This study was undertaken to determine adherence rates to side effect monitoring guidelines of second-generation antipsychotics (SGAs) approximately 10 years after their publication to assess the quality of care being provided to patients with mental illness at an urban community mental health center located in the Southeast United States. Results indicated an initial combined collection of fasting blood glucose (FBG) and fasting lipid profile (FLP) of 30%. At the 3-month time point, 20% of FBG and FLP were checked and at 1 year 14%. Study results suggest there is a need for practice improvements to increase quality of care.

Yes / Cognitive deficits in schizophrenia remain an unmet clinical need. Improved understanding of the neuro- and psychopathology of these deficits depends on the availability of carefully validated animal models which will assist the development of novel therapies. There is much evidence that at least some of the pathology and symptomatology (particularly cognitive and negative symptoms) of schizophrenia results from a dysfunction of the glutamatergic system which may be modelled in animals through the use of NMDA receptor antagonists. The current review examines the validity of this model in rodents. We review the ability of acute and sub-chronic treatment with three non-competitive NMDA antagonists; phencyclidine (PCP), ketamine and MK801 (dizocilpine) to produce cognitive deficits of relevance to schizophrenia in rodents and their subsequent reversal by first- and second-generation antipsychotic drugs. Effects of NMDA receptor antagonists on the performance of rodents in behavioural tests assessing the various domains of cognition and negative symptoms are examined: novel object recognition for visual memory, reversal learning and attentional set shifting for problem solving and reasoning, 5-Choice Serial Reaction Time for attention and speed of processing; in addition to effects on social behaviour and neuropathology. The evidence strongly supports the use of NMDA receptor antagonists to model cognitive deficit and negative symptoms of schizophrenia as well as certain pathological disturbances seen in the illness. This will facilitate the evaluation of much-needed novel pharmacological agents for improved therapy of cognitive deficits and negative symptoms in schizophrenia.

Les antipsychotiques de deuxième génération (ADG) sont de plus en plus employés dans le traitement de troubles psychiatriques. Selon de nombreuses observations cliniques, les effets secondaires reliés à la prise d’ADG diffèrent chez les patients atteints de schizophrénie (SCZ) et de maladies affectives (MA) éprouvent divers. Ainsi, il s’avère nécessaire d’étudier la fréquence et l'intensité des effets secondaires induits par les ADG qui pourraient différer selon le diagnostic. Pour ce faire, nous avons effectué une revue systématique de la littérature afin d’identifier l’ensemble des études rapportant les effets secondaires de cinq ADG (aripiprazole, olanzapine, quétiapine, rispéridone et ziprasidone) dans le traitement de la schizophrénie ou des maladies affectives. Les effets secondaires métaboliques et extrapyramidaux ont été recueillis séparément pour les deux groupes de patients, puis ont été combinés dans une méta-analyse. Des méta-régressions ainsi que des sous-analyses ont également été effectuées dans le but de regarder l’effet de différents modérateurs (i.e. âge, genre, et dose). Dans la présente méta-analyse, 107 études ont été inclues. Les résultats montrent que le traitement avec l’olanzapine a occasionné une plus importante prise de poids chez les patients SCZ comparativement aux patients MA. De plus, le traitement à la quétiapine a amené une hausse significative du taux de LDL et de cholestérol total dans le groupe SCZ par rapport au groupe MA. Selon nos résultats, les symptômes extrapyramidaux étaient plus fréquents dans le groupe MA, excepté pour le traitement à l'olanzapine qui a induit davantage de ces symptômes chez les patients SCZ. Également, nos résultats suggèrent que les patients SCZ seraient plus vulnérables à certains effets métaboliques induits par les ADG dû à une possible susceptibilité génétique ou à la présence de facteurs de risque associés au style de vie. D'autre part, les patients MA en comparaison aux SCZ étaient plus enclins à souffrir de troubles du mouvement induits par les ADG. Bref, les ADG semblent exacerber certains types d’effets secondaires tout dépendant de la maladie dans laquelle on les utilise. / Second generation antipsychotics (SGAs) are extensively prescribed for psychiatric disorders. Based on clinical observations, schizophrenia (SCZ) and affective disorders (AD) patients experience different SGAs side effects. The expanded use of SGAs in psychiatry suggests a need to investigate whether there is a difference in the incidence and severity of side-effects related to diagnosis. A comprehensive literature search was conducted to identify studies reporting side effects of five SGAs (aripiprazole, olanzapine, quetiapine, risperidone and ziprasidone) in the treatment of SCZ or AD. The metabolic and extrapyramidal side effects were collected separately for each group, and then were combined in a meta-analysis. Meta-regression and sub-analyses were also performed to investigate the role of different moderators (e.g., age, dose and gender). One hundred and seven studies were included in the analysis. Olanzapine induced a body weight gain significantly higher in SCZ patients than in AD patients. In addition, quetiapine treatment led to significantly higher LDL and total cholesterol mean change in the SCZ group relative to the AD group. Based on our results, the incidence of extrapyramidal side effects was more frequent in the AD group, except for olanzapine that caused more parkinsonism in SCZ patients. Our results suggest that SCZ patients may be more vulnerable to some SGA-induced metabolic disturbances, in which lifestyle risk factors and a possible inherent genetic vulnerability may play a role. Most of the studied SGAs caused more movement disorders in AD patients than in schizophrenics. It might be that an antipsychotic induces severity of side effect according to the phenotype.

Les antipsychotiques de deuxième génération (ADG) sont de plus en plus employés dans le traitement de troubles psychiatriques. Selon de nombreuses observations cliniques, les effets secondaires reliés à la prise d’ADG diffèrent chez les patients atteints de schizophrénie (SCZ) et de maladies affectives (MA) éprouvent divers. Ainsi, il s’avère nécessaire d’étudier la fréquence et l'intensité des effets secondaires induits par les ADG qui pourraient différer selon le diagnostic. Pour ce faire, nous avons effectué une revue systématique de la littérature afin d’identifier l’ensemble des études rapportant les effets secondaires de cinq ADG (aripiprazole, olanzapine, quétiapine, rispéridone et ziprasidone) dans le traitement de la schizophrénie ou des maladies affectives. Les effets secondaires métaboliques et extrapyramidaux ont été recueillis séparément pour les deux groupes de patients, puis ont été combinés dans une méta-analyse. Des méta-régressions ainsi que des sous-analyses ont également été effectuées dans le but de regarder l’effet de différents modérateurs (i.e. âge, genre, et dose). Dans la présente méta-analyse, 107 études ont été inclues. Les résultats montrent que le traitement avec l’olanzapine a occasionné une plus importante prise de poids chez les patients SCZ comparativement aux patients MA. De plus, le traitement à la quétiapine a amené une hausse significative du taux de LDL et de cholestérol total dans le groupe SCZ par rapport au groupe MA. Selon nos résultats, les symptômes extrapyramidaux étaient plus fréquents dans le groupe MA, excepté pour le traitement à l'olanzapine qui a induit davantage de ces symptômes chez les patients SCZ. Également, nos résultats suggèrent que les patients SCZ seraient plus vulnérables à certains effets métaboliques induits par les ADG dû à une possible susceptibilité génétique ou à la présence de facteurs de risque associés au style de vie. D'autre part, les patients MA en comparaison aux SCZ étaient plus enclins à souffrir de troubles du mouvement induits par les ADG. Bref, les ADG semblent exacerber certains types d’effets secondaires tout dépendant de la maladie dans laquelle on les utilise. / Second generation antipsychotics (SGAs) are extensively prescribed for psychiatric disorders. Based on clinical observations, schizophrenia (SCZ) and affective disorders (AD) patients experience different SGAs side effects. The expanded use of SGAs in psychiatry suggests a need to investigate whether there is a difference in the incidence and severity of side-effects related to diagnosis. A comprehensive literature search was conducted to identify studies reporting side effects of five SGAs (aripiprazole, olanzapine, quetiapine, risperidone and ziprasidone) in the treatment of SCZ or AD. The metabolic and extrapyramidal side effects were collected separately for each group, and then were combined in a meta-analysis. Meta-regression and sub-analyses were also performed to investigate the role of different moderators (e.g., age, dose and gender). One hundred and seven studies were included in the analysis. Olanzapine induced a body weight gain significantly higher in SCZ patients than in AD patients. In addition, quetiapine treatment led to significantly higher LDL and total cholesterol mean change in the SCZ group relative to the AD group. Based on our results, the incidence of extrapyramidal side effects was more frequent in the AD group, except for olanzapine that caused more parkinsonism in SCZ patients. Our results suggest that SCZ patients may be more vulnerable to some SGA-induced metabolic disturbances, in which lifestyle risk factors and a possible inherent genetic vulnerability may play a role. Most of the studied SGAs caused more movement disorders in AD patients than in schizophrenics. It might be that an antipsychotic induces severity of side effect according to the phenotype.

Background Polypharmacy is often prescribed for bipolar disorder, yet medication non-adherence remains a serious problem. This study investigated the regularity in the daily dosage taken of mood stabilizers and second generation antipsychotics. Methods Daily self-reported data on medications taken and mood were available from 241 patients with a diagnosis of bipolar disorder who received treatment as usual. Patients who took the same mood stabilizer or second generation antipsychotic for ≥ 100 days were included. Approximate entropy was used to determine serial regularity in daily dosage taken. Generalized estimating equations were used to estimate if demographic or clinical variables were associated with regularity. Results There were 422 analysis periods available from the 241 patients. Patients took drugs on 84.4% of days. Considerable irregularity was found, mostly due to single-day omissions and dosage changes. Drug holidays (missing 3 or more consecutive days) were found in 35.8% of the analysis periods. Irregularity was associated with an increasing total number of psychotropic drugs taken (p = 0.009), the pill burden (p = 0.026), and the percent of days depressed (p = 0.049). Conclusion Despite low missing percent of days, daily drug dosage may be irregular primarily due to single day omissions and dosage changes. Drug holidays are common. Physicians should expect to see partial adherence in clinical practice, especially with complex drug regimens. Daily dosage irregularity may impact the continuity of drug action, contribute to individual variation in treatment response, and needs further study.

Ce projet de recherche, réalisé sous la direction de la Dre Leila Ben Amor et la co-direction du Dr Emmanuel Stip, fut possible avec le soutient de la Bourse Daoussis du Département de psychiatrie, de la Faculté de médecine de l’Université de Montréal. / Les antipsychotiques de seconde génération (ASG) peuvent induire des changements métaboliques, tels la prise de poids, la perturbation du métabolisme des glucides et la dyslipidémie. Dans la population pédiatrique, les études analysant les effets métaboliques secondaires à une poly-thérapie par ASG (changement d’ASG et/ou combinaison de deux ASG) sont très rares et à notre connaissance, jusqu’à présent, aucune étude naturalistique n’a comparé directement ces effets selon l’utilisation des ASG en monothérapie (un seul ASG prescrit à la fois) ou en poly-thérapie. L’objectif de cette étude rétrospective est de comparer les changements métaboliques secondaires aux ASG en monothérapie avec ceux des ASG en poly-thérapie. À cet effet, de 147 enfants et adolescents naïfs d’antipsychotiques (âge moyen 12.8 ans ; IC 95% 9.8 à 15.9) sélectionnés entre novembre 2005 et juin 2013, 116 (78.9%) ont reçu des ASG en monothérapie et 31 (21.1%) en poly-thérapie. Nous avons analysé, à l’aide du modèle linéaire mixte, la variation du poids, de l’indice de masse corporelle ajusté pour l’âge et le sexe (IMC-z) et de la glycémie à jeun entre les deux groupes de traitement par ASG, avec le facteur répétitif le temps, relatif au niveau prétraitement et après 1, 3, 6, 12 et 24 mois de suivi. Nos résultats démontrent que le type de thérapie par ASG (monothérapie ou poly-thérapie) n’a pas eu d’impact significatif sur les changements métaboliques entre les deux groupes. Au total, après 24 mois de traitement par ASG, nos résultats montrent une augmentation significative de la moyenne du poids de 12.8 kg (IC 95% 10.4 à 15.0), de l’IMC-z de 0.44 (IC 95% 0.21 à 0.68) et de la glycémie à jeun de 0.29 mmol/L (IC 95% 0.11 à 0.47). L’incidence d’embonpoint/obésité fut de 22.6%, l’augmentation de plus que 0.5 de l’IMC-z de 9.4%, celle de l’intolérance au glucose de 9.6% et celle de diabète de type II de 3.1%. En conclusion, notre étude confirme le risque significatif de complications métaboliques durant le traitement sur 24 mois par ASG, sans différence significative entre leur utilisation en monothérapie ou en poly-thérapie. / Second generation antipsychotics (SGA) can induce metabolic changes such as weight gain, glucose abnormalities and dyslipidemia. In the pediatric population, studies analysing the SGA polytherapy (switch of SGA and/or combination of two SGA) induced metabolic effects are scarce and, to our knowledge, no naturalistic study, until now, directly compared metabolic changes between the SGA monotherapy (a single SGA prescribed during the follow-up) and SGA polytherapy use. The objective of this retrospective study is to compare SGA monotherapy induced metabolic changes to those secondary to SGA polytherapy. To this end, from 147 antipsychotic-naïve children and adolescents (mean age 12.8 years; 95% CI 9.8 to 15.9) selected between November 2005 and June 2013, 116 (78.9%) received a SGA monotherapy and 31 (21.1%) a SGA polytherapy. We used the linear mixed model to compare weight, body mass index adjusted for age and sex (BMI z score) and fasting glucose changes between the two SGA treatment groups with the repeated factor the time relative to baseline at 1, 3, 6, 12 and 24 months. Our results show that the type of therapy (monotherapy or polytherapy) did not have a significant impact on the metabolic changes between the two groups. Overall, after 24 months of SGA treatment, mean weight increased significantly by 12.8 kg (95% CI 10.4 to 15.0), BMI z score by 0.44 (95% CI 0.21 to 0.68), fasting glucose levels by 0.29 mmol/l (95% CI 0.11 to 0.47). Incidence of overweight/obese was 22.6%, BMI z score increase over 0.5 was 9.4%, glucose intolerance was 9.4% and type II diabetes was 3.1%. In conclusion, our study confirms the significant risk of metabolic complications during 24 months SGA treatment, without a significant difference between monotherapy and polytherapy use.

Background Polypharmacy is often prescribed for bipolar disorder, yet medication non-adherence remains a serious problem. This study investigated the regularity in the daily dosage taken of mood stabilizers and second generation antipsychotics. Methods Daily self-reported data on medications taken and mood were available from 241 patients with a diagnosis of bipolar disorder who received treatment as usual. Patients who took the same mood stabilizer or second generation antipsychotic for ≥ 100 days were included. Approximate entropy was used to determine serial regularity in daily dosage taken. Generalized estimating equations were used to estimate if demographic or clinical variables were associated with regularity. Results There were 422 analysis periods available from the 241 patients. Patients took drugs on 84.4% of days. Considerable irregularity was found, mostly due to single-day omissions and dosage changes. Drug holidays (missing 3 or more consecutive days) were found in 35.8% of the analysis periods. Irregularity was associated with an increasing total number of psychotropic drugs taken (p = 0.009), the pill burden (p = 0.026), and the percent of days depressed (p = 0.049). Conclusion Despite low missing percent of days, daily drug dosage may be irregular primarily due to single day omissions and dosage changes. Drug holidays are common. Physicians should expect to see partial adherence in clinical practice, especially with complex drug regimens. Daily dosage irregularity may impact the continuity of drug action, contribute to individual variation in treatment response, and needs further study.

Les antipsychotiques de seconde génération (ASG) peuvent induire des effets métaboliques tels qu’une prise de poids, des troubles cardio-métaboliques, des effets endocriniens et dans de très rares cas une mort soudaine d’origine cardiaque. Les effets indésirables métaboliques potentiels des ASG doivent être surveillés. L’Alliance canadienne pour la surveillance de l’efficacité et de l’innocuité des antipsychotiques (CAMESA) propose des lignes directrices à cet effet. Les objectifs de cette étude rétrospective sont d’évaluer, à long terme, les taux d’enfants et d’adolescents recevant pour la première fois un ASG bénéficiant d’un monitoring dans les cliniques de santé mentale et de documenter les facteurs qui peuvent les influencer. À cet effet, les dossiers médicaux de 180 enfants et adolescents (âge moyen 13,3 ± 3,1 ans, 54,4 % garçons), traités pour la première fois par ASG entre janvier 2016 et juin 2018, ont été examinés. Les périodes de monitoring ont été divisées en baseline, de 1 à 6 et de 9 à 24 mois. La population étudiée a été stratifiée en enfants (4- 12 ans) vs adolescents (13-18 ans). Les caractéristiques sociodémographiques, le diagnostic psychiatrique et les comorbidités, les types d’ASG et les comédications prescrites, les mesures anthropométriques (MA), la pression artérielle (PA), les bilans sanguins (BS), l’électrocardiogramme (ECG) et les années de pratique du psychiatre ont été collectés. Des tableaux croisés ont été utilisés pour présenter les taux de monitoring. Les catégories ont été comparées par analyse de co-variable. Les taux de patients monitorés ont été comparés à travers les catégories de monitoring, en ayant recours au test exact de Fisher. Nos résultats démontrent des taux de monitoring pour MA, BS et PA de : 55 %, 47,8 % et 46,7 % au baseline ; 50 %, 41,7 % et 45,2 % à 1-6 mois ; et 47,2 %, 41,5 % et 40,6 % à 9-24 mois, respectivement. Des taux de monitoring plus élevés étaient associés de manière significative au statut d’adolescent (MA, BS et PA au baseline ; MA et PA à 1-6 mois), à un diagnostic de trouble psychotique et / ou affectif (MA, BS et PA au baseline ; MA et PA à 1-6 mois; BS à 9-24 mois), avoir ≤ 1 comorbidités psychiatriques (BS à 1-6 mois), et à l’expérience du clinicien (BS et ECG à 1-6 mois). En conclusion, cinq ans après les recommandations de CAMESA, le monitoring métabolique est effectué chez moins de la moitié des patients et diminue tout au long de la durée du traitement. Dans notre échantillon, les catégories d’âge, de diagnostic, de comorbidités psychiatriques et d’expérience du clinicien ont influencé les taux de monitoring. Toutefois, des progrès importants doivent encore être réalisés pour parvenir à un taux de monitoring satisfaisant. / Second generation antipsychotics (SGA) can induce metabolic effects such as weight gain, cardiometabolic disorders, endocrine effects and in very rare cases sudden cardiac death. The potential metabolic side effects of second generation antipsychotics need to be monitored. The Canadian Alliance for Monitoring the Efficacy and Safety of Antipsychotics (CAMESA) offers guidelines for this purpose. The objectives of this retrospective study are to evaluate, the long-term rates of youths receiving monitoring in mental health clinics and document the factors that may influence them. To this end, the charts of 180 children and adolescents (average age 13.3 ± 3.1 years, 54.4 % males) receiving SGA treatment for the first time between January 2016 and June 2018 were reviewed. Monitoring was divided into baseline and 1 to 6 and 9 to 24-month periods. The population under study was stratified into children (4-12 years) vs adolescents (13-18 years). Sociodemographic characteristics, psychiatric diagnosis and comorbidities, prescribed SGAs and comedications, anthropometric measurements (AM), blood pressure (BP), blood tests (BT), electrocardiogram (ECG) and the psychiatrist’s years of practice were collected. Cross tables were used to present the monitoring rates. Categories were compared by covariate analysis. Rates of patients monitored across categories were compared using Fisher’s exact test. Our results show that monitoring rates for AM, BT, and BP were: 55 %, 47.8 %, and 46.7 % at baseline, 50 %, 41.7 %, and 45.2 % at 1 to 6 months, and 47.2 %, 41.5 %, and 40.6 % at 9 to 24 months, respectively. Higher monitoring rates were significantly associated with adolescent status vs child (baseline AM, BT, and BP; 1-6-month AM and BP), a diagnosis of psychotic and/or affective disorder (baseline AM, BT, and BP; 1-6-month AM and BP; 9-24-month BT), having ≤ 1 psychiatric comorbidities (1-6-month BT), and clinician’s experience (1-6-month BT and ECG). In conclusion, five years after publication of the CAMESA guidelines, metabolic monitoring is conducted for less than half of patients and decreases over time. In our sample, age, diagnostic category, psychiatric comorbidities, and clinician’s experience influenced the monitoring rates. Major progress still needs to be made before reaching a satisfactory level of monitoring.

The morbidity and societal burden of youth bipolar spectrum disorders (BSD) are high. These disorders are multisystemic in that adult populations there are clear interactions with inflammatory processes and steroidal physiological systems. There are much less data concerning these areas of study in youth populations with BSD. This is surprising given the association of youth-onset BSD with puberty and its associated physiological changes. In this mini-review, we overview the theoretical role of inflammatory processes and steroidal physiological systems in youth BSD, describe the greater literature in adult populations, detail the literature in youth populations when available, and overview current proposed molecular mechanistic pathways and interaction effects based on the available data. We also attend to the interplay of this complex system with body composition and weight gain, an especially important consideration in relation to the role of second generation antipsychotics as the first line treatment for youth with BSD in major clinical guidelines. A developmental model of early onset BSD for boys is hypothesized with pubertal hormonal changes increasing risk for first (hypo-)manic/depressive episode. The dramatic androgen rise during puberty might be relevant for first onset of BSD in boys. A shift from general hypercortisolism driven by glucocorticoid resistance to hypocortisolism with further disease progression is assumed, while increased levels of inflammation are functionally associated with endocrine dysregulation. The interacting role of overweight body habitus and obesity in youth with BSD further indicates leptin resistance to be a central moderator of the dynamic neurobiology of BSD in youth. The intent of this mini-review is to advance our knowledge of youth BSD as multisystemic disorders with important contributions from endocrinology and immunology based on a developmental perspective. This knowledge can influence current clinical care and more importantly inform future research.

The morbidity and societal burden of youth bipolar spectrum disorders (BSD) are high. These disorders are multisystemic in that adult populations there are clear interactions with inflammatory processes and steroidal physiological systems. There are much less data concerning these areas of study in youth populations with BSD. This is surprising given the association of youth-onset BSD with puberty and its associated physiological changes. In this mini-review, we overview the theoretical role of inflammatory processes and steroidal physiological systems in youth BSD, describe the greater literature in adult populations, detail the literature in youth populations when available, and overview current proposed molecular mechanistic pathways and interaction effects based on the available data. We also attend to the interplay of this complex system with body composition and weight gain, an especially important consideration in relation to the role of second generation antipsychotics as the first line treatment for youth with BSD in major clinical guidelines. A developmental model of early onset BSD for boys is hypothesized with pubertal hormonal changes increasing risk for first (hypo-)manic/depressive episode. The dramatic androgen rise during puberty might be relevant for first onset of BSD in boys. A shift from general hypercortisolism driven by glucocorticoid resistance to hypocortisolism with further disease progression is assumed, while increased levels of inflammation are functionally associated with endocrine dysregulation. The interacting role of overweight body habitus and obesity in youth with BSD further indicates leptin resistance to be a central moderator of the dynamic neurobiology of BSD in youth. The intent of this mini-review is to advance our knowledge of youth BSD as multisystemic disorders with important contributions from endocrinology and immunology based on a developmental perspective. This knowledge can influence current clinical care and more importantly inform future research.