While studies show that olanzapine carries increased risks of adverse events like thromboembolism and sudden cardiac death, and database reports list thousands of adverse outcomes including deaths, there is no evidence establishing the specific figure of 200,000 deaths caused by olanzapine.
<h4>Background</h4>Olanzapine is a second-generation atypical antipsychotic drug which is commonly used in the treatment of schizophrenia. It has been associated with metabolic adverse effects such as weight gain, hyperglycaemia, dyslipidaemia, and this has been shown to contribute to the reduction of life expectancy of patients with schizophrenia. This systematic review aimed to assess whether adjunctive aripiprazole is effective at reducing metabolic adverse effects caused by olanzapine.<h4>Methods</h4>A systematic review was conducted for this study. A systematic search strategy was developed, recorded, and applied to multiple databases. The literature search found a total of 853 results with the final inclusion of 7 research articles. Based on specific inclusion and exclusion criteria, a wide range of study designs were included in the review, such as randomized control trials (RCTs), open label trials, and case series. Key outcomes were identified, which included glucose levels, lipid profile, body weight, BMI, and waist circumference. The results were recorded and analyzed using narrative synthesis.<h4>Results</h4>Statistically significant decreases in fasting triglycerides were consistent across multiple studies. Adjunctive aripiprazole shows potential weight loss benefits, with some studies reporting significant reductions in weight and BMI. Effects on cholesterol and fasting glucose showed reductions, and others showed minimal or no impact. Psychiatric symptom control remained stable in most studies, suggesting that aripiprazole does not negatively affect schizophrenia symptoms while potentially providing metabolic advantages.<h4>Conclusion</h4>Adjunctive aripiprazole had variable effects on metabolic parameters in patients on olanzapine therapy; however, reductions in triglycerides appeared consistent among most of the data, and some studies reported significant weight loss. This highlighted that aripiprazole does have some effect in reducing metabolic adv
This systematic review aimed to assess whether adjunctive aripiprazole is effective at reducing metabolic adverse effects caused by olanzapine. Methods A systematic review was conducted for this study. A systematic search strategy was developed, recorded, and applied to multiple databases. The literature search found a total of 853 results with the final inclusion of 7 research articles. Based on specific inclusion and exclusion criteria, a wide range of study designs were included in the review, such as randomized control trials (RCTs), open label trials, and case series. Key outcomes were identified, which included glucose levels, lipid profile, body weight, BMI, and waist circumference.
Conclusion Adjunctive aripiprazole had variable effects on metabolic parameters in patients on olanzapine therapy; however, reductions in triglycerides appeared consistent among most of the data, and some studies reported significant weight loss. This highlighted that aripiprazole does have some effect in reducing metabolic adverse effects caused by olanzapine. Keywords: adjunctive, aripiprazole, metabolic adverse effects, olanzapine, schizophrenia PRISMA flow diagram illustrating the selection process for studies included in the systematic review.
As a result, people living with schizophrenia are twice as likely to die from CVD compared to those in the general population [ 12 ]. It is also documented that the life expectancy of people living with schizophrenia is reduced by over 20 years [ 13 ] and 60% of this excess mortality was caused by physical illness [ 14 ]. Deaths from cardiovascular disease are the major contributor to this excess mortality caused by physical illness and it has been suggested that the gap in mortality between people with schizophrenia and the general population may be widening even further [ 15 ].
Metric 1 2 3 Weight/BMI Weight Weight Weight −2.9 lbs (1.3 kg) +0.43 kg −2.2 kg p = 0.003 p = 0.325 p = 0.026 BMI BMI BMI −0.4 kg/m 2 −0.007 kg/m 2 −0.8 kg/m 2 p = 0.003 p = 0.681 p = 0.028 Waist circumference −0.76 cm +0.73 cm Not recorded p = 0.063 p = 0.510 Fasting triglycerides −51.7 mg/dL −0.34 mmol/L −74.0 mg/dL p = 0.001 p = 0.001 p = 0.006 Fasting cholesterol (total, HDL and LDL) Total Total No results for Olanzapine group in isolation ‐3 mg/dL −0.18 mmol/L p = 0.208 p = 0.138 HDL HDL 0.4 mg/dL +0.05 mmol/L p = 0.999 p = 0.079 LDL LDL −0.2 mg/dL −0.07 mmol/L p = 0.665 p = 0.469 Fasting glucose −2 mg/dL +0.15 mmol/L No results for Olanzapine group in isolation p = 0.704 p = 0.17 Psychiatric control score using PANSS No significant difference between groups +1 No results for Olanzapine group in isolation p = 0.611 Metric 4 5 6 7 Weight/BMI No data Claims significant change in both Not recorded Weight −0.7 kg p < 0.05 BMI −0.2 kg/m 2 p < 0.05 Weight reduction not stated BMI −0.73 kg/m 2 p = 0.000 Waist circumference Not recorded Not recorded Not recorded Not recorded Fasting triglycerides No data Claims significant decrease Slight decrease data in bar graph so cannot provide exact figures p > 0.05 No data Claims no significant change Not recorded Fasting cholesterol (total, HDL and LDL) No data Claims significant change HDL and LDL not recorded Slight decrease data in bar graph so cannot provide exact figures p > 0.05 HDL and LDL not recorded No data Claims no significant change Not recorded Fasting
1 patient dropped out one for medication changes making them ineligible 18 patients on olanzapine, 55 overall 43. 3 dropped out of the original 46 Inclusion criteria Outpatients between the ages of 18 and 65 with a diagnosis of schizophrenia or schizoaffective disorder were included after providing written consent. Subjects were eligible for the study if their body mass index (BMI) was ≥ 30 kg/m 2 ; or ≥ 27 kg/m 2 with other risk factors (treatment for hypertension of blood pressure (BP) > 140/90 mmHg; lipid abnormalities: total cholesterol ≥ 200 mg/dL, triglyceride ≥ 150 mg/dL; or fasting glucose ≥ 100 mg/dL).
<h4>Background</h4>Olanzapine is an atypical antipsychotic used to treat schizophrenia and manic episodes. Its potential thromboembolic risk has been reported, but the evidence remains controversial. This study aimed to comprehensively evaluate the association between olanzapine and pulmonary embolism (PE) and venous thromboembolism (VTE).<h4>Methods</h4>This study combined meta-analysis and signal mining from the FDA Adverse Event Reporting System (FAERS) database to assess the association between olanzapine and pulmonary embolism (PE) and venous thromboembolism (VTE).<h4>Results</h4>From 55,905 olanzapine-related adverse event reports in the Faers database, 1,233 significant signals were identified, including serious adverse events not fully documented on the drug label, such as pulmonary embolism and venous embolism. A meta-analysis of eight studies showed that olanzapine use significantly increased the risk of VTE and pulmonary embolism (OR = 2.07, 95% CI: 1.37-3.14, <i>P</i> = 0.0006).<h4>Conclusion</h4>These findings suggest that olanzapine is associated with an increased risk of thromboembolic events; therefore, enhanced clinical surveillance and further investigation into its safety are necessary.<h4>Systematic review registration</h4>https://www.crd.york.ac.uk/prospero/, identifier CRD420251003254.
Two case reports documented pulmonary embolism and venous thromboembolism events that occurred after the initiation of olanzapine treatment ( 12 , 13 ). A retrospective study conducted by the Becksa County Medical Examiner's Office in 2008 found a temporal association between olanzapine use and pulmonary embolism in four antipsychotic drug-related deaths that occurred between 1998 and 2005 ( 14 ). Subsequent studies have shown that olanzapine may significantly increase the incidence of venous thromboembolism and pulmonary embolism, particularly in older patients ( 15 ).
For multiple entries with the same CASEID, the report with the latest FDA_DT was retained; if both CASEID and FDA_DT were identical, the report with the highest PRIMARYID was selected ( 27 ). In addition, clinical characteristics of patients who experienced adverse events following
Higher ROR or PRR values reflect greater signal strength, indicating a stronger association between olanzapine and the reported ADE. Table 1 Four-grid table of ratio imbalance measurement method. Drug Target Event Other events Total Target Drugs a b a + b Other medicines c d c + d Total a + c b + d a + b + c + d a: The number of reports that record both the target drug and its corresponding specific adverse events; b: The number of reports of other atypical adverse events caused by the target drug; c: The number of reports of similar adverse events caused by non-target drugs; d: The number of reports containing non-target drugs and their related adverse events.
This difference may be related to the anticholinergic effect of olanzapine, which can increase prolactin concentrations and thus cause breast enlargement and lactation in men ( 33 ). A large amount of patient weight information was missing in the reports collected in this study, which may have caused some interference in the assessment of weight-related adverse events (such as weight gain). Among reports with clear age data, the age group with the largest number of reports was 18–64 years old. The reports are mainly sourced from the United States, Canada and the United Kingdom. The majority of reporters were doctors (29.8%).
From the perspective of patient outcomes, the main outcomes were hospitalization (2,0471, 36.6%), death (6,375, 11.4%), life-threatening (4,280, 7.7%), disability (960, 1.7%), and other serious events (15,779, 28.2%). This suggests the importance of monitoring olanzapine-related ADEs, as detailed in Table 3 . Judging from the distribution of reporting time ( Figure 1 ), the number of reports showed a gradually increasing trend, among which the largest number of reports was submitted in 2,023 (7,393 reports), accounting for 13%. The number of reports was the lowest in 2016 (3,974), accounting for 7%, and increased by 10.3% per year from 2016 to 2023.
After excluding two SOCs (product issues and social environment) that were not directly related to olanzapine-related adverse events, there were 1,233 valid signals remaining, covering 25 SOCs. According to the ranking of adverse event reports, the top 10 SOCs are mental illness, various neurological diseases, various examinations, various injuries, etc. ( Table 4 ).
This indicates that the proportion of recorded cases of metabolic syndrome is extremely low, suggesting that this factor is not the main driving factor of the observed thrombotic signals. In addition, metabolic abnormalities caused by olanzapine can also lead to impaired endothelial function and increase the risk of thrombosis ( 48 ). Vascular endothelial injury is another key mechanism underlying thrombosis. Studies have shown that olanzapine can induce oxidative stress and inflammatory responses, resulting in endothelial cell damage and dysfunction ( 49 ).
A retrospective cohort study of nursing home residents showed that the adjusted hazard ratio (HR) for hospitalization due to VTE in patients using risperidone was 1.98 (95% CI, 1.40–2.78) ( 15 ). This indicates a risk level similar to olanzapine.
The pro-inflammatory response caused by olanzapine may be involved in the occurrence of myocarditis ( 70 – 74 ). Infectious aspiration pneumonia: The significant anticholinergic and sedative effects of high-dose olanzapine inhibit the swallowing reflex and throat coordination, increasing the risk of aspiration and aspiration pneumonia. Chronic inflammation associated with metabolic syndrome may also weaken lung defenses ( 74 – 79 ). Therefore, potential adverse events such as cardiovascular, blood, and respiratory system events need to be monitored during clinical use of olanzapine to guide safer and more individualized drug use strategies.
To examine the recent literature regarding sudden death in patients with schizophrenia and synthesize salient conclusions based on this evidence. Sudden cardiac death (SCD) is the largest subset of sudden unexpected death (SUD), with up to 40% of SUD from cardiovascular causes. SCD has been associated with exposure to both first and second-generation antipsychotics. Clozapine [odds ratio (OR) 3.67, 95% confidence interval (CI) 1.94-6.94] confers the highest risk of SCD followed by risperidone (OR 3.04, 95% CI 2.39-3.86) then olanzapine (OR 2.04, 95% CI 1.52-2.74). SCD not associated with antipsychotic use has been correlated to several modifiable and nonmodifiable risk factors - obesity, smoking, dyslipidemia, diabetes, hypertension, age, sex, and history of cardiovascular disease. Other subsets of SUD include hematological and pulmonary causes, including agranulocytosis leading to sepsis, deep vein thrombosis leading to pulmonary embolisms, and aspiration pneumonia leading to sepsis. There is a huge paucity in genetic and pharmacogenetic data focused on SUD in schizophrenia. Future studies should emphasize the genetic aspects as well as clarify the underlying molecular mechanisms of these pathways. Additionally, early detection of those patients at high risk for SUD and discovery of preventive measures should also be emphasized.
Everything we examined (3)
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