Clozapine-Associated Pulmonary Embolism: A High-Mortality, Dose-Independent and Early-Onset Adverse Effect

Sarvaiya, Nilofar; Lapitskaya, Yevgeniya; Dima, Lorena; Manu, Peter

doi:10.1097/mjt.0000000000000806

Cited by 20 publications

(21 citation statements)

References 22 publications

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“…In our review, there were 12 (28.57%) females and 30 (71.43%) males, showing an increased incidence in male antipsychotic users rather than female users (Table 1 ). These findings are similar to those of previous reviews which found between 63.3% and 75% of patients were males [ 9 , 12 , 16 ]. In a meta-analysis that included a total of 31,514,226 subjects from 22 studies, Dai et al observed patients taking first- and second-generation antipsychotics [ 17 ].…”

Section: Reviewsupporting

confidence: 93%

Clozapine-Related Thromboembolic Events

Vela¹,

Dave²,

Cancarevic³

2021

Cureus

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Clozapine is an atypical antipsychotic used for treatment-resistant schizophrenia. Venous thromboembolism (VTE) is a rare side effect of clozapine which can be fatal. This article summarizes current evidence regarding the risk of VTE associated with the use of clozapine. We performed a PubMed (MeSH) and Google Scholar search for the last two decades. Studies or case reports performed in humans were included in the review, of which 42 case reports of patients taking clozapine at VTE onset were included in the analysis of this review. According to the articles reviewed, the mean age was 42.9 years, with more males (71.43%) than females (28.57%). The average clozapine dose was 285.62 mg/day. VTE onset occurred within the first six months in 71.8% of the cases. Overall, 70.37% of the patients had comorbidities, and 87.5% had risk factors for VTE. In total, 68.57% were prescribed other medications at VTE onset, and 60% were being treated with another antipsychotic concomitantly. Finally, 32.5% of the patients died, while 67.5% survived. In 60% of the cases, clozapine was discontinued after VTE. In our literature review, we observed that among clozapine users, VTE occurred at a wide dose range, and most of the events occurred within the first six months. As many patients who are prescribed clozapine have risk factors for VTE, the risk should be considered at the time of prescribing. Further research should be conducted to elucidate the risk of VTE in clozapine users and the benefits of thromboprophylaxis.

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Section: Reviewsupporting

confidence: 93%

Clozapine-Related Thromboembolic Events

Vela¹,

Dave²,

Cancarevic³

2021

Cureus

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“…Previous studies have reported a potential link between mental illness, use of antipsychotic drugs, and PTE [10,11,[14][15][16]. In the present study, victims with mental illness or antipsychotic drug use appear to form an independent group.…”

Section: Discussionsupporting

confidence: 50%

“…All patients had been diagnosed with mental disorders and used antipsychotic drugs, such as clozapine, olanzapine, and chlorpromazine, for a certain period. Dima et al retrospectively analyzed 23 reported cases of clozapine-related PTE and found that 87% occurred within six months [14]. In our series, as shown in Figure 1, 4 patients had taken antipsychotic drugs for less than six months and the other ve for 3 to more than 20 years; however, given the limitation of sample size in our study, the relationship between the length of time taking antipsychotic drugs and PTE may not be accurately re ected.…”

Section: Discussionmentioning

confidence: 67%

“…In our series, as shown in Figure 1, 4 patients had taken antipsychotic drugs for less than six months and the other ve for 3 to more than 20 years; however, given the limitation of sample size in our study, the relationship between the length of time taking antipsychotic drugs and PTE may not be accurately re ected. Nevertheless, the relationship between the use of antipsychotic drugs and DVT has been continually revealed, with the possible reasons being attributed to the fact that: (1) the sedative effect of antipsychotic drugs reduces the amount of exercise in patients with mental illness, thereby increasing venous blood siltation [16]; and (2) clozapine and olanzapine can cause obesity, which is associated with both venous stasis and hypercoagulability by decreasing brinolytic activity, enhancing platelet activation, and increasing levels of coagulation factors and brinogen [10,14,17]. In fact, DVT has been reported to be a psychological disease in itself, and it has even been highlighted that the effect of antipsychotic treatment may not be the only factor leading to venous thromboembolism but psychosis itself may play a certain role, which is supported by evidence that higher levels of p-selectin and Factor VIII can be detected in mental patients [15].…”

Section: Discussionmentioning

confidence: 99%

“…There were more men (68/113, 60.18%) than women (45/113, 39.82%) in the over 40 age groups (Tables 1 and 2). In contrast, women accounted for the majority of victims under the age of 40 (14).…”

Section: Demographics Analysis Of Pte Casesmentioning

confidence: 98%

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Forensic Pathological Analysis of Death Due to Pulmonary Thromboembolism: a Retrospective Study Based on 145 Cases

Chen¹,

Wang²,

Zhang

et al. 2021

Preprint

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Pulmonary thromboembolism (PTE) is a common cause of sudden unexpected death in forensic practice following deep vein thrombosis (DVT). It remains easy to overlook the special procedure used for the detection of PTE during autopsies; therefore, the relationship between PTE and the associated risk factors is in need of analysis. In the present study, 145 fatal cases of PTE found during autopsies performed from 2004 to 2019 at the Center of Forensic Investigation of China Medical University were retrospectively evaluated; the demographic data, risk factors, original location of DVT, and time interval from the formation of DVT to PTE were analyzed. In addition, the difference in lung-to-heart weight ratio between the PTE and disease-free accident groups was calculated with matching for gender and age. The 40–59 age group accounted for more than half of the total cases (51.03%). Immobilization, trauma or fracture (especially of the pelvis, femur, tibia, or fibula), surgery, pregnancy and cesarean section, mental disorders and the use of antipsychotics were the top 5 high-risk factors for fatal PTE. Among the victims, 92.9% (130/140) died within 60 days of the first exposure to risk factors. Most DVT were formed and shed in lower limb veins, especially popliteal veins and their branches, which caused 87.6% of the thrombi distributed in bilateral pulmonary arteries. No significant difference in the lung-to-heart weight ratio was found between the PTE and control groups. The present study provides valuable information for the prevention and treatment of thrombosis during clinical events and may also be important for alerting forensic examiners to conduct special PTE detection in cases with potential risk factors.

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Schizophrenia and Related Psychoses

2021

The Maudsley Prescribing Guidelines in Psychiatry

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Despite disagreements about nomenclature, patients who develop schizophrenic or schizophrenialike symptoms in later life are often seen in clinical practice. Questions about the etiology of late-life psychotic disorders and about their similarities or differences from early-onset disorders remain unanswered. Neuroimaging techniques have been used to study patients with late onset of psychosis, and in substantial subgroups of patients (from 25% to 100% in various studies) compared with agematched control subjects, structural and functional abnormalities have been found. We review the literature on imaging in late-life schizophrenia and related psychotic disorders, and we present data from our own investigations of patients with these disorders. We discuss the potential usefulness of imaging evaluations in patients with late-onset disorders, and we offer suggestions for future investigations.

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Clozapine-Associated Pulmonary Embolism: A High-Mortality, Dose-Independent and Early-Onset Adverse Effect

Cited by 20 publications

References 22 publications

Clozapine-Related Thromboembolic Events

Clozapine-Related Thromboembolic Events

Forensic Pathological Analysis of Death Due to Pulmonary Thromboembolism: a Retrospective Study Based on 145 Cases

Schizophrenia and Related Psychoses

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