Therapeutic Drug Levels of Second Generation Antipsychotics in Youth: A Systematic Review

Whitney, Zachary; Boyda, Heidi N.; Procyshyn, Ric M.; Elbe, Dean; Black, Tyler; Eslami, Ali; Barr, Alasdair M.

doi:10.1089/cap.2014.0044

Cited by 25 publications

(14 citation statements)

References 70 publications

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“…Many neuropsychiatric drugs are not approved for use in children or adolescents [416,1308]. To date, therapeutic reference ranges for most neuropsychopharmacological drugs are based upon studies performed in adults, and data about the correlation of concentration with therapeutic response or adverse drug reactions in the paediatric population are scarce [327,1298]. The relative lack of clinical trials and the resultant off-label use could lead to a higher risk of dosing errors and adverse drug reactions.…”

Section: Recommendationmentioning

confidence: 99%

Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017

Bergemann²,

et al. 2017

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Therapeutic drug monitoring (TDM) is the quantification and interpretation of drug concentrations in blood to optimize pharmacotherapy. It considers the interindividual variability of pharmacokinetics and thus enables personalized pharmacotherapy. In psychiatry and neurology, patient populations that may particularly benefit from TDM are children and adolescents, pregnant women, elderly patients, individuals with intellectual disabilities, patients with substance abuse disorders, forensic psychiatric patients or patients with known or suspected pharmacokinetic abnormalities. Non-response at therapeutic doses, uncertain drug adherence, suboptimal tolerability, or pharmacokinetic drug-drug interactions are typical indications for TDM. However, the potential benefits of TDM to optimize pharmacotherapy can only be obtained if the method is adequately integrated in the clinical treatment process. To supply treating physicians and laboratories with valid information on TDM, the TDM task force of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued their first guidelines for TDM in psychiatry in 2004. After an update in 2011, it was time for the next update. Following the new guidelines holds the potential to improve neuropsychopharmacotherapy, accelerate the recovery of many patients, and reduce health care costs.

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Section: Recommendationmentioning

confidence: 99%

Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017

Bergemann²,

et al. 2017

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“…It was recently shown that the long-term effectiveness of SGAs in youths needs to be improved, with high rate of clinicians-decided and patients-decided discontinuation [ 92 ]. A possible improvement strategy is to increase our knowledge on therapeutic drug monitoring, but to date empirical information on paediatric populations is scant [ 93 , 94 ]. Close paediatrician-child psychiatrist collaboration should be the first action to achieve this improvement.…”

Section: Discussionmentioning

confidence: 99%

Update on the safety of second generation antipsychotics in youths: a call for collaboration among paediatricians and child psychiatrists

et al. 2016

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During the past decade, a substantial increase in the use of second generation antipsychotics (SGAs) has occurred for a number of juvenile psychiatric disorders, often as off-label prescriptions. Although they were thought to be safer than older, first generation antipsychotics, mainly due to a lower risk of neurological adverse reactions, recent studies have raised significant concerns regarding their safety regarding metabolic, endocrinological and cardiovascular side effects. Aim of this paper is to update with a narrative review, the latest findings on safety of SGAs in youths. Results suggest that different SGAs may present different safety profiles. Metabolic adverse events are the most frequent and troublesome, with increasing evidences of heightened risk for type II diabetes mellitus. Results are discussed with specific emphasis on possible strategies of an active monitoring, which could enable both paediatricians and child psychiatrists to a possible prevention, early detection, and a timely management of such effects.

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“…There are studies on the pharmacokinetics of olanzapine in adolescents; however, a meta-analysis of these studies reported that the data are highly variable, and more research is needed on the pharmacokinetics of olanzapine. 20 The suggested pediatric dose of olanzapine based on the scaling method from the adult dose of 5 mg has varied from 0.06 to 0.13 mg/kg/day. 16,21 The mean dose of olanzapine used in our study was 0.14 mg/kg, which is close to the dose proposed for children.…”

Section: Discussionmentioning

confidence: 99%

Olanzapine versus metoclopramide for the treatment of breakthrough chemotherapy–induced vomiting in children: An open‐label, randomized phase 3 trial

Radhakrishnan

Pai

Swaminathan

et al. 2020

Pediatric Blood & Cancer

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Background Breakthrough chemotherapy–induced vomiting (CIV) is defined as CIV occurring after adequate antiemetic prophylaxis. Olanzapine and metoclopramide are two drugs recommended for the treatment of breakthrough CIV in children, without adequate evidence. We conducted an open‐label, single‐center, phase 3 randomized controlled trial comparing the safety and efficacy of olanzapine and metoclopramide for treating breakthrough CIV. Procedure Children aged 5‐18 years who developed breakthrough CIV after receiving highly emetogenic chemotherapy or moderately emetogenic chemotherapy were randomly assigned to the metoclopramide or olanzapine arm. The primary objective of the study was to compare the complete response (CR) rates between patients receiving olanzapine or metoclopramide for treating breakthrough CIV during 72 hours after the administration of the study drug. Secondary objectives were to compare CR rates for nausea and toxicities between the two arms. Results Eighty patients were analyzed (39 in the olanzapine arm and 41 in the metoclopramide arm). CR rates were significantly higher in the olanzapine arm compared with the metoclopramide arm for vomiting (72% vs 39%, P = 0.003) and nausea (59% vs 34%, P = 0.026). Seven patients in the metoclopramide arm crossed over to the olanzapine arm and none crossed over in the olanzapine arm (P < 0.001). The mean nausea score in the olanzapine arm was significantly lower than the metoclopramide arm after the initiation of the rescue antiemetic (P = 0.01). Hyperglycemia and drowsiness were more commonly seen in the olanzapine arm. Conclusion Olanzapine is superior to metoclopramide for the treatment of breakthrough CIV in children. Drowsiness and hyperglycemia need to be monitored closely in children receiving olanzapine for breakthrough CIV.

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Therapeutic Drug Levels of Second Generation Antipsychotics in Youth: A Systematic Review

Abstract: TDM may be indicated in any circumstance in which cytochrome P450 inhibitors or inducers are coprescribed. Further research is required for establishing a sounder safety profile for SGA use in the pediatric population.

Cited by 25 publications

References 70 publications

Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017

Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017

Update on the safety of second generation antipsychotics in youths: a call for collaboration among paediatricians and child psychiatrists

Olanzapine versus metoclopramide for the treatment of breakthrough chemotherapy–induced vomiting in children: An open‐label, randomized phase 3 trial

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