Second-generation Antipsychotics Group Research Articles

Pregnancy Outcomes With Exposure to Second-Generation Antipsychotics During the First Trimester.

Objective: To investigate the risk of major congenital malformations associated with exposure to second-generation antipsychotics (SGAs) in the first trimester.Methods: Pregnant women who received consultation on drug exposure from the Japan Drug Information Institute in Pregnancy from October 2005 to December 2016 were asked to complete a questionnaire at 1 month after the expected delivery date. The questionnaire included items on pregnancy outcome, date of delivery, gestational age at delivery, malformations in the infant that were confirmed by the pediatrician's report, and the following parameters at birth: height, weight, head circumference, and chest circumference. Odds ratios (ORs) for major congenital malformations among live-born children of pregnant women with SGA exposure during the first trimester (SGA group) relative to children of women not exposed to SGAs and medications known to be teratogenic (comparison group) were estimated using an inverse probability of treatment weighting approach.Results: Of 404 women with SGA exposure during the first trimester, there were 351 live births, 3 stillbirths, 34 spontaneous abortions, and 16 elective abortions. The rate of major congenital malformations among live-born children was 0.9% (3/351) in the SGA group and 1.8% (70/3,899) in the comparison group. No statistically significant differences were observed in the adjusted OR for major congenital malformations (adjusted OR = 0.44; 95% CI, 0.12-1.48; P = .179).Conclusions: SGA exposure during the first trimester is not associated with an increased risk of major congenital malformations. These findings might be reassuring for pregnant women who require SGAs.

Predicting relapse with residual symptoms in schizophrenia: A secondary analysis of the PROACTIVE trial

IntroductionLittle attention has been paid to the contribution of individual residual symptom to predict relapse in patients with schizophrenia receiving oral or long-acting injectable (LAI) antipsychotics. MethodWe used the data from the Preventing Relapse on Oral Antipsychotics Compared to Injectables - Evaluating Efficacy (PROACTIVE) study, in which 305 outpatients with schizophrenia were randomly allocated to either biweekly LAI-risperidone (LAI-R) or daily oral second-generation antipsychotics (SGA) and assessed for up to 30 months. Baseline individual symptoms that could predict subsequent relapse were identified, using a Cox proportional hazards model. Moreover, among those who relapsed during the study (n = 73), individual symptoms were compared between baseline and biweekly ratings 8 to 2 weeks before relapse, using the linear mixed model. ResultsA greater score in grandiosity at baseline was significantly associated with subsequent relapse (adjusted HR = 1.24, p = 0.006). When the two treatment groups were separately analyzed, more severe grandiosity (adjusted HR = 1.43, p = 0.003) and less severe hallucinatory behavior (adjusted HR = 0.70, p = 0.013) at baseline were significantly associated with relapse in the oral SGA group, but none was identified in the LAI-R group. Emotional withdrawal was significantly worse 8 and 2 weeks before relapse compared to the baseline (p = 0.032 and p = 0.043, respectively). DiscussionMore severe grandiosity and less hallucination may have led to more frequent relapses in patients with schizophrenia receiving oral antipsychotics, which was not a case in those receiving LAI-R. The exploratory analysis indicates an increase in emotional withdrawal before relapse may be a useful marker for earlier interventions to possibly avert relapse.

Comparison of Olanzapine versus Other Second-Generation Antipsychotics in the Improvement of Insight and Medication Discontinuation Rate in Schizophrenia.

BackgroundIn the last decade, olanzapine became widely used in mental health service worldwide even after being criticized for its metabolic side effects. Patients with schizophrenia on olanzapine were usually found to stay on their medications longer than the other second-generation antipsychotics (SGAs) except clozapine. The reason for this is unknown.ObjectiveThis prospective study compared the influences of olanzapine and other SGAs except clozapine on improving insight and medication discontinuation rate in schizophrenia.MethodsA total of 148 patients with schizophrenia medically indicated for initiation of treatment with olanzapine or other SGAs were evaluated for symptoms, insight, attitudes toward medication, side effects, body weight and fasting lipid and glucose parameters at admission and before discharge, and follow-up calls one-year after discharge documented whether they were regularly taking prescribed psychotropic medication or not.ResultsAfter an average of 72.8 days of inpatient treatment, the olanzapine and other SGAs group exhibited similar levels of symptom improvement with an average reduction of 28.7 in the Positive and Negative Syndrome Scale (PANSS) total score. The Olanzapine group exhibited better improvement in insight assessed using the G12 item of PANSS and Insight and Treatment Attitudes Questionnaire (ITAQ), more metabolic side effects indexed with total cholesterol, triglycerides levels and weight gain, and a lower medication discontinuation rate than the other SGAs group.ConclusionAlthough general symptom improvement was similar, olanzapine significantly improved insight and presented less medication discontinuation compared to other SGAs, which might partially explain why patients on olanzapine stayed longer on their medications.

Risk of Diabetes Hospitalization or Diabetes Drug Intensification in Patients With Depression and Diabetes Using Second-Generation Antipsychotics Compared to Other Depression Therapies.

Use of second-generation antipsychotics (SGAs) for treatment of depression has increased, and patients with depression and comorbid diabetes or cardiovascular disease are more likely to use SGAs than those without these conditions. We compared SGA and non-SGA depression pharmacotherapies on the risk of diabetes hospitalization or treatment intensification in adults with depression and preexisting diabetes. This was a retrospective cohort study of US commercially insured adults (2009-2015 Truven MarketScan Commercial Claims and Encounters Database) aged 18-64 years old with type 2 diabetes mellitus and unipolar depression previously treated with a selective serotonin reuptake inhibitor or serotonin-norepinephrine reuptake inhibitor. New users of SGAs versus non-SGAs, as well as specific treatments (aripiprazole, quetiapine, bupropion, mirtazapine, and tricyclic antidepressants [TCAs]) were matched on class/medication-specific high-dimensional propensity score. Cox proportional hazard models were used to compare the risk of diabetes-related hospitalization or treatment intensification. We identified 6,625 SGA (aripiprazole = 3,461; quetiapine = 1,977; other = 1,187) and 23,921 non-SGA patients for inclusion (bupropion = 15,511; mirtazapine = 1,837; TCAs = 5,989; other = 584) with a mean age of 51 years. In the matched cohort, the rate of diabetes-related hospitalization or drug intensification was 47.9 per 100 person-years in the SGA group and 43.5 per 100 person-years in the non-SGA group (adjusted hazard ratio [aHR] = 1.03; 95% CI, 0.96-1.11). When comparing treatment subgroups, the risk of events was lower for bupropion versus TCAs (aHR = 0.85; 95% CI, 0.76-0.98), quetiapine versus mirtazapine (aHR = 0.82; 95% CI, 0.67-0.99), and quetiapine versus TCAs (aHR = 0.84; 95% CI, 0.72-0.98). For other comparisons, differences were small and not statistically significant. While drug-specific effects on risk of diabetes hospitalization or treatment intensification most likely guide clinical decision making, we observed only modest differences in risk. The overall impact of SGAs on diabetes control depends not only on direct effects on glucose metabolism but also on effectiveness of depression symptom relief. Future studies evaluating other diabetes outcomes (glycosylated hemoglobin, diabetes complications) are needed.

The effect of antipsychotic medications on acoustic startle latency in schizophrenia

Prepulse inhibition of the acoustic startle reflex (PPI) is extensively studied as a biomarker of schizophrenia (SCZ); however, antipsychotic medication can confound the measure. Latency, the time between the startling stimulus and the reflexive eye blink, provides an index of neural processing speed and is 90% heritable. SCZ subjects have slower latency than controls (CON). This study examined the effects of antipsychotic medication on startle latency. 108 CON and 132 SCZ subjects in three medication subgroups (94 on second-generation antipsychotics (SGA), 25 on first-generation antipsychotics (FGA), 13 unmedicated (NoMed)) were tested on a standard acoustic startle paradigm designed to measure startle magnitude, PPI, and latency. Latency was slower in SCZ compared to CON subjects (p=0.005). Latency did not differ between the three SCZ medication groups. When CON were added to that model, both the NoMed subjects (p=0.04) and the SGA subjects (p=0.003) were slower than CON subjects. For PPI, CON did not differ from SCZ analyzed as a single group. When SCZ subjects were divided into medication groups, PPI was lower in NoMed subjects than the CON group (p=0.03), the SGA group (p=0.02) and the FGA group (p=0.05). SCZ subjects on any medication did not differ from CON. Thus, latency was partially normalized by antipsychotic medication, but this did not obscure the slower latency in SCZ compared to CON. Therefore latency is both trait and state related, whereas medication normalized PPI and obscured any difference between SCZ and CON.

Effects of chronic antipsychotic treatment on neurophysiological correlates of the auditory oddball task in schizophrenia: A preliminary report from a multicentre study

IntroductionThe effects of chronic antipsychotic administration on the human brain are debated. In particular, first-generation (FGAs) and second-generation antipsychotics (SGAs) seem to have different impacts on brain function and structure in subjects with schizophrenia. Few studies have investigated the effect of chronic administration of FGAs and SGAs on indices of brain function, such as event-related potentials (ERP) or neuropsychological performance.ObjectivesWithin the Italian Network for Research on Psychoses study, subjects stabilized on FGAs or SGAs were compared on P300, an ERP component, thought to reflect attention, working memory and context integration and on neurocognitive indices.MethodsERPs were recorded in 110 chronic, stabilized patients with Schizophrenia (28 used FGAs) during a standard auditory oddball task. P300 latency and amplitude were assessed at Pz channel. MATRICS Consensus Cognitive Battery (MCCB) was used for cognitive assessment.ResultsCompared with the SGAs group, patients on FGAs showed significant increased P300 latency (P = 0.003; Cohen's d = 0.67) and significant decreased P300 amplitudes (P = 0.023; Cohen's d = 0.38). The two groups did not differ on psychopathology and MCCB scores. Multiple linear regressions revealed that “FGAs vs. SGAs” (β = 0.298, P = 0.002) and MCCB neurocognitive composite T-score (β = –0.273, P = 0.004) were independent predictors of P300 latency, whereas only age (β = –0.220, P = 0.027) was an independent predictor of P300 amplitude.ConclusionsFGAs seem to affect the functional brain activity more than SGAs, particularly slowing cortical processing. Our results suggest that discrepant findings concerning P300 latency in schizophrenia might be related to the type of antipsychotic treatment used. Longitudinal studies are needed to further address this issue.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Effects of first-generation antipsychotics versus second-generation antipsychotics on quality of life in schizophrenia: a double-blind, randomised study

Whether or not second-generation antipsychotics (SGAs) represent an advantage over first-generation antipsychotics (FGAs) in the treatment of schizophrenia is not certain. Effectiveness studies published in the past 10 years have not unequivocally confirmed the superiority of SGAs over FGAs. We aimed to compare quality of life in patients with schizophrenia on an FGA strategy with those on an SGA strategy. In the multicentre, randomised, double-blind Neuroleptic Strategy Study (NeSSy), we recruited participants (aged 18-65 years) with schizophrenia (ICD-10: F20.X) who required treatment initiation or a change in treatment, from 14 psychiatric university hospitals and state hospitals in Germany. Double randomisation allowed for restricted selection of a treatment within each antipsychotic drug group (FGA or SGA) for an individual patient: first, patients were assigned with a random number table to two of six possible drug pairs, each pair consisting of an FGA (haloperidol [3-6 mg] or flupentixol [6-12 mg]) given orally and an SGA (aripiprazole [10-20 mg], olanzapine [10-20 mg], or quetiapine [400-800 mg]) given orally, and the investigator then selected which pair was best suited to the patient; a second, double-blind random assignment allocated either the FGA or the SGA from the investigator-chosen pair to the patient. Treatment duration was 24 weeks. Primary outcomes were change from baseline to week 24 in quality of life (SF-36) and clinical global impression (CGI-I), analysed in all randomly assigned patients who received at least one dose of the study drug. Safety was assessed in a safety set, consisting of all randomly assigned patients who received at least one dose of the study drug, coinciding with the set of the efficacy analyses. The study is registered with ClinicalTrials.gov, number NCT01164059; German Clinical Trials Register, number DRKS00000304; WHO ICTRP, number U1111-1112-9727; and EudraCT, number 2009-010966-47. Between April 1, 2010, and May 31, 2013, 149 patients were randomly assigned, 69 to FGA treatment and 80 to SGA treatment. 136 patients received at least one dose of study drug (63 in the FGA group, 73 in the SGA group). Mean area under the curve (AUC) values of SF-36 were significantly higher in the SGA group than in the FGA group (85·1 [SD 14·7] vs 79·7 [17·3], p=0·0112). Mean AUC values for CGI-I scores decreased in both groups, but were not significantly different between the two groups (3·39 [SD 0·89] in the FGA group vs 3·26 [0·92] in the SGA group, p=0·3423). 30 (48%) of 63 patients given FGAs had at least one adverse event compared with 42 (57%) of 73 patients given an SGA (p=0·3019); the most common were nervous system disorders (18 [60%] of 30 in the FGA group vs 19 [45%] of 42 in the SGA group) and psychiatric disorders (ten [33%] vs 16 [38%]). One patient died after cessation of study drug (olanzapine), most likely as a result of an illicit drug overdose. The increase in body-mass index (BMI) was significantly higher in the SGA group than in the FGA group (p=0·0021 at week 6 and p=0·0041 at week 24). Improvement of patient-reported quality of life was significantly higher in patients with schizophrenia given SGAs than in those given FGAs, when treatment selection was individualised. This advantage, however, has to be weighed against the potential metabolic adverse effects of some SGAs. German Federal Ministry of Education and Research.

Meta-analysis of population-based studies comparing risk of cerebrovascular accident associated with first- and second-generation antipsychotic prescribing in dementia.

Second-generation antipsychotics (SGAs) are often prescribed in the treatment of Behavioral and Psychological Symptoms of Dementia (BPSD), however, their use has been discouraged in light of clinical trials suggesting that they cause an increased risk of cerebrovascular accidents (CVAs). Aim of the study was to assess relative risk of CVA in dementia patients prescribed SGA rather than first-generation antipsychotics (FGAs), through meta-analysis of population-based studies. A literature search was conducted using several relevant databases. Five studies were included in the review and data were pooled to conduct meta-analysis using the inverse variance method. A total of 79,910 patients were treated with SGAs and 1287 cases of CVA were reported. Of 48,135 patients treated with FGAs, a total of 511 cases of CVA were reported. The relative risk of CVA was 1.02 (95% CI 0.56-1.84) for the SGA group. There was no significant difference in the risk of stroke (p = 0.96) between groups, but significant heterogeneity was found among the results of included studies (p < 0.001). Meta-analysis of population-based data suggested that the use of SGAs as opposed to FGAs to control BPSD is not associated with significantly increased risk of CVA. Copyright © 2016 John Wiley & Sons, Ltd.

Survival analysis of the use of first and second generation antipsychotics among patients suffering schizophrenia: A nationwide population-based cohort study

Few studies have investigated the relationship between the use of different generations of antipsychotics and mortality with contradictory results. The aim of this study is to compare mortality among patients suffering schizophrenia taking different generations of antipsychotics in a nationwide population-based cohort study in Taiwan. A total of 812 patients suffering newly diagnosed schizophrenia under monotherapy of second generation antipsychotics (SGAs) comprised the group of cases. The matched controls were under monotherapy of first generation antipsychotics (FGAs). Each case was matched individually with their initial antipsychotics prescription calendar year and month, gender, and age. Cox regression analyses were applied to estimate survival time, adjusting for gender, age, residence, insurance premium, Charlson comorbidity index, hospital admission days, and hospital admission times. An analysis including the number of antipsychotic prescriptions, a proxy indicator of adherence, into the fully adjusted model to reveal the effect of adherence on survival of patients served as a sensitivity analysis. Subjects receiving SGAs had lower admission times and inpatient days, more antipsychotic prescriptions, and longer follow-up time than FGAs. Compared with the FGAs group, the adjusted hazard ratio of mortality was 0.58 (95% confidence interval =0.34-0.96, p=.034) for SGAs group. After controlling for the number of antipsychotic prescriptions, the difference in mortality between antipsychotic generations was non-significant. The results of this study suggest that SGAs were better than FGAs in mortality among patients suffering schizophrenia. The difference in mortality can be explained by the better medication adherence of SGAs.

Divergent effects of first-generation and second-generation antipsychotics on cortical thickness in first-episode psychosis.

Whether there are differential effects of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) on the brain is currently debated. Although some studies report that FGAs reduce grey matter more than SGAs, others do not, and research to date is limited by a focus on schizophrenia spectrum disorders. To address this limitation, this study investigated the effects of medication in patients being treated for first-episode schizophrenia or affective psychoses. Cortical thickness was compared between 52 first-episode psychosis patients separated into diagnostic (i.e. schizophrenia or affective psychosis) and medication (i.e. FGA and SGA) subgroups. Patients in each group were also compared to age- and sex-matched healthy controls (n = 28). A whole-brain cortical thickness interaction analysis of medication and diagnosis was then performed. Correlations between cortical thickness with antipsychotic dose and psychotic symptoms were examined. The effects of medication and diagnosis did not interact, suggesting independent effects. Compared with controls, diagnostic differences were found in frontal, parietal and temporal regions. Decreased thickness in FGA-treated versus SGA-treated groups was found in a large frontoparietal region (p < 0.001, corrected). Comparisons with healthy controls revealed decreased cortical thickness in the FGA group whereas the SGA group showed increases in addition to decreases. In FGA-treated patients cortical thinning was associated with higher negative symptoms whereas increased cortical thickness in the SGA-treated group was associated with lower positive symptoms. Our results suggest that FGA and SGA treatments have divergent effects on cortical thickness during the first episode of psychosis that are independent from changes due to illness.

Sex differences in the effect of four second‐generation antipsychotics on QTc interval in patients with schizophrenia

We examined sex differences in the effect of olanzapine (OLZ), risperidone (RIS), aripiprazole (ARP), or quetiapine (QTP) on mean corrected QT (QTc) intervals among 222 patients with schizophrenia. Subjects were patients with schizophrenia who were treated with either OLZ (n = 69), RIS (n = 60), ARP (n = 62), or QTP (n = 31). Electrocardiographic measurements were conducted, and the QT interval was corrected using Bazett's correction formula. The mean QTc interval of the QTP group was significantly longer than that of the RIS group (p = 0.002) or ARP group (p = 0.029). The mean QTc interval of the OLZ group was also significantly longer than that of the RIS group (p = 0.006). In female participants, the difference in the mean QTc interval among the four second-generation antipsychotic (SGA) groups was statistically significant (p = 0.002), whereas in male patients, there was no significant difference in the mean QTc interval among the four SGA groups. Post hoc analyses showed that sex differences in QTc interval were observed only in OLZ treatment group (p = 0.007). To our knowledge, this is the first study to demonstrate sex differences in the effect of four SGAs on the QTc interval.

2236 – Service costs and cost factors of child and adolescent psychiatric patients treated with antipsychotics in taiwan

With the widespread of atypical antipsychotics used among children and adolescents, the treatment effectiveness has been of great interest alongside with the efficacy and safety in this population. The study was designed to assess whether second-generation antipsychotics (SGAs) are associated with lower service costs in the real world. Factors associated with service costs were also examined. The claim data (PIMC) of 1996-2008 from the National Insurance Plan of Taiwan was used. Patients aged less than 20 with an incident use of antipsychotics and last for 12 months during this period were included for analysis. Comparisons were made between 8 SGAs and 2 first-generation antipsychotics (FGAs). Changes in service costs were examined with 95% confidence interval. Multivariate regressions with propensity scores adjustment were performed to explore factors associated with psychiatric service costs. A total of 343 treatment encounters were included and results showed no difference in psychiatric services costs in the SGAs group as the total service costs were offset to high antipsychotics costs of SGAs, though antiparkinsonian costs were not different between two groups. Factor positively associated with service costs were relapse (RR=4.0, p< 0.0001) and EPS incidence (RR=1.6, p< 0.008), while types of antipsychotics and diagnoses were not significant factors after adjusting for covariates. Service costs were not different between FGAs and SGAs groups and medication costs were significantly higher in the SGAs group. Relapse and EPS incidence were factors of high costs among children and adolescents psychiatric patients treated with antipsychotics in Taiwan.

Metabolic syndrome and antipsychotic monotherapy treatment among schizophrenia patients in Malaysia

ObjectiveThe objective of this study is to determine the prevalence of metabolic syndrome among schizophrenia patients receiving antipsychotic monotherapy in Malaysia. MethodA cross-sectional study was conducted at multiple centres between June 2008 and September 2011. Two hundred and five patients who fulfilled the DSM IV-TR diagnostic criteria for schizophrenia and who had been on antipsychotic medication for at least one year, were screened for metabolic syndrome. Patients receiving a mood stabilizer were excluded from the study. Metabolic syndrome was defined by using the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults Treatment Panel III (ATP III) modified for Asian waist circumference. ResultsIn the first-generation antipsychotic (FGA) group, the highest prevalence of metabolic syndrome was among patients treated with trifluoperazine and flupenthixol decanoate (66.7% each). For the second-generation antipsychotic (SGA) group, the highest prevalence of metabolic syndrome was among patients treated with clozapine (66.7%). The component with the highest prevalence in metabolic syndrome was waist circumference in both FGA and SGA groups except for aripiprazole in SGA. ConclusionThe prevalence of metabolic syndrome in schizophrenia patients receiving antipsychotic monotherapy in Malaysia was very high. Intervention measures are urgently needed to combat these problems.

Poster #208 NEW RESULTS ALTER BALANCE OF EVIDENCE IN META-ANALYSIS OF LONG-ACTING INJECTABLE VS. ORAL ANTIPSYCHOTICS IN SCHIZOPHRENIA

To review data on efficacy and safety of second-generation antipsychotics (SGAs) in children and adolescents with psychotic and bipolar spectrum disorders.Medline/PubMed/Google Scholar search for studies comparing efficacy and/or tolerability: (i) between two or more SGAs; (ii) between SGAs and placebo; and (iii) between at least one SGA and one first-generation antipsychotic (FGA). The review focused on three major side-effect clusters: 1. body weight, body mass index, and cardiometabolic parameters, 2. prolactin levels, and 3. neuromotor side effects.In total, 34 studies with 2719 children and adolescents were included. Studies lasted between 3 weeks and 12 months, with most studies (79.4%) lasting 3 months or less. Nine studies (n = 788) were conducted in patients with schizophrenia, 6 (n = 719) in subjects with bipolar disorder, and 19 (n = 1212) in a mixed population. Data on efficacy showed that, except for clozapine being superior for refractory schizophrenia, there were no significant differences between SGAs. By contrast, safety assessments showed relevant differences between SGAs. Mean weight gain ranged from 3.8 kg to 16.2 kg in patients treated with olanzapine (n = 353), from 0.9 kg to 9.5 kg in subjects receiving clozapine (n = 97), from 1.9 kg to 7.2 kg in those on risperidone (n = 571), from 2.3 kg to 6.1 kg among patients taking quetiapine (n = 133), and from 0 kg to 4.4 kg in those treated with aripiprazole (n = 451). Prolactin levels increased the most in subjects on risperidone (mean change ranging from 8.3 ng/mL to 49.6 ng/mL), followed by olanzapine (−1.5 ng/mL to + 13.7 ng/mL). Treatment with aripiprazole was associated with decreased prolactin levels, while clozapine and quetiapine were found to be mostly neutral. With respect to neuromotor side effects, SGAs were associated with less parkinsonism and akathisia than FGAs. Most of the studies comparing neuromotor side effects between SGAs found no significant differences.SGAs do not behave as a homogeneous group in children and adolescents with psychotic and mood disorders. Except for clozapine, the heterogeneity within the SGA group is mainly due to differences in the rates and severity of adverse events, especially regarding weight gain as a proxy for the risk of cardiometabolic disturbances.

TNF-α −308 G>A polymorphism and weight gain in patients with schizophrenia under long-term clozapine, risperidone or olanzapine treatment

Atypical or second-generation antipsychotics (SGAs) are associated with excessive body weight gain (BWG) and other components of metabolic syndrome. Among all SGAs, clozapine and olanzapine are known to cause the most significant weight gain, followed by risperidone and quetiapine. The genetic variant of tumor necrosis factor α ( TNF-α), −308 G>A polymorphism (rs1800629), has been implicated in clozapine-induced BWG in several studies. We hypothesized that TNF-α −308 G>A polymorphism has a general effect on SGA-induced BWG. The present study was conducted to examine the association between TNF-α −308 G>A polymorphism and BWG during treatment for schizophrenia using a variety of second generation antipsychotics (SGAs). A total of 500 patients with schizophrenia treated with clozapine ( n = 275), olanzapine ( n = 79) or risperidone ( n = 146) for an average of 49.9 months were recruited. Subjects with an increase in weight of more than 7% from the baseline before the current SGA treatment to the weight at the survey point were defined as having BWG. The association between TNF- α −308 G>A polymorphism and BWG was studied, and the effect of non-genetic factors such as baseline BMI, SGA treatment duration and SGA type on the association was controlled by logistic regression. The results revealed that there was no significant association between BWG and TNF-α −308 G>A polymorphism (GG/GA/AA or GG/GA+AA) in each separate SGA group or collectively. These findings suggest that TNF-α −308 G>A polymorphism does not play a major role in SGA-induced weight gain.

P.3.a.025 Metabolic syndrome in inpatients with serious mental illness

Whether or not second-generation antipsychotics (SGAs) represent an advantage over first-generation antipsychotics (FGAs) in the treatment of schizophrenia is not certain. Effectiveness studies published in the past 10 years have not unequivocally confirmed the superiority of SGAs over FGAs. We aimed to compare quality of life in patients with schizophrenia on an FGA strategy with those on an SGA strategy.In the multicentre, randomised, double-blind Neuroleptic Strategy Study (NeSSy), we recruited participants (aged 18–65 years) with schizophrenia (ICD-10: F20.X) who required treatment initiation or a change in treatment, from 14 psychiatric university hospitals and state hospitals in Germany. Double randomisation allowed for restricted selection of a treatment within each antipsychotic drug group (FGA or SGA) for an individual patient: first, patients were assigned with a random number table to two of six possible drug pairs, each pair consisting of an FGA (haloperidol [3–6 mg] or flupentixol [6–12 mg]) given orally and an SGA (aripiprazole [10–20 mg], olanzapine [10–20 mg], or quetiapine [400–800 mg]) given orally, and the investigator then selected which pair was best suited to the patient; a second, double-blind random assignment allocated either the FGA or the SGA from the investigator-chosen pair to the patient. Treatment duration was 24 weeks. Primary outcomes were change from baseline to week 24 in quality of life (SF-36) and clinical global impression (CGI-I), analysed in all randomly assigned patients who received at least one dose of the study drug. Safety was assessed in a safety set, consisting of all randomly assigned patients who received at least one dose of the study drug, coinciding with the set of the efficacy analyses. The study is registered with ClinicalTrials.gov, number NCT01164059; German Clinical Trials Register, number DRKS00000304; WHO ICTRP, number U1111–1112–9727; and EudraCT, number 2009–010966–47.Between April 1, 2010, and May 31, 2013, 149 patients were randomly assigned, 69 to FGA treatment and 80 to SGA treatment. 136 patients received at least one dose of study drug (63 in the FGA group, 73 in the SGA group). Mean area under the curve (AUC) values of SF-36 were significantly higher in the SGA group than in the FGA group (85·1 [SD 14·7] vs 79·7 [17·3], p=0·0112). Mean AUC values for CGI-I scores decreased in both groups, but were not significantly different between the two groups (3·39 [SD 0·89] in the FGA group vs 3·26 [0·92] in the SGA group, p=0·3423). 30 (48%) of 63 patients given FGAs had at least one adverse event compared with 42 (57%) of 73 patients given an SGA (p=0·3019); the most common were nervous system disorders (18 [60%] of 30 in the FGA group vs 19 [45%] of 42 in the SGA group) and psychiatric disorders (ten [33%] vs 16 [38%]). One patient died after cessation of study drug (olanzapine), most likely as a result of an illicit drug overdose. The increase in body-mass index (BMI) was significantly higher in the SGA group than in the FGA group (p=0·0021 at week 6 and p=0·0041 at week 24).Improvement of patient-reported quality of life was significantly higher in patients with schizophrenia given SGAs than in those given FGAs, when treatment selection was individualised. This advantage, however, has to be weighed against the potential metabolic adverse effects of some SGAs.German Federal Ministry of Education and Research.

P.3.c.015 Haloperidol versus atypical antipsychotics in the long-term treatment of schizophrenia

The objective of this study is to determine the prevalence of metabolic syndrome among schizophrenia patients receiving antipsychotic monotherapy in Malaysia.A cross-sectional study was conducted at multiple centres between June 2008 and September 2011. Two hundred and five patients who fulfilled the DSM IV-TR diagnostic criteria for schizophrenia and who had been on antipsychotic medication for at least one year, were screened for metabolic syndrome. Patients receiving a mood stabilizer were excluded from the study. Metabolic syndrome was defined by using the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults Treatment Panel III (ATP III) modified for Asian waist circumference.In the first-generation antipsychotic (FGA) group, the highest prevalence of metabolic syndrome was among patients treated with trifluoperazine and flupenthixol decanoate (66.7% each). For the second-generation antipsychotic (SGA) group, the highest prevalence of metabolic syndrome was among patients treated with clozapine (66.7%). The component with the highest prevalence in metabolic syndrome was waist circumference in both FGA and SGA groups except for aripiprazole in SGA.The prevalence of metabolic syndrome in schizophrenia patients receiving antipsychotic monotherapy in Malaysia was very high. Intervention measures are urgently needed to combat these problems.

PHARMACOGENETICS OF SCHIZOPHRENIA: TARDIVE DYSKINESIA AND WEIGHT GAIN

The presence of the metabolic syndrome (MetS) is an important risk factor for cardiovascular disease and diabetes. There are limited data on the prevalence of MetS in patients with schizophrenia at the onset of the disorder and specifically no data on patients treated in the era when only first-generation antipsychotics were available.Data from a historic cohort of consecutively admitted first-episode patients with schizophrenia treated with first-generation antipsychotics (FGAs) were compared with an age and sex matched series of consecutive first-episode patients treated only with second-generation antipsychotics (SGAs). Rates of MetS were compared at baseline and after on average 3 years of treatment exposure.At first episode there was no difference in the prevalence of MetS between the historic and the current cohort. Rates of MetS increased over time in both groups, but patients started on SGAs had a three times higher incidence rate of MetS (Odds Ratio 3.6, CI 1.7–7.5). The average increase in weight and body mass index was twice as high in patients started on SGA. The difference between the FGA and SGA group was no longer significant when patients started on clozapine and olanzapine were excluded.Rates of MetS at the first episode of schizophrenia today are not different from those of patients 15 to 20 years ago. This finding counters the notion that the high rates of metabolic abnormalities in patients with schizophrenia currently reported are mainly due to lifestyle changes over time in the general population. Some SGAs have a significantly more negative impact on the incidence of MetS compared to FGAs in first-episode patients.

Typical and atypical antipsychotics differentially affect long-term incidence rates of the metabolic syndrome in first-episode patients with schizophrenia: A retrospective chart review

The presence of the metabolic syndrome (MetS) is an important risk factor for cardiovascular disease and diabetes. There are limited data on the prevalence of MetS in patients with schizophrenia at the onset of the disorder and specifically no data on patients treated in the era when only first-generation antipsychotics were available. MethodsData from a historic cohort of consecutively admitted first-episode patients with schizophrenia treated with first-generation antipsychotics (FGAs) were compared with an age and sex matched series of consecutive first-episode patients treated only with second-generation antipsychotics (SGAs). Rates of MetS were compared at baseline and after on average 3 years of treatment exposure. ResultsAt first episode there was no difference in the prevalence of MetS between the historic and the current cohort. Rates of MetS increased over time in both groups, but patients started on SGAs had a three times higher incidence rate of MetS (Odds Ratio 3.6, CI 1.7–7.5). The average increase in weight and body mass index was twice as high in patients started on SGA. The difference between the FGA and SGA group was no longer significant when patients started on clozapine and olanzapine were excluded. ConclusionRates of MetS at the first episode of schizophrenia today are not different from those of patients 15 to 20 years ago. This finding counters the notion that the high rates of metabolic abnormalities in patients with schizophrenia currently reported are mainly due to lifestyle changes over time in the general population. Some SGAs have a significantly more negative impact on the incidence of MetS compared to FGAs in first-episode patients.

C.09.01 Perspectives on how schizophrenia has impacted patient lives and those of their families

Whether or not second-generation antipsychotics (SGAs) represent an advantage over first-generation antipsychotics (FGAs) in the treatment of schizophrenia is not certain. Effectiveness studies published in the past 10 years have not unequivocally confirmed the superiority of SGAs over FGAs. We aimed to compare quality of life in patients with schizophrenia on an FGA strategy with those on an SGA strategy.In the multicentre, randomised, double-blind Neuroleptic Strategy Study (NeSSy), we recruited participants (aged 18–65 years) with schizophrenia (ICD-10: F20.X) who required treatment initiation or a change in treatment, from 14 psychiatric university hospitals and state hospitals in Germany. Double randomisation allowed for restricted selection of a treatment within each antipsychotic drug group (FGA or SGA) for an individual patient: first, patients were assigned with a random number table to two of six possible drug pairs, each pair consisting of an FGA (haloperidol [3–6 mg] or flupentixol [6–12 mg]) given orally and an SGA (aripiprazole [10–20 mg], olanzapine [10–20 mg], or quetiapine [400–800 mg]) given orally, and the investigator then selected which pair was best suited to the patient; a second, double-blind random assignment allocated either the FGA or the SGA from the investigator-chosen pair to the patient. Treatment duration was 24 weeks. Primary outcomes were change from baseline to week 24 in quality of life (SF-36) and clinical global impression (CGI-I), analysed in all randomly assigned patients who received at least one dose of the study drug. Safety was assessed in a safety set, consisting of all randomly assigned patients who received at least one dose of the study drug, coinciding with the set of the efficacy analyses. The study is registered with ClinicalTrials.gov, number NCT01164059; German Clinical Trials Register, number DRKS00000304; WHO ICTRP, number U1111–1112–9727; and EudraCT, number 2009–010966–47.Between April 1, 2010, and May 31, 2013, 149 patients were randomly assigned, 69 to FGA treatment and 80 to SGA treatment. 136 patients received at least one dose of study drug (63 in the FGA group, 73 in the SGA group). Mean area under the curve (AUC) values of SF-36 were significantly higher in the SGA group than in the FGA group (85·1 [SD 14·7] vs 79·7 [17·3], p=0·0112). Mean AUC values for CGI-I scores decreased in both groups, but were not significantly different between the two groups (3·39 [SD 0·89] in the FGA group vs 3·26 [0·92] in the SGA group, p=0·3423). 30 (48%) of 63 patients given FGAs had at least one adverse event compared with 42 (57%) of 73 patients given an SGA (p=0·3019); the most common were nervous system disorders (18 [60%] of 30 in the FGA group vs 19 [45%] of 42 in the SGA group) and psychiatric disorders (ten [33%] vs 16 [38%]). One patient died after cessation of study drug (olanzapine), most likely as a result of an illicit drug overdose. The increase in body-mass index (BMI) was significantly higher in the SGA group than in the FGA group (p=0·0021 at week 6 and p=0·0041 at week 24).Improvement of patient-reported quality of life was significantly higher in patients with schizophrenia given SGAs than in those given FGAs, when treatment selection was individualised. This advantage, however, has to be weighed against the potential metabolic adverse effects of some SGAs.German Federal Ministry of Education and Research.