regression models were employed to adjust for treatment group differences at baseline and NNTs and NNHs with their 95% confidence intervals were calculated.

The NNTs for all-cause discontinuation of olanzapine were: 12.2.(95% CI: 5.8; 229.7) for olanzapine vs. risperidone, and 6.2 (3.1 ; 37.8) for olanzapine vs. typicals. The NNH for 7% weight gain was -3.7 (-2.6 ; -9.5) for olanzapine vs. typicals.

Treatment effectiveness and tolerability varied among medications. The NNTs for olanzapine therapy were consistently better when compared to other treatment cohorts. The weight-gain NNHs for olanzapine treatment were less favourable when compared to other antipsychotic medications.