https://onlinelibrary.wiley.com/doi/pdf/10.1002/j.2051-5545.2011.tb00014.x

Physical illness in patients with severe mental disorders.I. Prevalence, impact of medications and disparities in health care

/pdf/practice-guideline-for-the-treatment-of-patients-with-major-ofberaz3o1.pdf

PRACTICE GUIDELINE FOR THE Treatment of Patients With Major Depressive Disorder

Methods We calculated the adjusted incidence of sudden cardiac death among current users of antipsychotic drugs in a retrospective cohort study of Medicaid enrollees in Tennessee. The primary analysis included 44,218 and 46,089 baseline users of single typical and atypical drugs, respectively, and 186,600 matched nonusers of antipsychotic drugs. To assess residual confounding related to factors associated with the use of antipsychotic drugs, we performed a secondary analysis of users of antipsychotic drugs who had no baseline diagnosis of schizophrenia or related psychoses and with whom nonusers were matched according to propensity score (i.e., the predicted probability that they would be users of antipsychotic drugs). Results Current users of typical and of atypical antipsychotic drugs had higher rates of sudden cardiac death than did nonusers of antipsychotic drugs, with adjusted incidencerate ratios of 1.99 (95% confidence interval [CI], 1.68 to 2.34) and 2.26 (95% CI, 1.88 to 2.72), respectively. The incidence-rate ratio for users of atypical antipsychotic drugs as compared with users of typical antipsychotic drugs was 1.14 (95% CI, 0.93 to 1.39). Former users of antipsychotic drugs had no significantly increased risk (incidencerate ratio, 1.13; 95% CI, 0.98 to 1.30). For both classes of drugs, the risk for current users increased significantly with an increasing dose. Among users of typical anti psychotic drugs, the incidence-rate ratios increased from 1.31 (95% CI, 0.97 to 1.77) for those taking low doses to 2.42 (95% CI, 1.91 to 3.06) for those taking high doses (P<0.001). Among users of atypical agents, the incidence-rate ratios increased from 1.59 (95% CI, 1 .03 to 2.46) for those taking low doses to 2.86 (95% CI, 2.25 to 3.65) for those taking high doses (P = 0.01). The findings were similar in the cohort that was matched for propensity score. Conclusions Current users of typical and of atypical antipsychotic drugs had a similar, dose-related increased risk of sudden cardiac death.

/pdf/atypical-antipsychotic-drugs-and-the-risk-of-sudden-cardiac-3x5jtbsoa2.pdf

Atypical Antipsychotic Drugs and the Risk of Sudden Cardiac Death

The Canadian Network for Mood and Anxiety Treatments (CANMAT) previously published treatment guidelines for bipolar disorder in 2005, along with international commentaries and subsequent updates in 2007, 2009, and 2013. The last two updates were published in collaboration with the International Society for Bipolar Disorders (ISBD). These 2018 CANMAT and ISBD Bipolar Treatment Guidelines represent the significant advances in the field since the last full edition was published in 2005, including updates to diagnosis and management as well as new research into pharmacological and psychological treatments. These advances have been translated into clear and easy to use recommendations for first, second, and third- line treatments, with consideration given to levels of evidence for efficacy, clinical support based on experience, and consensus ratings of safety, tolerability, and treatment-emergent switch risk. New to these guidelines, hierarchical rankings were created for first and second- line treatments recommended for acute mania, acute depression, and maintenance treatment in bipolar I disorder. Created by considering the impact of each treatment across all phases of illness, this hierarchy will further assist clinicians in making evidence-based treatment decisions. Lithium, quetiapine, divalproex, asenapine, aripiprazole, paliperidone, risperidone, and cariprazine alone or in combination are recommended as first-line treatments for acute mania. First-line options for bipolar I depression include quetiapine, lurasidone plus lithium or divalproex, lithium, lamotrigine, lurasidone, or adjunctive lamotrigine. While medications that have been shown to be effective for the acute phase should generally be continued for the maintenance phase in bipolar I disorder, there are some exceptions (such as with antidepressants); and available data suggest that lithium, quetiapine, divalproex, lamotrigine, asenapine, and aripiprazole monotherapy or combination treatments should be considered first-line for those initiating or switching treatment during the maintenance phase. In addition to addressing issues in bipolar I disorder, these guidelines also provide an overview of, and recommendations for, clinical management of bipolar II disorder, as well as advice on specific populations, such as women at various stages of the reproductive cycle, children and adolescents, and older adults. There are also discussions on the impact of specific psychiatric and medical comorbidities such as substance use, anxiety, and metabolic disorders. Finally, an overview of issues related to safety and monitoring is provided. The CANMAT and ISBD groups hope that these guidelines become a valuable tool for practitioners across the globe.

/pdf/canadian-network-for-mood-and-anxiety-treatments-canmat-and-3lm5mpt404.pdf

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder

Antipsychotic medications can induce cardiovascular and metabolic abnormalities (such as obesity, hyperglycemia, dyslipidemia and the metabolic syndrome) that are associated with an increased risk of type 2 diabetes mellitus and cardiovascular disease. Controversy remains about the contribution of individual antipsychotic drugs to this increased risk and whether they cause sudden cardiac death through prolongation of the corrected QT interval. Although some drug receptor-binding affinities correlate with specific cardiovascular and metabolic abnormalities, the exact pharmacological mechanisms underlying these associations remain unclear. Antipsychotic agents with prominent metabolic adverse effects might cause abnormalities in glucose and lipid metabolism via both obesity-related and obesity-unrelated molecular mechanisms. Despite existing guidelines and recommendations, many antipsychotic-drug-treated patients are not assessed for even the most easily measurable metabolic and cardiac risk factors, such as obesity and blood pressure. Subsequently, concerns have been raised over the use of these medications, especially pronounced in vulnerable pediatric patients, among whom their use has increased markedly in the past decade and seems to have especially orexigenic effects. This Review outlines the metabolic and cardiovascular risks of various antipsychotic medications in adults and children, defines the disparities in health care and finally makes recommendations for screening and monitoring of patients taking these agents.

Metabolic and cardiovascular adverse effects associated with antipsychotic drugs

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(00)02035-3.pdf

QTc-interval abnormalities and psychotropic drug therapy in psychiatric patients

Background Sudden death has been linked to antipsychotic therapy, but the relative risk associated with specific drugs is unknown.

Aims To assess the risk of sudden unexplained death associated with antipsychotic drug therapy and its relation to drug dose and individual agents.

Method A case—control study of psychiatric in-patients dying suddenly in five hospitals in the north-east of England and surviving controls matched for age, gender and mental disorder. Logistic regression analysis was used to identify significant risk factors, and odds ratios were calculated.

Results Sixty-nine case—control clusters were identified. Probable sudden unexplained death was significantly associated with hypertension, ischaemic heart disease and current treatment with thioridazine (adjusted odds ratio=5.3, 95% CI 1.7-16.2, P =0.004). There was no significant association with other individual antipsychotic drugs.

Conclusions Thioridazine alone was associated with sudden unexplained death, the likely mechanism being druginduced arrythmia.

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/B0CB4E57FFF91DCB9EFCF5CD3F8741FF/S0007125000161124a.pdf/div-class-title-thioridazine-and-sudden-unexplained-death-in-psychiatric-in-patients-div.pdf

J. G. Reilly

Papers

QTc-interval abnormalities and psychotropic drug therapy in psychiatric patients

Thioridazine and sudden unexplained death in psychiatric in-patients.