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Tolu‐Akinnawo OZ, Awoyemi T, Guzman RB, Naveed A. Olanzapine-induced cardiomyopathy: A mimicker of obesity cardiomyopathy? Clin Cardiol 2024; 47:e24278. [PMID: 38767024 PMCID: PMC11103636 DOI: 10.1002/clc.24278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Accepted: 04/24/2024] [Indexed: 05/22/2024] Open
Abstract
Olanzapine, an atypical antipsychotic medication, has gained prominence in the treatment of schizophrenia and related psychotic disorders due to its effectiveness and perceived safety profile. However, emerging evidence suggests a potential link between olanzapine use and adverse cardiovascular effects, including cardiomyopathy. This narrative review explores the mechanisms, clinical implications, and management strategies associated with olanzapine-induced cardiomyopathy. A comprehensive review of the literature was conducted to investigate the relationship between olanzapine and cardiomyopathy. The search included epidemiological studies, clinical case reports, and mechanistic research focusing on the pathophysiology of olanzapine-induced cardiomyopathy. The review also examined treatment strategies for managing this potential complication. Olanzapine-induced cardiomyopathy is hypothesized to be associated with metabolic disturbances and receptor antagonism. The metabolic effects of olanzapine, such as weight gain, insulin resistance, and dyslipidemia, share similarities with obesity-related cardiomyopathy. Additionally, olanzapine's antagonism of certain receptors may contribute to cardiovascular stress. The review highlighted that patients with new-onset heart failure and significant weight gain while on olanzapine should be closely monitored for signs of cardiomyopathy. Early detection and prompt withdrawal of olanzapine, along with initiation of goal-directed medical therapy, are crucial for mitigating this potentially life-threatening condition. The relationship between olanzapine and cardiomyopathy is complex and not yet fully understood. However, the potential for significant cardiovascular risk necessitates vigilance among healthcare providers. Early identification and management of olanzapine-induced cardiomyopathy can improve patient outcomes. Further research is needed to elucidate the precise mechanisms behind this adverse effect and to develop optimized treatment strategies for patients requiring antipsychotic therapy.
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Flores Chang M, Guevara N, Argueta M, Jimenez Y, Vitaly A, Baghdadi S. Case Report: A rare case of symptomatic bradycardia secondary to aripiprazole in a patient with bipolar disorder type I. F1000Res 2022; 11:1233. [PMID: 38283125 PMCID: PMC10818102 DOI: 10.12688/f1000research.126979.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/14/2022] [Indexed: 01/30/2024] Open
Abstract
It is well known that typical antipsychotic drugs have been implicated as a cause of ventricular arrhythmias and cardiac arrest; studies have shown that conventional antipsychotics increase the risk of hospitalization for ventricular arrhythmias or cardiac arrest nearly 2-fold. However, atypical antipsychotics are not associated with an increased risk of hospitalization for ventricular arrhythmias or cardiac arrest. The use of atypical antipsychotics increased since they were first discovered and now are the mainstay of treatment, but with their broad use, heart effects have been documented, such as prolonged QT interval. Clozapine has been linked to severe cardiac problems, and risperidone has been linked to an increased risk of ventricular arrhythmias and cardiac arrest. We present a case of a patient with bipolar disorder who presented with symptomatic bradycardia secondary to aripiprazole.
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Affiliation(s)
- Mailing Flores Chang
- Department of Medicine, Internal Medicine, St. Barnabas Health System, The Bronx, New York, 10487, USA
| | - Nehemias Guevara
- Department of Medicine, Internal Medicine, St. Barnabas Health System, The Bronx, New York, 10487, USA
| | - Marlon Argueta
- Department of Medicine, Internal Medicine, St. Barnabas Health System, The Bronx, New York, 10487, USA
| | - Yomary Jimenez
- Department of Medicine, Internal Medicine, St. Barnabas Health System, The Bronx, New York, 10487, USA
| | - Adler Vitaly
- Department of Medicine, Internal Medicine, St. Barnabas Health System, The Bronx, New York, 10487, USA
| | - Salim Baghdadi
- Department of Medicine, Internal Medicine, Division of Cardiology, St. Barnabas Hospital Health System, The Bronx, New York, 10457, USA
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Li XQ, Tang XR, Li LL. Antipsychotics cardiotoxicity: What's known and what's next. World J Psychiatry 2021; 11:736-753. [PMID: 34733639 PMCID: PMC8546771 DOI: 10.5498/wjp.v11.i10.736] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 07/08/2021] [Accepted: 09/02/2021] [Indexed: 02/06/2023] Open
Abstract
Chronic use of antipsychotic medications entails a dilemma between the benefit of alleviating psychotic symptoms and the risk of troubling, sometimes life-shortening adverse effects. Antipsychotic-induced cardiotoxicity is one of the most life-threatening adverse effects that raises widespread concerns. These cardiotoxic effects range from arrhythmia to heart failure in the clinic, with myocarditis/cardiomyopathy, ischemic injuries, and unexplained cardiac lesions as the pathological bases. Multiple mechanisms have been proposed to underlie antipsychotic cardiotoxicity. This review aims to summarize the clinical signs and pathological changes of antipsychotic cardiotoxicity and introduce recent progress in understanding the underlying mechanisms at both the subcellular organelle level and the molecular level. We also provide an up-to-date perspective on future clinical monitoring and therapeutic strategies for antipsychotic cardiotoxicity. We propose that third-generation antipsychotics or drug adjuvant therapy, such as cannabinoid receptor modulators that confer dual benefits - i.e., alleviating cardiotoxicity and improving metabolic disorders - deserve further clinical evaluation and marketing.
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Affiliation(s)
- Xiao-Qing Li
- Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
| | - Xin-Ru Tang
- Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
| | - Li-Liang Li
- Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
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D’Errico S, Russa RL, Maiese A, Santurro A, Scopetti M, Romano S, Zanon M, Frati P, Fineschi V. Atypical antipsychotics and oxidative cardiotoxicity: review of literature and future perspectives to prevent sudden cardiac death. J Geriatr Cardiol 2021; 18:663-685. [PMID: 34527032 PMCID: PMC8390928 DOI: 10.11909/j.issn.1671-5411.2021.08.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Oxidative stress is considered the principal mediator of myocardial injury under pathological conditions. It is well known that reactive oxygen (ROS) or nitrogen species (RNS) are involved in myocardial injury and repair at the same time and that cellular damage is generally due to an unbalance between generation and elimination of the free radicals due to an inadequate mechanism of antioxidant defense or to an increase in ROS and RNS. Major adverse cardiovascular events are often associated with drugs with associated findings such as fibrosis or inflammation of the myocardium. Despite efforts in the preclinical phase of the development of drugs, cardiotoxicity still remains a great concern. Cardiac toxicity due to second-generation antipsychotics (clozapine, olanzapine, quetiapine) has been observed in preclinical studies and described in patients affected with mental disorders. A role of oxidative stress has been hypothesized but more evidence is needed to confirm a causal relationship. A better knowledge of cardiotoxicity mechanisms should address in the future to establish the right dose and length of treatment without impacting the physical health of the patients.
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Affiliation(s)
- Stefano D’Errico
- Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy
| | - Raffaele La Russa
- Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy
- IRCSS Neuromed Mediterranean Neurological Institute, Pozzilli, Italy
| | - Aniello Maiese
- IRCSS Neuromed Mediterranean Neurological Institute, Pozzilli, Italy
- Department of Surgical Pathology, Medical, Molecular and Critical Area, University of Pisa, Pisa, Italy
| | - Alessandro Santurro
- Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Rome, Italy
| | - Matteo Scopetti
- Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Rome, Italy
| | - Silvia Romano
- Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Rome, Italy
| | - Martina Zanon
- Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy
| | - Paola Frati
- IRCSS Neuromed Mediterranean Neurological Institute, Pozzilli, Italy
- Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Rome, Italy
| | - Vittorio Fineschi
- IRCSS Neuromed Mediterranean Neurological Institute, Pozzilli, Italy
- Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Rome, Italy
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5
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Koller D, Almenara S, Mejía G, Saiz-Rodríguez M, Zubiaur P, Román M, Ochoa D, Wojnicz A, Martín S, Romero-Palacián D, Navares-Gómez M, Abad-Santos F. Safety and cardiovascular effects of multiple-dose administration of aripiprazole and olanzapine in a randomised clinical trial. Hum Psychopharmacol 2021; 36:1-12. [PMID: 32991788 DOI: 10.1002/hup.2761] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 09/09/2020] [Accepted: 09/14/2020] [Indexed: 01/21/2023]
Abstract
OBJECTIVE To assess adverse events (AEs) and safety of aripiprazole (ARI) and olanzapine (OLA) treatment. METHODS Twenty-four healthy volunteers receiving five daily oral doses of 10 mg ARI and 5 mg OLA in a crossover clinical trial were genotyped for 46 polymorphisms in 14 genes by qPCR. Drug plasma concentrations were measured by high-performance liquid chromatography tandem mass spectrometry. Blood pressure (BP) and 12-lead electrocardiogram were measured in supine position. AEs were also recorded. RESULTS ARI decreased diastolic BP on the first day and decreased QTc on the third and fifth day. OLA had a systolic and diastolic BP, heart rate and QTc lowering effect on the first day. Polymorphisms in ADRA2A, COMT, DRD3 and HTR2A genes were significantly associated to these changes. The most frequent adverse drug reactions (ADRs) to ARI were somnolence, headache, insomnia, dizziness, restlessness, palpitations, akathisia and nausea while were somnolence, dizziness, asthenia, constipation, dry mouth, headache and nausea to OLA. Additionally, HTR2A, HTR2C, DRD2, DRD3, OPRM1, UGT1A1 and CYP1A2 polymorphisms had a role in the development of ADRs. CONCLUSIONS OLA induced more cardiovascular changes; however, more ADRs were registered to ARI. In addition, some polymorphisms may explain the difference in the incidence of these effects among subjects.
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Affiliation(s)
- Dora Koller
- Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teófilo Hernando, School of Medicine, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria La Princesa (IP), Madrid, Spain
| | - Susana Almenara
- Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teófilo Hernando, School of Medicine, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria La Princesa (IP), Madrid, Spain
| | - Gina Mejía
- Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teófilo Hernando, School of Medicine, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria La Princesa (IP), Madrid, Spain.,UICEC Hospital Universitario de La Princesa, Platform SCReN (Spanish Clinical Research Network), Instituto de Investigación Sanitaria La Princesa (IP), Madrid, Spain
| | - Miriam Saiz-Rodríguez
- Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teófilo Hernando, School of Medicine, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria La Princesa (IP), Madrid, Spain.,Research Unit, Fundación Burgos por la Investigación de la Salud, Hospital Universitario de Burgos, Burgos, Spain
| | - Pablo Zubiaur
- Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teófilo Hernando, School of Medicine, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria La Princesa (IP), Madrid, Spain
| | - Manuel Román
- Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teófilo Hernando, School of Medicine, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria La Princesa (IP), Madrid, Spain.,UICEC Hospital Universitario de La Princesa, Platform SCReN (Spanish Clinical Research Network), Instituto de Investigación Sanitaria La Princesa (IP), Madrid, Spain
| | - Dolores Ochoa
- Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teófilo Hernando, School of Medicine, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria La Princesa (IP), Madrid, Spain.,UICEC Hospital Universitario de La Princesa, Platform SCReN (Spanish Clinical Research Network), Instituto de Investigación Sanitaria La Princesa (IP), Madrid, Spain
| | - Aneta Wojnicz
- Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teófilo Hernando, School of Medicine, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria La Princesa (IP), Madrid, Spain
| | - Samuel Martín
- Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teófilo Hernando, School of Medicine, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria La Princesa (IP), Madrid, Spain.,UICEC Hospital Universitario de La Princesa, Platform SCReN (Spanish Clinical Research Network), Instituto de Investigación Sanitaria La Princesa (IP), Madrid, Spain
| | - Daniel Romero-Palacián
- Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teófilo Hernando, School of Medicine, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria La Princesa (IP), Madrid, Spain
| | - Marcos Navares-Gómez
- Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teófilo Hernando, School of Medicine, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria La Princesa (IP), Madrid, Spain
| | - Francisco Abad-Santos
- Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teófilo Hernando, School of Medicine, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria La Princesa (IP), Madrid, Spain.,UICEC Hospital Universitario de La Princesa, Platform SCReN (Spanish Clinical Research Network), Instituto de Investigación Sanitaria La Princesa (IP), Madrid, Spain
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The Use, Safety, and Efficacy of Olanzapine in a Level I Pediatric Trauma Center Emergency Department Over a 10-Year Period. Pediatr Emerg Care 2020; 36:70-76. [PMID: 28697164 DOI: 10.1097/pec.0000000000001231] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
OBJECTIVES Olanzapine is a second-generation antipsychotic increasingly used in emergency medicine for many indications. Literature on its use in children is sparse. Our objectives were to describe the use, safety, and efficacy of olanzapine in pediatric emergency patients. METHODS A structured chart review was performed of patients 18 years old or younger receiving olanzapine from 2007 to 2016 in the emergency department of a pediatric level I trauma center. RESULTS A total of 285 children received olanzapine. Mean age was 16.4 years (range, 9-18 years); 121 were male (42.8%). Primary indications for olanzapine included agitation (n = 166, 58.3%), headache (n = 58, 20.4%), nausea/vomiting/abdominal pain (n = 37, 12.5%), unspecified pain (n = 20, 7%), and other (n = 4, 1.4%). Route of olanzapine administration was intramuscular (n = 160, 56%; median dose, 10 mg; range, 2.5-20), intravenous (n = 101, 36%; median dose, 5 mg; range, 1.25-5), and oral (n = 24, 8%; median dose, 10 mg; range, 5-10). For agitated patients, 28 (17%) received another sedative within 1 hour. For headache patients, 5 (8.6%) received another analgesic. For gastrointestinal complaints, 5 patients (13.5%) received another analgesic/antiemetic. Adverse respiratory events were hypoxia (pulse oximetry reading, in percentage, <92%; n = 7, 2.4%), supplemental oxygen placement (n = 9, 3.2%), and intubation (n = 2, 0.7%). No patient died or had a dysrhythmia. One patient experienced dystonia. CONCLUSIONS Olanzapine seems safe when used for a variety of conditions in pediatric emergency patients. It may be effective for acute agitation, primary headache, and gastrointestinal complaints.
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Andor M, Dehelean L, Romosan AM, Buda V, Radu G, Caruntu F, Bordejevic A, Manea MM, Papava I, Bredicean CA, Romosan RS, Tomescu M. A novel approach to cardiovascular disturbances in patients with schizophrenia spectrum disorders treated with long-acting injectable medication. Neuropsychiatr Dis Treat 2019; 15:349-355. [PMID: 30774346 PMCID: PMC6354682 DOI: 10.2147/ndt.s186892] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
PURPOSE This research article assesses the cardiovascular impact of long-term injectable antipsychotic therapy on patients diagnosed with schizophrenia spectrum disorders. In our study, we attempted to quantify the potential causes of cardiovascular damage, assess cardiovascular parameters, and correlate them with the time elapsed from the onset of the psychosis until the initiation of injectable antipsychotic therapy, as well as the duration of long-acting therapy, and finally, to compare two of the most utilized long-acting injectable (LAI) medications (olanzapine vs risperidone). PATIENTS AND METHODS This cross-sectional study recruited 64 patients of 2 outpatient clinics undergoing treatment with LAI antipsychotics for schizophrenic spectrum disorder. The study reports outpatients' clinical data, laboratory blood sample findings, routine echocardiography, as well as speckle tracking echocardiography. RESULTS Among patients with longer durations of pre-long-acting antipsychotic treatment, body mass indices, mitral velocity wave values (E and A waves), and the global longitudinal strain (GLS) measurements significantly correlated with patients' myocardial contractility. The study also found that GLS was significantly lower in the group in which pre-LAI duration was prolonged, and was not influenced by the duration of LAI treatment. Furthermore, patients receiving olanzapine showed significantly improved myocardial contractility as measured by the aforementioned parameters, in comparison with patients treated with risperidone. CONCLUSION The results of our study indicate that patients suffering from schizophrenia and who are left untreated or poorly treated for a longer period of time may develop myocardial impairment. The changes may be both secondary to a high prevalence of cardiovascular risk factors and may also be generated by the disease per se. The group who received olanzapine demonstrated improved results for a longer period of time without proper medication.
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Affiliation(s)
- Minodora Andor
- Medical Semiology II, Department of Internal Medicine I, "Victor Babeş" University of Medicine and Pharmacy, Timişoara, Romania
| | - Liana Dehelean
- Discipline of Psychiatry, Department of Neurosciences, "Victor Babeş" University of Medicine and Pharmacy, Timisoara, Romania,
| | - Ana-Maria Romosan
- Discipline of Psychiatry, Department of Neurosciences, "Victor Babeş" University of Medicine and Pharmacy, Timisoara, Romania,
| | - Valentina Buda
- Pharmacology and Clinical Pharmacology, 2nd Department, "Victor Babeş" University of Medicine and Pharmacy, Timişoara, Romania
| | - Gabriela Radu
- Medical Semiology II, Department of Internal Medicine I, "Victor Babeş" University of Medicine and Pharmacy, Timişoara, Romania
| | - Florina Caruntu
- Medical Semiology II, Department of Internal Medicine I, "Victor Babeş" University of Medicine and Pharmacy, Timişoara, Romania
| | - Aurora Bordejevic
- Medical Semiology II, Department of Internal Medicine I, "Victor Babeş" University of Medicine and Pharmacy, Timişoara, Romania
| | - Minodora Marinela Manea
- Department of Psychology, Medical Education, "Iuliu Haţieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Ion Papava
- Discipline of Psychiatry, Department of Neurosciences, "Victor Babeş" University of Medicine and Pharmacy, Timisoara, Romania,
| | - Cristina Ana Bredicean
- Discipline of Psychiatry, Department of Neurosciences, "Victor Babeş" University of Medicine and Pharmacy, Timisoara, Romania,
| | - Radu Stefan Romosan
- Discipline of Psychiatry, Department of Neurosciences, "Victor Babeş" University of Medicine and Pharmacy, Timisoara, Romania,
| | - Mirela Tomescu
- Medical Semiology II, Department of Internal Medicine I, "Victor Babeş" University of Medicine and Pharmacy, Timişoara, Romania
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The risk factors, frequency and diagnosis of atypical antipsychotic drug-induced hypothermia: practical advice for doctors. Int Clin Psychopharmacol 2019; 34:1-8. [PMID: 30398998 DOI: 10.1097/yic.0000000000000244] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Hypothermia is unpredictable and life-threatening adverse effect of atypical antipsychotic drug (APD) treatment, which has been little described. The aim of this article is to increase the awareness that hypothermia induced by APD drugs is more common than the current published case reports may suggest, and risk factors increase its development. Moreover, valuable guidelines regarding how to detect the early stages of hypothermia in clinical practice are included. A literature search for reports on APD-induced hypothermia in PubMed, Academic Search Complete, Medline Complete and eHealthMe databases was conducted. The literature search apart from eHealthMe database resulted in 524 articles, which included 34 case reports. Hypothermia was mostly induced by olanzapine (14) and risperidone (10). However, the data from Food and Drug Administration reports revealed several dozen more cases of APD-induced hypothermia (591case reports) compared with the published case reports (e.g. olanzapine-262 and risperidone-161). Hypothermia, mostly mild (61% of cases), has developed mainly in men (71%) having schizophrenia, a few hours after commencement of treatment or in the presence of risk factors. Owing to the increased risk of hypothermia development during APD treatment, doctors should routinely measure body temperature of patients, especially during the first days of the therapy. Early diagnosis of hypothermia and appropriate treatment may prevent death.
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Monda V, Salerno M, Sessa F, Bernardini R, Valenzano A, Marsala G, Zammit C, Avola R, Carotenuto M, Messina G, Messina A. Functional Changes of Orexinergic Reaction to Psychoactive Substances. Mol Neurobiol 2018; 55:6362-6368. [PMID: 29307079 DOI: 10.1007/s12035-017-0865-z] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2017] [Accepted: 12/26/2017] [Indexed: 10/18/2022]
Abstract
It is becoming increasingly apparent the importance of the central nervous system (CNS) as the major contributor to the regulation of systemic metabolism. Antipsychotic drugs are used often to treat several psychiatric disorders, including schizophrenia and bipolar disorder However, antipsychotic drugs prescription, particularly the second-generation ones (SGAs), such as clozapine and olanzapine, is related to a considerable weight gain which usually leads to obesity. The aim of this paper is to assess the influence of orexin A on sympathetic and hyperthermic reactions to several neuroleptic drugs. Orexin A is a neuropeptide which effects both body temperature and food intake by increasing sympathetic activity. Orexin A-mediated hyperthermia is reduced by haloperidol and is blocked by clozapine and olanzapine. Orexin A-mediated body temperature elevation is increased by risperidone. These hyperthermic effects are delayed by quietapine. In this paper, it is discussed the orexinergic pathway activation by neuroleptic drugs and its influence on human therapeutic strategies. With the aim to determine that neuroleptic drugs mediate body temperature control through to the orexinergic system, we summarized our previously published data. Psychiatric disorders increase the risk of developing metabolic disorders (e.g., weight gain, increased blood pressure, and glucose or lipid levels). Therefore, the choice of antipsychotic drug to be prescribed, based on the relevant risks and benefits of each individual drug, has an essential role in human health prevention.
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Affiliation(s)
- Vincenzo Monda
- Department of Experimental Medicine, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy
| | - Monica Salerno
- Department of Clinical and Experimental Medicine, University of Foggia, Viale Pinto, 1, 71122, Foggia, Italy
| | - Francesco Sessa
- Department of Clinical and Experimental Medicine, University of Foggia, Viale Pinto, 1, 71122, Foggia, Italy
| | - Renato Bernardini
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Anna Valenzano
- Department of Clinical and Experimental Medicine, University of Foggia, Viale Pinto, 1, 71122, Foggia, Italy
| | - Gabriella Marsala
- Struttura Complessa di Farmacia, Azienda Ospedaliero-Universitaria, Ospedali Riuniti di Foggia, Foggia, Italy
| | - Christian Zammit
- Anatomy Department, Faculty of Medicine and Surgery, University of Malta, Msida, Malta
| | - Roberto Avola
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Marco Carotenuto
- Clinic of Child and Adolescent Neuropsychiatry, Department of Mental Health, Physical and Preventive Medicine, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Giovanni Messina
- Department of Clinical and Experimental Medicine, University of Foggia, Viale Pinto, 1, 71122, Foggia, Italy.
| | - Antonietta Messina
- Department of Experimental Medicine, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy
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10
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Cole JB, Moore JC, Dolan BJ, O’Brien-Lambert A, Fryza BJ, Miner JR, Martel ML. A Prospective Observational Study of Patients Receiving Intravenous and Intramuscular Olanzapine in the Emergency Department. Ann Emerg Med 2017; 69:327-336.e2. [DOI: 10.1016/j.annemergmed.2016.08.008] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2016] [Revised: 07/22/2016] [Accepted: 08/01/2016] [Indexed: 11/16/2022]
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11
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Zonnenberg C, Bueno-de-Mesquita JM, Ramlal D, Blom JD. Hypothermia due to Antipsychotic Medication: A Systematic Review. Front Psychiatry 2017; 8:165. [PMID: 28936184 PMCID: PMC5594062 DOI: 10.3389/fpsyt.2017.00165] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2017] [Accepted: 08/23/2017] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Hypothermia is a rare, but potentially fatal adverse effect of antipsychotic drug (APD) use. Although the opposite condition, hyperthermia, has been researched extensively in the context of the malignant antipsychotic syndrome, little is known about hypothermia due to APDs. OBJECTIVE This study aimed to review the literature on hypothermia in the context of APD use, and formulate implications for research and clinical care. METHODS A systematic search was made in PubMed and Ovid Medline. RESULTS The literature search yielded 433 articles, including 57 original case descriptions of hypothermia developed during APD use with non-toxic plasma levels. All cases together indicate that the risk of developing hypothermia is highest during the 7 days following initiation, or increase in dosage, of APDs, especially in the presence of additional predisposing factors, such as advanced age, exposure to cold, adjuvant use of benzodiazepines, and (subclinical) hypothyroidism. In addition, data derived from drug-monitoring agencies suggest that the prevalence of APD-related hypothermia is at least 10 times higher than suggested by the literature. CONCLUSION We conclude that health-care professionals need to monitor the body temperature of patients starting with (an increased dose of) APDs for a duration of 7-10 days to prevent hypothermia, especially in the presence of multiple risk factors. Moreover, systematic studies are needed to establish the actual prevalence of APD-related hypothermia as well as the relative risk for individual APDs.
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Affiliation(s)
| | | | | | - Jan Dirk Blom
- Parnassia Psychiatric Institute, The Hague, Netherlands.,Faculty of Social Sciences, Leiden University, Leiden, Netherlands.,Department of Psychiatry, University of Groningen, Groningen, Netherlands
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12
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Puttegowda B, Theodore J, Basappa R, Nanjappa MC. Olanzapine Induced Dilated Cardiomyopathy. Malays J Med Sci 2016; 23:82-84. [PMID: 27547120 PMCID: PMC4976704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2014] [Accepted: 12/08/2014] [Indexed: 06/06/2023] Open
Abstract
A 28-year-old male patient with bipolar disorder taking olanzapine and lorazepam for almost 10 years presented with weight gain, diabetes, and anasarca was examined in this study. Evaluation of the patient revealed he was in heart failure. The reason for his heart failure was ambiguous and an investigation into it revealed negative results. Literature search conducted showed a few reported cases of putative olanzapine induced cardiomyopathy. One such relatively rare case is presented here.
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Affiliation(s)
| | - Joseph Theodore
- Correspondence: Dr Joseph Theodore, MD (India), Sri Jayadeva Institute of Cardiovascular Sciences and Research, Jaya Nagar 9th Block, BG Road, Bangalore 560069, India, Tel: +9181-0505 1480, Fax: +9180-2653 4477,
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Huang LC, Huang LY, Tseng SY, Hou YM, Hsiao CC. Amisulpride and symptomatic bradycardia: a case report. Gen Hosp Psychiatry 2015; 37:497.e1-2. [PMID: 26162544 DOI: 10.1016/j.genhosppsych.2013.12.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2013] [Revised: 12/10/2013] [Accepted: 12/10/2013] [Indexed: 01/11/2023]
Abstract
OBJECTIVE Amisulpride is a second-generation antipsychotic agent indicated for the treatment of schizophrenia and other major psychotic illnesses. Amisulpride-induced bradycardia is a rare condition of unknown etiology and mechanism. Asymptomatic bradycardia has been associated with amisulpride in only two cases. In our case, the association was rated as "probable" on the Naranjo adverse drug reaction probability scale. METHOD Case report. RESULTS A 45-year-old male patient developed symptomatic bradycardia during usage of amisulpride (400-800 mg/day), which dramatically improved after the complete termination of amisulpride usage. The psychiatric condition remained relatively stable without bradycardia after administration of another antipsychotic agent [risperidone (3 mg/day)]. CONCLUSION This is the first case report of symptomatic bradycardia associated with the use of amisulpride. Although bradycardia is a rare adverse reaction to antipsychotics, this finding may alert psychiatrists and physicians to this antipsychotic drug side effect. Further study is needed to disclose the role of antipsychotics in bringing about symptomatic bradycardia.
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Affiliation(s)
- Li-Chung Huang
- Department of Psychiatry, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi City, Taiwan; Chia Nan University of Pharmacy and Science, Tainan, Taiwan
| | - Li-Yen Huang
- Department of Cardiology, Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan
| | - Shih-Yen Tseng
- Department of Pharmachology, Taichung Veterans General Hospital Chia Yi Branch, Chia-Yi City, Taiwan
| | - Yuh-Ming Hou
- Department of Psychiatry, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi City, Taiwan
| | - Cheng-Cheng Hsiao
- Department of Psychiatry, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi City, Taiwan.
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Jana AK, Praharaj SK, Roy N. Olanzapine-induced Orthostatic Hypotension. CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE 2015; 13:113-4. [PMID: 25912545 PMCID: PMC4423158 DOI: 10.9758/cpn.2015.13.1.113] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/15/2014] [Revised: 11/19/2014] [Accepted: 11/20/2014] [Indexed: 12/19/2022]
Abstract
Olanzapine is an atypical antipsychotic which is efficacious in the treatment of schizophrenia. The adverse effect profile for olanzapine is benign except for higher rates of metabolic events. Orthostatic hypotension is less commonly reported with olanzapine as compared to first-generation and few atypical antipsychotics. We report a case where olanzapine, in a dose dependent fashion, caused transient postural hypotension.
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Affiliation(s)
- Amlan Kusum Jana
- Department of Psychiatry, KPC Medical College and Hospital, Kolkata, West Bengal
| | | | - Nirmalya Roy
- Department of Psychiatry, KPC Medical College and Hospital, Kolkata, West Bengal
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Psychotropic drug-associated electrocardiographic presentation of diffuse J-waves in hypothermia: case report and literature review. Heart Vessels 2015; 31:996-1002. [PMID: 25666953 DOI: 10.1007/s00380-015-0646-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2014] [Accepted: 01/30/2015] [Indexed: 10/24/2022]
Abstract
The use of psychotropic drugs is often associated with electrocardiographic (ECG) QT-interval prolongation, but there are few reports of J-waves. This report describes the case of a schizophrenic patient under treatment with several psychotropic drugs (olanzapine, valproate, and flunitrazepam), in whom ECG J-waves diffusely appeared during a hypothermic episode. We further performed a literature review of psychotropic drug-related J-waves in hypothermia. The present case highlights the importance of recognizing psychotropic drug-related ECG J-waves on an early warning sign to ensure appropriate monitoring and/or treatment for possible life-threatening side effects of such medications.
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Cheng F, Zhao Z. Machine learning-based prediction of drug-drug interactions by integrating drug phenotypic, therapeutic, chemical, and genomic properties. J Am Med Inform Assoc 2014; 21:e278-86. [PMID: 24644270 DOI: 10.1136/amiajnl-2013-002512] [Citation(s) in RCA: 192] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
OBJECTIVE Drug-drug interactions (DDIs) are an important consideration in both drug development and clinical application, especially for co-administered medications. While it is necessary to identify all possible DDIs during clinical trials, DDIs are frequently reported after the drugs are approved for clinical use, and they are a common cause of adverse drug reactions (ADR) and increasing healthcare costs. Computational prediction may assist in identifying potential DDIs during clinical trials. METHODS Here we propose a heterogeneous network-assisted inference (HNAI) framework to assist with the prediction of DDIs. First, we constructed a comprehensive DDI network that contained 6946 unique DDI pairs connecting 721 approved drugs based on DrugBank data. Next, we calculated drug-drug pair similarities using four features: phenotypic similarity based on a comprehensive drug-ADR network, therapeutic similarity based on the drug Anatomical Therapeutic Chemical classification system, chemical structural similarity from SMILES data, and genomic similarity based on a large drug-target interaction network built using the DrugBank and Therapeutic Target Database. Finally, we applied five predictive models in the HNAI framework: naive Bayes, decision tree, k-nearest neighbor, logistic regression, and support vector machine, respectively. RESULTS The area under the receiver operating characteristic curve of the HNAI models is 0.67 as evaluated using fivefold cross-validation. Using antipsychotic drugs as an example, several HNAI-predicted DDIs that involve weight gain and cytochrome P450 inhibition were supported by literature resources. CONCLUSIONS Through machine learning-based integration of drug phenotypic, therapeutic, structural, and genomic similarities, we demonstrated that HNAI is promising for uncovering DDIs in drug development and postmarketing surveillance.
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Affiliation(s)
- Feixiong Cheng
- Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
| | - Zhongming Zhao
- Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, Tennessee, USA Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, USA
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Docx MKF, Simons A, Ramet J, Mertens L, Govaert P. Olanzapine-associated hypothermia in an adolescent anorexic girl. ACTA ACUST UNITED AC 2012. [DOI: 10.4236/ojcd.2012.24017] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Janse A, Marijnissen RM. Quetiapine-Induced Bradycardia Without QT Interval Prolongation in an Elderly Woman. PRIMARY CARE COMPANION TO THE JOURNAL OF CLINICAL PSYCHIATRY 2011; 11:172-3. [PMID: 19750071 DOI: 10.4088/pcc.08l00683] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Affiliation(s)
- André Janse
- Department of Geriatric Medicine, Gelderse Vallei Hospital, Elde ; and Department of Gerontopsychiatry, De Gelderse Roos Mental Health Care, Arnhem , The Netherlands
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Snarr BS, Phan SV, Garner A, VandenBerg AM, Barth KS. Symptomatic bradycardia with oral aripiprazole and oral ziprasidone. Ann Pharmacother 2010; 44:760-3. [PMID: 20215494 DOI: 10.1345/aph.1m621] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
OBJECTIVE To describe the case of a patient who developed symptomatic bradycardia upon initiation of oral ziprasidone and later with oral aripiprazole, both of which resolved shortly after discontinuation of therapy. CASE SUMMARY An 18-year-old female with bipolar disorder was started on oral ziprasidone 80 mg at night and the dose was subsequently increased to 120 mg for management of acute mania and delusions. The patient developed symptomatic bradycardia (heart rate 31-35 beats/min), which resolved after ziprasidone was decreased to 80 mg. Three months later, the patient was readmitted for treatment of bipolar mania with psychotic features in the context of medication nonadherence. She was started on oral aripiprazole 15 mg daily (subsequently increased to 20 mg) in conjunction with 600 mg lithium carbonate twice daily. The patient again developed symptomatic bradycardia that resolved after discontinuation of aripiprazole. DISCUSSION This is the first case report of symptomatic bradycardia associated with the use of ziprasidone or aripiprazole. The Naranjo probability scale suggests that the likelihood of the atypical antipsychotic as the cause of bradycardia is probable for both ziprasidone and aripiprazole. Symptomatic bradycardia with the use of other atypical antipsychotics has been reported in the literature. Little is known about the mechanisms that contribute to the antipsychotic-associated bradycardic response. CONCLUSIONS Further studies are needed to better determine the relationship between antipsychotics and reflex bradycardia. Although bradycardia remains a relatively uncommon phenomenon seen with the use of these medications, the severity of this potential adverse effect warrants consideration when initiating antipsychotic therapy.
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Affiliation(s)
- Brian S Snarr
- Department of Medicine, Medical University of South Carolina, Charleston, USA
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Hypothermia and rhabdomyolysis following olanzapine injection in an adolescent with schizophreniform disorder. Gen Hosp Psychiatry 2009; 31:376-8. [PMID: 19555799 DOI: 10.1016/j.genhosppsych.2008.09.009] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2008] [Revised: 08/28/2008] [Accepted: 09/04/2008] [Indexed: 11/21/2022]
Abstract
Hypothermia and rhabdomyolysis are infrequent adverse effects of antipsychotic drugs. Here we report a case of an adolescent with schizophreniform disorder who developed both of them simultaneously after intramuscular injection of olanzapine. A 17-year-old male patient was hospitalized for treatment of psychotic symptoms, which persisted on risperidone 3 mg/day for 3 weeks. Then his antipsychotic drug was shifted to oral olanzapine 10 mg/day. The next day, he received intramuscular injection of olanzapine 5 mg and soon developed hypothermia, rhabdomyolysis, hypotension and bradycardia. These symptoms subsided gradually in the next 2 weeks after supportive treatment was given. Such adverse effects were not observed in the following 7 months. Possible pharmacological mechanisms were discussed. Physicians should be cautious about patients' clinical symptoms after giving olanzapine injection or rapid titration in dosage.
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Olanzapine blocks the sympathetic and hyperthermic reactions due to cerebral injection of orexin A. Peptides 2007; 29:120-6. [PMID: 18053616 DOI: 10.1016/j.peptides.2007.10.016] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2007] [Revised: 10/08/2007] [Accepted: 10/17/2007] [Indexed: 12/01/2022]
Abstract
Since experiments regarding a possible relation between olanzapine and orexin A has been scarcely reported in international literature, this experiment tested the effect of olanzapine on the sympathetic and thermogenic effects induced by orexin A. The firing rates of the sympathetic nerves to interscapular brown adipose tissue (IBAT), along with IBAT, colonic temperatures and heart rate were monitored in urethane-anesthetized male Sprague-Dawley rats before an injection of orexin A (1.5 nmol) into the lateral cerebral ventricle and over a period of 150 min after the injection. The same variables were monitored in rats with an intraperitoneal administration of olanzapine (10mg/kg bw), injected 30 min before the orexin administration. The results show that orexin A increases the sympathetic firing rate, IBAT, colonic temperatures and heart rate. This increase is blocked by the injection of olanzapine. These findings indicate that olanzapine affects the complex reactions related to activation of orexinergic system.
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van Marum RJ, Wegewijs MA, Loonen AJM, Beers E. Hypothermia following antipsychotic drug use. Eur J Clin Pharmacol 2007; 63:627-31. [PMID: 17401555 PMCID: PMC1914304 DOI: 10.1007/s00228-007-0294-4] [Citation(s) in RCA: 61] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2006] [Accepted: 03/07/2007] [Indexed: 11/30/2022]
Abstract
Objective Hypothermia is an adverse drug reaction (ADR) of antipsychotic drug (APD) use. Risk factors for hypothermia in ADP users are unknown. We studied which risk factors for hypothermia can be identified based on case reports. Method Case reports of hypothermia in APD-users found in PUBMED or EMBASE were searched for risk factors. The WHO international database for Adverse Drug Reactions was searched for reports of hypothermia and APD use. Results The literature search resulted in 32 articles containing 43 case reports. In the WHO database, 480 reports were registered of patients developing hypothermia during the use of APDs which almost equals the number of reports for hyperthermia associated with APD use (n = 524). Hypothermia risk seems to be increased in the first days following start or dose increase of APs. APs with strong 5-HT2 antagonism seem to be more involved in hypothermia; 55% of hypothermia reports are for atypical antipsychotics. Schizophrenia was the most prevalent diagnosis in the case reports. Conclusion Especially in admitted patients who are not able to control their own environment or physical status, frequent measurements of body temperature (with a thermometer that can measure low body temperatures) must be performed in order to detect developing hypothermia.
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Affiliation(s)
- Rob J van Marum
- Geriatric Department, University Medical Centre, P.O. Box 85500, 3508 AB, Utrecht, The Netherlands.
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Theisen FM, Grabarkiewicz J, Fegbeutel C, Hübner A, Mehler-Wex C, Remschmidt H. Olanzapine overdose in children and adolescents: two case reports and a review of the literature. J Child Adolesc Psychopharmacol 2005; 15:986-95. [PMID: 16379519 DOI: 10.1089/cap.2005.15.986] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Although the atypical antipsychotic olanzapine is increasingly being used in child and adolescent psychiatry, reports of olanzapine overdose in this young population are scarce. We report on two cases of adolescents who attempted suicide with an overdose of olanzapine: (1) A 14-year-old female ingested 275 mg olanzapine, which produced the highest reported nonlethal serum level (1503 ng/mL) and caused somnolence, agitation (acutely), and extrapyramidal symptoms (EPS; after 54 hours) but no major clinical complications. The serum olanzapine level dropped to 129 ng/mL within 48 hours; and (2) a 17-year-old male ingested 400 mg olanzapine, the highest reported nonlethal dose of olanzapine in adolescents, which produced respiratory suppression requiring intubation and mechanical ventilation; he recovered after 3 days. Based on clinical monitoring and postmortem data, the 2 patients survived the ingestion of high doses of olanzapine. We also provide a review of the literature, encompassing all reported cases of olanzapine overdose in children and adolescents and discuss symptoms, diagnosis, and treatment options, based on pharmacokinetic and pharmacodynamic considerations.
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Affiliation(s)
- Frank M Theisen
- Clinical Research Group, Department of Child and Adolescent Psychiatry and Psychotherapy, Philipps-University, Marburg, and District General Hospital Frankenburg, Germany
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