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      Monitoring of Adverse Drug Reaction-Related Parameters in Children, Youth, and Young Adults Prescribed Antipsychotic Drugs by General Practitioners

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          Abstract

          Objective: The aim of the study was to assess monitoring of adverse drug reaction (ADR)-related parameters in children, youth, and young adults treated with second-generation antipsychotic drugs (SGAs) prescribed by general practitioners (GPs).

          Methods: This retrospective follow-up study included children, youth, and young adults aged 0 − 24 years, who had an initial prescription of an SGA recorded in the Clinical Practice Research Datalink between 2000 and 2017, and who were prescribed an SGA more than once for a duration of at least 6 months. It included an assessment of which ADR-related physical parameters (weight, height, body–mass index, waist circumference, pulse, blood pressure, and heart examination) and laboratory parameters (glucose, HbA1c, lipids, and prolactin) were monitored in children, youth, and young adults at least once every 6-month period, stratified by sex, age categories, and calendar years.

          Results: In total, 7006 patients were included and the mean duration of follow-up was 1.6 years. Monitoring frequencies of all parameters were below 25%. Blood pressure and weight were monitored in 23.6% and 23.4%, respectively, of all children, youth, and young adults during the first half year; waist circumference was monitored in 0.2%. Females were monitored more often than males, some differences between age categories were observed, and monitoring frequencies increased after 2000, but did not exceed 35% in any year.

          Conclusion: Monitoring frequencies of ADR-related parameters in children, youth, and young adults treated with SGAs prescribed by a GP were low. Monitoring in primary care should be improved to enable a better evaluation of the benefit–risk balance during antipsychotic drug therapy.

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          Data Resource Profile: Clinical Practice Research Datalink (CPRD)

          The Clinical Practice Research Datalink (CPRD) is an ongoing primary care database of anonymised medical records from general practitioners, with coverage of over 11.3 million patients from 674 practices in the UK. With 4.4 million active (alive, currently registered) patients meeting quality criteria, approximately 6.9% of the UK population are included and patients are broadly representative of the UK general population in terms of age, sex and ethnicity. General practitioners are the gatekeepers of primary care and specialist referrals in the UK. The CPRD primary care database is therefore a rich source of health data for research, including data on demographics, symptoms, tests, diagnoses, therapies, health-related behaviours and referrals to secondary care. For over half of patients, linkage with datasets from secondary care, disease-specific cohorts and mortality records enhance the range of data available for research. The CPRD is very widely used internationally for epidemiological research and has been used to produce over 1000 research studies, published in peer-reviewed journals across a broad range of health outcomes. However, researchers must be aware of the complexity of routinely collected electronic health records, including ways to manage variable completeness, misclassification and development of disease definitions for research.
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            Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia: a systematic review and network meta-analysis

            Summary Background Schizophrenia is one of the most common, burdensome, and costly psychiatric disorders in adults worldwide. Antipsychotic drugs are its treatment of choice, but there is controversy about which agent should be used. We aimed to compare and rank antipsychotics by quantifying information from randomised controlled trials. Methods We did a network meta-analysis of placebo-controlled and head-to-head randomised controlled trials and compared 32 antipsychotics. We searched Embase, MEDLINE, PsycINFO, PubMed, BIOSIS, Cochrane Central Register of Controlled Trials (CENTRAL), WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov from database inception to Jan 8, 2019. Two authors independently selected studies and extracted data. We included randomised controlled trials in adults with acute symptoms of schizophrenia or related disorders. We excluded studies in patients with treatment resistance, first episode, predominant negative or depressive symptoms, concomitant medical illnesses, and relapse-prevention studies. Our primary outcome was change in overall symptoms measured with standardised rating scales. We also extracted data for eight efficacy and eight safety outcomes. Differences in the findings of the studies were explored in metaregressions and sensitivity analyses. Effect size measures were standardised mean differences, mean differences, or risk ratios with 95% credible intervals (CrIs). Confidence in the evidence was assessed using CINeMA (Confidence in Network Meta-Analysis). The study protocol is registered with PROSPERO, number CRD42014014919. Findings We identified 54 417 citations and included 402 studies with data for 53 463 participants. Effect size estimates suggested all antipsychotics reduced overall symptoms more than placebo (although not statistically significant for six drugs), with standardised mean differences ranging from −0·89 (95% CrI −1·08 to −0·71) for clozapine to −0·03 (−0·59 to 0·52) for levomepromazine (40 815 participants). Standardised mean differences compared with placebo for reduction of positive symptoms (31 179 participants) varied from −0·69 (95% CrI −0·86 to −0·52) for amisulpride to −0·17 (−0·31 to −0·04) for brexpiprazole, for negative symptoms (32 015 participants) from −0·62 (−0·84 to −0·39; clozapine) to −0·10 (−0·45 to 0·25; flupentixol), for depressive symptoms (19 683 participants) from −0·90 (−1·36 to −0·44; sulpiride) to 0·04 (−0·39 to 0·47; flupentixol). Risk ratios compared with placebo for all-cause discontinuation (42 672 participants) ranged from 0·52 (0·12 to 0·95; clopenthixol) to 1·15 (0·36 to 1·47; pimozide), for sedation (30 770 participants) from 0·92 (0·17 to 2·03; pimozide) to 10·20 (4·72 to 29·41; zuclopenthixol), for use of antiparkinson medication (24 911 participants) from 0·46 (0·19 to 0·88; clozapine) to 6·14 (4·81 to 6·55; pimozide). Mean differences compared to placebo for weight gain (28 317 participants) ranged from −0·16 kg (−0·73 to 0·40; ziprasidone) to 3·21 kg (2·10 to 4·31; zotepine), for prolactin elevation (21 569 participants) from −77·05 ng/mL (−120·23 to −33·54; clozapine) to 48·51 ng/mL (43·52 to 53·51; paliperidone) and for QTc prolongation (15 467 participants) from −2·21 ms (−4·54 to 0·15; lurasidone) to 23·90 ms (20·56 to 27·33; sertindole). Conclusions for the primary outcome did not substantially change after adjusting for possible effect moderators or in sensitivity analyses (eg, when excluding placebo-controlled studies). The confidence in evidence was often low or very low. Interpretation There are some efficacy differences between antipsychotics, but most of them are gradual rather than discrete. Differences in side-effects are more marked. These findings will aid clinicians in balancing risks versus benefits of those drugs available in their countries. They should consider the importance of each outcome, the patients' medical problems, and preferences. Funding German Ministry of Education and Research and National Institute for Health Research
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              The fear of needles: A systematic review and meta-analysis

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                Author and article information

                Journal
                J Child Adolesc Psychopharmacol
                J Child Adolesc Psychopharmacol
                cap
                Journal of Child and Adolescent Psychopharmacology
                Mary Ann Liebert, Inc., publishers (140 Huguenot Street, 3rd Floor New Rochelle, NY 10801 USA )
                1044-5463
                1557-8992
                February 2022
                14 February 2022
                14 February 2022
                : 32
                : 1
                : 36-44
                Affiliations
                [ 1 ]Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
                [ 2 ]Karakter Child and Adolescent Psychiatry, Zwolle, The Netherlands.
                [ 3 ]Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht, The Netherlands.
                [ 4 ]Research Group Innovation of Pharmaceutical Care, University of Applied Sciences, Utrecht, The Netherlands.
                Author notes
                [*]Address correspondence to: Eibert R. Heerdink, PhD, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80082, Utrecht 3508 TB, The Netherlands e.r.heerdink@ 123456uu.nl

                Funding: The authors declare that the study was funded solely by Utrecht University.

                Author information
                https://orcid.org/0000-0002-5946-7209
                Article
                10.1089/cap.2021.0026
                10.1089/cap.2021.0026
                8884168
                34619039
                45f6a567-62c3-41f8-966c-12531a4c7054
                © Lenneke Minjon et al. 2022; Published by Mary Ann Liebert, Inc.

                This Open Access article is distributed under the terms of the Creative Commons Attribution Noncommercial License [CC-BY-NC] ( http://creativecommons.org/licenses/by-nc/4.0/) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are cited.

                History
                Page count
                Figures: 2, Tables: 2, References: 46, Pages: 9
                Categories
                Original Articles

                adverse effects,antipsychotic agents,youth,drug monitoring,primary health care

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