olanzapine and Venous-Thrombosis

Olanzapine, a second generation antipsychotic, has previously been associated with an increased risk of venous thromboembolism (VTE). In this mini-review we describe a case of a thirty-year-old schizophrenic patient who was diagnosed with a deep venous thrombosis (DVT) six months after starting olanzapine therapy, as well as seventeen other VTE cases in patients using olanzapine reported to the Netherlands Pharmacovigilance Centre Lareb. In 14 of these reports, patients had reported additional risk factors for VTE. We found disproportionate Reporting Odds Ratios (RORs) in the global database VigiBase for olanzapine and the reactions deep vein thrombosis (ROR of 1.38 with a 95% CI (Confidence Interval) of 1.22-1.57) and pulmonary embolism (ROR of 1.99 with a 95% CI of 1.81-2.19). The mechanism behind the association of olanzapine with VTE could be explained by two risk factors, substantial weight gain and lethargy, both common side effects of olanzapine. So far, a direct effect of olanzapine on platelet aggregation or coagulation has not been found. Schizophrenic patients are more likely to have diagnostic delay in the diagnosis of VTE, as symptoms such as lethargy and impaired pain perception result in diminished pain perception and pain expression, while they are at increased risk of developing VTE. Currently no validated risk score is available for detection of psychiatric patients who might benefit from pharmacologic VTE prophylaxis. In patients developing a VTE while being treated with olanzapine, discontinuation of olanzapine could be considered based on the individual risk profile, control of psychotic symptoms and antipsychotic treatment options.

Topics: Adult; Antipsychotic Agents; Fibrinolytic Agents; Follow-Up Studies; Humans; Injections, Intramuscular; Male; Netherlands; Olanzapine; Risk Assessment; Schizophrenia, Paranoid; Treatment Outcome; Ultrasonography, Doppler; Venous Thrombosis

Topics: Adult; Aggression; Antipsychotic Agents; Autopsy; Benzodiazepines; Bipolar Disorder; Catatonia; Death, Sudden; Female; Humans; Hypothyroidism; Incidence; Lorazepam; Obesity; Olanzapine; Ovarian Neoplasms; Patient Admission; Patient Transfer; Pulmonary Embolism; Restraint, Physical; Risk; Valproic Acid; Venous Thrombosis

1. Several studies suggest an association between venous thromboembolism and the use of antipsychotic drugs, especially clozapine, but the biological mechanisms are unknown. It has been suggested that antipsychotic drugs enhance aggregation of platelets and thereby increase the risk of venous thrombosis. The purpose of the present study was to examine the effects of clozapine and its main metabolite, N-desmethyl clozapine, as well as olanzapine, risperidone and haloperidol, on platelet adhesion and aggregation and on plasma coagulation in vitro. 2. Blood was collected from healthy subjects free of medication. Platelet adhesion to different protein surfaces and aggregation were measured in microplates. The coagulation methods of activated partial thromboplastin time (APTT) and prothrombin time were performed in platelet-poor plasma. 3. Clozapine was the only compound that increased platelet adhesion and aggregation and shortened APTT. The effect appeared at therapeutic concentrations and was significant but weak. 4. This weak effect of clozapine on haemostasis may explain, in part, the association of this compound and venous thromboembolism.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Blood Coagulation; Blood Platelets; Clozapine; Dose-Response Relationship, Drug; Female; Haloperidol; Humans; In Vitro Techniques; Male; Middle Aged; Olanzapine; Partial Thromboplastin Time; Platelet Adhesiveness; Platelet Aggregation; Prothrombin Time; Risperidone; Thromboembolism; Venous Thrombosis

Topics: Adult; Antiphospholipid Syndrome; Antipsychotic Agents; Benzodiazepines; Coma; Drug Overdose; Epilepsy, Complex Partial; Humans; Male; Olanzapine; Pulmonary Embolism; Schizophrenia, Paranoid; Thrombophilia; Venous Thrombosis

Topics: Antipsychotic Agents; Benzodiazepines; Drug Therapy, Combination; Female; Humans; Hyperprolactinemia; Middle Aged; Olanzapine; Psychotic Disorders; Thromboembolism; Venous Thrombosis

Clozapine has recently been associated with venous thromboembolism. The aim of this study was to describe three elderly patients in whom olanzapine therapy was associated with venous thromboembolism. During a 4-month period at the same psychogeriatric clinic, three elderly patients (an 89-year-old male, a 78-year-old male and an 83-year-old female) developed deep venous thrombosis shortly after treatment with olanzapine was initiated. Two of the patients also had symptoms consistent with a diagnosis of pulmonary embolism. None had previously been diagnosed with venous thromboembolism. These cases indicate that venous thromboembolism might be associated with the use of olanzapine, at least in geriatric patients. Subjects treated with olanzapine should be monitored clinically for venous thromboembolism to ensure early detection and prompt intervention, and a possible discontinuation of treatment with olanzapine should be considered after a diagnosis of venous thromboembolism.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Female; Humans; Male; Olanzapine; Pirenzepine; Pulmonary Embolism; Thromboembolism; Venous Thrombosis