AUCTORES
Globalize your Research
Research | DOI: https://doi.org/10.31579/2642-973X/025
Emeritus Professor of Psychiatry, New York USA.
*Corresponding Author: Saeed Shoja Shafti, Emeritus Professor of Psychiatry, New York USA
Citation: Saeed Shoja Shafti. (2022). Neuroleptic Malignant Syndrome: Typical Antipsychotic Drugs Versus Atypical Antipsychotic Medications. Brain and Neurological Disorders 5(2); DOI:10.31579/2642-973X/025
Copyright: © 2022, S Shoja S, this is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 18 March 2022 | Accepted: 10 June 2022 | Published: 17 June 2022
Keywords: typical antipsychotic; atypical antipsychotic; neuroleptic malignant syndrome; schizophrenia
Introduction: Neuroleptic malignant syndrome is an idiosyncratic reaction and a severe disorder caused by an adverse reaction to drugs with dopamine receptor- antagonist properties and is characterized by a tetrad of rigidity, fever, altered mental status, and autonomic instability. In the present assessment, typical or conventional antipsychotics have been contrasted with atypical antipsychotics with respect to recorded cases of neuroleptic malignant syndrome among a sample of nonwestern psychiatric inpatients.
Methods: For assessment, all the cases with a diagnosis of neuroleptic malignant syndrome during the last sixty-two months, after exclusion of other conceivable differential diagnoses, were incorporated in the current retrospective, record-based evaluation. The clinical diagnosis was based on the Diagnostic and Statistical Manual of Mental Disorders, 5th edition. The valuation of independent variables was analyzed by ‘Compression of proportions. Statistical significance is defined as p value ≤0.05.
Results: Amongst 19814 psychiatric inpatients, in the course of sixty-two months, eighteen cases received the diagnosis of neuroleptic malignant syndrome. As said by the findings, neuroleptic malignant syndrome was meaningfully more frequent among males, in comparison with females, and it was importantly more prevalent among cases suffering from schizophrenia, in comparison with bipolar disorder. Also, the highest risk of neuroleptic malignant syndrome was found in the age group of 30-39. In the current assessment, only one of the patients, who had received haloperidol, died due to aspiration pneumonia and respiratory failure, and the most prevalent symptom was fever, which was observable in one hundred percent of cases. In addition to a similar clinical profile, ‘Compression of proportions’ did not show any significant difference between the conventional (typical) antipsychotics versus the atypical antipsychotic medications with respect to the occurrence of neuroleptic malignant syndrome.
Conclusion: As said by the findings, no significant difference was evident between the typical antipsychotic drugs versus the atypical antipsychotic medications, with respect to incidence and clinical profile of neuroleptic malignant syndrome.
Neuroleptic malignant syndrome (NMS) is an idiosyncratic reaction and a severe disorder caused by an adverse reaction to drugs with dopamine receptor-antagonist properties or the quick withdrawal of dopaminergic drugs [1]. It is characterized by a tetrad of rigidity, fever, autonomic instability, and altered mental status, ranging from confusion to coma, and later complications like renal and respiratory failure [2]. Moreover, it may be presented by leukocytosis, low serum iron levels and elevated creatine phosphokinase (CPK) levels [3, 4]. So, failure to diagnose NMS early and beginning of suitable management can result in serious medical complications and, finally, death. On the other hand, while diagnostic criteria for NMS are present, atypical presentations that lack one or more typical features pose a diagnostic problem to clinicians. Consequently, though controversial, the concept of atypical NMS has been suggested for such cases [5]. While there is no specific check able to diagnose NMS, serum creatine phosphokinase (CPK) elevation has been reported in over 90% of cases [6]. NMS happens most often during the first week of treatment or after increasing the dose of the antipsychotic drug [7]. The incidence of NMS is not well -known, but the rate of it's happening with typical antipsychotics has been reported to vary from 0.02% to 2.44% [8, 9]. In recent times, the frequency of NMS has declined from around 0.01% to 0.02% due to more alertness of clinicians and accessibility of newer antipsychotic drugs [10]. Primary reports of mortality rates from NMS were in excess of thirty percent, but increased physician attentiveness and institution of newer antipsychotic drugs over the last few years have reduced them to closer to ten percent [11]. While the underlying pathophysiologic mechanisms of NMS are complex and still under examination, perhaps a marked and sudden reduction in central dopaminergic activity resulting from D2 dopamine receptor blockade within the nigrostriatal, hypothalamic, and mesolimbic/ cortical pathways may explain the clinical features of NMS including rigidity, hyperthermia, and altered mental status, respectively [12]. The main risk factors for developing NMS are the commencement or escalation in dosage of an antipsychotic drug and the potency and administration form of that medication (13). Often complicating the diagnosis of NMS is the great number of drug-induced conditions that can have motor and cognitive features that are like NMS [14]. Also, though usage of antipsychotic medications is connected with a variety of adverse motor effects, several other classes of medications at toxic levels may cause symptoms similar to NMS [15]. Despite the fact that the risk of developing NMS due to atypical antipsychotics looks less than conventional neuroleptics, now the usage of atypical antipsychotics is increasing, so the frequency of NMS due to these medications may also increase [16, 17]. On the other hand, the introduction of atypical antipsychotics has further complicated the diagnosis of NMS, and it is supposed that atypical agents might cause atypical forms of NMS because of their different pharmacological properties [18]. Case reports and reviews propose that the clinical features of NMS associated with atypical medications differ from those precipitated by typical antipsychotics [19]. Atypical NMS is reported with the use of atypical antipsychotics such as clozapine, risperidone, aripiprazole, and olanzapine [20]. Therefore, the diagnosis of NMS remains controversial and presents an important challenge to physicians [5]. Nonetheless, while NMS is a diagnosis of exclusion, as a variety of medical disorders can present with analogous symptoms [21], early recognition and intervention are crucial because NMS can lead to severe complications, such as respiratory failure, rhabdomyolysis, seizures, acute kidney injury, and death [22]. In the present assessment, typical or conventional antipsychotics are compared with atypical antipsychotics with respect to recorded cases of NMS among a sample of non-western psychiatric patients.
Razi psychiatric hospital in the south of Tehran was selected as the field of research in the current retrospective evaluation. For appraisal, all the patients with a diagnosis of NMS during the last 62 months, after exclusion of other conceivable differential diagnoses, like serotonin syndrome, meningitis and encephalitis, were incorporated in the current examination. The clinical diagnosis, as well, was in line with the ‘Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5)’ [23].
Analysis of independent variables was performed by ‘comparison of proportions. Statistical significance is defined as P-value ≤0.05. ‘Med-Calc’ statistical software, version 15.2, was the statistical software tool for analysis.
As stated by results, among 19814 psychiatric patients hospitalized in the above-mentioned hospice, in the course of 62 months (April of 2013 - August 2018), 18 cases received the diagnosis of NMS. While 38.88% (n=7) of cases had received parenteral antipsychotics (haloperidol, IM or IV), 61.11% (n=11) of them had used only oral medications. According to the findings, NMS was meaningfully more frequent among male cases, in comparison with female patients, and it was importantly more prevalent among patients suffering from schizophrenia, in comparison with patients with diagnoses of bipolar I or II disorder (Table 1).
Also, while it was considerably more widespread amid the 18-65-year-old age-group, in comparison with adolescents or elderly patients (Table 1), the highest risk of NMS was found in the age group of 30-39, in comparison with 20-29 and 40-49 (Table 2). In the current assessment, only one of the patients, who had received haloperidol, died two weeks after the appearance of NMS due to aspiration pneumonia and respiratory failure (5.55%). Moreover, the most predominant clinical symptom was fever, which was palpable in all cases (mean total average = 39.71 ± 0.58 Celsius) (Table 3). The mean total days between admissions to the psychiatric ward and diagnosis of NMS was around 3.05 ± 2.54 days, and the mean total days of treatment for NMS was around 7.83 ± 6.11 days. Comparing the prescribed typical antipsychotics [haloperidol (n=9), thioridazine (n=1), chlorpromazine (n=1)] and atypical antipsychotics [olanzapine (n=4), risperidone (n=3)], ‘Compression of proportions’ did not display any statistically important difference between the conventional (typical) antipsychotics versus the atypical antipsychotic medications with respect to incidence of NMS (z = 1.33, p<0 xss=removed>
Though NMS happens only infrequently, it remains an unpredictable and potentially deadly neurologic situation that clinicians must be able to diagnose as soon as possible, since early diagnosis and correct medical management are crucial to make sure of improved conclusions [24]. While incomplete or extraordinary NMS cases have been reported due to atypical agents, it should always be kept in mind that all atypical antipsychotic drugs, including clozapine, have the probability of inducing NMS, even though not a common phenomenon [25]. If NMS is not quickly identified and treated, it can be deadly due to cardiac arrest, pneumonia, pulmonary embolism, renal failure, disseminated intravascular coagulation or permanent damage, such as neurological sequels [3, 11]. Along with the findings of the present evaluation, there was no substantial difference between conventional and atypical antipsychotics with reference to prompting NMS, a finding which was rather in accord with the outcomes of Khouri et al. [7], Ananth et al. [26], Trollor et al. [18], Croarkin et al. [27], and Teo et al. [5]. Also, while the outcome of the current assessment was in agreement with the results of Khaldi et al. [28], who indicated that atypical antipsychotics can cause NMS even when prescribed in monotherapy, it was not in harmony with the outcome of Anzai et al. [29], who said that monotherapy or combination therapy with most atypical antipsychotic agents without typical antipsychotic agents was not likely to cause NMS as an adverse reaction compared to haloperidol monotherapy. So, as said by Ananth et al. [26], induction of NMS by clozapine, though not common and in incomplete or extraordinary forms [25], indicates that low incidence of extrapyramidal symptoms (EPS) and low EPS-inducing potential do not stop the happening of NMS, and D2 dopamine receptor blocking potential does not have direct association with the incident of NMS. In addition, in contrary to Teo et al. [ 5]) and Trollor et al. [18], who supposed that the advent of atypical antipsychotics has further complicated the diagnosis of NMS and atypical medications might cause atypical forms of NMS owing to their different pharmacological properties, and Sarkar et al. [19] and Pileggi et al. [30], who had stated that case reports and reviews suggest that the clinical features of NMS associated with atypical antipsychotics differ from that precipitated by typical antipsychotics, and drug re-challenge and follow-up care have not been underlined in many reports of NMS, in the current examination no uncommon exhibition of NMS that lacks one or more distinctive features was implicitly manifest due to atypical antipsychotics. Nevertheless, while the suggestion of Teo et al. [5] was concerning atypical NMS precipitated by quetiapine and clozapine overdoses, in the current evaluation, NMS was discernible with standard amounts of risperidone and olanzapine, which may show different symptomatology in comparison with the aforesaid medicines. So, our conclusion is a bit in accord with Trollor et al. [18], who believed that NMS accompanying atypical antipsychotic medications displays in a characteristic mode, except that clozapine-induced NMS, which appears less probable to present with extrapyramidal features, including rigidity and tremor [31, 32]. Also, in the present estimation, no delayed type of NMS, which, in the words of Suzuki et al. [33], might be relatively more frequent in senior and pre-senior patients than in younger patients, was manifest, and the mean total period between admission in the psychiatric ward and transmission to the ICU was around one week, which was in agreement with the outcomes of Chen et al. [3], who stated that two-thirds of cases of NMS develop within the first week. Similarly, since the only teenager in the current estimation had received olanzapine, so again our result is a little in harmony with the suggestion of Croarkin et al. [27], who indicated that adolescents can develop NMS during treatment with atypical antipsychotics and its symptoms are similar to those described in adults. Furthermore, in the present study, there was only one death due to NMS, which was induced by haloperidol; an outcome that was compatible with the finding of Ananth et al. (26), who believed that the mortality rate of NMS with atypical antipsychotic medications was lesser than conventional antipsychotic drugs. Nevertheless, the death rate may basically be a reflection of physicians' awareness and resulting from early treatment. Anyhow, while NMS is a life-threatening complication of antipsychotic drugs, and it is often assumed to be infrequent, observations suggest that, rather than overestimating its incidence, we are more likely to underrate it [34]. Even though less common now than in the past, because of greater alertness, it remains a risk in susceptible patients receiving typical or atypical antipsychotic medicines. Accordingly, decreasing the risk factors, early identification of suspected cases, and rapid management can meaningfully decrease mortality and morbidity in this hazardous situation. Cooperation between psychiatry and other medical fields may be the key to a fruitful consequence [34]. On the other hand, while routine examination of serum CPK in patients on antipsychotic medications who demonstrate features of NMS is endorsed to help diagnosis [35], diagnosis and appropriate treatment can be delayed when a patient does not present with classical signs of NMS [5]. So, the diagnosis of NMS should mainly be determined by clinical symptoms [2]. Though NMS can be hard to diagnose and it is a diagnosis of exclusion, we should remember that, since there is a great changeability re its clinical presentation, clinicians should not exclude this syndrome too quickly in a patient treated with neuroleptics [7]. Narrow periods of study, due to inapt recordings in the last span, and unsatisfactory cases with the diagnosis of NMS, as available samples, despite the size of the field of investigation, do not permit generalization of the results to more than a pilot study.
As said by the findings, no significant difference was evident between the typical antipsychotic drugs versus the atypical antipsychotic medications, with respect to incidence and clinical profile of neuroleptic malignant syndrome.
The author acknowledges physicians and personnel of Razi Psychiatric Hospital for their valuable support and assistance.
Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.
Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.
Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.
Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.
We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.
The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.
Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.
Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.
Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.
Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.
Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.
This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.
Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.
As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.
Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.
International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.
Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.
Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.
I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!
"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
