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      The Use of Atypical Antipsychotics in Treating a Pediatric Psychiatric Patient

      case-report
      1 , 2 , , 3 , 4 , 5 , 6
      ,
      Cureus
      Cureus
      atypical antipsychotics, olanzapine, pediatrics, psychiatry, plan

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          Abstract

          Approaches to enhancing mental health management entail several perspectives and efforts to promote competent treatment. In light of this, we present a case report to describe the nature of events encountered during the management of a psychiatric patient. The paper commences by providing a general introduction and background of the concept of atypical antipsychotics before adding a thesis statement that healthcare providers should be knowledgeable regarding psychopharmacotherapy to effectively design and implement safe patient care. The paper's method involved the review of a case scenario and discussion of the concepts using evidence-based guidance and perspectives. In the case scenario, a pediatric patient significantly gains weight and develops extrapyramidal effects like dystonias, and erratic, jerky neck movements as a consequence of treatment with olanzapine. The most effective care plan involves stopping the medication, reviewing treatment options, and incorporating physical exercise. Most importantly, the plan encourages achieving an adequate heart rate above 100 beats per minute to maintain sufficient perfusion during exercise. The paper concludes by summarizing the perspectives from the studies reviewed.

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          Olanzapine. Pharmacokinetic and pharmacodynamic profile.

          Multicentre trials in patients with schizophrenia confirm that olanzapine is a novel antipsychotic agent with broad efficacy, eliciting a response in both the positive and negative symptoms of schizophrenia. Compared with traditional antipsychotic agents, olanzapine causes a lower incidence of extrapyramidal symptoms and minimal perturbation of prolactin levels. Generally, olanzapine is well tolerated. The pharmacokinetics of olanzapine are linear and dose-proportional within the approved dosage range. Its mean half-life in healthy individuals was 33 hours, ranging from 21 to 54 hours. The mean apparent plasma clearance was 26 L/h, ranging from 12 to 47 L/h. Smokers and men have a higher clearance of olanzapine than women and nonsmokers. After administering [14C]olanzapine, approximately 60% of the radioactivity was excreted in urine and 30% in faeces. Olanzapine is predominantly bound to albumin (90%) and alpha 1-acid glycoprotein (77%). Olanzapine is metabolised to its 10- and 4'-N-glucuronides, 4'-N-desmethylolanzapine [cytochrome P450 (CYP) 1A2] and olanzapine N-oxide (flavin mono-oxygenase 3). Metabolism to 2-hydroxymethylolanzapine via CYP2D6 is a minor pathway. The 10-N-glucuronide is the most abundant metabolite, but formation of 4'-N-desmethylolanzapine is correlated with the clearance of olanzapine. Olanzapine does not inhibit CYP isozymes. No clinically significant metabolic interactions were found between olanzapine and diazepam, alcohol (ethanol), imipramine, R/S-warfarin, aminophylline, biperiden, lithium or fluoxetine. Fluvoxamine, an inhibitor of CYP1A2, increases plasma concentrations of olanzapine; inducers of CYP1A2, including tobacco smoke and carbamazepine, decrease olanzapine concentrations. Orthostatic changes were observed when olanzapine and diazepam or alcohol were coadministered. Pharmacodynamic interactions occurred between olanzapine and alcohol, and olanzapine and imipramine, implying that patients should avoid operating hazardous equipment or driving an automobile while experiencing the short term effects of the combinations. Individual factors with the largest impact on olanzapine pharmacokinetics are gender and smoking status. The plasma clearance of olanzapine generally varies over a 4-fold range, but the variability in the clearance and concentration of olanzapine does not appear to be associated with the severity or duration of adverse effects or the degree of efficacy. Thus, dosage adjustments appear unnecessary for these individual factors. However, dosage modification should be considered for patients characterised by a combination of factors associated with decreased oxidative metabolism, for example, debilitated or elderly women who are nonsmokers.
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            Second-Generation Antipsychotics and Extrapyramidal Adverse Effects

            Antipsychotic-induced extrapyramidal adverse effects are well recognized in the context of first-generation antipsychotic drugs. However, the introduction of second-generation antipsychotics, with atypical mechanism of action, especially lower dopamine receptors affinity, was met with great expectations among clinicians regarding their potentially lower propensity to cause extrapyramidal syndrome. This review gives a brief summary of the recent literature relevant to second-generation antipsychotics and extrapyramidal syndrome. Numerous studies have examined the incidence and severity of extrapyramidal syndrome with first- and second-generation antipsychotics. The majority of these studies clearly indicate that extrapyramidal syndrome does occur with second-generation agents, though in lower rates in comparison with first generation. Risk factors are the choice of a particular second-generation agent (with clozapine carrying the lowest risk and risperidone the highest), high doses, history of previous extrapyramidal symptoms, and comorbidity. Also, in comparative studies, the choice of a first-generation comparator significantly influences the results. Extrapyramidal syndrome remains clinically important even in the era of second-generation antipsychotics. The incidence and severity of extrapyramidal syndrome differ amongst these antipsychotics, but the fact is that these drugs have not lived up to the expectation regarding their tolerability.
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              A commentary on the efficacy of olanzapine for the treatment of schizophrenia: the past, present, and future

              Abstract Olanzapine is a second-generation atypical antipsychotic with proven efficacy for the treatment of schizophrenia. Approved in 1996, olanzapine is one of the most studied antipsychotics, resulting in a considerable amount of clinical data across diverse patient populations. Despite the fact that olanzapine is associated with a known risk of metabolic side effects, including weight gain, many clinicians continue to prescribe olanzapine for the treatment of schizophrenia with the expectation of additional therapeutic antipsychotic efficacy relative to other first-line atypical antipsychotics. The goal of this narrative is to revisit the role of oral olanzapine in the management of patients with schizophrenia, including those with recently diagnosed schizophrenia (“first-episode”), those with an established schizophrenia diagnosis who experience acute exacerbations, those receiving long-term antipsychotic treatment as a maintenance intervention, and those with suboptimal response to antipsychotic treatment, including treatment resistance. Collectively, data from published literature support the favorable efficacy of olanzapine compared with other first- and second-generation antipsychotics, including lower rates of treatment discontinuation and clinically meaningful improvements in the symptoms of schizophrenia. The development of antipsychotic medications with the favorable efficacy of olanzapine, but with reduced weight gain, could address a major unmet need in the treatment of schizophrenia.
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                Author and article information

                Journal
                Cureus
                Cureus
                2168-8184
                Cureus
                Cureus (Palo Alto (CA) )
                2168-8184
                2 August 2022
                August 2022
                : 14
                : 8
                : e27594
                Affiliations
                [1 ] Department of Neonatology, Port-of-Spain General Hospital, Port-of-Spain, TTO
                [2 ] Research, The University of the West Indies, St. Augustine Campus, Faculty of Medicine, St. Augustine, TTO
                [3 ] Research, GMERS Medical College, Gandhinagar, IND
                [4 ] Research, Government Medical College, Kottayam, IND
                [5 ] Research, Rajah Muthiah Medical College and Hospital, Chidambaram, IND
                [6 ] Department of Pediatrics, University of Kentucky Children's Hospital, Lexington, USA
                Author notes
                Article
                10.7759/cureus.27594
                9434710
                36059361
                317ceb54-a541-4d30-98d9-a92a663c1e4a
                Copyright © 2022, Jogie et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 2 August 2022
                Categories
                Pediatrics
                Psychiatry

                atypical antipsychotics,olanzapine,pediatrics,psychiatry,plan

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