New-generation Antipsychotics Research Articles

The pharmacogenetics of the new-generation antipsychotics - A scoping review focused on patients with severe psychiatric disorders.

Exploring the possible correlations between gene variations and the clinical effects of the new-generation antipsychotics is considered essential in the framework of personalized medicine. It is expected that pharmacogenetic data will be useful for increasing the treatment efficacy, tolerability, therapeutic adherence, functional recovery, and quality of life in patients with severe psychiatric disorders (SPD). This scoping review investigated the available evidence about the pharmacokinetics, pharmacodynamics, and pharmacogenetics of five new-generation antipsychotics, i.e., cariprazine, brexpiprazole, aripiprazole, lumateperone, and pimavanserin. Based on the analysis of 25 primary and secondary sources and the review of these agents' summaries of product characteristics, aripiprazole benefits from the most relevant data about the impact of gene variability on its pharmacokinetics and pharmacodynamics, with significant consequences on this antipsychotic's efficacy and tolerability. The determination of the CYP2D6 metabolizer status is important when administering aripiprazole, either as monotherapy or associated with other pharmacological agents. Allelic variability in genes encoding dopamine D2, D3, and serotonin, 5HT2A, 5HT2C receptors, COMT, BDNF, and dopamine transporter DAT1 was also associated with different adverse events or variations in the clinical efficacy of aripiprazole. Brexpiprazole also benefits from specific recommendations regarding the CYP2D6 metabolizer status and the risks of associating this antipsychotic with strong/moderate CYP2D6 or CYP3A4 inhibitors. US Food and Drug Administration (FDA) and European Medicines Agency (EMA) recommendations about cariprazine refer to possible pharmacokinetic interactions with strong CYP3A4 inhibitors or inducers. Pharmacogenetic data about cariprazine is sparse, and relevant information regarding gene-drug interactions for lumateperone and pimavanserin is yet lacking. In conclusion, more studies are needed to detect the influence of gene variations on the pharmacokinetics and pharmacodynamics of new-generation antipsychotics. This type of research could increase the ability of clinicians to predict favorable responses to specific antipsychotics and to improve the tolerability of the treatment regimen in patients with SPD.

Cariprazine as a useful treatment for patients with schizophrenia and antipsychotic-induced extrapyramidal symptoms: a case report and literature review

IntroductionThe discovery of second-generation antipsychotics represented an authentic breakthrough for the management of psychotic disorders. Nevertheless, they still don’t adequately manage some aspects of these disorders, such as negative symptoms (NS), cognitive impairment, or extra-pyramidal symptoms (EPS). New-generation antipsychotics present different pharmacological mechanisms and have been reported to ameliorate these aspects. Among them, cariprazine acts as a D2/D3 partial agonist with variable affinity with serotoninergic receptors, and many studies show its efficacy for preventing and treating positive symptoms as well as for the management of NS and EPS.ObjectivesTo report a case of a patient diagnosed with schizophrenia with highly invalidating antipsychotic-induced EPS that remitted after switching to cariprazine, while maintaining clinical stability. To review literature about cariprazine and its relationship with NS and EPS.MethodsWe describe the case of a 66-year-old woman diagnosed with schizophrenia and under treatment with three-month injectable paliperidone 175mg. During her follow-up at outpatient clinic, she presented a progressively highly invalidating non-trembling parkinsonian syndrome attributable to medication. Paliperidone plasmatic levels were within therapeutic range. An antipsychotic switch was agreed, and cariprazine was started.ResultsThe switch from a second-generation antipsychotic to cariprazine entailed the remission of a highly invalidating EPS while improving some of the NS and maintaining psychopathological stability.ConclusionsAssessing and differentiating NS and EPS is of an utmost importance during the follow-up of patients under antipsychotic treatment. Cariprazine is an interesting alternative when treating patients diagnosed with psychotic disorders that present mostly NS and antipsychotic-induced EPS.DisclosureNo significant relationships.

Psychosis.

Psychosis can manifest in primary psychotic disorders, neurologic diseases, and medical conditions. This article reviews the definition of psychotic symptoms and the evaluation and management of psychosis in primary psychiatric and neurologic disorders frequently seen in neurologic practice. Emerging evidence supports significant connections between psychosis and structural and functional brain changes in both primary psychotic and neurologic disorders. In addition to antidopaminergic activity, the mechanism of new-generation antipsychotics shifts to act on serotonin receptors, which potentially contributes to their benefits in the treatment of negative symptoms of psychosis and a lesser frequency of extrapyramidal side effects compared with typical antipsychotics. This is also helpful in the treatment of psychosis in patients who have neurodegenerative diseases and are vulnerable to developing extrapyramidal side effects from typical antipsychotics. Even with significant overlap, management of psychosis in primary psychotic disorders differs from the approach of psychosis in neurologic diseases. This article helps clinicians learn how to practically evaluate psychosis from both psychiatric and neurologic perspectives.

Effects of Trans-ancestry Schizophrenia Risk Gene Polymorphisms on Working Memory and Underlying Brain Mechanisms

Abstract One of the main goals of the new generation of antipsychotics is to improve cognitive functions of schizophrenia patients, which makes it necessary to identify genes related to not only schizophrenia but also its cognitive impairments. Starting with 58 trans-ancestry risk variants found in a genome-wide association study of Chinese schizophrenia patients, we conducted two studies with four samples to systematically examine these variants’ potential roles in working memory. Study 1 was a behavioral study (Sample I included 510 healthy volunteers who completed the n-back, dot-pattern expectancy [DPX], delayed match-to-sample [DMS], and spatial span tasks; Sample II included 819 healthy volunteers and 893 schizophrenia patients who completed the n-back and DPX tasks). Study 2 was an fMRI study (Sample III included 163 healthy volunteers and 52 schizophrenia patients, who were scanned with fMRI during an n-back task; and Sample IV included 89 healthy volunteers, who were scanned during a spatial span task). Sample I identified rs11210892 as the only SNP that was associated with performance on multiple tasks (n-back, DPX, and DMS) after Bonferroni correction. Sample II replicated this association on the n-back task and the DPX task. FMRI data showed that the risk allele “G” of rs11210892 was associated with an increased activation within the right dorsolateral prefrontal cortex (Sample III) and the bilateral striatum (Sample IV). We conclude that rs11210892 is significantly associated with working memory and its neural underpinnings, so the genes near this SNP might be potential gene targets for treating cognitive impairment associated with schizophrenia.

New-generation Antipsychotics and Cardiovascular Risk

To critically review the current landscape of literature on cardiotoxicity of “new-generation antipsychotics,” defined as those approved by the Food and Drug Administration in the last 10 years. There is a paucity of data regarding the cardiovascular risks of these medications. Based on the investigations that have been published, iloperidone appears to be the greatest risk of corrected QT prolongation followed by asenapine whereas lurasidone, cariprazine, and brexpiprazole were not found to have significant effects on corrected QT. However, the evidence was low quality. In terms of metabolic effects, asenapine, iloperidone, cariprazine, and brexpiprazole all had mild to moderate effects whereas lurasidone had no significant effects observed. Further investigation is warranted for all of these medications to better understand their cardiovascular effects.

Effects of Asenapine and Paliperidone on Depression, Anxiety and Analgesy in Mice: Alterations in Brain Neurotrophic Factors, Neurogenesis, and Blood Enzyme Levels.

Schizophrenia, an important brain neurodevelopmental disorder, is observed in 1% of the global population. New-generation antipsychotics have been developed as alternatives to typical antipsychotics for more effective and safe therapy. Chronic administration of asenapine and paliperidone compared to haloperidol on depression, anxiety and analgesy in the forced swimming test (FST), elevated plus maze (EPM) and hot plate tests were examined in mice. Moreover effects of drugs, on expression levels of brain neurotrophic factors [brain-derived neurotrophic factor (BDNF), cAMP response element binding protein (CREB),nerve growth factor (NGF), synapsin and fibroblast growth factor 2 (FGF2)] in the hippocampus of mice, neurogenesis and neurodegeneration, and blood enzyme levels were also investigated. In FST, haloperidol (0.25 mg/kg) significantly increased immobility time while both asenapine (0.075 mg/kg) and paliperidone (0.25 and 0.50 mg/kg) significantly diminished this parameter. In EPM test, haloperidol significantly increased both % time spent in open arms and % open arm entries. Asenapine (0.075 mg/kg) and paliperidone (0.50 mg/kg) significantly increased % time spent in the open arms. They also increased % open arm entries, but this parameter failed to reach a statistically significant value. In hot plate test, haloperidol (0.125 and 0.25 mg/kg) and paliperidone (0.25 and 0.50 mg/kg) significantly increased the latency to lick the hind paws but asenapine had no effect. Asenapine and paliperidone upregulated more neurotrophic factors in the brain and caused less neurodegeneration compared to haloperidol. Investigated drugs had no effect on liver enzymes and plasma glucose levels. Asenapine and paliperidone may be preferred over classical antipsychotics since they have antidepressant-like effect, upregulate more neurotrophic factors and cause less neurodegeneration in naive mice without having diabetogenic and liver damaging effects. Paliperidone seems to possess superior effects compared to asenapine since it also exerts analgesic-like effect.

Movement disorders and chronic psychosis: Five new things.

To discuss selected peer-reviewed research articles published between 2014 and 2016 and highlight 5 clinically relevant messages related to hyperkinetic and hypokinetic movement disorders in patients with chronic psychosis. A recent population-based study complemented data from clinical trials in showing increased risk of developing extrapyramidal symptoms with antipsychotic use. A community service-based longitudinal study showed that dopamine transporter imaging could help identify subgroups of patients with parkinsonism associated with antipsychotics with a progressive course, potentially manageable with l-dopa. Data from recent noteworthy clinical trials showed that a new VMAT-2 inhibitor and, for pharmacologically refractory tardive dyskinesia, deep brain stimulation of the globus pallidus internus are promising interventions. Finally, a population-based study has confirmed that hyperkinesias (encompassing chorea, dystonia, and stereotypies) may be early predictors of psychosis even in childhood and adolescence. Movement disorders associated with new-generation antipsychotics, including widely used agents (e.g., aripiprazole), are not rare occurrences. Better monitoring is needed to assess their true effect on patients' quality of life and functioning and to prevent underascertainment.

Antipsychotikainduzierte tardive Syndrome

Tardive dyskinesia(TD) remains arelevant clinical problem despite the increasing use of new-generation antipsychotics. Antipsychotic-induced tardive syndromes are difficult to treat and have alow tendency of remission. Therefore, prophylaxis is of utmost importance, with the responsible use of antipsychotics as aprime desideratum. With respect to managing tardive dyskinesia, discontinuing the antipsychotic, if possible, albeit not backed up by unequivocal evidence, is still the main recommendation. If this is not possible, the switch to an antipsychotic with alower TD risk is the next-preferred option. Other symptomatic treatments have been explored, but clinical trials have provided inhomogeneous results and only very few compounds are approved for the treatment of tardive dyskinesia. This manuscript summarizes the current evidence with respect to the phenomenology, course, prevention and treatment of tardive syndromes.

Changes in psychopathology in schizophrenia patients starting treatment with new-generation antipsychotics: therapeutic drug monitoring in a naturalistic treatment setting

Previous studies on the relationship between plasma levels of new-generation antipsychotics (NGAs) and clinical response did not account for inter- and intra-individual variability in drug levels. Therefore, the present study calculated the ratio of observed versus expected NGA plasma levels and investigated its relationship with changes in the Positive and Negative Syndrome Scale (PANSS). Data of patients starting monotherapy with a NGA were collected 2, 4, 8, and 12 weeks after initiation of treatment. Next to the assessment of changes in psychopathology (PANSS) the ratio of observed versus expected plasma level was calculated. A total number of 221 ratios were eligible for analysis. About half of them ranged from 0.5–2 and were considered “normal”, whereas the others were considered either “too low” or “too high”. Psychopathological symptoms improved over the course of treatment, but changes in PANSS from baseline did not correlate significantly with the ratios of observed versus expected plasma levels at any assessment. The lack of linear correlation can be explained by the fact that 92% of the observed NGA plasma levels were at ≥50% of the lower limit of the therapeutic reference range, i.e., within the asymptote of the logistic plasma level-effect relationship. Accordingly, our findings indicate that the great majority of patients were treated with NGA doses that led to optimal plasma levels, based on the clinical impression of the treating psychiatrist only. Thus, calculating the ratio of observed versus expected plasma level may not be necessary in a routine clinical setting.

An updated clozapine treatment guide against clozaphobic attitudes

In recent years, clozapine-related publications are gradually increasing. Despite all the new generation of antipsychotics, one-third of patients with scizophrenia are still treatment-resistant. Clozapine is a unique and gold standard antipsychotics with FDA approval for treatment-resistant schizophrenia cases following failure with antipsyhotics from two separate groups with sufficient doses for at least six weeks duration and also preventing suicidal behavior in patients with schizophrenia and schizoaffective disorder. While at least 30% of schizophrenia patients are treatment- resistant and suicide rate is 5%; clozapine, both in Turkey and around the world, is used 10–15 times less in 2–10% of patients. This is not easy to explain rationally like in phobias. Although this cannot be exactly labeled as phobia or clozaphobia, labeling it as a clozaphobic attitude might be appropriate. In our opinion, claiming that prescription of clozapine less than required by the psychiatrists in Turkey due to this clozaphobic attitude is an important public health problem would not be an exaggeration. In addition to clozaphobic attitude, one of the major reasons underlying this attitude is clinicians’ lack of adequate awareness and experience in managing the potential serious adverse events. Clozapine causes major adverse events such as agranulocytosis, myocarditis/ cardiomyopathy, and epileptic seizures along with side effects such as weight gain, constipation, metabolic syndrome which might compromise patient’s health. In addition, daytime sedation, urinary incontinence at night, and hipersalivation can adveresly affect the quality of life of patients. Blood count monitoring for 18 weeks is another reason for reluctant use of clozapine. All these side effects and challenges can be overcome with specific approaches. The FDA promoted a rational use of clozapine with REMS (Risk Evaluation and Mitigation Strategy) program. In this review, updated information about clozapine have been outlined and clinicians were aimed to be informed by the pharmacoeconomics advantages of clozapine and how to overcome the potential adverse events in clozapine use.

Histamine H1 receptor occupancy by the new-generation antipsychotics olanzapine and quetiapine: a positron emission tomography study in healthy volunteers.

Histamine H1 antagonists have hypnotic, appetite-promoting, and sedative side effects. Most second-generation antipsychotics have potent antagonistic effects on histamine H1 receptor (H1R). Positron emission tomography (PET) can measure the H1R occupancy (H1RO) in vivo, although there are no reports regarding antipsychotics. We studied the H1RO of olanzapine and quetiapine in vivo with respect to their plasma concentrations and subjective drowsiness by performing human PET imaging studies with [(11)C]doxepin, a potent PET ligand of H1R. Six healthy Japanese male volunteers were enrolled. Cross-randomized PET imaging was performed after a single oral administration of olanzapine (2.5 mg), quetiapine (25 mg), or placebo. PET data were analyzed by region of interest and voxel-by-voxel analysis. We concurrently measured plasma drug concentrations by liquid chromatography/tandem mass spectrometry and evaluated subjective sleepiness. The binding potential ratios of olanzapine and quetiapine in the cerebral cortex were significantly lower than that of the placebo. The H1RO values of olanzapine and quetiapine in the cortex were approximately 61-80 and 56-81%, respectively. The binding potential ratios of the drugs were significantly lower than that of the placebo in the dorsolateral prefrontal and lateral temporal cortices, and anterior and posterior cingulate gyri. The H1RO values in the cortex were significantly correlated with subjective sleepiness but not plasma drug concentrations. Olanzapine and quetiapine have high H1RO values in the human brain under their clinical minimum doses. This study provides a foundation of the properties by which new-generation antipsychotics block the central histaminergic system in humans.

Measuring adherence to medication in schizophrenia: the relationship between attitudes toward drug therapy and plasma levels of new-generation antipsychotics.

Background:Nonadherence to medication is still a major problem in the treatment of schizophrenia. The current longitudinal study investigated whether the patients’ attitudes toward treatment correlated with the ratio of observed vs expected plasma levels of antipsychotic drugs as an objective measurement of adherence.Methods:Data of patients starting monotherapy with a new-generation antipsychotic were collected 2, 4, and 12 weeks after the initiation of treatment. Next to the assessment of patients’ attitudes toward medication by means of the Drug Attitude Inventory, the ratio of the observed vs expected plasma level was calculated. Antipsychotic-induced side effects were evaluated by means of the Udvalg for Kliniske Undersogelser Side Effect Rating Scale.Results:A total of 93 patients were eligible for statistical analysis. About one-half of the ratios of observed vs expected plasma levels ranged from 0.5 to 2 and were considered normal, whereas the other ratios were considered either too low (<0.5) or too high (>2). No consistent correlation between patients’ attitude toward drug therapy and the individual ratios of observed vs expected plasma levels of medication was detected. This finding was not affected by side effects.Conclusions:Our results highlight the importance of recognizing the complex nature of adherence to medication in schizophrenia patients. Importantly, we found no consistent correlation between subjective and objective measures of medication adherence. Therefore, monitoring adherence to medication remains a challenge in clinical practice.

Treatment of aggressive behavior problems in boys with intellectual disabilities using zuclopenthixol.

Disruptive or challenging behavior problems pose a threat to children and adolescents with intellectual disabilities and their caregivers. Psychopharmacological treatment is mostly studied with new-generation antipsychotics and has been criticized for adverse side effects. This study examined the effect of the classic antipsychotic zuclopenthixol. A total of 39 boys (ages 8.0-17.11 years) with learning disabilities were included and examined for a response to zuclopenthixol during a 6 week period of open label treatment. Doses started low and were adapted individually. From responders, zuclopenthixol was randomly withdrawn for 12 weeks. Responses to withdrawal were observed by external raters using the Modified Overt Aggression Scale. Of all patients included into the study, 15 were not randomized because of insufficient therapeutic effect, adverse event, or noncompliance. Kaplan-Meier estimations showed less aggressive behavior problems for the continuing subgroup (n=9) than in the placebo group (n=15). Individual doses stayed <10 mg/day. Zuclopenthixol proved to be effective in reducing challenging behavior in boys even at low doses.

The glutamate hypothesis of schizophrenia

For many years, the dopamine hypothesis of schizophrenia has been the leading theory explaining the aetiology of schizophrenia. However, since the first observation showed that NMDA-receptor antagonists (e. g., PCP) can induce all kinds of schizophrenia symptoms in humans, the glutamate hypothesis of schizophrenia has been established as an additional explanation model. Apart from the PCP-induced psychoses, many other findings from all areas of modern neuroscience have confirmed and extended the glutamate hypothesis. This review discusses the available evidence for the glutamate hypothesis and puts the different findings into relation. Consecutively, the possibilities for a pharmacological modulation of the glutamate system and recent clinical trials are discussed. To sum up, one could note that the glutamate hypothesis of schizophrenia is now well-established. The development of glutamatergic antipsychotics is still in the early stages, but there is hope for a new generation of antipsychotics based on the glutamate hypothesis of schizophrenia. However, recent findings from registration trials could not provide positive findings for the recently developed glutamatergic drugs.

Long-Acting Injectable Formulations of New-Generation Antipsychotics: A Review from a Clinical Perspective

Antipsychotics are the mainstay of the long-term treatment of patients with schizophrenia. In this context, the evidence also supports the effectiveness of long-acting injections (LAIs) or depots of antipsychotics regarding their relapse-preventing properties. When a LAI formulation of risperidone was launched as the first second-generation depot, there was a renaissance of interest in these formulations. In the meantime, olanzapine, paliperidone, and aripiprazole have been approved by regulatory authorities as LAIs in various countries. All studies using the new-generation depots have shown a clear advantage over placebo regarding relapse prevention and symptom reduction. Safety profiles of the long-acting compounds are comparable to their oral formulations with the exception of olanzapine pamoate injections, which can sometimes lead to a post-injection delirium. Despite the fact that many treatment guidelines recommend LAI antipsychotics as an important treatment option for the long-term management of schizophrenia, they are still most frequently used in chronically ill patients with considerable compliance problems. It is imperative to overcome this indication bias in order to be able to utilize all available treatment options in the long-term management of schizophrenia. There is little evidence on comparisons between LAIs and their oral mother compounds, and even less concerning effectiveness comparisons between different depots. The purpose of this manuscript is to review the recent clinical evidence on new-generation depot antipsychotics.

A new generation of antipsychotics: pharmacology and clinical utility of cariprazine in schizophrenia.

Cariprazine is a potential antipsychotic awaiting approval from the US Food and Drug Administration. It is a dopamine D2- and D3-receptor partial agonist, with higher affinity for D3 receptors, as opposed to the D2 antagonism of most older antipsychotic agents. Like most lipophilic antipsychotics, it undergoes extensive hepatic metabolism by cytochrome P450 (CYP), mainly the highly variable 3A4, with the formation of active metabolites. However, the parent compound – particularly its active didesmethyl derivative – is cleared very slowly, with elimination half-lives in schizophrenic patients ranging from 2–5 days for cariprazine to 2–3 weeks for didesmethyl-cariprazine. Exposure to the latter was several times that for cariprazine, although didesmethyl-cariprazine did not reach steady state within the 3 weeks of 12.5 mg/day dosing. Preliminary information on its therapeutic role comes from press releases and a few abstracts presented at scientific meetings. In short-term controlled trials, it was more effective than placebo in reducing positive and negative symptoms of schizophrenia, with an effective dose range of 1.5–12 mg/day. Although cariprazine was associated with a higher incidence of akathisia and extrapyramidal side effects than placebo, it did not cause weight gain, metabolic abnormalities, prolactin increase, or corrected QT prolongation. Similarly, cariprazine’s efficacy and tolerability for the treatment of bipolar disorder (manic/mixed and depressive episodes) was established in the dose range of 3–12 mg/day, although again no long-term data are available. Well-designed clinical trials, mainly direct “head-to-head” comparisons with other second-generation antipsychotic agents, are needed to define the therapeutic role and safety profile of cariprazine in schizophrenia and bipolar mania.

2304 – Relationships between psychopathological dimensions, cognitive deficits and functional capacity/real-life functioning in patients with schizophrenia

An impairment of functional capacity and real-life functioning has widely been reported in patients with schizophrenia, even when clinical remission has been achieved. The relative contribution of negative symptoms and neurocognitive deficits to such an impairment is still debated. In the present study, we investigated the relationships of functional capacity and real-life functioning with psychopathology and cognitive deficits in 35 schizophrenia patients, all treated with new-generation antipsychotics. The MATRICS Cognitive Consensus Battery was used to assess cognitive functions. Real-life functioning was evaluated with the Quality of Life Scale (QLS). Functional capacity was assessed with the Performance-Based Skills Assessment-Brief (UPSA-B). Psychopathological dimensions were calculated from PANSS items. Multiple Regression Analyses (MRA) were conducted, in which dependent variables were the indices of functional capacity/real life functioning while independent variables were psychopathological dimensions, neurocognitive indices, general abilities and education. The results of MRA on the QLS indices showed the following percentages of variance explained: negative psychopathological dimension, 64% for “intrapsychic functions” and 46% for “interpersonal relationships”; speed of processing, 13% for “work functioning” and 11% for “interpersonal relationships”; visual learning, 12% for “work functioning”; positive psychopathological dimension, 11% for “intrapsychic functions” and 5% for “interpersonal relationships”; working memory, 7% for “intrapsychic functions”. As to the MRA on UPSA-B total score, working memory explained 57% of the variance while speed of processing explained 12% of it. Our findings suggest that both negative symptoms and cognitive impairment have a strong relationship with real-life functioning while cognitive impairment is the only aspect associated to functional capacity.

Risperidone-induced acromegaly: a case report

Today, considering their adverse side effects, the first-generation antipsychotics have been replaced by the new-generation antipsychotics (also known as second-generation antipsychotic agents). The superiority of new-generation antipsychotics compared with first-generation antipsychotic agents in terms of side effects, especially movement disorders, are acknowledged by clinicians. But in recent years during the use of second-generation antipsychotic agents, endocrine side effects have been noteworthy. In our study with a diagnosis of paranoid schizophrenia treated with risperidone for 14 years and operated with the diagnosis of pituitary macroadenoma, a 32-year-old female patient is presented in the light of the literature examining the framework of the history of disease.

English

Since the 1990s, the arrival of the new generation of antipsychotics, the atypical antipsychotics (AAP), heralded a new era in the management on psychotic patients as they are associated with much less side effects as the older drugs. However, the psychiatric community soon realized a new problem had emerged with these drugs, namely severe metabolic side effects. Several monitoring guidelines were soon published to guide treating physicians on how to deal with this issue. This study was aimed to assess adherence to the recommended guidelines by Malaysian doctors. Data concerning metabolic monitoring over 1 year were collected from 405 subjects newly started on AAP after June 2005, when the recommended guidelines were first implemented. Results showed that almost all the recommended tests/procedures were performed in less than 50% of patients during the recommended designated times. We recommend that the guidelines, which now serve only as a &ldquo;guide&rdquo;, be made a compulsory practice to safeguard the health of our patients. &nbsp; Key words:&nbsp;Atypical antipsychotics, metabolic syndrome, monitoring guidelines.

P-771 - The use of new generation antipsychotics in people with intellectual disability

The New Generation Antipsychotics (NGAs) are frequently used in People with Intellectual Disability (PWID), especially for treating aggressive behaviour. However there is very limited research to fully establish evidence-based approaches for their use in this population. Aim To evaluate the effectiveness of NGAs, in particular olanzapine and risperidone, in treating aggressive behaviour in PWID for who previous medication with First Generation Antipsychotics (FGAs) were not effective. Method 62 subjects with intellectual disability underwent to a two-arm, parallel group pragmatic trial of olanzapine and risperidone with balanced randomisation and blind assessment of outcomes after a switch from a treatment with FGAs. Psychiatric disorders were evaluated by Diagnostic Assessment for the Severely Handicapped (DASH). Aggressive behaviour was assessed by Overt Aggression Scale (OAS) and clinical outcome by Clinical Global Impression (CGI) Scale. Side effects were assessed with specific scales, laboratory and instrumental tests. Results Both risperidone and olanzapine resulted to be more effective than FGAs in reducing aggressive behavior and in treating concurrent psychiatric disorders. The degree of improvement in our sample was very high for OAS and CGI scores. Both compounds resulted to be well tolerated, with side-effects similar to those encountered in other patient populations. Conclusion Our findings seem to confirm previous literature on that olanzapine and risperidone can be effective in reducing aggressive behaviour in PWID. Although NGAs have shown greater efficacy and safety than FGAs, there is still a need for controlled trial and more methodically researches to confirm their benefit.