Generation Antipsychotic Drugs Research Articles

IN VITRO AND IN SILICO SCREENING OF 6-FLUORO-3-(PIPERIDIN-4-YL) BENZO[D]ISOXAZOLE DERIVATIVES FOR BLOOD BRAIN BARRIER PERMEABILITY

Blood Brian Barrier (BBB) is a physiologically and metabolically significant membrane that enables and limits the uptake of specific molecules by the brain, thus preserving the homeostasis within the Central nervous System (CNS).All the Antipsychotic drugs are permeable across the BBB, however most of First/Second generation antipsychotic drugs employed in the medical field are known to be associated with Extrapyramidal symptoms (EPS). Hence our interest is devoted in the development of novel antipsychotic drugs that ameliorate psychosis with least frequency of EPS. In our previous study the newly synthesized molecules, 6-fluoro-3-(piperidin-4-yl) benzo[d]isoxazole derivatives (S1-S4) which have shown positive alterations in chemical properties and biological activities demonstrating significant neuroleptic properties. However possibility and efficiency of these synthesized molecules to penetrate through the Blood Brain Barrier will be of utmost importance to determine its treatment efficacy. In this line of investigation, in the present study, in silico and in vitro methods are employed to evaluate the permeability in comparison with that of standard antipsychotic drugs, Resperidone and Haloperidol. In vitro analysis was done by Parallel artificial Membrane Permeability Assay (PAMPA) in PBS, where in permeability of S2(8.3x10-6) and S3(6.6x10-6) molecules showed higher permeability than known standards Warfarin(1x10-6), Resperidone(2.3x10-6) and Haloperidol(3.5x10-6), and the molecules exhibited recovery above 50% and in silico studies also showed high permeability rate with all the synthesized molecules. Thus we can conclude that, all the synthesized molecules have the potential to develop into promising Antipsychotic drugs.Key words: Antipsychotics, Blood Brain Barrier, EPS, PAMPA, In silicoÂ

New functional activity of aripiprazole revealed: Robust antagonism of D2 dopamine receptor-stimulated Gβγ signaling

The dopamine D2 receptor (DRD2) is a G protein-coupled receptor (GPCR) that is generally considered to be a primary target in the treatment of schizophrenia. First generation antipsychotic drugs (e.g. haloperidol) are antagonists of the DRD2, while second generation antipsychotic drugs (e.g. olanzapine) antagonize DRD2 and 5HT2A receptors. Notably, both these classes of drugs may cause side effects associated with D2 receptor antagonism (e.g. hyperprolactemia and extrapyramidal symptoms). The novel, “third generation” antipsychotic drug, aripiprazole is also used to treat schizophrenia, with the remarkable advantage that its tendency to cause extrapyramidal symptoms is minimal. Aripiprazole is considered a partial agonist of the DRD2, but it also has partial agonist/antagonist activity for other GPCRs. Further, aripiprazole has been reported to have a unique activity profile in functional assays with the DRD2. In the present study the molecular pharmacology of aripiprazole was further examined in HEK cell models stably expressing the DRD2 and specific isoforms of adenylyl cyclase to assess functional responses of Gα and Gβγ subunits. Additional studies examined the activity of aripiprazole in DRD2-mediated heterologous sensitization of adenylyl cyclase and cell-based dynamic mass redistribution (DMR). Aripiprazole displayed a unique functional profile for modulation of G proteins, being a partial agonist for Gαi/o and a robust antagonist for Gβγ signaling. Additionally, aripiprazole was a weak partial agonist for both heterologous sensitization and dynamic mass redistribution.

Do antipsychotic drugs increase seizure frequency in epilepsy patients?

To investigate whether addition of antipsychotic drugs (APD) would increase seizure frequency in epilepsy patients who were already treated with anti-epileptic drugs (AED), we compared a one-year seizure control outcome in 150 epilepsy patients with APD treatment for psychiatric conditions and 309 epilepsy patients without APD treatment matched for ages at epilepsy onset and the baseline evaluation and types of epilepsy. The seizure frequency was recorded at the baseline (immediately before the start of APD) and after the 1st, 3rd, 6th and 12th months. The seizure outcome at each of the four follow-up points was compared with the baseline. The seizure outcome was compared between the two groups as a whole and according to the types of epilepsy (idiopathic generalized and partial epilepsies). In the APD group, the seizure outcome was also analyzed according to the types of APD (first and second generation APD and combination of first and second generation APD) and the types of psychiatric conditions (psychosis and non-psychosis). The seizure outcome was significantly better in the APD group than control group at all the four follow-up points. According to the epilepsy types, the improvement in the seizure outcome was only observed in the patients with partial epilepsy. Of the APD group, there was no significant difference in the seizure outcome according to the types of APD or the psychiatric conditions. In epilepsy patients who are already treated with AED, APD treatment seems safe in seizure control outcome for treatment of psychiatric conditions.

Olanzapine-activated AMPK signaling in the dorsal vagal complex is attenuated by histamine H1 receptor agonist in female rats.

Weight gain and its related metabolic disorders are major side effects associated with second generation antipsychotic drug treatment. The dorsal vagal complex (DVC) and AMP-activated protein kinase (AMPK) are implicated in the regulation of food intake and body weight. Blocking the histamine H1 receptor contributes to antipsychotic-induced weight gain. The present study investigated the time-dependent effect of olanzapine treatment (8, 16, and 36 d) on DVC AMPK signaling in olanzapine-induced weight gain and whether these changes are associated with olanzapine-induced H1 receptor antagonism. During the 8-day olanzapine treatment, the rats were hyperphagic and rapidly gained weight. The phosphorylation of AMPK (pAMPK) (activated AMPK) as well as its directly downstream phospho-acetyl-coenzyme A carboxylase was significantly increased. The pAMPK/AMPK ratio, an indicator of AMPK activity, was significantly positively correlated with feeding efficiency and weight gain. As treatment was prolonged (16 and 36 d of olanzapine treatment), the rats were no longer hyperphagic, and there were no longer any changes in DVC AMPK signaling. Although the DVC H1 receptor protein expression was not significantly altered by olanzapine, the pAMPK expression was significantly positively correlated with the H1 receptor level after the 8-, 16-, and 36-day olanzapine treatments. Moreover, we showed that an H1 receptor agonist, 2-(3-trifluoromethylphenyl) histamine, significantly inhibited the olanzapine-induced hyperphagia and DVC AMPK activation in a dose-dependent manner. These results suggest a time-dependent role of DVC AMPK in olanzapine-induced obesity. Thus, olanzapine-induced DVC AMPK activation may be at least partially related to olanzapine's antagonistic effect on the H1 receptor.

The activation of the Akt/PKB signalling pathway in the brains of clozapine-exposed rats is linked to hyperinsulinemia and not a direct drug effect.

The second generation antipsychotic drug clozapine is a much more effective therapy for schizophrenia than first generation compounds, but the reasons for this are poorly understood. We have previously shown that one distinguishing feature of clozapine is its ability to raise glucagon levels in animal models and thus causes prolonged hyperinsulinemia without inducing hypoglycaemia. Previous studies have provided evidence that defects in Akt/PKB and GSK3 signalling can contribute to development of psychiatric diseases. Clozapine is known to activate Akt/PKB in the brain, and some studies have indicated that this is due to a direct effect of the drug on the neurons. However, we provide strong evidence that elevated insulin levels induced by clozapine are in fact the real cause of the drug's effects on Akt/PKB and GSK3 in the brain. This suggests that the elevated levels of insulin induced by clozapine may contribute to this drug's therapeutic efficacy.

Serotonin and Sexual Dysfunction

Editorial Sexual dysfunction is a common side effect of psychotropic drugs and has received much attention because of its negative effects on quality of life and adherence to antidepressant agents. In patients with depression, sexual dysfunction can be attributed to the underlying disorder or to antidepressant drugs. Sexual dysfunction also can occur with first generation antipsychotic drugs and second-generation antipsychotic drugs (e.g., thioridazine and risperidone, respectively). In patients with schizophrenia, sexual dysfunction can be attributed to the underlying illness as well as to antipsychotic induced hyperprolactinemia due to dopamine blockade in tuberoinfundibular pathway [1].

Anatomical specificity in the modulation of activity-regulated genes after acute or chronic lurasidone treatment

Lurasidone is a novel second generation antipsychotic drug characterized by a multi-receptor profile. Besides the high affinity for 5-HT2A and D2 receptors, it is also characterized by potent 5-HT7 receptor antagonism, which may be beneficial for mood and cognition. Considering that dose-dependent changes in receptor occupancy may differentially impact gene transcription, we aimed at investigating the effects of acute and chronic treatments with different doses of lurasidone (1, 3 and 10mg/kg) in rats on the expression of the activity-regulated genes Arc, Zif268 and Npas4, which are markers of neuronal activation and are also associated with neuroadaptive mechanisms. Our results show dose-dependent and anatomically-selective differences after acute and chronic lurasidone treatment. Indeed, the effects produced by acute treatment seem to reflect the modulatory activity of lurasidone at selected neurotransmitter receptors. In fact, low doses of the drug acted in the hippocampus, while high doses acted in the striatum, reflecting the high predominance of D2 receptor expression in this brain region. On the contrary, chronic treatment with lurasidone revealed a different profile of IEGs modulation, possibly reflecting neuroadaptive changes set in motion in response to repetitive drug exposure. In summary, the multi-receptor profile of lurasidone leads to the recruitment of different brain structures in a dose-related manner and this may be important for its therapeutic properties, particularly with respect to antidepressant activity and cognition.

Repeated aripiprazole treatment regulates Bdnf, Arc and Npas4 expression under basal condition as well as after an acute swim stress in the rat brain

Despite the rapid control of schizophrenic symptoms is due to the ability of antipsychotic drugs (APDs) to block D2 receptors in the mesolimbic pathway, it is now well-established that the therapeutic effects rely on adaptive mechanisms set in motion by their long-term administration. Such neuroplastic mechanisms depend on the pharmacological profile of the drug employed, with marked differences existing between first and second generation APDs. On these bases, the major accomplishment of this work was to investigate neuroadaptive changes set in motion by repeated treatment with aripiprazole, a novel APD that is unique for being a partial agonist at dopamine D2 receptors. Moreover, given that stress plays a critical role in the exacerbation of disease symptoms, we also investigated whether aripiprazole could influence the dynamic response of the brain to an acute challenge.We found that repeated aripiprazole treatment in rats regulates the expression of different markers of neuroplasticity such as Bdnf, Arc and Npas4 in a brain-region specific fashion; more importantly, the expression of these molecules was significantly up-regulated by an acute swim stress only in aripiprazole-treated animals, which is suggestive of increased ability to cope with the adverse event. We indeed found an overall facilitation of Bdnf expression, an effect that is mainly evident in the prefrontal cortex on the pool of transcripts undergoing dendritic localization.Overall, our results provide novel information regarding the mechanisms through which aripiprazole may regulate brain function and could contribute to improve neuroplastic defects that are associated with schizophrenia symptomatology.

The effect of naltrexone on body fat mass in olanzapine-treated schizophrenic or schizoaffective patients: A randomized double-blind placebo-controlled pilot study

Olanzapine (OLZ), a commonly prescribed second generation antipsychotic drug, is associated with obesity and metabolic syndrome and may contribute to increased cardiovascular morbidity and mortality. Opioidergic neurotransmission may be implicated in the development of these metabolic disturbances. The objective of this study was to assess the effects of opioid blockade on OLZ-treated patients' metabolic status. Patients with schizophrenia or schizoaffective disorder (n=30) on a stable dose of OLZ were randomized in a double-blind fashion to receive an opioid receptor antagonist, naltrexone (NTX), (n=14) or placebo (n=16). The primary outcome measure was the change in body mass index (BMI) at 12 weeks. Secondary measures included body fat and fat-free mass, along with homeostasis model assessment-estimated insulin resistance (HOMA-IR), plasma lipids and liver function tests (LFTs). There was no significant change in BMI between the treatment arms. However, in comparison to the OLZ + placebo combination, the OLZ + NTX group displayed a significant decrease in the fat and increase in fat-free mass along with a trend towards improvement in HOMA-IR values. There were no significant differences in plasma lipids and LFTs. These findings suggest that addition of NTX to OLZ may attenuate OLZ-induced body fat mass gain. A larger study of longer duration will be needed to confirm these results.

Antidiabetic-drug combination treatment for glucose intolerance in adult female rats treated acutely with olanzapine

Second generation antipsychotic drugs are routinely used as treatment for psychotic disorders. Many of these compounds, including olanzapine, cause metabolic side-effects such as impaired glucose tolerance and insulin resistance. Individual antidiabetic drugs can help control elevated glucose levels in patients treated with antipsychotics, but the effects of combining antidiabetics, which routinely occurs with Type 2 diabetes mellitus patients, have never been studied. Presently, we compared the effects of the three different antidiabetics metformin (500mg/kg, p.o.), rosiglitazone (30mg/kg, p.o.) and glyburide (10mg/kg, p.o.) on metabolic dysregulation in adult female rats treated acutely with olanzapine. In addition, dual combinations of each of these antidiabetics were compared head-to-head against each other and the individual drugs. The animals received two daily treatments with antidiabetics and were then treated acutely with olanzapine (10mg/kg, i.p.). Fasting glucose and insulin levels were measured, followed by a 2h glucose tolerance test. Olanzapine caused a large and highly significant glucose intolerance compared to vehicle treated rats. Rosiglitazone decreased glucose levels non-significantly, while both metformin and glyburide significantly decreased glucose levels compared to olanzapine-only treated animals. For antidiabetic dual-drug combinations, the rosiglitazone-metformin group showed an unexpected increase in glucose levels compared to all of the single antidiabetic drugs. However, both the metformin-glyburide and rosiglitazone-glyburide groups showed significantly greater reductions in glucose levels following olanzapine than with single drug treatment alone for metformin or rosiglitazone, bringing glucose levels down to values equivalent to vehicle-only treated animals. These findings indicate that further study of antidiabetic dual-drug combinations in patients treated with antipsychotic drugs is warranted.

Routine exercise ameliorates the metabolic side-effects of treatment with the atypical antipsychotic drug olanzapine in rats

Second generation antipsychotic (SGA) drugs are effective treatments for psychosis. Common side-effects of SGAs include metabolic dysregulation and risk of cardiometabolic disorders. Metabolic side-effects, including glucose intolerance, can be accurately modelled in rodents. The benefits of interventions used for treating metabolic side-effects of SGAs are mostly unknown. In a 9wk longitudinal study, female rats were given daily olanzapine (10mg/kg s.c.) or vehicle. Animals were either sedentary or allowed 1 or 3h daily access to a running wheel, with total wheel revolutions electronically quantified to reflect exercise intensity. Glucose tolerance tests were performed once weekly to measure glycemic control. Drug levels were measured at week 4. At week 9, abdominal fat and skeletal muscle levels of Glucose Transporter 4 (GLUT4) were measured. Exercise intensity progressively increased over time in all groups given access to running wheels; however, rats treated with olanzapine consistently exercised less than those given the vehicle. Olanzapine caused acute and persistent glucose intolerance throughout the study, which was markedly, though incompletely, ameliorated by exercise. Exercise did not affect glycemic regulation in vehicle-treated rats. Olanzapine-treated rats showed greater central adiposity. Levels of GLUT4 in skeletal muscle were higher in both groups of exercising than in sedentary rats, and GLUT4 values were negatively correlated with glucose intolerance. Routine exercise reduced olanzapine-induced glucose intolerance and increased skeletal muscle levels of GLUT 4, the insulin-responsive transporter that mediates glucose uptake into cells. The current animal model is suitable for evaluating physiological pathways involved with glucose intolerance.

Chronic risperidone exposure does not show any evidence of bone mass deterioration in animal model of schizophrenia

It has been shown that bone mass is centrally regulated. Thus schizophrenia being a disease of the central nervous system is an interesting model for studying bone. Most second generation antipsychotic drugs including risperidone are used in the treatment of schizophrenia. Weight gain and metabolic disturbances are common side effects. The aims of this study were to investigate bone mass, body composition and light microscopic pathology examinations of femur in an animal model of schizophrenia (pharmacologically induced by postnatally administered phencyclidine-PCP) and to further examine the effects of chronic treatment with risperidone on these parameters in rats. Four groups of male rats were studied:1) control group-NaCl postnatally administered, n=9; 2) PCP group-postnatal PCP administration to rat pups (on day 2,6,9 and 12), n=6; 3) risperidone group-rats treated with risperidone alone for 9weeks from day 35 (NaCl-RSP group, n=7); 4) PCP rats treated with risperidone for 9weeks from day 35 (PCP-RSP group, n=7). Bone mass and body composition were measured in vivo by dual X ray absorptiometry (areal DXA and fat mass). Light microscopic analysis of the femoral metaphysis was performed in all groups after sacrificing the animals. Postnatal phencyclidine (PCP) administration to rat pups caused a long lasting reduction of total bone mass versus control animals (aDXA 128±2mg/cm(2) vs 139±5mg/cm(2), p<0.05). Examination of the femoral bone revealed a decrease in the number and thickness of the metaphyseal trabecule and cortical thinning. There was a decrease in total and retroperitoneal fat. Nine weeks of administration of risperidone alone to rats, resulted in significant weight gain and had no effect on bone mass versus control animals (aDXA was 136±7mg/cm(2) vs 139±5mg/cm(2), p>0.05). Furthermore, there were no changes in the light microscopic analysis of femoral metaphysis in comparison with controls. When PCP rats were treated with risperidone, they did not change their body weight nor bone mass versus PCP alone (aDXA 126±2mg/cm(2) vs 128±2mg/cm(2), p>0.05) but intriguingly on examination of the femoral bone an increase in the number and thickness of the metaphyseal trabecule was found (trabecular thickness 0.6±0.1μm vs 0.35±0.1μm, p<0.01). This study shows that in the PCP rat model of schizophrenia bone mass is reduced. When PCP rats were treated with risperidone bone mass remained unchanged but intriguingly and unexpectedly light microscopic examination of femoral metaphysis showed an increase in thickness of metaphyseal trabeculae. The mechanism of risperidone's action on bone remains to be clarified.

Use of Clozapine in Older Asian Patients with Schizophrenia between 2001 and 2009

BackgroundTo date there has been no large-scale international study that examined the use of clozapine in older patients with schizophrenia. This study examined the use of clozapine and its demographic and clinical correlates in older patients with schizophrenia in East Asia during the period between 2001 and 2009.MethodInformation on 1,157 hospitalized patients with schizophrenia aged 50 or older in five East Asian countries and territories (China, Hong Kong, Korea, Singapore and Taiwan) was extracted from the database of the Research on Asian Psychotropic Prescription Patterns (REAP) project. Socio-demographic and clinical characteristics and prescription of psychotropic medications were recorded.ResultsClozapine was prescribed for 20.6% of the pooled sample; 19.0% in 2001, 19.4% in 2004 and 22.9% in 2009. Multiple logistic regression analysis of the whole sample revealed that patients taking clozapine had a longer duration of illness, more negative symptoms and were less likely to receive first generation antipsychotic and anticholinergic drugs, but more likely to report weight gain compared to those not receiving clozapine. Compared to those in other sites, older patients in China were more likely to receive clozapine.ConclusionsThe prescription of clozapine for older Asian schizophrenia inpatients has remained at a stable level during the past decade. The appropriateness of use of clozapine in China needs to be further explored.

Does changing from a first generation antipsychotic (perphenazin) to a second generation antipsychotic (risperidone) alter brain activation and motor activity? A case report

BackgroundIn patients with schizophrenia, altered brain activation and motor activity levels are central features, reflecting cognitive impairments and negative symptoms, respectively. Newer studies using nonlinear methods have addressed the severe disturbances in neurocognitive functioning that is regarded as one of the core features of schizophrenia. Our aim was to compare brain activation and motor activity in a patient during pharmacological treatment that was switched from a first- to a second-generation antipsychotic drug. We hypothesised that this change of medication would increase level of responding in both measures.Case presentationWe present the case of a 53-year-old male with onset of severe mental illness in adolescence, ICD-10 diagnosed as schizophrenia of paranoid type, chronic form. We compared brain activation and motor activity in this patient during pharmacological treatment with a first-generation (perphenazin), and later switched to a second-generation (risperidone) antipsychotic drug. We used functional magnetic resonance imaging (fMRI) to measure brain activation and wrist worn actigraphy to measure motor activity.ConclusionOur study showed that brain activation decreased in areas critical for cognitive functioning in this patient, when changing from a first to a second generation antipsychotic drug. However the mean motor activity level was unchanged, although risperidone reduced variability, particularly short-term variability from minute to minute. Compared to the results from previous studies, the present findings indicate that changing to a second-generation antipsychotic alters variability measures towards that seen in a control group, but with reduced brain activation, which was an unexpected finding.

Metabolic side effects of second generation antipsychotic drugs in adolescents

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Comparative effectiveness of depot and oral second generation antipsychotic drugs in schizophrenia: A nationwide study in Hungary

We conducted a nationwide, full-population based investigation to evaluate the comparative effectiveness of all marketed second generation antipsychotic drugs (SGA) prescribed for outpatients with the diagnosis of schizophrenia in Hungary. Using the national central register, our observational follow-up study included all patients with schizophrenia or related disorder between 01/01/2006 and 30/06/2008. The study cohort comprised 9567 patients who started new SGA during the inclusion period (01/07/2007–30/06/2008). All-cause medication discontinuation of 8 SGAs (1 depot and 7 oral formulations) marketed during the inclusion period, and the time to all-cause discontinuation were the main outcomes. Statistical models included the Kaplan–Meier and the Cox proportional hazards models with propensity score adjustment. Patients treated with a depot formulation risperidone had the longest time to discontinuation with a median of 215 days (95%CI:181–242 days), which was statistically significantly different compared to patients treated with the rest of the medications: olanzapine (136 days, 95%CI:121–153 days), aripiprazole (102 days, 95%CI:81–126 days), ziprasidone (93 days, 95%CI:82–119 days), quetiapine (89 days, 95%CI:81–100 days), clozapine (76 days, 95%CI:54–92 days), amisulpride (73 days, 95%CI:62–85 days), and risperidone (55 days, 95%CI: 41–63 days). Our results in Hungary are partly similar to those of a recent register-based study in Finland with patients who were discharged from their first hospitalization for schizophrenia (Tiihonen et al., 2006, 2011); namely the median times to all-cause medication discontinuation were <120 days for the majority of the oral SGA. In terms of medication differences, our data support the superior effectiveness of the depot formulation regarding all-cause discontinuation, followed by olanzapine at the efficacy rank order.

Metabolic Side-Effects of the Novel Second-Generation Antipsychotic Drugs Asenapine and Iloperidone: A Comparison with Olanzapine

BackgroundThe second generation antipsychotic (SGA) drugs are widely used in psychiatry due to their clinical efficacy and low incidence of neurological side-effects. However, many drugs in this class cause deleterious metabolic side-effects. Animal models accurately predict metabolic side-effects for SGAs with known clinical metabolic liability. We therefore used preclinical models to evaluate the metabolic side-effects of glucose intolerance and insulin resistance with the novel SGAs asenapine and iloperidone for the first time. Olanzapine was used as a comparator.MethodsAdults female rats were treated with asenapine (0.01, 0.05, 0.1, 0.5, 1.0 mg/kg), iloperidone (0.03, 0.5, 1.0, 5.0, 10.0 mg/kg) or olanzapine (0.1, 0.5, 1.5, 5.0, 10.0 mg/kg) and subjected to the glucose tolerance test (GTT). Separate groups of rats were treated with asenapine (0.1 and 1.0 mg/kg), iloperidone (1.0 and 10 mg/kg) or olanzapine (1.5 and 15 mg/kg) and tested for insulin resistance with the hyperinsulinemic-euglycemic clamp (HIEC).ResultsAsenapine showed no metabolic effects at any dose in either test. Iloperidone caused large and significant glucose intolerance with the three highest doses in the GTT, and insulin resistance with both doses in the HIEC. Olanzapine caused significant glucose intolerance with the three highest doses in the GTT, and insulin resistance with the higher dose in the HIEC.ConclusionsIn preclinical models, asenapine shows negligible metabolic liability. By contrast, iloperidone exhibits substantial metabolic liability, comparable to olanzapine. These results emphasize the need for appropriate metabolic testing in patients treated with novel SGAs where current clinical data do not exist.

487 – Modern antipsychotic drugs gives fewer side effects and lower deaths

Introduction Is there any difference in deaths and frecquency of different somatic diagnosis after the use of second generation antipsychotic drugs? Objectives Using different databases of diagnos F20(schizophrenia),contact with health care system in Southwest part of Sweden(1,7 million inhabitants) Using antipsychotic drugs. By comparing Fist Generation antipsychotic drugs (FGA) with the Second Generation Antipsychotic drugs (SGA) about death, costs, the frecquency of diagnosis of different diseases mlike diabetes,stroke,coronary heart disease and hypertension. Aims Identify the effects in different pharmacological treatments in Sweden. Methods Indivuals with the diagnos F20 can be identified by the civic registration number in the batabase for health care contacts, death register, drug costs from the Swedish Board of Health andWelfare for the different used drugs and data from The national Insurance about absenteism were merged in a computer file. The data were coded so no one could identifie any individual.We used the costs for open care and DRG for the different hospitals to count the costs for the health care of the patients. We studied the patients july 2005 -.decembre 2009. Results We studied the data of 4593 individuals with the ICD-10 diagnosis F20 -The death rate was 2,4 higher than in the total population.-not lower with drug treatment than without. The total cost varied between in euro 2700-4000.The higher cost is for SGA No difference in hospital costs between the two types of antipsychotic drugs. About the concomitant disorders Aripiprazol had a tendency have lower freguency.SGA has lower deaths. Conclusions Advantages with SGA.

New approaches for the management of bipolar disorder: role of sublingual asenapine in the treatment of mania

Bipolar disorder is a prevalent disorder that tends to become progressive without treatment and with inadequate treatment. Second generation (atypical) antipsychotic drugs have increasingly been used as adjunctive treatment or monotherapy for mania, but they have the potential for significant adverse effects and their role in maintenance treatment remains unclear. Asenapine is a new atypical antipsychotic medication formulated in a sublingual preparation that has been studied for mania but not maintenance therapy. Evidence indicating efficacy, adverse effects, and potential benefits and drawbacks of using asenapine in the treatment of bipolar disorder based on currently available published data are summarized.

Secondary effects of antipsychotic treatment in naïve or quasi-naïve children and adolescents: Design of a follow-up protocol and baseline results

IntroductionThe prescribing of anti-psychotic drugs has become a normal clinical practice. MethodsThis article presents a longitudinal, multicentre 12-months-long study conducted on 266 children and adolescents who were prescribed a first or second generation antipsychotic drug for the first time, and the baseline results of the study. The follow-up protocol had its purpose to detect the possible appearance of metabolic, cardiological, and motor changes. ResultsWhen the presence of side effects was evaluated using the UKU (clinical side-effects scale) statistically significant differences were found between naïve (patients who had never taken an anti-psychotic drug) and quasi-naïve patients (those who have taken anti-psychotic drugs for a period of less than 30 days), with a greater number of the latter showing symptoms of: anxiety/laxity/tiredness (P=0.0049), drowsiness/sedation (P<0.001), increase in dream duration (P<0.001), increase in dreams (P=0.0199), emotional indifference (P=0.0194), hypokinesia/akinesia (P=0.0224), paresthesias (P=0.0049), accommodation disorder (P=0.0254), increase in salivation (P<0.001), polyuria/polydipsia (P=0.0076), increase in sweating (P=0.0076), increase in sexual desire (P=0.0117), decrease in sexual desire (P=0.0053), tension headaches (P=0.0405). When the presence of extrapyramidal symptoms was assessed using the MPRC-IMS (Maryland Psychiatry Research Center-Involuntary Movement Scale), it was observed that the quasi-naïve patients had a statistically higher number of dyskinesia (P=0.002), Parkinsonism (P=0.0004) and akathisia (P=0.0437) symptoms compared to the naïve patients. ConclusionsThese results show that, in the childhood–adolescent population, the presence of secondary effects begins to be observed from the first dose of the antipsychotic drug.