Second-generation Antipsychotics Treatment Research Articles

Long-term second-generation antipsychotics decreases bone formation and resorption in male patients with schizophrenia.

Patients with schizophrenia with second-generation antipsychotics (SGAs) treatment have shown an increased risk of bone fragility and susceptibility to fracture; however, it is still unclear whether this risk is derived from the effect of antipsychotics on balance of bone metabolism. We investigated the changes of two bone turnover biomarkers (BTMs) concentrations in people with schizophrenia receiving SGAs: procollagen type I aminoterminal propeptide (PINP) and C-terminal telopeptide of type I collagen (CTX-1) as BTMs of osteogenesis and bone resorption, respectively, to explore how antipsychotics contribute to bone fragility. We recruited 59 Chinese male patients with schizophrenia (32 drug-naïve first-episode (DNFE) patients and 27 chronic patients) to undergo 8 weeks SGAs treatment. Fasting peripheral blood samples of pre- and posttreatment were collected, plasma levels of PINP and CTX-1 were measured. The interaction effects of group and time on PINP and CTX-1 concentrations were found (P = .016 and P = .008). There was a significant decrease for both BTMs concentrations of the posttreatment compared to the pretreatment (P<.001 and P = .003). Chronic patients had significantly higher changes of BTMs concentrations compared to DNFE patients (P = .048 and P = .024). There was a positive correlation of the two BTMs of pretreatment with disease course in DNFE group (r = .37, P = .039;r = .38, P = .035) and a negative correlation of PINP of pretreatment with age in the chronic group (r=-.40, P = .039). Long-term SGAs medication inhibited osteogenesis in a dose- and time-dependent manner and damaged the balance of bone formation and bone resorption.

Group-Based Trajectory Modeling to Identify Patterns of Antipsychotic-Associated Weight Gain Among Children and Adolescents.

Antipsychotic-associated weight gain (AAWG) is a common adverse effect of second-generation antipsychotic (SGA) medications among children and adolescents. This study applied group-based trajectory modeling to identify latent trajectories of AAWG among children and adolescents and associated risk factors. This was a retrospective analysis of the IQVIA Ambulatory EMR-US database from 2016 to 2021. The cohort consisted of patients aged 6 to 19 years who were SGA naive and received at least 90 days of continuous SGA prescriptions. Group-based trajectory modeling was used to identify latent trajectories of AAWG development during a 24-month period since SGA initiation, and multinomial logistic regression analysis was conducted to examine the risk factors associated with the identified AAWG trajectories. A total of 16,262 patients were included. Group-based trajectory modeling identified the following 4 distinctive AAWG trajectories: persistent severe weight gain (4.2%), persistent moderate weight gain (20.1%), minor weight change (69.6%), and gradual weight loss (6.1%). Compared with the minor weight change group, younger age (12-17 vs 5-11: odds ratio [OR], 0.634; 95% confidence interval [CI], 0.521-0.771), lower baseline body mass index z -score (OR, 0.216; 95% CI, 0.198-0.236), and receiving olanzapine as the initial SGA (olanzapine vs aripiprazole: OR, 1.686; 95% CI, 1.673-1.699) were more likely to follow severe weight gain trajectories. The area under the receiver operating characteristic curves for comparing severe weight gain versus minor weight change groups and moderate weight vs minor weight change groups in the multinomial regression model were 0.91 and 0.8, respectively. A quarter of pediatric SGA recipients experienced persistent weight gain during the SGA treatment. The risk of having persistent AAWG can be predicted using patient characteristics collected before SGA initiation and the initial SGA agent.

Association Between Abnormal Metabolic Parameters and Receiving Subsequent Interventions in Children and Adolescents Initiating Second-Generation Antipsychotics.

Objectives: This study aimed to examine the association between abnormal readings of metabolic parameters detected during second-generation antipsychotic (SGA) treatment and the likelihood of receiving subsequent adverse drug event interventions. Methods: This was a nested case-control study conducted on patients 1-17 years of age with at least two prescriptions of SGAs between January 2010 and January 2019 using TriNetX EMR data. Following an incident density sampling procedure, patients who received the SGA metabolic adverse event intervention (mAEI) (case) were matched with three nonrecipients (controls). The abnormal readings of metabolic parameters within 30 days before the initiation of mAIEs were further identified. These metabolic parameters include body mass index (BMI) and laboratory parameters such as cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, blood glucose, HbA1c, thyroid hormones, liver enzymes, and prolactin. The association of abnormal metabolic parameters with subsequent mAEIs was assessed using a conditional logistic regression model, after adjusting for demographic and other clinical risk factors. Results: One thousand eight hundred eighty-four children and adolescents met the inclusion criteria and were prescribed SGA mAEIs. The most common types of mAEIs prescribed were weight management pharmacotherapy (40.6%), switching from a high or medium metabolic risk profile SGA to a low-risk one (30.9%), nonpharmacological treatment (25.4%), and switching from SGA polytherapy to monotherapy (11.7%). The conditional logistic regression analysis on matched mAEI recipients and nonrecipients showed that patients with an abnormal BMI had 43% higher odds of receiving mAEI (odds ratio [95% confidence interval]: 1.43 [1.13-1.79]). However, the presence of an abnormal laboratory reading was not associated with the initiation of mAEIs. Conclusions: The prescribing of mAEIs were associated with the presence of obesity, but not with abnormal readings of other metabolic parameters, suggesting that additional data are needed to clarify the long-term implication of SGA metabolic adverse events other than weight gain and to inform the appropriate timing for interventions.

Multilocus Genetic Profile Reflecting Low Dopaminergic Signaling Is Directly Associated with Obesity and Cardiometabolic Disorders Due to Antipsychotic Treatment.

Treatment with second-generation antipsychotics (SGAs) can cause obesity and other cardiometabolic disorders linked to D2 receptor (DRD2) and to genotypes affecting dopaminergic (DA) activity, within reward circuits. We explored the relationship of cardiometabolic alterations with single genetic polymorphisms DRD2 rs1799732 (NG_008841.1:g.4750dup -> C), DRD2 rs6277 (NG_008841.1:g.67543C>T), COMT rs4680 (NG_011526.1:g.27009G>A), and VNTR in both DRD4 NC_000011.10 (637269-640706) and DAT1 NC_000005.10 (1392794-1445440), as well as with a multilocus genetic profile score (MLGP). A total of 285 psychiatric patients treated with SGAs for at least three months were selected. Cardiometabolic parameters were classified according to ATP-III and WHO criteria. Blood samples were taken for routinely biochemical assays and PCR genotyping. Obesity (BMI, waist (W)), high diastolic blood pressure (DBP), and hypertriglyceridemia (HTG) were present in those genetic variants related to low dopaminergic activity: InsIns genotype in rs1799732 (BMI: OR: 2.91 [1.42-5.94]), DRD4-VNTR-L allele (W: OR: 1.73 [1.04-2.87]) and 9R9R variant in DAT1-VNTR (W: OR: 2.73 [1.16-6.40]; high DBP: OR: 3.33 [1.54-7.31]; HTG: OR: 4.38 [1.85-10.36]). A low MLGP score indicated a higher risk of suffering cardiometabolic disorders (BMI: OR: 1.23 [1.05-1.45]; W: OR: 1.18 [1.03-1.34]; high DBP: OR: 1.22 [1.06-1.41]; HTG: OR: 1.20 [1.04-1.39]). The MLGP score was more sensitive for detecting the risk of suffering these alterations. Low dopaminergic system function would contribute to increased obesity, BDP, and HTG following long-term SGA treatment.

Impact of the AACAP practice parameters on the metabolic adverse event monitoring for second-generation antipsychotics (SGAs) in children and adolescents

IntroductionThe objective of our study was to evaluate the impact of the publication of the American Academy of Child and Adolescent Psychiatry (AACAP) practice parameters for SGA metabolic monitoring in 2011 on SGA metabolic monitoring uptake among pediatric SGA recipients. MethodsThis was a retrospective study of children 1–17 years of age who initiated SGA treatment from Jan 2010 to December 2018 using a national Electronic Medical Records database. A segmented regression of interrupted time-series (ITS) analysis was conducted to analyze the change of metabolic monitoring rates for Body Mass Index (BMI), Blood Glucose (BG), and Total Cholesterol (CHL) 9 quarters pre- and 26 quarters post-the publication of the AACAP practice parameters. ResultsThe analytical cohort included 9620 children and adolescents who initiated SGA treatment during the study period. The ITS results showed that the publication of the AACAP practice parameter for SGA metabolic monitoring was associated with a 12.61 percentage points (p < 0.0002) immediate increase in BMI monitoring rate, (increased from 29.10% in Q4 2011 to 40.10% in Q3 2012). There was a positive trend of BMI monitoring rate prior to the publication of AACAP practice parameters, which continued during the post-publication period. Neither immediate nor sustained changes in the association of monitoring rates for BG and CHL were observed after the issuance of the guidelines. ConclusionThe publication of AACAP practice parameters for SGA monitoring was associated with a significant improvement in the monitoring for BMI, but not for BG and CHL in children and adolescents.

Prospective, randomized, multicenter clinical trial evaluating longitudinal changes in brain function and microstructure in first-episode schizophrenia patients treated with long-acting injectable paliperidone palmitate versus oral antipsychotics.

Widespread anatomical alterations and abnormal functional connectivity have shown strong association with symptom severity in first-episode schizophrenia (FES) patients. Second-generation antipsychotic treatment might slow disease progression and possibly modify the cerebral plasticity in FES patients. However, whether a long-acting injectable antipsychotic (paliperidone palmitate [PP]), available in monthly and every-3-months formulations, is more effective than oral antipsychotics (OAP) in improving cerebral organization has been unclear. Therefore, in the current longitudinal study, we evaluated the differences in functional and microstructural changes of 68 FES patients in a randomized clinical trial of PP vs OAP. When compared to OAP treatment, PP treatment was more effective in decreasing abnormally high fronto-temporal and thalamo-temporal connectivity, as well as increasing fronto-sensorimotor and thalamo-insular connectivity. Consistent with previous studies, multiple white matter pathways showed larger changes in fractional anisotropy (FA) and mean diffusivity (MD) in response to PP compared with OAP treatment. These findings suggest that PP treatment might reduce regional abnormalities and improve cerebral connectivity networks compared with OAP treatment, and identified changes that may serve as reliable imaging biomarkers associated with medication treatment efficacy.

The regulatory effects of second-generation antipsychotics on lipid metabolism: Potential mechanisms mediated by the gut microbiota and therapeutic implications.

Second-generation antipsychotics (SGAs) are the mainstay of treatment for schizophrenia and other neuropsychiatric diseases but cause a high risk of disruption to lipid metabolism, which is an intractable therapeutic challenge worldwide. Although the exact mechanisms underlying this lipid disturbance are complex, an increasing body of evidence has suggested the involvement of the gut microbiota in SGA-induced lipid dysregulation since SGA treatment may alter the abundance and composition of the intestinal microflora. The subsequent effects involve the generation of different categories of signaling molecules by gut microbes such as endogenous cannabinoids, cholesterol, short-chain fatty acids (SCFAs), bile acids (BAs), and gut hormones that regulate lipid metabolism. On the one hand, these signaling molecules can directly activate the vagus nerve or be transported into the brain to influence appetite via the gut-brain axis. On the other hand, these molecules can also regulate related lipid metabolism via peripheral signaling pathways. Interestingly, therapeutic strategies directly targeting the gut microbiota and related metabolites seem to have promising efficacy in the treatment of SGA-induced lipid disturbances. Thus, this review provides a comprehensive understanding of how SGAs can induce disturbances in lipid metabolism by altering the gut microbiota.

The Use of Second-Generation Antipsychotics in Patients with Severe Schizophrenia in the Real World: The Role of the Route of Administration and Dosage-A 5-Year Follow-Up.

To assess the impact of the route of administration and doses of second-generation antipsychotics (SGAs) on treatment adherence, hospital admissions, and suicidal behaviour in patients with severe schizophrenia (Clinical Global Impression-Severity-CGI-S ≥ 5), we implemented an observational 5-year follow-up study. A total of 37.5% of the patients on oral antipsychotics (Aps) and 11.5% of those on long-acting injectables (LAIs) abandoned the treatment (p &lt; 0.001). There were no differences in treatment discontinuation between the LAI-AP standard and high-dose groups. A total of 28.1% of the patients on oral Aps had at least one hospitalisation, as well as 13.1% of patients on LAIs (p &lt; 0.001). There were fewer hospitalisations of patients on LAIs in the high-dose group (p &lt; 0.05). Suicide attempts were recorded for 18% of patients on oral Aps but only for 4.6% of patients on LAIs (p &lt; 0.001). No differences were found between the dosage groups on LAIs. Tolerability was good for all Aps and somewhat better for LAIs than oral Aps in terms of side effects (p &lt; 0.05). There were no differences between the standard and high-dose groups. More patients discontinued treatment due to side effects in the oral AP group (p &lt; 0.01). LAI SGA treatment was more effective than oral AP in terms of adherence and treatment outcomes for managing people with severe schizophrenia. Moreover, significant improvements were found that favour high-dose LAI SGA treatment for some of these patients. This study highlights the need to consider LAI antipsychotics and high-dose strategies for patients with severe schizophrenia.

Analysis of color vision and cognitive function in first-episode schizophrenia before and after antipsychotic treatment

BackgroundA large body of recent research has demonstrated that patients with schizophrenia exhibit significant changes in visual function and ocular tissue structure in the early stages of onset. It is therefore possible to explore a novel scientific breakthrough in the etiology of schizophrenia by transforming the traditional study of brain structure and function with a view to examining the potential field of eye tissue and function. However, few studies have investigated the correlation between iris characteristics and schizophrenia, and evidence is lacking in this regard. Thus, further exploration is needed. PurposeThis study was designed to analyze the characteristics of iris structure, color vision function and cognitive function, as well as the changes therein in patients with the first-episode drug-free schizophrenia before and after antipsychotic treatment. It aimed to preliminarily identify easily-measurable biomarkers for early clinical screening and diagnosis of schizophrenia. MethodsThis study recruited 61 patients (22 males) with first-episode schizophrenia. Prior to the commencement of treatment with antipsychotic drugs, the Montreal Cognitive Assessment (MoCA) and Farnsworth-Munsell Dichotomous (D-15 Hue Test) were used as assessment tools to evaluate cognitive function and color vision function, respectively. Over a 6-week period, patients received a second-generation antipsychotic treatment (all converted to olanzapine equivalent dose) as prescribed by the doctor, and the Positive and Negative Syndrome Scale (PANSS) was applied to evaluate the clinical treatment effects before treatment (baseline), as well as at the 2nd, 4th, and 6th weeks after drug treatment. On the basis of iris characteristics, the patients were divided into groups. The observed differences in drug treatment effects between the groups were then compared and analyzed to further clarify the relationship between treatment efficacy and iris characteristics. Finally, changes in the cognitive function and color vision function of patients at baseline and at the 6th week after drug treatment were compared, and the effects of antipsychotic drug treatment on the above-mentioned functions were analyzed. ResultsOn the basis of structural iris characteristics, 61 patients were classified as follows: 28 patients without iris crypts and 33 with iris crypts; 35 without iris pigment dots and 26 with iris pigment dots; 42 without iris wrinkles and 19 with iris wrinkles. No significant difference was observed in the PANSS scores of all of the patients at baseline; however, significant differences were found in patients with iris crypts and iris pigment dots at each follow-up timepoint (i.e., at the 2nd, 4th, and 6th week). Moreover, it is noteworthy that, compared with other patients, the PANSS scores of patients without specific iris structure characteristics (iris crypts and pigment dots) decreased significantly (P<0.05), which indicated that the drug therapy was highly effective. Excluding the interference of drug factors, a significant correlation was found between the results of the D-15 (color vision function) and MoCA (cognitive function) in first-episode untreated patients (r = −0.401, P < 0.05). In addition, the MoCA scores (mean difference = 2.36, t = 10.05, P ˂ 0.01) were significantly higher after 6 weeks of antipsychotic drug treatment compared to conditions at baseline. ConclusionsThe findings of this study demonstrated that color vision function of patients with schizophrenia improved with the improvement of cognitive function. The structural characteristics of the iris with crypts and pigment dots could have a significant impact on the drug treatment effect of schizophrenia and could be considered as a potential biomarker for detecting and recognizing schizophrenia.

Pre-diabetes screening for children and adolescents taking second-generation antipsychotics

There has been a continual rise in the off-label use of second generation antipsychotics (SGA) or atypical antipsychotics to treat children with anxiety disorders, autism, attention deficit hyperactivity disorder, mood disorder, and conduct disorders when other therapeutic treatment has failed. Despite the positive efficacy of SGAs, Wiedeman et al., (2021) in a narrative review, summarized that weight gain with SGAs ranged from 4.4 to 8.5 kg over 12 weeks for different SGA medications and that rapid weight gain on initiation of SGA treatment significantly affected long term weight gain.

Association of Social Determinants of Health With Adherence to Second-generation Antipsychotics for People With Bipolar Disorders in a Medicaid Population.

About 7 million people, 2.8% of US adults, have bipolar disorder (BD). While second-generation antipsychotics (SGA) are indicated as acute and maintenance treatments for BD, therapeutic success requires medication adherence and reported nonadherence estimates to range as high as 60%. Identifying patient risk factors for nonadherence is important for reducing it. The objective of this study was to quantify the associations of risk factors, including social determinants of health, with SGA nonadherence among patients with BD. In this cross-sectional study of 2015-2017 MassHealth Medicaid data, we examined several definitions of adherence and used logistic regression to identify risk factors for nonadherence (medication possession ratio <0.8) among all adults aged 18-64 diagnosed with BD who could be followed for 12 months following SGA initiation. Among 5197 patients, the mean (±SD) age was 37.7 (±11.4) years, and 42.3% were men. Almost half (47.7%) of patients were nonadherent to SGAs when measured by medication possession ratio. The prevalence of nonadherence peaked at middle age for men and younger for women. Nonadherence was less common among Massachusetts' Department of Mental Health clients (odds ratio=0.60, 95% confidence limit: 0.48-0.74) and among those who used other psychotropic medications (odds ratios between 0.45 and 0.81); in contrast, increase in neighborhood socioeconomic stress was associated with increased odds of nonadherence. Adherence to SGA treatment is suboptimal among people with BD. Recognizing risk factors, including those related to social determinants of health, can help target interventions to improve adherence for people at high risk and has implications for adherence-based quality measures.

Metformin acts on the gut-brain axis to ameliorate antipsychotic-induced metabolic dysfunction.

Antipsychotic-induced metabolic dysfunction (AIMD) is an intractable clinical challenge worldwide. The situation is becoming more critical as second-generation antipsychotics (SGAs), to a great extent, have replaced the role of first-generation antipsychotics in managing major psychiatric disorders. Although the exact mechanisms for developing AIMD is intricate, emerging evidence has indicated the involvement of the microbiota-gut-brain axis in AIMD. SGAs treatment may change the diversity and compositions of intestinal flora (e.g., decreased abundance of Bacteroidetes and Akkermansia muciniphila, and increased Firmicutes). Short-chain fatty acids and other metabolites derived from gut microbiota, on the one hand, can regulate the activity of intestinal endocrine cells and their secretion of satiety hormones (e.g., glucagon-like peptide 1, peptide YY, cholecystokinin and ghrelin); on the other hand, can activate the vagus nerve or transport into the brain to exert a central modulation of foraging behaviors via binding to neuropeptide receptors. Interestingly, metformin, a classical antidiabetic agent, is capable of alleviating AIMD possibly by regulating the microbiota-gut-brain axis. That is, metformin can not only partially reverse the alterations of gut microbial communities due to SGAs treatment, but also play a positive role in rectifying the disturbances of peripheral and central satiety-related neuropeptides. Current evidence has indicated a promising role for metformin on ameliorating AMID, but further verifications in well-designed clinical trials are still warranted.

The Relationship between the Second-Generation Antipsychotics Efficacy and the Traditional Chinese Medicine Body Constitutions in Patients with Schizophrenia.

Background: Schizophrenia requires lifelong treatment; Second-generation Antipsychotics (SGAs) have become the most prescribed medication for schizophrenia patients. The efficacy of various SGAs treatment may differ in schizophrenia patients with various traditional Chinese medicine (TCM) body constitution (BC) types. Method: This study applied a longitudinal quantitative research design, where a total of 66 participants were recruited. The Positive and Negative Symptom Scale (PANSS) and the Clinical Global Impression (CGI) score were used to evaluate patients’ psychopathology status in hospitalization, and body constitution questionnaires were conducted by face-to-face interviews in the 1st, 3rd, and 6th week of hospitalization. Results: More than 60% of schizophrenia patients who were treated with SGAs were classified to have unbalanced BC types including Yin-Xu, Yang-Xu and Stasis. Generalized estimating equation analysis revealed significant time effects in CGI and PANSS score improvements in both unbalanced and gentleness (balance) BC types, but no significant changes in the group and group-time interaction in the CGI and PANSS scores in different BC type groups. Conclusions: Schizophrenia patients under SGAs treatment had a higher proportion of unbalanced BC types which may lead to poorer physical or mental statuses, such as overweight problems. Health care providers could apply interventions according to patients’ BC types for disease prevention.

Identifying Other People’s Perspective and their Facial Emotions – A Comparison between Patients on Long-term Second-generation Antipsychotic Treatment for Schizophrenia and Neurotypical Controls

Previous studies report that the inhibition of one’s own perspective in favour of acknowledging somebody else’s perspective relates to the neurotypical development of Theory of Mind (ToM) processes. ToM processing seems to be negatively affected in patients diagnosed with schizophrenia (PwS). Different tasks, using different populations, have been used to examine ToM (e.g. Hinting, facial emotion recognition, on-line perspective-taking), making generalizations problematic. We investigated ToM processing, using different paradigms, in one patient group on long-term second-generation antipsychotic treatment for schizophrenia and in neurotypical controls. Methods: Twenty-five patients on treatment with second-generation anti-psychotic medication for schizophrenia for more than ten years and neurotypical controls took part in a Hinting task, a facial emotion recognition task, and an on-line visual computational perspective-taking task. A battery of neuropsychological tests provided the input of a Principal Component Analysis (PCA). Results: Patients performed significantly less effectively than controls on the Hinting Task, and even patients in remittance struggled more with the task. No significant differences in facial emotion recognition between groups were found. The on-line perspective-taking task results revealed that controls, but not patients, presented an intrusion of the other perspective when judging their own perspective (altercentric behaviour). Reaction time results revealed that patients were significantly slower than controls when evaluating the “Other” perspective. The results of the perspective-taking task were examined further by relating them to components from the PCA. Errors in perspective-taking appeared correlated mostly to difficulties in mentalizing and cognitive control (neurotypical participants) and to hinting comprehension skills (patients). Conclusions: Results suggest that mentalizing and cognitive control are relevant functions for perspective-taking and that even after long-term treatment with second-generation antipsychotics, patients still have more difficulties in judging the Other perspective. The facial emotion recognition task suggested that facial emotion recognition is a separate interpretation skill not directly related to ToM

151-LB: Impact of Concurrent Use of Selective Serotonin Reuptake Inhibitors and Second-Generation Antipsychotic Medications on Cardiometabolic Health in Children

Around 20% of Canadian children are diagnosed with a mental health disorder. Selective serotonin reuptake inhibitors (SSRIs) and second-generation antipsychotics (SGAs) are common treatments. Treatment with SSRIs or SGAs is associated with increased cardiometabolic complications, and risk for type 2 diabetes in children. Little is known about the metabolic effects of concurrent use of SSRIs with SGAs. Our aim was to determine if the combination of SSRI and SGA treatment was associated with cardiometabolic complications in children. Cross-sectional data were collected from children with mental health disorders (aged 5-18 years), recruited from Child and Adolescent Psychiatry at BC Children’s Hospital. Children were classified as naïve (n=242), SSRI-treated (n=123), SGA-treated (n=112), or SSRI+SGA treated (n=98). Anthropometric data and a fasting blood sample were collected. Relationships between treatment groups and cardiometabolic risk factors were determined by adjusted linear and logistic regression models. SSRI+SGA-treated children had higher waist circumference z-scores (0.91 ± 0.89 vs. 0.48 ± 0.95; P&amp;lt;0.05) and a greater odds of waist circumference ≥90th percentile (OR=2.63, 95% CI: 1.34, 5.18; P&amp;lt;0.05) compared to SSRI-treated children. SSRI+SGA-treated children had higher plasma total cholesterol (4.63 ± 0.93 vs. 4.34 ± 0.84 mmol/L; P&amp;lt;0.05, adjusted by age, sex, and BMI z-scores) and a greater odds of plasma total cholesterol ≥5.18 mmol/L (OR=2.36, 95% CI: 1.05, 5.30; P&amp;lt;0.05, adjusted by age, sex, and BMI z-scores) than SGA-treated children. No differences in plasma fasting glucose, insulin, or insulin resistance (HOMA-IR) were observed between the treatment groups. Concurrent SSRI+SGA treatment is associated with elevated waist circumference and plasma total cholesterol in children. Our findings suggest greater cardiometabolic complications in children concurrently treated with SSRIs and SGAs. Disclosure R. Thandi: None. A. M. Wiedeman: None. A. M. Devlin: None. C. Panagiotopoulos: Advisory Panel; Self; Dexcom, Inc., Speaker’s Bureau; Self; Eli Lilly and Company. Funding BC Mental Health and Substance Use Services

Effects of a conventional mood stabilizer alone or in combination with second‐generation antipsychotics on recurrence rate and discontinuation rate in bipolar I disorder in the maintenance phase: A systematic review and meta‐analysis of randomized, placebo‐controlled trials

A systematic review and meta-analysis of double-blind, randomized placebo-controlled trials were conducted to examine how soon an increase in recurrence risk could be observed among bipolar I disorder (BDI) patients who were clinically stable with the combination therapy of mood stabilizers with second-generation antipsychotics (SGA+MS) treatment following second-generation antipsychotics discontinuation (i.e., MS alone) compared with SGA+MS maintenance. Embase, PubMed, and CENTRAL databases were used for systematic literature searches until May/22/2020. The primary outcome was the recurrence rate of any mood episode at 6months. The secondary outcomes were the recurrence rates of manic/hypomanic/mixed and depressive episodes and all-cause discontinuation at 6months. The recurrence rates at 1, 2, 3, 9, and 12months were also investigated. Eight studies (mean study duration=58.25±33.63weeks) were identified (SGA+MS group [n=1,456: 3 aripiprazole+MS studies, 1 lurasidone+MS study, 1 olanzapine+MS study, 2 quetiapine+MS studies, 1 ziprasidone+MS study] and placebo+MS group [n=1,476]). Pooled SGA+MS exhibited lower recurrence rates of any mood episode, manic/hypomanic/mixed episodes, and depressive episodes as well as reduced all-cause discontinuation at every observational point. The risk ratios (95% confidence interval) of the recurrence rate at 6months were 0.51 (0.39-0.86) for any mood episode, 0.42 (0.30-0.59) for manic/hypomanic/mixed episodes, and 0.39 (0.28-0.54) for depressive episodes. The RR for all-cause discontinuation was 0.67 (0.50-0.89). Both aripiprazole+MS and quetiapine+MS outperformed placebo+MS in the recurrence of any mood, manic/hypomanic/mixed, and depressive episodes at 6months. SGA+MS prevented recurrence for up to 12months for BDI compared with placebo+MS.

Impact of Antipsychotic Guidelines on Laboratory Monitoring in Children with Neurodevelopmental Disorders.

Objectives: The Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guidelines provide monitoring recommendations for children who are treated with second-generation antipsychotics (SGAs). The objective of this study was to determine the impact of the CAMESA guidelines on SGA monitoring in children with neurodevelopmental disorders.Methods: A retrospective chart review compared laboratory monitoring in children treated with SGAs who were referred to a tertiary psychopharmacology clinic before (2008–2011) and after (2013–2016) CAMESA publication. Chi-squared tests were used to detect changes in SGA use and monitoring between the two time periods.Results: A total of 345 charts were reviewed (n = 136 pre-CAMESA, n = 209 post-CAMESA). The proportion of children taking an SGA increased significantly (35% vs. 49%; p = 0.02) as did the duration of SGA treatment before tertiary assessment (18.6 months vs. 27.2 months; p = 0.03). SGA monitoring data were missing in 40% of charts pre-CAMESA and in 31% of charts post-CAMESA. The proportion of patients with any available laboratory monitoring did not change between the time periods (35% pre-CAMESA vs. 39% post-CAMESA; p = 0.56). Similarly, the proportion of patients with full laboratory monitoring was not significantly different between time periods (15% pre-CAMESA vs. 25% post-CAMESA; p = 0.23).Conclusions: SGA monitoring rates did not significantly improve after CAMESA guideline publication. To maximize benefit and mitigate risks of these medications, there is a need to identify barriers to SGA monitoring.

Real-World Patterns of Utilization and Costs Associated with Second-Generation Oral Antipsychotic Medication for the Treatment of Bipolar Disorder: A Literature Review.

ObjectiveTreatment with second-generation antipsychotics (SGAs) for bipolar disorder, including bipolar I disorder (BD-I), is common. This review evaluated real-world utilization patterns with oral SGAs in the United States (US) for bipolar disorder (and BD-I specifically when reported) and economic burden associated with these patterns.MethodsStructured, systematic searches of MEDLINE®, EMBASE®, and National Health Service Economic Evaluation Database identified primary research studies (published 2008–2018) describing real-world SGA use in adults with bipolar disorder/BD-I.ResultsAmong 769 studies screened, 39 met inclusion criteria. Most studies (72%) were analyses of commercial or Medicare/Medicaid claims databases. Patient-related (eg, demographic, comorbidities) and disease-related (eg, mania, psychosis) factors were associated with prescribed SGA. Suboptimal utilization patterns (ie, nonadherence, nonpersistence, treatment gaps, medication switching, and discontinuation) were common for patients treated with SGAs. Also common were SGAs prescribed with another psychotropic medication and SGA combination treatment (use of ≥2 SGAs concurrently). Suboptimal adherence and SGA combination treatment were both associated with increased health care resource use (HCRU); suboptimal adherence was associated with higher total direct medical and indirect costs.LimitationsDifferent definitions for populations and concepts limited between-study comparisons. Focusing on SGAs limits contextualizing findings within the broader treatment landscape (eg, lithium, anticonvulsants). Given the nature of claims data, prescribing rationale (eg, acute episodes vs maintenance) and factors influencing observed utilization patterns could not be fully derived.ConclusionDespite increased use of SGAs to treat bipolar disorder over the last decade, reports of suboptimal utilization patterns of SGAs (eg, nonadherence, nonpersistence) were common as was combination treatment. Patterns of SGA use associated with additional HCRU and/or costs were suboptimal adherence and SGA combination treatment; economic consequences associated with other utilization patterns (eg, nonpersistence) were unclear. Strategies to improve SGA treatment continuity, particularly adherence, may improve clinical and economic outcomes among people living with bipolar disorder.

Greater Arterial Stiffness in Children with or without Second-generation Antipsychotic Treatment for Mental Health Disorders: Rigidité Artérielle Plus Importante Chez Les Enfants Avec ou Sans Traitement Par Antipsychotiques de la Deuxième Génération Pour des Troubles de Santé Mentale.

Second-generation antipsychotics (SGAs) are used for a variety of mental disorders and are associated with cardiometabolic side effects in children. The objective of this study was to assess the cardiovascular health of children with mental disorders that are SGA-treated or SGA-naive. SGA-treated (n = 47) or SGA-naive (n = 37) children (aged 6 to 18 years) with mental disorders and control children (n = 83, no mental disorder) underwent assessment for cardiac function and morphology by echocardiography, aortic pulse wave velocity (PWV), and carotid intima-media thickness (cIMT). Body mass index (BMI) z-scores, waist circumference z-scores, systolic and diastolic blood pressure (BP) percentiles for height and sex, and fasting plasma glucose, insulin, triglycerides, and cholesterol were also assessed. Differences between SGA-treated, SGA-naive, and control children were assessed by linear and log-linear regression models. SGA-treated children had greater BMI z-scores and overweight/obesity (BMI ≥ 85th percentile for age and sex) and hypertension than SGA-naive and control children. The PWV geometric mean was 11.1% higher in SGA-treated (95%CI, 3.95 to 18.77) and 12.9% higher in SGA-naive children (95% CI, 5.60 to 20.59) compared to controls in models adjusted for age, sex, BMI, and systolic BP percentile. Left ventricular (LV) end-diastolic dimension/body surface area (BSA), LV end-systolic dimension/BSA, and LV ejection fraction were lower in SGA-treated and SGA-naive children compared to controls in models adjusted for sex and age. Children with mental disorders have greater arterial stiffness and altered cardiac structure/function than children with no mental health diagnosis. SGA treatment in children is not associated with alterations in cardiovascular structure/function.

Long-Term Metabolic Monitoring of Youths Treated with Second-Generation Antipsychotics 5 Years after Publication of the CAMESA Guidelines Are We Making Progress? Surveillance Métabolique à Long Terme des Jeunes Traités par Antipsychotiques de Deuxième Génération, Cinq ans Après la publication des Lignes Directrices Camesa: Faisons-Nous des Progrès?

The potential metabolic adverse effects of second-generation antipsychotics (SGA) need to be monitored. The Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics (CAMESA) offers guidelines for this purpose. We aimed to evaluate the long-term rates of youths receiving monitoring in mental health clinics and document the factors that may influence them. The charts of 180 patients (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-month and 9- to 24-month periods. Population under study was stratified into children (4 to 12 years) and adolescents (13 to 18 years). Sociodemographic characteristics, psychiatric diagnosis and comorbidities, prescribed SGAs and comedications, anthropometric measures (AM), blood pressure (BP), blood tests (BT), electrocardiogram, 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 exact test. 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 (baseline, 1 to 6 months), a diagnosis of psychotic and/or affective disorder (baseline, 1 to 6 months, 9 to 24 months), having ≤1 psychiatric comorbidities (1 to 6 months), high SGA dose (baseline, 1 to 6 months), and clinician's experience (baseline, 9 to 24 months). Significantly lower monitoring rates were associated with the psychostimulant/atomoxetine comedication (baseline, 1 to 6 months, 9 to 24 months). Five years after publication of the CAMESA guidelines, metabolic monitoring is conducted for less than half of patients. In our sample, age, diagnostic category, psychiatric comorbidities, SGA dose, clinician's experience, and comedications influenced the monitoring rates. Major progress still needs to be made before reaching a satisfactory level of monitoring.