Few studies have examined whether UK military veterans are at an increased risk of dementia. We explored the risk of dementia in Scottish military veterans aged up to 73 years in comparison with people who have never served.

Retrospective cohort study of 78 000 veterans and 253 000 people with no record of service, matched for age, sex and area of residence, with up to 37 years follow-up, using Cox proportional hazard analysis to compare risk of dementia in veterans and non-veterans, overall and by subgroup.

Dementia was recorded in 0.2% of both veterans and non-veterans overall, Cox proportional hazard ratio 0.98, 95% confidence interval (CI) 0.82–1.19, p = 0.879 (landmark age: 50 years), with no difference for men but increased risk in veteran women and Early Service Leavers. Post-traumatic stress disorder (PTSD) was associated with a higher risk of dementia in both veterans and non-veterans, although possibly to a lesser degree in veterans. A history of mood disorder was strongly associated with developing dementia, greater in veterans than in non-veterans, odds ratio 1.54, 95% CI 1.01–2.35, p = 0.045.

There was no evidence to suggest that military service increased the risk of dementia, although this may change as the cohort ages. The well-documented association with PTSD shows no evidence of being stronger in veterans; by contrast, the association of mood disorder with dementia is much stronger in veterans. Healthcare providers should carefully assess the cognitive status of older veterans presenting with depressive illness in order to identify early dementia and ensure optimum management.

To compare the longer-term metabolic effects and efficacy of paliperidone ER and olanzapine in patients with schizophrenia.

Prospective 6-month randomized study evaluating flexible doses of paliperidone ER and oral olanzapine (OLA). Primary endpoint was the change in triglyceride to high-density lipoprotein (TG:HDL) ratio, a sensitive measure of insulin resistance. Additional endpoints were the Positive and Negative Syndrome Scale (PANSS), body weight, lipids, homoeostasis model of insulin resistance (HOMA-IR) and adverse events (AEs).

239 patients were randomized to paliperidone ER, 220 to olanzapine. Demographics and baseline characteristics were comparable. Mean doses were 6.9±1.3 mg/day for paliperidone ER and 11.6±2.3 mg/day for olanzapine. The TG:HDL ratio for olanzapine significantly worsened from baseline to endpoint (0.42±1.19;p< 0.0001); it remained unchanged for paliperidone ER (-0.08±1.10;p=0.4718; between-group difference p< 0.0001). PANSS total scores at endpoint significantly improved (olanzapine -16.6±15.0; paliperidone ER -13.5±15.9; both p< 0.0001 vs. baseline); the between-group difference met prespecified non-inferiority criteria. Endpoint weight change was 3.8±5.9kg for olanzapine and 1.2±4.6kg for paliperidone ER (p< 0.0001). Insulin resistance in HOMA-IR did not change with paliperidone ER (p=0.1507) but significantly worsened with olanzapine (p=0.003 vs. baseline). The most frequently reported treatment-emergent AEs (>=5%) were weight increase (OLA 18.2%;Pali ER 9.6%), insomnia (OLA 1.4%;Pali ER 9.6%), somnolence (OLA 9.5%;Pali ER 3.3%) and schizophrenia (OLA 1.8%;Pali ER 5.0%).

In this randomized controlled study paliperidone ER was superior to olanzapine with regards to insulin resistance, weight gain, lipid changes and other relevant metabolic endpoints. Efficacy was non-inferior between paliperidone ER and olanzapine.

Évaluer la tolérance, la sécurité d’emploi et la réponse à un traitement par palmitate de palipéridone (PP) à doses flexibles chez des patients non aigus atteints de schizophrénie, après échec d’un traitement par un autre antipsychotique injectable à action prolongée : décanoate d’halopéridol (Déc-Hal), décanoate de flupentixol (Déc-Fpt), décanoate de fluphénazine (Déc-Flu), zuclopenthixol (Zuc) ou rispéridone à libération prolongée (RIS-LP).

Étude internationale, prospective, ouverte, de six mois, chez des patients atteints de schizophrénie, non aigus mais insuffisamment contrôlés par d’autres antipsychotiques injectables à action prolongée.

Taux de réponse (amélioration ≥ 20 % du score total à la PANSS [Positive and Negative Syndrome Scale]), score à la PSP (Personal and Social Performance scale), événements indésirables (EIs).

Les analyses ont été réalisées sur la population en intention de traiter de façon stratifiée pour chaque traitement : 53 patients Déc-Hal, 35 Déc-Fpt, 44 Déc-Flu, 42 Zuc, 56 RIS-LP. Les scores totaux moyens à la PANSS initiale variaient de 67,7 ± 20,3 [RIS-LP] à 75,7 ± 13,2 [Déc-Hal]. Entre 71,4 % [RIS-LP] et 85,7 % [Déc-Fpt] des patients ont terminé l’étude. À la fin de l’étude, 53,7 % [Zuc], 54,7 % [Déc-Hal], 59,1 % [Déc-Flu], 61,1 % [RIS-LP] et 61,8 % [Déc- Fpt] des patients ont vu leur score total à la PANSS diminuer d’au moins 20 %. Les scores moyens de PSP de base étaient de 48,7 [Déc-Hal], 59,6 [Déc-Fpt], 53,5 [Déc-Flu], 52,9 [Zuc] et 60,1 [RIS-LP], et le changement en fin d’étude était respectivement de : 5,2 ; 6,1 ; 6,0 ; 6,4 ; et 5,2 (p ≤ 0,0163 pour tous les traitements). Les EIs rapportés au moins une fois dans tous les sous-groupes : douleur au site d’injection, insomnie, trouble psychotique.

Le PP à doses flexibles a été bien toléré et a permis une réponse thérapeutique cliniquement significative chez des patients non aigus atteints de schizophrénie, après échec d’un traitement par d’autres antipsychotiques injectables à action prolongée.

There are concerns that people with mental disorders may not receive proper somatic care within health care systems, and face the risk of poor physical health outcomes and premature death.

To study whether patients with diabetes and comorbid mental illness are at higher risk of amputation of the lower limbs and mortality than diabetic patients without mental illness.

To pinpoint possible disparities in physical health outcomes and mortality in diabetic patients with or without mental disorders.

National Swedish registers; Prescribed Drug Register, Patient Register and Cause of Death Register. All subjects that were prescribed antidiabetics during 2006, at age 35–79, were included (n = 229,956). Subjects with at least 2 hospital inpatient stays during 1996–2005 for psychotic disorders, i.e. schizophrenia/affective psychosis (n = 2,791), or non-psychotic disorders, i.e. depression/anxiety (n = 2,327) were identified. The study population was followed from 2007–2009. A Poisson regression model estimated the effect of mental illness on the likelihood of amputation or death. Incidence rate ratios (IRR) and 95% confidence intervals (CI) were calculated.

Diabetic patients with comorbid psychotic and non-psychotic illness were more likely to die than patients without mental illness, also when suicides and events of undetermined intent were excluded (IRR = 2.44, CI 2.18–2.72 and IRR = 2.43, CI 2.17–2.71, respectively). The risk of amputation was particularly enhanced in diabetic patients with depression or anxiety (IRR = 4.39, CI 2.58-7.49).

In diabetic patients there exist unsettling disparities in physical health outcomes and mortality that are associated with whether a person is mentally ill or not.

Évaluer la tolérance, la sécurité d’emploi et l’efficacité de doses flexibles de PP chez des patients adultes en période d’exacerbation aiguë d’une schizophrénie, après échec d’un traitement par antipsychotiques oraux.

Étude internationale, prospective, ouverte, de six mois.

Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Severity (CGI-S), événements indésirables (EI), changement de poids.

Deux cent douze patients (population en intention de traiter) : âge moyen 36,4 ± 12,1 ans, 59,0 % d’hommes, 85,4 % souffrant de schizophrénie paranoïde ont été inclus. La principale raison de la substitution d’un antipsychotique oral par le PP était un manque d’efficacité (45,8 %). 70,3 % des patients ont terminé l’étude de six mois. Les raisons les plus fréquentes d’arrêt précoce ont été : le choix du patient (9,4 %), des EI (9,0 %), les perdus de vue (4,7 %), le manque d’efficacité (2,8 %). Le score total moyen à la PANSS initiale (98,5 ± 20,1) a diminué, et ce dès j8, pour atteindre 67,4 ± 24,0 à la fin de l’étude (diminution de −31,0 ± 29,0, p < 0,0001). 66,7 % des patients ont eu une amélioration de plus de 30 % du score PANSS total et le pourcentage de patients jugés manifestement malades ou pire (CGI-S) a diminué de 75,1 % à 20,5 %. Les EIs (≥ 5 % patients) : douleur au site d’injection (13,7 %), insomnie (10,8 %), trouble psychotique (10,4 %), céphalées (6,1 %) et anxiété (6,1 %). Le changement moyen de poids a été de 2,6 ± 5,6 kg (IC 95 % [1,8; 3,4]).

Ces résultats confirment que le PP à doses flexibles est bien toléré et permet une réponse clinique précoce et cliniquement significative chez des patients en période d’exacerbation aiguë de leur trouble schizophrénique, après échec d’un traitement par antipsychotiques oraux.

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

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

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

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

Évaluer l’amélioration fonctionnelle chez des patients atteints de schizophrénie sous palmitate de paliperidone (PP) à doses flexibles après échec d’un traitement par antipsychotiques oraux.

Analyse menée dans deux sous-groupes de patients atteints de schizophrénie : aigus (n = 202) et non aigus (n = 593) après échec d’un traitement par antipsychotiques oraux, inclus dans une étude internationale, prospective, de six mois.

Changement du score total à la PANSS (Positive and Negative Syndrome Scale), à la PSP (Personal and Psychosocial Performance scale), et à la Mini-ICF-APP (Mini International Classification of Functionality, Disability and Health Rating for Activity and Participation Disorders in Psychological Illnesses).

Les deux sous-groupes ont présenté une amélioration significative du score total à la PANSS : de 98,5 ± 20,1 à l’inclusion à 67,4 ± 24,0 à la fin de l’étude (diminution moyenne = −31,0 ± 29,0) chez les patients aigus et de 71,5 ± 14,6 à 59,7 ± 18,1 (diminution moyenne = −11,7 ± 15,9) chez les patients non aigus. Cette réponse thérapeutique était associée à une augmentation significative du score total à la PSP de 43,9 ± 15,0 à 62,9 ± 17,1 (amélioration moyenne = 19,0 ± 18,7, p <0,0001) chez les patients aigus, et de 58,1 ± 13,4 à 66,1 ± 15,7 (amélioration moyenne =8,0 ± 14,0, p < 0,0001) chez les patients non aigus. Il existait une amélioration significative du score à la Mini-ICF-APP qui diminuait de 26,8 ± 8,5 à 18,5 ± 9,8 (diminution moyenne = −8,0 ± 10,4, p < 0,0001) chez les patients aigus et de 19,8 ± 7,9 à 15,9 ± 8,8 (diminution moyenne = −4,0 ± 7,5, p < 0,0001) chez les patients non aigus.

L’amélioration symptomatique sous PP à doses flexibles chez des patients aigus ou non-aigus atteints de schizophrénie après échec d’un traitement par antipsychotique oral s’est accompagnée d’une amélioration fonctionnelle cliniquement significative.

Évaluer la tolérance, la sécurité d’emploi et la réponse à un traitement mensuel par palmitate de paliperidone (PP) à doses flexibles chez des patients adultes atteints de schizophrénie, non-aigus mais symptomatiques, après échec d’un traitement par antipsychotiques oraux.

Analyse d’un groupe de patients atteints de schizophrénie, non-aigus mais symptomatiques, inclus dans une étude internationale, ouverte, prospective de six mois, évaluant la symptomatologie clinique : PANSS (Positive and Negative Syndrome Scale) et CGIS-S (Clinical Global Impression-Severity Scale), les événements indésirables (EIs) et le changement de poids.

Cinq cent quatre-vingt-treize patients (population en intention de traiter) : 63,1 % d’hommes, âge moyen 38,4 ± 11,8 ans, 78,6 % souffrant de schizophrénie paranoïde. La principale raison de la substitution d’un antipsychotique oral par le PP était un manque d’efficacité (24,3 %). 74,5 % des patients ont terminé l’étude de six mois. Les raisons les plus fréquentes d’arrêt précoce étaient : le choix du patient (9,3 %), des effets indésirables (EIs) (6,1 %), les perdus de vue (3,0 %) et le manque d’efficacité (2,5 %). Le score total moyen à l’échelle PANSS a diminué de 71,5 ± 14,6 à l’inclusion à 59,7 ± 18,1 à la fin de l’étude (soit une différence de −11,7 ± 15,9 points ; 95 % IC 95 % [−13,0 ; −10,5] ; p <0,0001). 64,0 % des patients ont eu une amélioration supérieure ou égale à 20 % du score total à la PANSS et le pourcentage de patients légèrement malades ou moins (CGI-S) est passé de 31,8 à 63,2 %. Les EIs touchant plus de 5 % des patients sont : douleur au site d’injection (12,3 %), insomnie (8,6 %), anxiété (6,7 %), trouble psychotique (6,1 %) et céphalées (5,6 %). Le changement moyen de poids a été de 1,2 ± 5,0 kg (IC 95 % [0,7 ; 1,6]).

Ces résultats confirment la bonne tolérance et l’efficacité thérapeutique du PP à doses flexibles chez des patients non aigus atteints de schizophrénie, après échec d’un traitement par antipsychotiques oraux.

To explore the effect of flexibly dosed paliperidone palmitate (PP) on negative, depression/anxiety, patient functioning and extrapyramidal symptoms in adult non-acute schizophrenia patients previously unsuccessfully treated with oral aripiprazole.

International, prospective 6-month open-label study. Outcomes analyzed were changes from baseline (BL) to last-observation-carried-forward endpoint (EP) in Positive and Negative Syndrome Scale (PANSS) negative subscale, PANSS negative and anxiety/depression Marder factors, patient functioning (Personal and Social Performance Scale (PSP) and Mini International Classification of Functioning (Mini-ICF)) and Extrapyramidal Symptom Rating Scale (ESRS).

: 46 patients were analyzed: 73.9% male, mean age 34.4±9.4 years, 78.3% paranoid schizophrenia, 67.4% completed the study. Mean prior oral aripiprazole dose was 22.7±10.7 mg/day. PANSS negative subscale score decreased from 20.3±5.0 at BL to 17.3±6.1 at EP (mean change -3.0±5.0; 95% confidence interval (CI) of change -4.4;–1.5; p<0.0001). PANSS negative symptoms Marder factor score improved from 19.5±5.8 to 16.6±5.9 (95%CI -4.5;-1.3, p<0.0001) and anxiety/depression Marder factor score improved from 10.3±3.6 to 8.5±2.9 (95%CI -3.0;-0.6, p=0.0031). Extrapyramidal symptoms in ESRS total score improved significantly from BL to EP by -0.6±3.4 (95% CI -1.6;0.4, p=0.0456). Patient functioning significantly improved in PSP (from 58.9±13.4 to 62.9±15.2, p=0.041) and Mini-ICF (from 19.0±7.78 to 16.1±9.84; 95%CI -5.1,-0.7; p=0.0079). The only treatment-emergent adverse event reported in at least 5 patients was anxiety (n=6).

Transition from unsuccessful treatment with oral aripiprazole to flexibly dosed paliperidone palmitate in non-acute schizophrenia patients was well tolerated and associated with significant improvements in negative, depressive, anxiety and extrapyramidal symptoms as well as patient functioning.

Effective antipsychotic treatment of schizophrenia should, beyond symptom control, translate into meaningful functional improvements. This study explored functional outcomes in patients with schizophrenia switched from previous unsuccessful treatment with oral antipsychotics to flexible doses of paliperidone palmitate (PP).

Two groups of acute (N=212) and non-acute (N=593) patients from an international prospective open-label 6-month study. Outcomes were change in Positive and Negative Syndrome Scale (PANSS) total score, Personal and Psychosocial Performance scale (PSP) and Mini International Classification of Functionality, Disability and Health Rating for Activity and Participation Disorders in Psychological Illnesses (Mini-ICF-APP).

Both groups significantly improved from baseline to endpoint in mean PANSS total score from 98.5±20.1 to 67.4±24.0 (mean change -31.0±29.0) in acute and from 71.5±14.6 to 59.7±18.1 (mean change -11.7±15.9) in non-acute patients (all p<0.0001). Patient functioning in PSP total score increased from 43.9±15.0 at baseline to 62.9±17.1 at endpoint (mean change 19.0±18.7; 95% confidence interval [CI] 16.4;21.6) in the acute and from 58.1±13.4 at baseline to 66.1±15.7 at endpoint (mean change 8.0±14.0; 95%CI 6.8;9.1) in the non-acute group (both groups p<0.0001). Illness-related disabilities of activity and participation within groups improved significantly in Mini-ICF-APP global score decreasing from 26.8±8.5 to 18.5±9.8 (mean change -8.0±10.4; 95%CI -9.5;-6.5) in acute and from 19.8±7.9 to 15.9±8.8 (mean change: -4.0±7.5; 95%CI - 4.6;-3.3) from baseline to endpoint in non-acute patients (both groups p<0.0001).

Symptom reduction in acute and non-acute patients with schizophrenia treated with PP after previous unsuccessful treatment with oral antipsychotics was associated with clinically meaningful functional improvements.

A majority of the studies on cognition in schizophrenia have been conducted in drug-treated patients. In healthy subjects, administration of antipsychotic medication has been found to have a negative impact on cognitive performance in domains such as speed of processing and attention. Antipsychotic drugs occupy the D2-dopamine receptor, a receptor subtype that has been related to cognitive function. Studies employing Positron Emission Tomography have shown that poor performance in several cognitive domains is associated to low D2-receptor binding. It is therefore crucial to examine cognition in drug-naïve patients with schizophrenia.

In FES patients: To examine the profile of cognitive impairments in the absence of antipsychotic medication and compare with the cognitive profile of patients who are on antipsychotic medication.

To study cognition in FES.

The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) battery was administered to 60 patients with early schizophrenia and 30 healthy controls, 50% of the patients were drug-naïve. This research is ongoing and a part of the Karolinska Schizophrenia Project (KaSP), a multidisciplinary research consortium that examines the pathophysiology of schizophrenia.

Preliminary findings show that patients perform worse than healthy controls in all cognitive domains, with no significant differences between drug-naïve and medicated patients. Attention and Visual memory were the domains with the greatest impairments. The results are compared with our previous meta-analytic findings in drug-naïve patients.

These preliminary findings confirm the existence of cognitive impairments at the early stage of schizophrenia in the absence of antipsychotic medication.

This study explores tolerability, safety and treatment response of flexible doses of the atypical long-acting antipsychotic paliperidone palmitate (PP) in adult patients with an acute exacerbation of schizophrenia previously unsuccessfully treated with oral antipsychotics.

International prospective open-label 6-month study. Outcome parameters were change in Positive and Negative Syndrome Scale (PANSS) total score, Clinical Global Impression-Severity Scale (CGI-S), treatment-emergent adverse events (TEAEs) and weight change.

212 acute patients, 59.0% male, mean age 36.4 ±12.1 years, 85.4% paranoid schizophrenia were enrolled. 70.3% of patients completed the study. Most frequent reasons for early discontinuation were subject choice (9.4%), or an adverse event (9.0%). Recommended initiation regimen of PP (150 mg eq on day 1 and 100 mg eq on day 8) was administered in 92.9% of subjects. Mean baseline PANSS total score decreased from 98.5±20.1 as of day 8 of treatment to 67.4±24.0 at endpoint (mean change -31.0±28.97; 95% confidence interval [CI]-35.0;-27.1; p<0.0001). 66.7% of patients improved ≥30% in PANSS total score and percentage of patients rated markedly ill or worse in CGI-S decreased from 75.1% at baseline to 20.5% at endpoint. TEAEs reported in ≥5% were injection site pain (13.7%), insomnia (10.8%), psychotic disorder (10.4%), headache (6.1%) and anxiety (6.1%). Mean weight change at endpoint was 2.6±5.6 kg (95%CI 1.8; 3.4).

These data support results from previous randomized controlled studies that flexibly dosed paliperidone palmitate is well tolerated and associated with an early and clinically relevant treatment response in acute schizophrenia patients previously unsuccessfully treated with oral antipsychotics.

Évaluer l’effet du palmitate de palipéridone (PP) à doses flexibles sur les symptômes négatifs, la dépression/anxiété, le fonctionnement et les symptômes extrapyramidaux chez des patients adultes souffrant de schizophrénie non-aiguë, en échec à un traitement par aripiprazole oral.

Étude internationale, prospective, en ouvert de 6 mois.

Variations entre début d’étude (baseline) et dernière observation rapportée sur la PANSS (Positive and Negative Syndrome Scale), la sous-échelle négative de la PANSS, les facteurs de Marder de la PANSS « symptômes négatifs » et « anxiété/dépression », les échelles de fonctionnement PSP (Personal and Social Performance) et Mini-ICF (Mini International Classification of Functioning) et l’échelle ESRS (Extrapyramidal Symptom Rating Scale).

Quarante-six patients analysés (73,9 % hommes, âge moyen 34,4 ± 9,4 ans, 78,3 % schizophrénie paranoïde). Parmi les patients, 67,4 % ont terminé l’étude. Avant l’inclusion, la dose moyenne d’aripiprazole oral était de 22,7 ± 10,7 mg/jour. Le score de la sous-échelle négative de PANSS s’est significativement amélioré de 20,3 ± 5,0 (baseline) à 17,3 ± 6,1 (fin d’étude) (variation moyenne = −3,0 ± 5,0 ; IC 95 % = −4,4 ; −1,5 ; p < 0,0001), ainsi que les scores des facteurs de Marder « symptômes négatifs » (de 19,5 ± 5,8 à 16,6 ± 5,9 ; IC95 % = −4,5 ; −1,3, p < 0,0001) et « anxiété/dépression » (de 10,3 ± 3,6 à,5 ± 2,9 ; IC95 % = −3,0 ; −0,6, p = 0,0031). Le score ESRS s’est aussi amélioré de manière significative (de −0,6 ± 3,4 ; IC 95 % = −1,6 ; 0,4, p = 0,0456). Le fonctionnement du patient s’est amélioré de manière significative sur les échelles PSP (de 58,9 ± 13,4 à 62,9 ± 15,2, p = 0,041) et Mini-ICF (de 19,0 ± 7,78 à 16,1 ± 9,84 ; IC 95 % −5,1, −0,7 ; p = 0,0079). Le seul événement indésirable sous traitement rapporté chez ≥ 5 patients a été l’anxiété (n = 6).

La transition d’un échec au traitement par aripiprazole oral à un traitement par PP à doses flexibles chez des patients souffrant de schizophrénie non-aiguë a été bien tolérée et s’est traduit par une amélioration significative des symptômes négatifs, dépressifs, anxieux et des symptômes extrapyramidaux, ainsi que du fonctionnement du patient.

Traduction de l’abstract résumé présenté au congrès EPA 2015 (European Congress of Psychiatry, Vienna, Austria, 28–31 March 2015)

To explore tolerability, safety and treatment response with flexible doses of paliperidone palmitate in adult patients with an acute episode of schizophrenia.

Interim analysis of a prospective 6-month, open-label, multicenter study in adult patients with schizophrenia. Outcomes were change in the Positive and Negative Syndrome Scale (PANSS) total score from baseline to endpoint, Clinical Global Impression-Severity Scale (CGI-S), patient functioning (Personal and Social Performance Scale; PSP), weight change and adverse events (AEs).

Of the first 104 patients included (54.8% male, mean age 37.6±11.8 years, 81.7% paranoid schizophrenia, recommended paliperidone palmitate initiation regimen used in 89% of subjects), 65.4% completed the study. Most frequent reasons for discontinuation were AE (13.5%), subject choice (8.7%) and loss to follow-up (5.8%). Mean total PANSS score decreased from 99.5±15.5 at baseline to 71.0±26.9 at endpoint (mean change -28.6±26.2; 95% confidence interval [CI] -33.8; - 23.4; p< 0.0001) with 60.6% of the patients showing improvement of ≥30%. Mean CGI-S score changed from 5.0±0.8 at baseline to 3.6±1.3 at endpoint (95%CI -1.7; -1.1; p< 0.0001). Patient functioning improved from a mean PSP baseline score of 42.7±13.9 to 59.0±18.7 at endpoint (95% CI of change 12.7; 19.9; p< 0.0001). AEs reported in ≥5% were psychotic disorder (15.4%), insomnia (14.4%), injection site pain (13.5%), headache (8.7%), salivary hypersecretion (6.7%) and anxiety (6.7%).

These data support results from recent randomized controlled studies that flexibly dosed paliperidone palmitate is safe, well tolerated and associated with clinically meaningful treatment response in patients suffering from an acute episode of schizophrenia.

To explore tolerability, safety and treatment response of flexibly dosed paliperidone palmitate (PP) in adult non-acute schizophrenia patients previously unsuccessfully treated with oral antipsychotic monotherapy of risperidone (RIS), paliperidone ER (Pali ER), olanzapine (OLA), quetiapine (QUE) or aripiprazole (ARI).

International, prospective 6-month open-label study. Outcomes were response (≥20% improvement in Positive and Negative Syndrome Scale (PANSS) total score at endpoint), patient functioning (Personal and Social Performance scale (PSP)), treatment-emergent adverse events (TEAEs) and Extrapyramidal Symptom Rating Scale (ESRS).

Intent-to-treat population: n=191 (RIS), n=104 (Pali ER), n=87 (OLA), n=46 (ARI), n=44 (QUE). Patients presented some differences in baseline demographics, e.g. in age, years since diagnosis and BMI. Baseline mean PANSS total scores ranged from 74.7±14.9 (ARI) to 70.8±13.1 (QUE) and 70.8±15.1 (RIS). Between 67.4% (ARI) and 83.2% (RIS) of patients completed the study. At endpoint, 74% (RIS), 58% (Pali ER), 61% (OLA), 66% (QUE) and 52% (ARI) of patients had improved ≥20% in PANSS total score. Mean PSP improvement at endpoint was: 10.4±13.8 (RIS), 7.0±13.8 (Pali ER), 4.5±15.9 (OLA), 7.9±12.4 (QUE) and 3.9±13.2 (ARI); all p<0.05. TEAEs reported at least once in all subgroups were injection site pain, insomnia and psychotic disorder. Mean change in ESRS from baseline to endpoint was -1.2±3.5 (RIS), - 0.7±4.1 (Pali ER), -1.3±4.4 (OLA), -0.3±3.2 (QUE) and -0.6±3.4 (ARI; p<0.05 for all except QUE).

PP was well tolerated and associated with clinically relevant treatment response in patients previously unsuccessfully treated with oral atypical antipsychotic monotherapy, regardless of the medication that was switched.

To explore tolerability, safety and treatment response of flexible doses of paliperidone palmitate in adult non-acute patients with schizophrenia previously unsuccessfully treated with oral antipsychotics.

Interim analysis of a prospective 6-month, open-label study. Outcomes were change in the Positive and Negative Syndrome Scale (PANSS) score, Clinical Global Impression-Severity Scale (CGI-S) and patient functioning (Personal and Social Performance Scale; PSP) from baseline to endpoint, weight change and adverse events (AEs).

Of the first 403 patients enrolled (63.3% male, mean age 39.4±12.0 years). 74.4% completed the study. Most frequent reasons for discontinuation were subject choice (10.7%), and AE (5.5%). The recommended initiation regimen was administered in 94.0% of subjects. Mean PANSS total score decreased from 71.9±15.2 at baseline to 60.8±18.4 at endpoint (mean change -11.1±15.4; 95% confidence interval [CI]-12.6;-9.6; p< 0.0001); 61.2% of the patients showed an improvement of ≥20% in PANSS total score. The percentage of patients rated mildly ill or less in CGI-S increased from 33.2% to 62.1%. Patient functioning improved from a mean PSP baseline score of 57.9±13.7 to 65.2±15.3 at endpoint (95%CI of change 6.0; 8.7; p< 0.0001). AEs reported in ≥5% were injection site pain (13.9%), insomnia (7.9%), anxiety (6.9%), psychotic disorder (5.7%) and somnolence (5.2%). Mean weight change from baseline to endpoint was 1.4±5.2kg (95%CI 0.8; 1.9).

These data support results from recent randomized controlled studies that flexibly dosed paliperidone palmitate is safe, well tolerated and associated with a clinically relevant treatment response in non-acute patients with schizophrenia previously unsuccessfully treated with oral antipsychotics.

To explore tolerability, safety and treatment response of flexibly dosed once-monthly paliperidone palmitate (PP) in adult nonacute patients with schizophrenia previously unsuccessfully treated with oral aripiprazole.

International prospective open-label 6-month study. Outcomes were change in Positive and Negative Syndrome Scale (PANSS), patient functioning (Personal and Social Performance Scale; PSP), disease severity (CGI-S and CGI-C), Extrapyramidal Symptom Rating Scale (ESRS) and treatment-emergent adverse events (TEAEs).

46 patients (73.9% male, mean age 34.4±9.4 years, 78.3% paranoid schizophrenia) were analyzed. The mean prior oral aripiprazole dose was 22.7±10.7 mg/day. 67.4% of patients completed the study. Mean PANSS total score decreased from 74.7±14.9 at baseline to 62.6±16.5 at LOCF endpoint (mean change -12.2±16.7; 95% confidence interval -17.1;-7.2; p<0.0001). 52.2% of patients showed a ≥20% improvement in PANSS total score, the percentage of patients rated mildly ill or less in CGI-S increased from 23.9% to 56.5% and 75.5% of patients were rated improved in CGI-C. Patient functioning in PSP improved from 58.9±13.4 to 62.9±15.2 (p=0.041). TEAEs reported in ≥5% were anxiety (n=6), injection site pain, bronchitis, insomnia and akathisia (n=4 each), and weight increase, depression and pain in extremities (n=3 each). Extrapyramidal symptoms measured by ESRS total scores improved significantly in completers from baseline to month 6 by -1.4±2.7 (p<0.007) and by -0.6±3.4 from baseline to LOCF endpoint (p=0.046).

Flexibly dosed paliperidone palmitate was well tolerated and associated with a clinically relevant symptomatic treatment response, improved functioning and less EPS in non-acute patients with schizophrenia previously unsuccessfully treated with oral aripiprazole.

To explore tolerability, safety and treatment response of flexibly dosed paliperidone palmitate (PP) in adult non-acute but symptomatic patients with schizophrenia previously unsuccessfully treated with risperidone long-acting injectable treatment (RLAT).

International, prospective 6-month open-label study. Major outcomes were clinical response (percentage of patients with ≥20% improvement in Positive and Negative Syndrome Scale (PANSS) total score at endpoint), functioning (Personal and Social Performance scale (PSP)), Extrapyramidal Symptom Rating Scale (ESRS), sleep quality, daytime drowsiness and treatment-emergent adverse events (TEAEs).

The intent-to-treat population comprised 56 patients (64.3% male, mean age 39.9±11.0 years, 71.4% paranoid schizophrenia). 71.4% of patients completed the 6-month study. Withdrawal of consent (8.9%) and adverse events (10.7%) were the most frequent reasons for early discontinuation. Mean PANSS baseline total score was 67.5±20.7 and decreased by -9.2 points at endpoint (95% confidence interval -15.0;-3.5, p<0.0001). At endpoint, 61.1% of patients had improved by ≥20% in PANSS total score. Patient functioning in PSP increased by 5.2±15.3 points (p=0.0163). Sleep quality and daytime drowsiness improved significantly (both p<0.0292). Extrapyramidal symptoms in ESRS significantly improved from 3.7±7.2 at baseline to 2.4±6.4 at endpoint (p=0.0011). TEAEs reported in ≥5% were psychotic disorder (10.7%), injection site pain, headache, schizophrenia, anxiety (7.1% each), constipation and somnolence (5.4% each). Mean body weight decreased by 0.9±4.5 kg from baseline to endpoint.

These data suggest that paliperidone palmitate is associated with a meaningful clinical response and functional improvement and is well tolerated with less EPS in non-acute, symptomatic schizophrenia patients previously unsuccessfully treated with RLAT.