Objective:Acute agitation in pediatrics is commonly encountered in hospital settings, can contribute to significant physical and psychological distress, and management is highly varied in practice. As such, the development of a standardized pharmacologic guideline is paramount. We aimed to develop a novel clinical pathway (CP) for management of acute agitation for all hospitalized pediatric patients in Canada. Methods:Healthcare professionals in Canada with expertise in treating and managing pediatric agitation formed a working group and developed a CP through conducting a literature review, engaging key partners, and obtaining interdisciplinary consensus (iterative real-time discussions with content experts). Once developed, the preliminary CP was presented to additional internal and external partners via multiple grand rounds and a webinar; feedback from participants guided final CP revisions. Results:The working group created a pediatric inpatient CP to guide pharmacologic management of agitation and serve as an easy-to-use clinical and educational resource with three complementary sections including: 1) a treatment algorithm, 2) a quick reference medication chart, and 3) two supporting documents, which provide a general overview of non-pharmacologic strategies prior to CP implementation and an illustrative scenario to accompany the medication chart to ensure effective utilization. Conclusions:This is the first CP to standardize pharmacological treatment and management of acute agitation in children in inpatient settings in Canada. Although further research is warranted to assess implementation and support process improvement, the CP can be adapted by individual institutions to assist in prompt pharmacological management of pediatric agitation to potentially improve outcomes for patients, families, and healthcare professionals.

A range of maladaptive behaviors, including irritability and aggression, are often encountered in autism spectrum disorder. Challenges in complex clinical decision making and management exist, and off-label antipsychotic prescribing is increasing in Canada. A literature review of various treatments, limited to randomized controlled trials in the pediatric population, was used to develop an algorithm for evaluating and managing irritability and aggression in autism spectrum disorder within a Canadian context, which is supported by expert consensus. Holistic consideration of biomedical, psychiatric, psychosocial, environmental, and developmental factors that affect behavior is emphasized. The algorithm highlights the multifactorial contributors to irritability and aggression in autism spectrum disorder and reserves the use of antipsychotic medication for managing the most severe and refractory cases. A comprehensive evaluation of the drivers of behavior when addressing irritability and aggression in autism spectrum disorder is crucial to identify treatable contributors and institute appropriate management.

Introduction:Motivated by challenges faced in outpatient sleep services for mental health and neurodevelopmental disorders (MHNDD) during the COVID-19 clinical shutdown, a pan-Canadian/international working group of clinicians and social scientists developed a concept for capturing challenging sleep and wake behaviours already at the referral stage in the community setting.Methods:In a quality improvement/quality assurance (QIQA) project, a visual logic model was the framework for identifying the multiple causes and possible interventions for sleep disturbances. Intake forms informed clinicians about situational experiences, goals/concerns, in addition to the questions from the Sleep Disturbances Scale for Children (SDSC), the ADHD Rating Scale-IV and medication history. Descriptive statistics were used to describe the sample.Results:66% of the pilot study patients (n = 41) scored in the SDSC red domains (highest scoring) with highest sub-scores for insomnia (falling asleep 73%; staying asleep: 51%) and daytime somnolence (27%). A total of 90% of patients were taking at least one medication; 59% sleep initiation/sleep medications, 41% in combination with further non-stimulant medications, 9% with stimulants, 27% with antidepressants and 18% with antipsychotics. Polypharmacy was observed in 62% of all patients and in 73% of the ones medicated for sleep disturbances. Qualitative information supported individualisation of assessments.Conclusion:Our intake process enabled a comprehensive understanding of patients' sleep and wake profiles prior to assessment, at the referral stage. The high prevalence of insomnia in patients, combined with polypharmacy, requires special attention in the triaging process at the community level.

Psychiatric manifestations in patients with tetrahydrobiopterin (BH4) defects are common, and may occur even with treatment of the underlying disorder. The neurobiological background of these conditions has been linked to abnormalities of neurotransmitters, such as dopamine, serotonin, norepinephrine, and gamma-aminobutyric acid. Here, we review the psychiatric profile of all patients with BH4 defects followed in the pediatric and adult metabolic clinics at our center. Three patients with autosomal recessive (AR) guanosine triphosphate cyclohydrolase (GTPCH) deficiency and three patients with 6-pyruvoyl tetrahydropterin synthase (PTPS) deficiency were reviewed. All patients had behavioral disturbances and two had significant psychiatric comorbidities. These included attention deficit/hyperactivity disorder, anxiety, depression, aggression, or oppositional defiant disorder. One patient with PTPS deficiency had a severe psychiatric presentation, requiring inpatient admission and temporary placement into foster care for intensive behavioral therapy. Another with AR GTPCH deficiency was diagnosed with aggressive behavioral dysregulation requiring intensive psychiatric treatment. Management of the psychiatric manifestations of BH4 defects can be challenging, due to lack of information and studies of interactions between psychiatric medications on the deficient neurotransmitters and their receptors in these conditions. Further studies are needed to establish safety and efficacy of these treatments.

Background Cyclooxygenase (COX) enzymes oxidise arachidonic acid to prostaglandins, which modulate neuronal function and inflammation in the central nervous system. Consensus guidelines suggest non-steroidal anti-inflammatory drugs as a possible adjunctive approach in adults with obsessive–compulsive disorder (OCD) and in children with acute-onset OCD subtypes. However, there is limited evidence to support this approach. The primary objective of this study is to determine the efficacy of the COX-2-selective inhibitor celecoxib as an adjunct to treatment-as-usual in children and youth with moderate-to-severe OCD. The safety of this intervention including adverse events will also be systematically assessed. Methods TheAdjunctiveCElecoxib in childhood-onsetOCD(ACE-OCD) study is a single-centre randomised, quadruple-blind, placebo-controlled superiority trial with two parallel groups: celecoxib 100 mg twice daily and placebo. Treatments will be added to participants’ routine clinical care, which will not change over the course of the study. Target recruitment is 80 participants ages 7–18 with no recent treatment changes. The primary outcome is OCD severity after 12 weeks of treatment, measured by clinician-administered Children’s Yale-Brown Obsessive Compulsive Scale (CY-BOCS). Secondary outcomes include CY-BOCS score after 6 weeks; difference in the proportion of participants achieving a clinically meaningful response or remission; mean clinical global impression of severity and improvement after 6 and 12 weeks; and proportion of participants reporting adverse events possibly or probably related to the study intervention. The primary analyses, carried out according to intention-to-treat principles, will compare the celecoxib to placebo group on each outcome of interest, adjusting for baseline scores using analysis of covariance or logistic regression. Participants will be offered a 12-week open-label celecoxib extension and will be invited to participate in an ancillary study for biomarker analyses. Ethics and dissemination This protocol has been approved by the University of British Columbia Children’s and Women’s Research Ethics Board and has received a No Objection Letter from Health Canada. The findings will be disseminated in peer-reviewed journals and presentations to multiple stakeholders including patients, parents and healthcare providers. Trial registration number NCT04673578.

OBJECTIVES:To inform dosing and describe the pharmacokinetic interaction, efficacy and safety of fluvoxamine-clomipramine combination therapy for treatment-resistant pediatric obsessive-compulsive disorder (OCD).METHODS:A retrospective chart review of OCD-affected patients at a tertiary care children's hospital between January 2010 and August 2017 was conducted. Those included were 18 years of age or younger at initiation of fluvoxamine-clomipramine combination therapy and had at least one set of serum concentration values capturing clomipramine and desmethylclomipramine levels.RESULTS:Six adolescents met study inclusion criteria. Fluvoxamine adequately inhibited clomipramine metabolism to desmethylclomipramine in a dose-dependent manner. Fluvoxamine-clomipramine combination therapy was generally well tolerated with no serious or life-threatening adverse effects reported.CONCLUSION:Fluvoxamine-clomipramine combination therapy permits use of lower clomipramine doses than typically used as clomipramine monotherapy and appears to be a safe alternative for pediatric OCD patients failing sequential selective serotonin reuptake inhibitor monotherapy trials. Inter-patient variability and saturable kinetics support therapeutic drug monitoring of serum clomipramine and desmethylclomipramine concentrations to optimize therapy. A proposed algorithm that aligns with current OCD treatment guidelines is described. Further study is needed to evaluate efficacy of this approach.

Objective Literature describing use of clozapine by children and adolescents is limited. The primary study objective was to assess the patterns of clozapine use in an inpatient child and adolescent population. Methods A retrospective review of child and adolescent inpatients receiving clozapine at a Canadian children's hospital from January 2000 through December 2014 was conducted. Interdisciplinary comprehensive data collection was conducted by experienced clinicians. Baseline population characteristics and psychiatric illness risk factors were captured. Illness symptoms and severity were assessed retrospectively using validated measures including the Brief Psychiatric Rating Scale (BPRS), Children's Global Assessment Scale (CGAS) and Clinical Global Impressions (CGI) scales. Estimated clozapine dosing requirements for each patient to achieve a serum level associated with response was calculated. Clozapine-related adverse events were captured. Results Twenty-eight inpatients (64% female) receiving clozapine during the study period were identified. Mean age at clozapine initiation was 15.8 years. Twenty-three patients (82%) were taking clozapine at discharge, and of these, 22 patients (96%) experienced at least minimal improvement in BPRS and CGAS scores. Patients took a mean of 33.1 days from clozapine start to reach their maximum clozapine dosage, a mean maximum of 57% of their estimated clozapine dose requirement. Mean length of stay following clozapine initiation was 60.7 days. We observed a high rate of benign hematological adverse events, but no episodes of severe neutropenia. The majority of patients were of ethnicity associated with high risk for metabolic adverse events. Conclusion Most hospitalized, treatment-refractory children requiring clozapine clinically improve despite experiencing high, but largely manageable, adverse event rates.

A a clinical pharmacy specialist in child and adolescent mental health, I am frequently asked how to switch patients from clonidine immediate-release (IR) to guanfacine extended-release (XR). This therapeutic switch may be required when poor adherence to a clonidine IR regimen (typically requiring 3–4 doses daily) is identified, when clonidine dose-optimization is limited by sedation, bradycardia or hypotension, or when coverage situations change. The latter may occur if, for example, new eligibility for a government program or a third party-payer occurs.

Background:Acute agitation in the pediatric emergency department (ED) has the potential to escalate into aggression and result in harm. Rapid and effective management may be warranted. Use of pro re nata (prn) oral immediate-release (IR) quetiapine, haloperidol, loxapine, and chlorpromazine has been observed in the pediatric ED at Surrey Memorial Hospital to manage this condition; however, evidence for oral prn antipsychotic use is limited in the pediatric population. Objectives:The primary objective is to characterize the dose of prn oral IR quetiapine used to manage acute agitation or aggression in a pediatric ED. Secondary objectives include characterizing the dose of prn oral IR haloperidol, loxapine, and chlorpromazine; and describing the 1-hour response rate, admission rate, length of stay (LOS), and adverse drug effects. Method:The medical records of pediatric patients who received at least one prn oral dose of IR quetiapine, haloperidol, loxapine, or chlorpromazine for acute agitation and aggression, without regard to the etiology of symptom presentation, between January 1, 2012 and December 31, 2016, were analyzed retrospectively. Results:Sixty-nine patients met the inclusion criteria. The mean dose of quetiapine was 32 mg/dose (0.54 mg/kg per dose); and the response rate was 53%. The mean haloperidol, loxapine, and chlorpromazine doses were 4 mg (0.07 mg/kg per dose), 13 mg (0.19 mg/kg per dose), and 29 mg/dose (0.53 mg/kg per dose) respectively; and the response rates were 36%, 30%, and 50%, respectively. Between 19% and 60% of patients were admitted, majority to the psychiatry ward. The median LOS in the ED was between 5 and 18 hours for nonadmitted patients. Extrapyramidal side effects (EPS) were reported with first-generation antipsychotics (FGA), but not with quetiapine. Conclusion:Quetiapine appears to be a viable agent for managing acute agitation and aggression in the pediatric ED with low rates of EPS. Further studies are encouraged to compare the effectiveness of quetiapine with FGA. A Clinical Trial Registration number is not applicable for this study.

We present a case of a preteen with autism spectrum disorder and severe self-injurious behavior who developed neuroleptic malignant syndrome on antipsychotics and required urgent electroconvulsive therapy and continued maintenance electroconvulsive therapy for ongoing clinical stability.

This is a review of the empirical literature regarding what has been described anecdotally as patients who are 'rapid metabolizers' of stimulant medication. The authors propose that this is a misnomer used to describe two types of atypical pharmacokinetic patterns of response: high-dose responders, short-duration responders and two types of atypical pharmacodynamics patterns of response: patients who develop either acute or chronic tolerance. The authors propose that use of more precise terminology should facilitate both patient education and research to better understand the physiology and clinical management of atypical response patterns to stimulant treatment. Presently, the understanding of the pharmacokinetics and pharmacodynamics of psychostimulants is still quite limited. Further scientific research is needed to understand unusual patterns of pharmacological response seen in the clinic. Careful identification and precise description of these patterns would facilitate understanding the pharmacokinetics and pharmacodynamics of stimulants impacts the atypical response patterns seen in the clinic.

1Department of Psychiatry, University of British Columbia, Vancouver, British Columbia 2Mood and Anxiety Disorders Clinic, British Columbia’s Children’s Hospital, Vancouver, British Columbia 3Sun Life Financial Chair in Adolescent Mental Health, Director, WHO Collaborating Center in Mental Health Policy and Training, Dalhousie University and the IWK Health Center, Halifax, Nova Scotia 4Fraser Health Authority, Vancouver, British Columbia 5Lower Mainland Pharmacy Services, Vancouver, British Columbia 6Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia 7Child and Adolescent Mental Health Programs, BC Children’s Hospital, Vancouver, British Columbia 8Department of Pharmacy, BC Children’s Hospital, Vancouver, British Columbia

Journal of Child and Adolescent PsychopharmacologyVol. 26, No. 6 Letters to the EditorManic Reaction in a Child Induced by Guanfacine-Extended ReleaseDean Elbe, Carina Perel-Panar, and Leslie WicholasDean ElbeDivision of Child and Adolescent Mental Health, BC Mental Health and Addiction Services, Vancouver, Canada.Department of Pharmacy, Children's and Women's Health Centre of British Columbia, Vancouver, Canada.Search for more papers by this author, Carina Perel-PanarDivision of Child and Adolescent Mental Health, BC Mental Health and Addiction Services, Vancouver, Canada.Department of Psychiatry, University of British Columbia, Vancouver, Canada.Search for more papers by this author, and Leslie WicholasDivision of Child and Adolescent Mental Health, BC Mental Health and Addiction Services, Vancouver, Canada.Department of Psychiatry, University of British Columbia, Vancouver, Canada.Search for more papers by this authorPublished Online:1 Aug 2016https://doi.org/10.1089/cap.2016.0050AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"Manic Reaction in a Child Induced by Guanfacine-Extended Release." Journal of Child and Adolescent Psychopharmacology, 26(6), pp. 566–567FiguresReferencesRelatedDetailsCited byAntihypertensive drugs and brain function: mechanisms underlying therapeutically beneficial and harmful neuropsychiatric effects27 July 2022 | Cardiovascular Research, Vol. 21European clinical guidelines for Tourette syndrome and other tic disorders—version 2.0. Part III: pharmacological treatment10 November 2021 | European Child & Adolescent Psychiatry, Vol. 31, No. 3Lifetime evolution of ADHD treatment15 May 2021 | Journal of Neural Transmission, Vol. 128, No. 7ADHD with Comorbid Bipolar Disorders: A Systematic Review of Neurobiological, Clinical and Pharmacological Aspects Across the LifespanCurrent Medicinal Chemistry, Vol. 26, No. 38Guanfacine17 September 2016 | Reactions Weekly, Vol. 1619, No. 1 Volume 26Issue 6Aug 2016 InformationCopyright 2016, Mary Ann Liebert, Inc.To cite this article:Dean Elbe, Carina Perel-Panar, and Leslie Wicholas.Manic Reaction in a Child Induced by Guanfacine-Extended Release.Journal of Child and Adolescent Psychopharmacology.Aug 2016.566-567.http://doi.org/10.1089/cap.2016.0050Published in Volume: 26 Issue 6: August 1, 2016Online Ahead of Print:May 26, 2016PDF download