clozapine and Pulmonary-Embolism

Since the 1950 s, several studies have reported that patients using first generation and/or second-generation antipsychotics had increased risk of venous thromboembolism events. These events include deep vein thrombosis and/or pulmonary embolism (PE). However, data about fatal PE in patients on antipsychotics (APs) remain scarce. Thus, the current study aimed to investigate sociodemographic, clinical and pharmacological characteristics related to psychiatric patients on APs and who died from a fatal PE. We reported a case-series, then conducted a literature review of relevant studies and performed a meta-analysis of studies with usable data. The main outcome of the study suggested a significantly high risk of fatal PE in patients using APs compared to nonusers (Odds Ratio=6.68, with 95% confidence interval 1.43-31.11). Clozapine was the most incriminated drug. Low potency first generation APs were the second most exhibited medication. Studies about the topic remain scarce with a high heterogeneity and a high probability of bias. Further studies are needed to ascertain this risk and to establish target preventive measures in this particularly vulnerable population.

Topics: Antipsychotic Agents; Clozapine; Humans; Odds Ratio; Pulmonary Embolism; Risk Factors; Venous Thromboembolism

To identify the clinical determinants of fever in clozapine users and their impact on management of clozapine treatment.. Articles published in English or French identified with a MEDLINE, Web of Sciences, Cochrane Library and PsycINFO search, from inception through February 2019, using the term "clozapine" in combination with "fever" OR "hyperthermia" OR "body temperature" OR "pyrexia" OR "febrile" OR "heat" OR "thermoregulation". Information extracted for each medical condition were frequency, time to onset after initiation of clozapine treatment, characteristics of fever, associated symptoms, laboratory tests used for diagnosis, course, lethality, discontinuation of clozapine. Data were synthesized narratively.. Our search yielded 394 unique hits published from 1993 to 2018. We included 73 articles in the review: two meta-analyses, 14 reviews, six epidemiological studies, 11 clinical studies and 40 case reports. During clozapine initiation, fever is most frequently benign and transient but should be closely monitored as it may be the first stage of potentially life-threatening adverse drug reactions (ADR) (agranulocytosis, neuroleptic malignant syndrome myocarditis, hepatitis, pancreatitis, nephritis, colitis, etc.). Other ADR associated with fever are independent of duration of exposure to clozapine (heat stroke, pneumonia, pulmonary embolism, necrotizing colitis). If fever is due to intercurrent infection, therapeutic drug monitoring is recommended to adjust clozapine daily dosage.. Benign causes of fever are much more frequent than life-threatening ADR during clozapine treatment. Discontinuation should not be considered as automatic in the event of fever, especially during the early phase of clozapine initiation.

Topics: Agranulocytosis; Antipsychotic Agents; Chemical and Drug Induced Liver Injury; Clozapine; Colitis; Dose-Response Relationship, Drug; Drug Monitoring; Fever; Hepatitis; Humans; Infections; Lupus Erythematosus, Systemic; Myocarditis; Nephritis; Neuroleptic Malignant Syndrome; Pancreatitis; Pneumonia; Pulmonary Embolism; Schizophrenia; Serositis

An increasing number of reports suggest a link between venous thromboembolism (VTE) and the use of antipsychotics. To better understand this association the available body of evidence has been critically scrutinised. Relevant articles were identified in the databases Scopus and PubMed. Several observational studies using different methodologies show an increased risk of VTE in psychiatric patients. This elevated risk seems to be related to the use of antipsychotic medication and in particular to the use of clozapine and low-potency first-generation drugs. Many studies investigating the association have, however, methodological limitations. The biological mechanisms involved in the pathogenesis of this possible adverse reaction are largely unknown but several hypotheses have been suggested such as drug-induced sedation, obesity, increased levels of antiphospholipid antibodies, enhanced platelet aggregation, hyperhomocysteinemia and hyperprolactinemia. The association may also be related to underlying risk factors present in psychotic patients. Physicians need to be aware of this possible adverse drug reaction. Although supporting evidence has not been published they should consider discontinuing or switching the antipsychotic treatment in patients experiencing VTE. In addition, although data is lacking, the threshold for considering prophylactic antithrombotic treatment should be low when risk situations for VTE arise, such as immobilisation, surgery and so on.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Case-Control Studies; Catatonia; Clozapine; Death, Sudden; Dehydration; Female; Humans; Male; Middle Aged; Models, Biological; Platelet Aggregation; Pulmonary Embolism; Restraint, Physical; Retrospective Studies; Risk; Risk Factors; Thrombophilia; Venous Thromboembolism; Young Adult

Topics: Antipsychotic Agents; Clozapine; Humans; Male; Middle Aged; Pulmonary Embolism; Schizophrenia

Cardiometabolic health significantly impacts on the mortality of people with severe mental illness. Clozapine has the greatest efficacy for Treatment Resistant Schizophrenia (TRS) but the greatest negative impact on cardiometabolic health. Balancing the risks and benefits of treatment, dignity, autonomy, liberty, mental and physical health can be challenging, particularly when imposing interventions with potentially life threatening adverse events, such as clozapine. We describe the successful administration of clozapine in the face of myocardial infarction, pulmonary embolism and hyperlipidaemia resulting in the termination of long-term seclusion for a gentleman with TRS in high secure psychiatric services.. The impact of clozapine on a 44-year-old gentleman with TRS, extreme violence requiring physical restraint and long-term segregation, and numerous other significant physical health complications is described. He had metabolic syndrome; a poor diet, sedentary lifestyle, Body Mass Index (BMI) of 31.5, poorly controlled lipids and had smoked heavily since childhood. During preparations to initiate clozapine, he suffered a myocardial infarction and pulmonary embolism. His compliance with secondary prevention medications was poor due to paranoid persecutory and somatic delusions. Despite these concerns, nasogastric administration of clozapine was approved and prescribed within nine months of his myocardial infarction and a month from his pulmonary embolism but was ultimately not required. Accepting oral medication, his mental state made a rapid and dramatic improvement. After spending 1046 days in seclusion, this was terminated 94 days after clozapine initiation. He has been compliant with all medications for 24 months, had no incidents of violence or seclusion, and has been transferred to medium secure services. His physical health stabilised despite continuing to lead a sedentary lifestyle and remaining obese (BMI of 35). He developed hypertension, Type II Diabetes Mellitus and his triglycerides rose to 22.2 mmol/L in the same month after clozapine initiation. However, with pharmacological intervention, 24 months later these are controlled, and he has had no further thromboembolic events.. We highlight that despite significant physical health concerns, clozapine can be successfully initiated and safely prescribed with a significantly positive effect on both the psychiatric and holistic care of patients with treatment resistant schizophrenia.

Topics: Adult; Antipsychotic Agents; Clozapine; Humans; Hyperlipidemias; Involuntary Treatment, Psychiatric; Male; Metabolic Syndrome; Myocardial Infarction; Pulmonary Embolism; Schizophrenia

Patients with psychiatric disorders in critical condition are difficult to treat. In this study, we report on a patient with underlying schizoaffective disorder who developed catatonia, cardiac arrest, and pulmonary embolism, as well as a successful treatment strategy.. The inpatient is a 41-year-old morbidly obese male with schizoaffective disorder whose clozapine dosage was titrated from 100 mg to 175 mg due to auditory hallucination and agitation. The patient abruptly developed acute cardiopulmonary symptoms associated with an elevated troponin-I level. He was transferred to a cardiac intensive care unit, where he remained for 3 days. He was also found to have excited catatonic symptoms, and the lorazepam-diazepam protocol was initiated to quickly relieve the catatonia. Once the coronary angiogram was read as normal, the patient was transferred back to the psychiatric ward. However, the patient then suffered from in-hospital cardiac arrest. He was resuscitated and again transferred to the medical intensive care unit. Computed tomography confirmed the diagnosis of a pulmonary embolism. The patient was treated with Rivaroxaban 30 mg/d for the first 21 days, followed by 20 mg daily for 3 months. To control his severe and refractory psychotic symptoms, the patient was re-prescribed clozapine. During the 15-month follow-up period, the patient demonstrated a fair response and tolerability to clozapine 150 mg without symptoms relapse and no thromboembolic event.. This report can serve to remind psychiatrists and physicians to be aware of fatal conditions in patients with psychiatric diseases and physical illnesses.

Topics: Adult; Antipsychotic Agents; Catatonia; Clozapine; Drug Therapy, Combination; Factor Xa Inhibitors; Hallucinations; Humans; Male; Obesity, Morbid; Psychotic Disorders; Pulmonary Embolism; Rivaroxaban; Treatment Outcome

Topics: Antipsychotic Agents; Clozapine; Drug Overdose; Humans; Male; Medication Errors; Middle Aged; Pulmonary Embolism; Schizophrenia

Topics: Adult; Antipsychotic Agents; Clozapine; Drug Resistance; Female; Humans; Pulmonary Embolism; Schizophrenia

Topics: Antipsychotic Agents; Clozapine; Humans; Male; Middle Aged; Pneumonia, Aspiration; Pulmonary Embolism; Schizophrenia

Topics: Adult; Cerebral Angiography; Clozapine; Electrocardiography; Humans; Male; Mental Disorders; Pulmonary Embolism; Serotonin Antagonists; Tomography, X-Ray Computed

Topics: Adult; Antipsychotic Agents; Clozapine; Humans; Male; Pulmonary Embolism; Schizophrenia, Paranoid

Antipsychotic drugs (APs) expose users to several adverse effects. Some reports describe an increased risk of venous thromboembolism for particular drugs in this family.. To examine the association between the risks of pulmonary embolism (PE) and AP use and assess any dose-effect relationships.. This is a retrospective analysis of data in 'Premier's Perspective' a large US hospital database for 2006. Adults in the AP group had at least one prescription of AP. Logistic regression analysis was performed to detect association between PE and AP use. The dose-effect relationship was assessed according to quantities and administration routes. Analyses were adjusted for potential confounders: age, sex, the components of the Charlson co-morbidity index, diagnoses of infection, sepsis, inflammatory bowel disease, psychotic disorders and hospital inpatient or outpatient status.. Among 28,723,771 adults included in 2006, 450,951 (1.6%) were prescribed AP. Haloperidol was most commonly prescribed (157,667 patients or 35.0%), but atypical APs represented over 78% of prescriptions. The risk of PE was higher in AP users than in the total population (OR = 1.17 [95%CI 1.13-1.21]; p < 0.001) and depended on the type of AP used: clozapine was associated with the highest risk. Risk seemed correlated to higher doses.. Non-hospital prescription data were unavailable, potentially underestimating the number of patients exposed. The relative timing of AP prescription and PE was not available. Results did not include deep vein thrombosis.. This study suggests an increased risk of PE with AP treatment, varying with type of AP and dependent on dose.

Topics: Adult; Aged; Antipsychotic Agents; Clozapine; Databases, Factual; Dose-Response Relationship, Drug; Female; Haloperidol; Humans; Logistic Models; Male; Middle Aged; Pulmonary Embolism; Retrospective Studies; Risk; United States

Lipomas usually extend in subcutaneous tissues and rarely may be compressive. We report a case of neck lipoma resulting in jugular vein thrombosis and pulmonary embolism in a patient treated by clozapine. Clozpine may be considered an associated risk factor for thrombosis. This case suggests that performing a regional evaluation may be particularly important when thrombophlebitis occurs.

Topics: Antipsychotic Agents; Clozapine; Head and Neck Neoplasms; Humans; Jugular Veins; Lipoma; Male; Middle Aged; Pulmonary Embolism; Radiography; Risk Factors; Venous Thrombosis

Clozapine-associated induction of venous thromboembolism has potentially catastrophic consequences. We report a case of sudden death caused by bilateral main pulmonary trunk thrombosis in a 31-year-old man receiving clozapine therapy. The patient presented with general weakness and exertional dyspnea. Bilateral main pulmonary trunk thrombosis was clearly demonstrated by helical chest computed tomography.

Topics: Adult; Antipsychotic Agents; Clozapine; Death, Sudden; Emergency Medicine; Fatal Outcome; Humans; Male; Pulmonary Embolism; Schizophrenia; Treatment Refusal

To describe the occurrence of pulmonary embolism (PE) as a rare adverse effect of clozapine that is treatable, but sometimes fatal, and survey the literature on the subject in the hope of increasing awareness of the potential danger that may result from drug interactions.. A 47-year-old woman treated with clozapine and paroxetine was admitted to the hospital with dyspnea and swelling of the leg. The patient was diagnosed as having PE and was treated with intravenous heparin. On hospital day 7, sudden acute respiratory failure developed and the patient died. Postmortem examination confirmed the existence of massive PE.. The woman had no identifiable risk factors other than receiving a combination of clozapine and paroxetine, with a demonstrated elevated clozapine blood concentration. Use of the Naranjo probability scale revealed a probable likelihood that the adverse reaction was drug related.. The association of antipsychotic drugs and venous thromboembolism has been previously described, but is still a rare finding. This case highlights the importance of monitoring and possibly discontinuing treatment when venous thrombosis is suspected. There should be careful monitoring, especially in patients with risk factors for thrombosis. Finally, antidepressant-antipsychotic drug combinations can increase the risk of rare adverse effects, such as venous thromboembolism, even in the absence of other risk factors.

Topics: Antidepressive Agents, Second-Generation; Antipsychotic Agents; Blood Coagulation; Clozapine; Drug Interactions; Fatal Outcome; Female; Humans; Middle Aged; Paroxetine; Pulmonary Embolism; Venous Thrombosis

Topics: Adult; Antipsychotic Agents; Clozapine; Humans; Male; Pulmonary Embolism; Schizophrenia; Thromboembolism; Venous Thrombosis

Topics: Antipsychotic Agents; Clozapine; Humans; Male; Middle Aged; Pulmonary Embolism; Schizophrenia; Tomography, Spiral Computed

To examine the association between the use of psychotropic drugs and fatal pulmonary embolism.. We conducted a national case-control study of fatal pulmonary embolism. Cases were 75 New Zealand men and women aged 15-59 years who died between 1 January 1990 and 31 December 1998, where the underlying cause of death was certified as codes 415.1, 451 or 453 of the International Classification of Diseases (9th Revision). Four controls, matched for sex and age, were selected from the general practice to which each case had belonged. Information was abstracted from the records of general practitioners, family planning clinics and psychiatric services. Odds ratios and 95% confidence intervals (95% CI) were estimated using conditional logistic regression. The key analyses were restricted to cases (n = 62) and controls (n = 243) without major risk factors for venous thromboembolism.. Compared to non-use, the adjusted odds ratio for current use of antipsychotic drugs was 13.3 (95% CI: 2.3-76.3). Low potency antipsychotics appeared to carry the highest risk (odds ratio: 20.8 [95% CI: 1.7-259.0]). The main drug involved was thioridazine. The odds ratio for current use of antidepressants was also increased, at 4.9 (95% CI: 1.1-22.5).. Our results for conventional antipsychotics are consistent with previous studies of non-fatal venous thromboembolism. The finding for antidepressants needs to be replicated in other studies.

Topics: Adolescent; Adult; Antipsychotic Agents; Case-Control Studies; Clozapine; Female; Humans; Male; Middle Aged; New Zealand; Psychotropic Drugs; Pulmonary Embolism; Risk Factors; Venous Thrombosis

Topics: Adverse Drug Reaction Reporting Systems; Antipsychotic Agents; Clozapine; Humans; Pulmonary Embolism; Thromboembolism; United States; Venous Thrombosis

Topics: Adult; Antipsychotic Agents; Clozapine; Humans; Male; Psychotic Disorders; Pulmonary Embolism; Risk Factors

Topics: Adult; Antipsychotic Agents; Cardiomyopathies; Clozapine; Death, Sudden, Cardiac; Factor V; Female; Humans; Myocarditis; Pulmonary Embolism; Risk Factors; Schizophrenia

Topics: Adult; Antipsychotic Agents; Clozapine; Humans; Male; Pulmonary Embolism; Schizophrenia

Data from the Swedish Adverse Reactions Advisory Committee suggest that use of clozapine is associated with venous thromboembolic complications. We summarise 12 cases of thromboembolism during clozapine treatment. In five cases the outcome was fatal.

Topics: Adult; Adverse Drug Reaction Reporting Systems; Antipsychotic Agents; Clozapine; Female; Humans; Male; Middle Aged; Pulmonary Embolism; Sweden; Venous Thrombosis

Topics: Adult; Antipsychotic Agents; Clozapine; Humans; Male; Pulmonary Embolism; Schizophrenia, Paranoid

Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Aged; Antipsychotic Agents; Clozapine; Female; Humans; Male; Middle Aged; Pulmonary Embolism; Risk Factors; Schizophrenia; Thromboembolism; United States; United States Food and Drug Administration; Venous Thrombosis

Topics: Aged; Antipsychotic Agents; Clozapine; Female; Humans; Pulmonary Embolism

Drugs have different kinds of adverse effects, one of the most serious being myocarditis. This condition is usually reported as an incidental finding, but can also be fatal. The drug clozapine, available on the European market since the 1970s, can cause myocarditis. This report describes the myocardial findings in a patient who died suddenly after taking increasing doses of clozapine. An allergic adverse reaction to clozapine is suspected. The immediate cause of death was an embolus of the central pulmonary artery.

Topics: Adult; Antipsychotic Agents; Clozapine; Fatal Outcome; Female; Humans; Myocarditis; Pulmonary Embolism