Sudden Death In Psychiatric Patients Research Articles

Pulmonary thromboembolism and sudden death in psychiatric patients: Two cases reports

Introduction. Pulmonary thromboembolism occurs usually by running a thrombus from the deep veins of the legs rarely periprostatic or periuteric veins. Virchow's triad of necessary conditions for the occurrence of thrombosis involves disruption of blood flow, disruption of blood chemistry and damage to the vessel wall. Venous thrombosis is often associated with the implementation of antipsychotic therapy. Case report. We reported two cases of sudden death of psychiatric patients who were in both cases fixed during hospitalization. The first case was a 26-year-old woman treated a year with the diagnose of postpartum reactive psychosis. She was hospitalized because of mental state worsening with a dominant depressed mood, visual and auditory hallucinations. Her therapy was determined by diazepam, clozapine, haloperidol and lamotrigine. Suddenly, the patient died on the fifth day of hospitalization. The autopsy showed massive thromboembolism of the pulmonary artery branches. Toxicological analysis revealed the presence of therapeutic doses of antipsychotics. The second case was a-45-yearold men, a long-time alcoholic. On admission, the diagnosis of delirium tremens was established, and diazepam and haloperidol were administered. On the fifth day of hospitalization, he suddenly died. The autopsy showed thromboembolism of the branch of the pulmonary artery. Toxicological analysis established the presence of nordiazepam in urine (0.06 mg/L). Both patients were fixed during hospitalization. Conclusion. Both presented psychiatric patients were younger than 50 years, were not overweight, did not have changes of the venous blood vessels. Nowadays, when the issue of medical responsibility often arises in these and similar cases of sudden death in patients treated in psychiatric clinics, the questions on medical malpractice could be expected.

Psychosis, depression, and high risk for sudden cardiac death: time for co-operation between psychiatrists and cardiologists

This editorial refers to ‘Psychotropic medications and the risk of sudden cardiac death during an acute coronary event’, by J. Honkola et al. , doi:10.1093/eurheartj/ehr368 Psychiatric patients have an excess rate of unexplained sudden death.1 Some studies have linked this to the disease itself and to an increased prevalence of other risk factors such as dyslipidaemia and diabetes in this population.2 However, a number of observations have suggested that the use of antipsychotic and antidepressant drugs might be at the root of these deaths.3⇓ Figure 1 The triangle of sudden death in psychiatric patients. The work coming from the University of Oulu4 can bring some clarity to this debate. Is this a population at higher risk for sudden cardiac death who should be screened and treated accordingly, or is the treatment they …

Data Question Association of Antipsychotics, Cardiac Deaths

Data Question Association of Antipsychotics, Cardiac Deaths

Sudden Deaths in Psychiatric Patients

Studies using death certificates have indicated an excess of sudden cardiac deaths among users of antipsychotic drugs compared to the general population, but they may have underestimated the presence of other known causes of sudden and unexpected death. To assess the causes and risk factors for sudden death discovered by contemporaneous investigation of all deaths occurring over a 26-year period (1984-2009) in adults (119,500 patient-years) receiving care in one large psychiatric hospital in New York. Circumstances of death, psychiatric diagnoses, psychotropic drugs, and past medical history were extracted from the root cause analyses of sudden, unexpected deaths. After cases involving suicide, homicide, and drug overdoses were excluded, the remaining explained and unexplained cases of sudden death were compared regarding clinical variables and the utilization of antipsychotics. One hundred cases of sudden death were identified. The death remained unexplained in 52 cases. The incidence of unexplained sudden death per 100,000 patient-years increased from 7 (95% CI, 3.7-19.4) in 1984-1998 to 125 (95% CI, 88.9-175.1) in 2005-2009. Explained and unexplained cases were similar regarding psychiatric diagnoses and use of all psychotropic classes, including first- and second-generation antipsychotics. Dyslipidemia (P = .012), diabetes (P = .054), and comorbid dyslipidemia and diabetes (P = .006) were more common in the unexplained group. In a consecutive cohort of psychiatric patients, the unexplained sudden deaths were not associated with higher utilization of first- or second-generation antipsychotics. The role of diabetes and dyslipidemia as risk factors for sudden death in psychiatric patients requires careful longitudinal studies.

Protective role of selenium supplementation against cardiac lesions induced by the combination of levomepromazine and risperidone in the rabbit

Neuroleptics are a suspected cause of sudden death in psychiatric patients, especially in those with pre-existing cardiac lesions. As these lesions were previously shown to be associated with selenium (Se) deficiency, the aim of the present study was to evidence the possible protective effect of Se supplementation against cardiac lesions induced by the combination of the neuroleptic drugs levomepromazine and risperidone in the rabbit. Two groups of 6 rabbits were treated with 3 mg/kg of levomepromazine daily intramuscularly combined with 1 mg/kg of risperidone intramuscularly every other week for 3 consecutive months, and one group additionally received a solution of sodium selenite (2 microg/kg/day) intramuscularly during the whole treatment period. Furthermore, one group of six untreated animals was given the Se supplementation and another group of six control animals received saline daily. Blood samples were drawn before and at the end of the treatment period for the measurement of serum Se levels. At the end of the study, all animals were sacrificed and their hearts were removed for the measurement of tissue Se concentrations. In addition, the hearts were prepared for histopathological examination. A variety of cardiac lesions was found in the neuroleptics-treated animals without supplementation and to a lesser extent in the control and Se-supplemented untreated animals. Importantly, only rare cardiac lesions were observed in neuroleptics-Se-treated animals. The most striking differences in Se concentrations were noted in the myocardium: as compared to controls, there was a 43% reduction in neuroleptics-treated, but non-Se-supplemented animals (p < .01), at the end of the treatment period, whereas only a 14% reduction (p < .05) was noted in the neuroleptics-Se-treated animals. These results confirm that neuroleptics induce cardiac lesions associated with Se deficiency. Selenium supplementation markedly decreased the incidence and severity of neuroleptics-induced cardiac lesions and these findings may serve as a basis for further evaluation of the protective role of Se supplementation in neuroleptics-treated patients. However, Se supplementation in normal animals without Se deficiency was also shown to be cardiotoxic.

Antipsychotic drugs and QT prolongation

Antipsychotic drugs (AD) are effective and frequently prescribed to more females than males. AD may cause serious cardiovascular side-effects, including prolonged QT interval, eventually leading to torsades de pointes (TdP) and sudden death. Epidemiologic data and case-control studies indicate an increased rate of sudden death in psychiatric patients taking AD. This review summarizes current knowledge about the QT prolonging effects of AD and gives practical suggestions. Amisulpride, clozapine, flupenthixol, fluphenazine, haloperidol, melperone, olanzapine, perphenazine, pimozide, quetiapine, risperidone, sulpiride, thioridazine and ziprasidone cause a QT prolongation ranging from 4 ms for risperidone to 30 ms for thioridazine. Our knowledge about the QT-prolonging effects of many AD is still limited. Females are under-represented in most studies. Many studies were conducted or supported by pharmaceutical companies. To avoid prodysrhythmia caused by QT prolongation, other factors influencing QT interval have to be considered, such as other drugs affecting the same pathway, hypokalemia, hypomagnesemia, bradycardia, increased age, female sex, congestive heart failure and polymorphisms of genes coding ion channels or enzymes involved in drug metabolism. Because the response of a patient to AD is individual, an electrocardiogram recording the QT interval has to be performed at baseline, after AD introduction and after occurrence of any factor that might influence the QT interval.

Hidden cardiac lesions and psychotropic drugs as a possible cause of sudden death in psychiatric patients: a report of 14 cases and review of the literature.

To confirm the hypothesis that psychotropic drugs, especially neuroleptics, lithium, and antidepressants, are implicated as a cause of unexpected sudden death in psychiatric patients because of their cardiotoxicity, especially when hidden cardiac lesions are present. We performed a full pathological examination of 14 psychiatric patients who unexpectedly and suddenly died between 1980 and 1999. Neuroleptics were involved in 13 instances, antidepressants in 9, and anxiolytics in 5. Psychotropic drugs were combined in all but a single patient. In all 14 patients, toxicological analyses discarded drug overdose as cause of death. At postmortem examination, the brain and abdominal organs were normal. In 13 patients, the following lesions were found in the heart and lungs: dilated cardiomyopathy (6 patients), left ventricular hypertrophy (2 patients, 1 of which was associated with mitral prolapse and anomalies of His bundle), arrhythmogenic cardiopathy of the right ventricle (1 patient), pericarditis (1 patient), mitral prolapse (1 patient), muscular bridge on the anterior interventricular artery (1 patient), and Mendelsons syndrome (1 patient). In 1 case, no changes were seen. Most of the drugs that were taken immediately prior to death can induce arrhythmias either by prolonging the QT interval, potentially resulting in torsades de pointes, or by widening QRS complexes, possibly leading to reentry and ventricular fibrillation. Our findings suggest that the arrhythmogenic effects of psychotropic drugs can be exacer bated when preexisting hidden cardiac lesions are present and can result in sudden death. Patients should be systematically evaluated for cardiac lesions prior to starting any treatment with psychotropic drugs; the minimal effective dosage should be used.

Antipsychotic drugs and QT interval prolongation.

The QTc prolongation by antipsychotic drugs is of major concern, especially in light of the data indicating an increased risk of sudden death in psychiatric patients taking these drugs. Sudden death in psychiatric patients could be partially attributed to drug-induced torsades de pointes and for this reason careful evaluation of QTc prolonging properties of antipsychotic drugs is needed. Antipsychotic drugs prolong QT interval usually by blocking the potassium IKr current. Improved understanding of ion channel structure and kinetics and its role in repolarization has tremendous impact on understanding of the mechanisms of drug-induced QT prolongation and torsades de pointes. Proarrhythmia caused by a QT-prolonging drug occurs infrequently, and usually multiple factors need to operate to precipitate such an event including a combination of two or more drugs affecting the same pathway, hypokalemia, and possibly genetic predisposition. Currently prescribed antipsychotics might cause QT prolongation ranging from 4-6 ms for haloperidol and olanzapine to 35 ms for thioridazine. The response of a patient to a drug is very individual and therefore an individualized system of drug administration and monitoring needs to be developed which takes into account baseline QTc duration and its changes after a drug was introduced. A systematic approach while stratifying psychiatric patients as those with short QTc (QTc < or = 0.41 sec), borderline QTc (QTC = 0.42-0.44 sec), and prolonged QTc (0.45 sec) is being proposed to improve the safety of administering antipsychotic drugs and to decrease the risk of drug-related sudden death in psychiatric patients.

Recent studies on ECG changes, antipsychotic use and sudden death in psychiatric patients

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Association of autonomic dysfunction and clozapine. Heart rate variability and risk for sudden death in patients with schizophrenia on long-term psychotropic medication.

Antipsychotic medications cause a wide range of adverse effects and have been associated with sudden death in psychiatric patients. To supply power spectral analysis of heart rate variability as a tool to examine the arrythmogenic effects of neuroleptics. Heart rate analysis was carried out in patients with schizophrenia on standard doses of neuroleptic monotherapy -- 21 were on clozapine, 18 on haloperidol and 17 on olanzapine -- and in 53 healthy subjects. Patients with schizophrenia on clozapine had significantly higher heart rate, lower heart rate variability and lower high-frequency and higher low-frequency components compared with patients on haloperidol or olanzapine and matched control subjects. Prolonged QTc intervals were more common in patients than controls. Patients treated with neuroleptic medications, especially clozapine, showed autonomic dysregulation and cardiac repolarisation changes. Physicians should be aware of this adverse reaction.

Sudden death in psychiatric patients.

The present study investigated histories of prior psychiatric treatment in cases of sudden death reported to the coroner. A matching survey linked the register of deaths reported to the coroner with a comprehensive statewide psychiatric case register covering both in-patient and community-based services. Sudden death was five times higher in people with histories of psychiatric contact. Suicide accounted for part of this excess mortality but deaths from natural causes and accidents were also elevated. Schizophrenic and affective disorders had similar suicide rates. Comorbid substance misuse doubled the risk of sudden death in affective and schizophrenic disorders. The rates of sudden death are sufficiently elevated to raise questions about current priorities in mental health care. There is a need both for greater attention to suicide risk, most notably among young people with schizophrenia, to the early detection of cardiovascular disorders and to the vigorous management of comorbid substance misuse.

1. Neuroleptic Induced Sudden Death — A Case Report and Critical Review

A case report illustrates possible pathophysiological mechanisms of sudden death in psychiatric patients. Difficulties with the tendency to implicate phenothiazines as the cause of death are discussed in light of evidence that the death investigation and autopsy are often incomplete. Some suggestions are made to reduce the risk of a fatal outcome following a violent incident.

Sudden Death in Psychiatric Patients:The Role of Neuroleptic Drugs—by George M. Simpson, M.D., John Davis, M.D., James W. Jefferson, M.D., and Jorge F. Perez-Cruet, M.D.; task force report 27 of the American Psychiatric Association, 1988, 35 pages. Single copies available free from the Office of Research, APA, 1400 K Street, N.W., Washington, D.C. 20005

<b>Sudden Death in Psychiatric Patients:</b>The Role of Neuroleptic Drugs—by George M. Simpson, M.D., John Davis, M.D., James W. Jefferson, M.D., and Jorge F. Perez-Cruet, M.D.; task force report 27 of the American Psychiatric Association, 1988, 35 pages. Single copies available free from the Office of Research, APA, 1400 K Street, N.W., Washington, D.C. 20005

Evaluation of Sudden Death in Psychiatric Patients with Special Reference to Phenothiazine Therapy: Forensic Pathology

The investigation of sudden unexpected death in psychiatric patients and the ensuing litigation has brought to our attention many unusual features important in the evaluation of such deaths. Certain pathophysiologic mechanisms of death, rarely encountered in routine forensic science practice, may be important in determining the cause of death in psychiatric patients, especially in cases where the autopsy is unrevealing. Of particular concern is a tendency in the current literature to implicate phenothiazines as a cause of death when the death investigation and the autopsies are incomplete. Thus, based on our experience and on a review of the current literature, we have set forth factors that the forensic pathologist should consider when faced with a sudden psychiatric death. A case report illustrates these unique aspects of scene investigation and analysis of terminal events and autopsy findings.