Metabolic Side Effects Of Antipsychotics Research Articles

Thermoneutral housing and preexisting obesity do not abolish the sexually dimorphic effects of olanzapine on weight gain in mice.

In contrast to what is seen clinically, male mice are resistant to antipsychotic-induced obesity. This is problematic as preclinical studies examining mechanisms of antipsychotic-induced metabolic dysfunction might be relevant to onlyhalf the population. This study sought to determine whether housing mice at thermoneutrality and under conditions of preexisting obesity, steps that have not been previously considered, would uncover a greater obesogenic effect of the antipsychotic olanzapine (OLZ). C57BL6/J mice were fed a low- or high-fat diet (HFD) for 4 weeks and then switched to a control HFD or an HFD supplemented with OLZ for 6 weeks. Irrespective of obesity, OLZ treatment attenuated weight gain and increased energy expenditure in male mice. In females, OLZ increased food intake and potentiated weight gain in mice with preexisting obesity. Despite taking steps to increase clinical translatability, this study did not unmask an obesogenic effect of OLZ in male mice. Interestingly, prior studies in female mice could have been underestimating the metabolic consequences of OLZ by not considering the importance of preexisting obesity. Uncovering the mechanisms conferring resistance to weight gain in males may provide clues for approaches to counter the metabolic side effects of antipsychotics clinically.

Factors influencing the outcome of integrated therapy approach in schizophrenia: A narrative review of the literature.

The integration of pharmacotherapy with psychosocial interventions has an important role to play in the improvement of functional outcome of subjects with schizophrenia (SCZ), in all stages of the disorder. It is essential for the adequate management of unmet therapeutic needs, such as negative symptoms and cognitive dysfunctions which account for most of the functional impairment of subjects with SCZ and do not respond to available antipsychotics. Enhancing the knowledge on factors involved in the effectiveness of integrated treatment plans is an important step forward for SCZ care. This review aims to identify factors that might influence the impact of integrated treatments on functional outcome. Most studies on the impact of psychosocial treatments on functional outcome of subjects with SCZ did not control for the effect of prescribed antipsychotics or concomitant medications. However, several factors relevant to ongoing pharmacological treatment might influence the outcome of integrated therapy, with an impact on the adherence to treatment (e.g., therapeutic alliance and polypharmacotherapy) or on illness-related factors addressed by the psychosocial interventions (e.g., cognitive dysfunctions or motivational deficits). Indirect evidence suggests that treatment integration should consider the possible detrimental effects of different antipsychotics or concomitant medications on cognitive functions, as well as on secondary negative symptoms. Cognitive dysfunctions can interfere with participation to an integrated treatment plan and can be worsened by extrapyramidal or metabolic side effects of antipsychotics, or concomitant treatment with anticholinergics or benzodiazepines. Secondary negative symptoms, due to positive symptoms, sedation, extrapyramidal side effects or untreated depression, might cause early drop-out and poor adherence to treatment. Researchers and clinicians should examine all the above-mentioned factors and implement appropriate and personalized integrated treatments to improve the outcome of SCZ.

Is there a relationship between clinical stage and cardiovascular disease risk in bipolar disorder?

Introduction Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in bipolar disorders(BD). The heart age of patients with BD was found to be 8.5 years higher than gender-age matched health controls. Metabolic side effects of antipsychotics, poor diet, insufficient physical activity, smoking and sedentary life style increase the risk of cardiovascular disease in bipolar patients. QRISK-3 is an approved risk classification that calculates the 10-year risk of developing a heart attack or stroke.ObjectivesThis study aims to determine whether there is a difference between cardiovascular disease risk scores and clinical stages of bipolar disorderMethods35 outpatients that were followed up in Selcuk University Medical Faculty were evaluated. The clinical stages and qrisk3 scores were calculated.Results68.6% (n:24) of the patients were female. 42.9% of patients were in stage 3b (recurrent relapses, complete remission between episodes). The mean age was 36.94 ±10.46 years. The mean heart age was 50.54±17.35. The mean Q risk3 score was 5.59±8.18. There was no difference between bipolar patients at stage 2 and stage 3 in terms of age(p=0.36 and gender(p=0.73). When we compared the qrisk3 total socres and heart age of the patients in stage 2 and 3, we could not find any difference between groups (p=0.74, p=0.57 respectively).ConclusionsEven though we could not find any difference of qrisk scores at different clinical stages of patients with BD, the CVD risk increases with the age. Prospective longitudinal follow-up studies are required to evaluate dual interaction of clinical stages and CVD risk in BD.DisclosureNo significant relationships.

Audit on the monitoring of metabolic side effects of antipsychotics in acute inpatient psychiatric units at Fieldhead Hospital

AimsThe current audit aims to assess the compliance with Prescribing Observatory for Mental Health (POMH-UK) guidance on monitoring of metabolic side effects of patients prescribed antipsychotics. Compliance was monitored to ensure that all patients prescribed continuing antipsychotics have their body mass index (BMI), blood pressure, blood glucose and lipids checked within the expected time limits of minimum once per year.BackgroundPatients diagnosed with Schizophrenia rank amongst the worst of chronic medical illnesses in terms of quality of life. This may in part be due to the use of long term antipsychotic medications, in particular the use of atypical antipsychotics which have been increasingly associated with metabolic side effects including hypertension, weight gain, glucose intolerance and dyslipidaemia. These side effects are related to the development of both diabetes mellitus and cardiovascular disease and can lead to increased mortality and morbidity, affecting compliance and engagement to healthcare services. Despite the availability of clinical guidelines, monitoring and screening of metabolic side effects in patients prescribed antipsychotics continues to be suboptimal.MethodThe audit involved a review of electronic records relating to physical health monitoring of patients at two acute inpatient units from January-March 2019. Demographic and clinical variables were collected which included ethnicity, diagnostic grouping as well as current medications. Data were collected on evidence of screening for hypertension, BMI, blood glucose and lipids. Descriptive statistics were applied to study the clinical features of the sample and examine whether performance met clinical practice standard.ResultThe audit overall demonstrated partial compliance with POMH-UK guidelines with a total of 31 patients admitted on long term antipsychotics. Of these patients, 86% were prescribed atypical antipsychotics with 14% prescribed typical antipsychotics. Screening only occurred in 68% of patients for lipid profile with only 71% for BMI and 74% for blood glucose. Blood pressure had the highest compliance rate of 87% of patients being screened.ConclusionEarly identification and monitoring of complications from metabolic syndrome may decrease the risk of more serious health outcomes and improve patients’ quality of life. However in clinical practice, standards are not always met in accordance with best practice recommendations. Requirement of a tailored guideline for physical health monitoring with weekly planned interventions as well as adequate training and awareness of healthcare staff is imperative to drive improvement and increase adherence rates.

Occurrence of metabolic diseases associated with antipsychotic use among Korean patients with schizophrenia.

Metabolic side effects of antipsychotics significantly affect adherence to medication. We aimed to identify factors associated with the occurrence of metabolic diseases among Korean patients with schizophrenia (SCZ) from the national health insurance system database. We evaluated the frequency of antidiabetic and antihyperlipidemic use after diagnosis of SCZ according to typical or atypical antipsychotic use. Among the 43,800 patients diagnosed with SCZ between 2008 and 2012, 29,591 patients who had no metabolic diseases before the diagnosis were included in the analysis to investigate the occurrence of metabolic diseases associated with antipsychotic use. The associations between the development of metabolic diseases and patient characteristics were evaluated using logistic regression analysis. Use of both typical and atypical antipsychotics (multivariate-adjusted odds ratio (OR), 1.2513; 95% confidence interval (CI), 1.0953-1.4294) was associated with higher incidence of metabolic diseases than without their use. Among the atypical antipsychotics, use of clozapine (multivariate-adjusted OR, 1.1959; 95% CI, 1.0086-1.4179) and quetiapine (multivariate-adjusted OR, 1.1284; 95% CI, 1.0446-1.2189) showed higher incidence of metabolic diseases compared to that without their use. Among the patients using ≥1 type of antidiabetic or antihyperlipidemic agents within 6years after diagnosis of SCZ, the proportion of patients using only atypical antipsychotics was greater than those using only typical antipsychotics. The use of both typical and atypical antipsychotics, and clozapine and quetiapine treatment, may be associated with the occurrence of metabolic diseases in patients with SCZ. Additional prospective studies with accurate dosage information are needed to validate our findings.

The effect of spinach-derived thylakoids on anthropometric parameters and metabolic profile in antipsychotic treatment: A case report

Background: Antipsychotics is the first line, evidence-based treatment of schizophrenia and other primary psychotic disorders. Metabolic adverse effects are common, including body weight gain, hypertension and metabolic syndrome. There is still no safe treatment for these adverse effects, except from lifestyle changes. Studies of thylakoids have shown body weight loss and improved metabolic parameters in overweight women. Case report: A 53-year old female with a history of unspecified nonorganic psychosis, treated with Quetiapin and Topimax (Topiramat), was given a supplement of 5g thylakoids daily for 12 weeks. She reported a rapid decrease of sweet craving and loss of body weight was observed. Conclusion: We report a successful treatment with thylakoid supplements of the metabolic side effects of antipsychotics in a female adult with a history of body weight problems and sweet craving. Further investigation and larger studies are needed. A safe treatment of metabolic side effects could increase quality of life for patients in need of antipsychotic treatment.

Chapter 25 - The use of melatonin to mitigate the adverse metabolic side effects of antipsychotics

Antipsychotic drugs are efficacious first-line treatments for many individuals diagnosed with a psychiatric illness. However, their adverse metabolic side-effect profile, which resembles the metabolic syndrome, represents a significant clinical problem that increases morbidity and limits treatment adherence. Moreover, the mechanisms involved in antipsychotic-induced adverse metabolic effects (AMEs) are unknown and mitigating strategies and interventions are limited. However, recent clinical trials show that nightly administration of exogenous melatonin may mitigate or even prevent antipsychotic-induced AMEs. This clinical evidence in combination with recent preclinical data implicate the circadian system in antipsychotic-induced AMEs and their mitigation. In this chapter, we provide an overview on the circadian system and its involvement in antipsychotic-induced AMEs, as well as the potential beneficial effect of nightly melatonin administration to mitigate them.

M201. MODERATORS OF WEIGHT GAIN IN RANDOMIZED CONTROLLED TRIALS OF SCHIZOPHRENIA – A META-REGRESSION ANALYSIS

BackgroundWeight gain is an important side effect of antipsychotics. Meta-analyses of randomized controlled trials indicate differences between the multiple antipsychotics in propensity to cause weight gain. However, antipsychotic-associated weight gain, in randomized controlled trials as well as in real life situations, might also depend on population characteristics and treatment-related factors.As a preparatory work for a systematic review and network-meta-analysis on metabolic side effects of antipsychotics (presented in another poster at this conference), we conducted a meta-regression analysis of potential moderators of weight gain.MethodsWe selected acute phase short-term, acute phase long-term as well as relapse prevention studies (all found by systematic reviews conducted by our group in the past) from our database of randomized controlled trials of antipsychotics in schizophrenia.We conductedi) meta-regression-analyses based on pairwise meta-analysis of the mean difference (MD) in change in weight (kg) between patients exposed to antipsychotics and placebo, andii) meta-regression-analyses based on single-arm meta-analysis of the change in weight (kg).We examined the moderators baseline weight, study duration, percentage women, and publication year.We conducted the analyses for all drugs pooled, placebo and per individual drug. For presentation of the results we focus on the drugs aripiprazole, haloperidol, quetiapine, olanzapine, and risperidone, because these are popular drugs in clinical practice, they differ in their receptor-binding profiles and multiple studies are available for these drugs.We conducted the analysis in R using the commands metacont, metagen and metareg from the package meta.ResultsThe dataset comprises 603 randomized controlled trials with 141 584 patients that examined 40 different antipsychotics. Trial duration varied between 3 and 156 weeks (median 8 weeks). 168 studies with 49 670 patients reported on change in body weight.We found no effect of baseline weight on antipsychotic-associated weight gain, however on placebo, lower baseline weight was associated with more weight loss.Moreover, on antipsychotics, higher percentage of women was associated with less weight gain, and, on placebo, higher percentage of women was associated with more weight loss.Longer study duration was not associated with increased weight gain. On placebo, longer studies were associated with more weight loss.There was no effect of publication year.DiscussionSurprisingly, we found no moderating effect of baseline weight and study duration on weight gain. However, our data suggests that men and women could have different risk of weight gain. Moreover, weight loss after switching to placebo might be higher in women and patients with less baseline weight. For interpretation, it must be noted that meta-regressions are observational evidence and thus prone to confounding. In addition, the scatter plots, presented on the poster, need to be considered to judge the robustness and magnitude of the moderated effects. Additional meta-regressions (planned to present on the poster) should address further potential moderators, such as antipsychotic dose, ethnicity, previous antipsychotic exposure and dropout rates.

Single nucleotide polymorphism MTHFR677C>T and the severity of metabolic side effects of antipsychotics in patients with schizophrenia: the results of a pilot study

To predict the development of side effects and personalized selection of drug therapy, it seems relevant to study the association of individual genetic risk factors with undesirable side effects of antipsychotics in chronic patients with schizophrenia. Thereby the purpose of this study was to evaluate the association between the carriage of the T-allele of the single nucleotide genetic polymorphism MTHFR677C>T and the severity of the metabolic side effects of antipsychotics. As a result of the study a greater risk of developing components of the metabolic syndrome was revealed, as well as a significantly higher fasting blood glucose level in the group of carriers of the minor T-allele of polymorphism MTHFR677C>T.

High-density lipoprotein-cholesterol and antipsychotic medication in overweight inpatients with schizophrenia: post-hoc analysis of a Japanese nationwide survey

BackgroundPatients with schizophrenia have an increased prevalence of metabolic disturbances compared with the general population. However, the mechanisms underlying the metabolic side effects of antipsychotics are unknown. The aim of the present study was to compare the levels of high-density lipoprotein (HDL)-cholesterol in Japanese schizophrenia patients medicated with olanzapine, risperidone, or aripiprazole monotherapy.MethodsThis study was a post-hoc analysis of a nationwide survey, which included 433 Japanese outpatients with schizophrenia and 674 inpatients. A brief questionnaire was compiled that covered demographic data, systolic blood pressure, diastolic blood pressure, and HDL-cholesterol after reviewing the relevant literature and guidelines. To compare demographic and clinical characteristics, analysis of variance was performed for continuous variables and the chi-square test was performed for categorical variables. For comparisons of HDL-cholesterol levels among the three antipsychotic groups, analysis of covariance was carried out with age, diastolic blood pressure, chlorpromazine-equivalent dosage, and waist circumference as confounding variables after stratification by body mass index (BMI) for each outpatient group and inpatient group.ResultsThe mean age was 57.9 ± 14.0 years and the mean BMI was 23.4 ± 4.5 kg/m2. HDL-cholesterol levels when stratified by BMI differed significantly (p = 0.019) between the three antipsychotic groups after age, diastolic blood pressure, chlorpromazine-equivalent dosage, and waist circumference in inpatients. A significant difference in HDL-cholesterol levels was only found in the overweight inpatient group, and no significant differences in HDL-cholesterol levels were found among the three antipsychotics for outpatients of all BMI stratifications or inpatients that were underweight or of normal weight. For post-hoc analysis of HDL-cholesterol levels in overweight inpatients, HDL-cholesterol was significantly lower in the olanzapine group than in the aripiprazole group (p = 0.023).ConclusionsThis study reveals a difference in HDL-cholesterol levels in overweight Japanese inpatients with schizophrenia resulting from the use of different antipsychotics. In the post-hoc analysis of HDL-cholesterol levels in overweight inpatients, HDL-cholesterol was significantly lower in the olanzapine group than in the aripiprazole group. Further studies incorporating more detailed evaluations, including diet and physical activity, are needed to clarify the differences in HDL-cholesterol according to antipsychotic use.

Metabolic Syndrome and Antipsychotics: The Role of Mitochondrial Fission/Fusion Imbalance.

Second-generation antipsychotics (SGAs) are known to increase cardiovascular risk through several physiological mechanisms, including insulin resistance, hepatic steatosis, hyperphagia, and accelerated weight gain. There are limited prophylactic interventions to prevent these side effects of SGAs, in part because the molecular mechanisms underlying SGAs toxicity are not yet completely elucidated. In this perspective article, we introduce an innovative approach to study the metabolic side effects of antipsychotics through the alterations of the mitochondrial dynamics, which leads to an imbalance in mitochondrial fusion/fission ratio and to an inefficient mitochondrial phenotype of muscle cells. We believe that this approach may offer a valuable path to explain SGAs-induced alterations in metabolic homeostasis.

Novel Treatments of Psychosis

Since the advent of chlorpromazine in the 1950s, D2 receptor antagonist activity has been synonymous with antipsychotic medications. This single mechanism of action may explain the similarities in efficacy among approved antipsychotics. Additionally, extrapyramidal and metabolic side effects of antipsychotics present a significant burden to patient quality of life. Development of the next generation of antipsychotics has focused on novel mechanisms of action including drugs that act through the N‐methyl‐d-aspartate (NMDA) system, modify second messenger activity, and modulate neuronal firing. This review surveys a selection of novel treatments with activity against positive symptoms. Each section includes a brief description of their mechanism of action, summarizes studies evaluating their clinical efficacy, and comments on safety and tolerability issues. Included in this review are compounds originally developed for treating psychotic disorders such as pimavanserin, pomaglumetad, and bitopertin. Other interventions are off-label uses of existing treatments such as bexarotene, rTMS, and sodium nitroprusside.

EPA-0680 - Towards collaborative intervention that improves the lives of patients with schizophrenia: clinicians as drivers of policy change

An evidence-based, integrated care package that addresses mental and physical health needs would help to transform the lives of people with schizophrenia. It should be underpinned with a co-ordinated approach by healthcare professionals and supported by the national healthcare system and by educational and research facilities. Collaboration between relevant stakeholders at national and local level is required to achieve this. The UK Prescribing Observatory for Mental Health (POMH-UK), based at the Royal College of Psychiatrists within the College Centre for Quality Improvement, illustrates one such collaboration. POMH-UK facilitates national, audit-based, quality improvement programmes (QIPs) that address the use of medicines in psychiatric practice. Since POMH-UK began in 2005, it has initiated QIPs addressing several topics relevant to the treatment of schizophrenia, including the use of high-dose and combined antipsychotics in acute adult inpatient and forensic settings, screening for the metabolic side effects of antipsychotics, the quality of assessment of side effects in patients treated with depot/long-acting injection antipsychotics, and medicines reconciliation at the point of hospital admission. Positive change in prescribing practice in psychiatric services has been achieved for many of these QIPs, although progress is gradual and gains are generally modest. Key elements of the QIPs are feedback of benchmarked performance for local clinical reflection and customised change interventions informed by the national audit findings and parallel qualitative work. The benefits and drawbacks of such an approach will be discussed, in the context of schizophrenia, with a view to evolving a model that other countries might replicate.

Monitoring and managing metabolic effects of antipsychotics: a cluster randomized trial of an intervention combining evidence-based quality improvement and external facilitation.

BackgroundTreatment of psychotic disorders consists primarily of second generation antipsychotics, which are associated with metabolic side effects such as overweight/obesity, diabetes, and dyslipidemia. Evidence-based clinical practice guidelines recommend timely assessment and management of these conditions; however, research studies show deficits and delays in metabolic monitoring and management for these patients. This protocol article describes the project ‘Monitoring and Management for Metabolic Side Effects of Antipsychotics,’ which is testing an approach to implement recommendations for these practices.Methods/DesignThis project employs a cluster randomized clinical trial design to test effectiveness of an evidence-based quality improvement plus facilitation intervention. Eligible study sites were VA Medical Centers with ≥300 patients started on a new antipsychotic prescription in a six-month period. A total of 12 sites, matched in pairs based on scores on an organizational practice survey, were then randomized within pairs to intervention or control conditions.Study participants include VA employees involved in metabolic monitoring and management of patients treated with antipsychotics at participating sites. The intervention involves researchers partnering with clinical stakeholders to facilitate tailoring of local implementation strategies to address barriers to metabolic side-effect monitoring and management. The intervention includes a Design Phase (initial site visit and subsequent development of a local implementation plan); Implementation Phase (guided by an experienced external facilitator); and a Sustainability Phase. Evaluation includes developmental, implementation-focused, progress-focused and interpretative formative evaluation components, as well as summative evaluation. Evaluation methods include surveys, qualitative data collection from provider participants, and quantitative data analysis of data for all patients prescribed a new antipsychotic medication at a study site who are due for monitoring or management of metabolic side effects during the study phases. Changes in rates of recommended monitoring and management actions at intervention and control sites will be compared using time series analyses.DiscussionImproving monitoring for metabolic side effects of antipsychotics, as well as promoting timely evidence-based management when these effects emerge, will lead to improved patient safety and long-term outcomes. This article discusses key strengths and challenges of the study.Trial registrationNCT01875861

Relationships between pharmacotherapy-induced metabolic changes and improved psychopathology in schizophrenia: data from a mirtazapine and first-generation antipsychotics combination trial

Clinical efficacy and metabolic side-effects of antipsychotics seem to correlate with each other. In this study, interrelationship of similar metabolic effects of mirtazapine and its earlier reported desirable effects on psychopathology in first-generation antipsychotics (FGAs)-treated schizophrenia were explored. Symptomatic FGAs-treated patients with schizophrenia received a 6-wk double-blind treatment with add-on mirtazapine (n = 20) or placebo (n = 16), followed by a 6-wk open-label mirtazapine treatment. Mirtazapine (but not placebo) induced an increase in body weight and cholesterol levels. The latter was associated with a clinical improvement in all (sub)scales of the Positive and Negative Syndrome Scale [PANSS; an increase of cholesterol by 1 mmol/l predicted 7 points reduction on the PANSS total score (r = 0.85, p = 0.001)]. In schizophrenia, mirtazapine-induced weight gain and increase of total cholesterol are associated with the improved efficacy of mirtazapine-FGAs combination--a novel observation with possible clinical and theoretical implications.

Atypical antipsychotics alter cholesterol and fatty acid metabolism in vitro

Haloperidol, a typical antipsychotic, has been shown to inhibit cholesterol biosynthesis by affecting Δ(7)-reductase, Δ(8,7)-isomerase, and Δ(14)-reductase activities, which results in the accumulation of different sterol intermediates. In the present work, we investigated the effects of atypical or second-generation antipsychotics (SGA), such as clozapine, risperidone, and ziprasidone, on intracellular lipid metabolism in different cell lines. All the SGAs tested inhibited cholesterol biosynthesis. Ziprasidone and risperidone had the same targets as haloperidol at inhibiting cholesterol biosynthesis, although with different relative activities (ziprasidone > haloperidol > risperidone). In contrast, clozapine mainly affected Δ(24)-reductase and Δ(8,7)-isomerase activities. These amphiphilic drugs also interfered with the LDL-derived cholesterol egress from the endosome/lysosome compartment, thus further reducing the cholesterol content in the endoplasmic reticulum. This triggered a homeostatic response with the stimulation of sterol regulatory element-binding protein (SREBP)-regulated gene expression. Treatment with SGAs also increased the synthesis of complex lipids (phospholipids and triacylglycerides). Once the antipsychotics were removed from the medium, a rebound in the cholesterol biosynthesis rate was detected, and the complex-lipid synthesis further increased. In this condition, apolipoprotein B secretion was also stimulated as demonstrated in HepG2 cells. These effects of SGAs on lipid homeostasis may be relevant in the metabolic side effects of antipsychotics, especially hypertriglyceridemia.

Monitoring Veterans for Metabolic Side Effects When Prescribing Antipsychotics

This study examined practices for monitoring metabolic side effects of antipsychotics at 32 Veterans Affairs (VA) facilities. This retrospective cohort analysis included outpatients receiving a new antipsychotic prescription from April 2008 through March 2009 in Veterans Integrated Service Networks 18–22 (N=12,009). Data from national and regional VA data sources were used to examine the extent to which weight, glucose (or hemoglobin A1c), and low-density lipoprotein (LDL) cholesterol were monitored within 30 days of the new prescription (baseline) and 60–120 days thereafter, consistent with American Diabetes and American Psychiatric Association consensus recommendations. Repeated-measures analysis using the generalized estimating equation for binary variables examined the association of patient characteristics with likelihood of monitoring. Monitoring of the three metabolic parameters was significantly greater at baseline than at follow-up (p<.001). Weight was the most frequently monitored parameter. Having a diagnosis of diabetes or dyslipidemia was significantly associated with greater monitoring rates. Although monitoring rates did not vary significantly by psychiatric diagnosis, patients without a psychiatric diagnosis were less likely to be monitored than those with schizophrenia. Compared with patients taking antipsychotics with the lowest metabolic risk, those taking high-risk antipsychotics were more likely to have weight monitored at baseline (adjusted odds ratio [AOR]=1.20), whereas patients prescribed medium-risk antipsychotics were more likely to be monitored at baseline for glucose (AOR=1.12) and LDL (AOR=1.11). Efforts to improve monitoring of antipsychotics' metabolic side effects are needed and should be applied for all patients regardless of diagnosis.

Melatonin: an overlooked factor in schizophrenia and in the inhibition of anti-psychotic side effects

This paper reviews melatonin as an overlooked factor in the developmental etiology and maintenance of schizophrenia; the neuroimmune and oxidative pathophysiology of schizophrenia; specific symptoms in schizophrenia, including sleep disturbance; circadian rhythms; and side effects of antipsychotics, including tardive dyskinesia and metabolic syndrome. Electronic databases, i.e. PUBMED, Scopus and Google Scholar were used as sources for this review using keywords: schizophrenia, psychosis, tardive dyskinesia, antipsychotics, metabolic syndrome, drug side effects and melatonin. Articles were selected on the basis of relevance to the etiology, course and treatment of schizophrenia. Melatonin levels and melatonin circadian rhythm are significantly decreased in schizophrenic patients. The adjunctive use of melatonin in schizophrenia may augment the efficacy of antipsychotics through its anti-inflammatory and antioxidative effects. Further, melatonin would be expected to improve sleep disorders in schizophrenia and side effects of anti-psychotics, such as tardive dyskinesia, metaboilic syndrome and hypertension. It is proposed that melatonin also impacts on the tryptophan catabolic pathway via its effect on stress response and cortisol secretion, thereby impacting on cortex associated cognition, amygdala associated affect and striatal motivational processing. The secretion of melatonin is decreased in schizophrenia, contributing to its etiology, pathophysiology and management. Melatonin is likely to have impacts on the metabolic side effects of anti-psychotics that contribute to subsequent decreases in life-expectancy.

Incentives to Reduce Metabolic Side Effects of Antipsychotics: Reply

Incentives to Reduce Metabolic Side Effects of Antipsychotics: Reply

Incentives to Reduce Metabolic Side Effects of Antipsychotics: Reply

Incentives to Reduce Metabolic Side Effects of Antipsychotics: Reply