clozapine and Venous-Thromboembolism

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

The association between antipsychotic medication and increased risk for deep vein thrombosis and pulmonary embolism has been reported since soon after the introduction of first-generation antipsychotic drugs in the 1950s. The causality of this association, its risk factors, and its implications for clinical practice have not been fully elucidated. We undertook a systematic literature review to evaluate the evidence for an association between antipsychotic medication and venous thromboembolic events and to identify risk factors for these adverse effects.. MEDLINE search for the 1990-2012 interval, followed by a manual review of identified publication for relevant cohort and case studies involving antipsychotic medication and thromboembolic events. Data regarding antipsychotic-related thromboembolic events have been presented in five autopsy series, three cohort studies, eight case-control and nine case series, and 13 individual case reports. Nine studies provided odds-ratios for thrombotic risk for all antipsychotic medications. There was substantial evidence-based agreement that antipsychotic drugs increase the risk of venous thromboembolic events. The average reported odds ratio was 3.51, compared with patients not receiving these drugs. The database identified a total of 438 reported of venous thromboembolic events with clozapine, nearly double the next most commonly reported medications risperidone (283) and olanzapine (241). The factors that increased risk were use of second-generation antipsychotics, low potency antipsychotics, antipsychotic polytherapy. Data also suggested a dose-dependent increase in the risk of thrombotic complications.. The risk factors for antipsychotic-related thrombolembolic events include recently started antipsychotic therapy (within the past 3 or 12 months), higher doses of drug, concomitant multiple antipsychotic therapy, intravenous or intramuscular administration of drug, and use of second-generation antipsychotics, particularly clozapine.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Humans; Odds Ratio; Olanzapine; Risk Factors; Risperidone; Thrombosis; Venous Thromboembolism

Clozapine is the most effective antipsychotic medication for treatment-refractory schizophrenia and is also approved for suicidality in schizophrenia patients. However, it can cause significant medical morbidity and requires intensive medical monitoring once prescribed. Perhaps due to lack of familiarity with its use, it is underused in clinical practice and its initiation often delayed. This article reviews the literature on clozapine in order to measure its potential effectiveness against its adverse effects and ultimately aims to serve as a useful summary for clinicians in their everyday prescribing.

Topics: Antipsychotic Agents; Clozapine; Drug Monitoring; Heart Diseases; Hematologic Diseases; Humans; Metabolic Diseases; Practice Guidelines as Topic; Practice Patterns, Physicians'; Quality of Life; Schizophrenia; Suicide Prevention; Venous Thromboembolism; Weight Gain

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

The possible association between clozapine and venous thromboembolism (VTE) is discussed.. Twenty-two cases of VTE associated with clozapine have been published. The average patient age at the time of occurrence was 38 years in the reported cases. Of the published cases with a known outcome, the mortality rate of a clotting complication while on clozapine was approximately 44%. The manufacturer of clozapine has calculated a mortality rate from pulmonary embolism to be one death per 3450 person years of use, approximately 28 times higher than the rate in the general population. The possible mechanism for the association between clozapine and VTE is probably multifactorial. A VTE usually occurs when one of three factors is present: damage to the vessel wall, static blood flow, or coagulation abnormalities. Clozapine, as well as other antipsychotics, has not been shown to cause direct damage to the vasculature in humans. However, static blood flow may be influenced by sedation and the sedentary lifestyle commonly associated with psychiatric disorders, their treatment, or both. Clozapine is associated with significant sedation and an average weight gain of 7-11 kg. There is also increasing evidence that clozapine and other antipsychotics may cause a variety of different coagulation abnormalities. Clozapine has been found to increase platelet adhesion as well as aggregation. Avoidance of risk factors, such as weight gain and sedentary lifestyle, may alleviate some of the risk of clozapine-induced VTE.. Available data indicate an association between clozapine and VTE; however, it is unknown whether the increased risk of VTE in patients receiving clozapine is because of prothrombotic effects of the drug. Risk of VTE versus the benefits of therapy should be considered when initiating clozapine therapy.

Topics: Adult; Antipsychotic Agents; Clozapine; Female; Humans; Male; Middle Aged; Venous Thromboembolism

Topics: Antipsychotic Agents; Clozapine; Fatal Outcome; Humans; Intracranial Thrombosis; Male; Portal Vein; Venous Thromboembolism; Young Adult