Comparative physiological effects of antipsychotic drugs in children and young people: a network meta-analysis.

BACKGROUND: The degree of physiological responses to individual antipsychotic drugs is unclear in children and adolescents. With network meta-analysis, we aimed to investigate the effects of various antipsychotic medications on physiological variables in children and adolescents with neuropsychiatric and neurodevelopmental conditions. METHODS: For this network meta-analysis, we searched Medline, EMBASE, PsycINFO, Web of Science, and Scopus from database inception until Dec 22, 2023, and included randomised controlled trials comparing antipsychotics with placebo in children or adolescents younger than 18 years with any neuropsychiatric and neurodevelopmental condition. Primary outcomes were mean change from baseline to end of acute treatment in bodyweight, BMI, fasting glucose, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, prolactin, heart rate, systolic blood pressure (SBP), and QT interval corrected for heart rate (QTc) for patients receiving either active treatment or placebo. For multigroup trials reporting several doses, we calculated a summary value for each physiological variable for all doses. After transitivity assessment, we fitted frequentist random-effects network meta-analyses for all comparisons in the network. A Kilim plot was used to summarise the results for all treatments and outcomes, providing information regarding the strength of the statistical evidence of treatment effects, using p values. Network heterogeneity was assessed with τ, risk of bias of individual trials was assessed with the Cochrane Collaboration's Tool for Assessing Risk of Bias, and the credibility of findings from each network meta-analysis was assessed with the Confidence in Network Meta-Analysis (CINEMA) app. This study is registered on PROSPERO (CRD42021274393). FINDINGS: Of 6676 studies screened, 47 randomised controlled trials were included, which included 6500 children (mean age 13·29 years, SD 2·14) who received treatment for a median of 7 weeks (IQR 6-8) with either placebo (n=2134) or one of aripiprazole, asenapine, blonanserin, clozapine, haloperidol, lurasidone, molindone, olanzapine, paliperidone, pimozide, quetiapine, risperidone, or ziprasidone (n=4366). Mean differences for bodyweight change gain compared with placebo ranged from -2·00 kg (95% CI -3·61 to -0·39) with molindone to 5·60 kg (0·27 to 10·94) with haloperidol; BMI -0·70 kg/m2 (-1·21 to -0·19) with molindone to 2·03 kg/m2 (0·51 to 3·55) with quetiapine; total cholesterol -0·04 mmol/L (-0·39 to 0·31) with blonanserin to 0·35 mmol/L (0·17 to 0·53) with quetiapine; LDL cholesterol -0·12 mmol/L (-0·31 to 0·07) with risperidone or paliperidone to 0·17 mmol/L (-0·06 to 0·40) with olanzapine; HDL cholesterol 0·05 mmol/L (-0·19 to 0·30) with quetiapine to 0·48 mmol/L (0·18 to 0·78) with risperidone or paliperidone; triglycerides -0·03 mmol/L (-0·12 to 0·06) with lurasidone to 0·29 mmol/L (0·14 to 0·44) with olanzapine; fasting glucose from -0·09 mmol/L (-1·45 to 1·28) with blonanserin to 0·74 mmol/L (0·04 to 1·43) with quetiapine; prolactin from -2·83 ng/mL (-8·42 to 2·75) with aripiprazole to 26·40 ng/mL (21·13 to 31·67) with risperidone or paliperidone; heart rate from -0·20 bpm (-8·11 to 7·71) with ziprasidone to 12·42 bpm (3·83 to 21·01) with quetiapine; SBP from -3·40 mm Hg (-6·25 to -0·55) with ziprasidone to 10·04 mm Hg (5·56 to 14·51) with quetiapine; QTc from -0·61 ms (-1·47 to 0·26) with pimozide to 0·30 ms (-0·05 to 0·65) with ziprasidone. INTERPRETATION: Children and adolescents show varied but clinically significant physiological responses to individual antipsychotic drugs. Treatment guidelines for children and adolescents with a range of neuropsychiatric and neurodevelopmental conditions should be updated to reflect each antipsychotic drug's distinct profile for associated metabolic changes, alterations in prolactin, and haemodynamic alterations. FUNDING: UK Academy of Medical Sciences, Brain and Behaviour Research Foundation, UK National Institute of Health Research, Maudsley Charity, the Wellcome Trust, Medical Research Council, National Institute of Health and Care Research Biomedical Centre at King's College London and South London and Maudsley NHS Foundation Trust, the Italian Ministry of University and Research, the Italian National Recovery and Resilience Plan, and Swiss National Science Foundation.

Examining the acceptability of actigraphic devices in children using qualitative and quantitative approaches: protocol for a systematic review and meta-analysis.

INTRODUCTION: Actigraphy is commonly used to record free living physical activity in both typically and atypically developing children. While the accuracy and reliability of actigraphy have been explored extensively, research regarding young people's opinion towards these devices is scarce. This review aims to identify and synthesise evidence relating to the acceptability of actigraphic devices in 5-11 year olds. METHODS AND ANALYSIS: Database searches will be applied to Embase, MEDLINE, PsychInfo and Social Policy and Practice through the OVID interface; and Education Resources Information Center (ERIC), British Education Index and CINAHL through the EBSCO interface from January 2018 until February 2023. Supplementary forward and backward citation and grey literature database searches, including Healthcare Management Information Consortium (HMIC) and PsycEXTRA will be conducted. Qualitative and quantitative studies, excluding review articles and meta-analyses, will be eligible, without date restrictions. Article screening and data extraction will be undertaken by two review authors and disagreements will be deferred to a third reviewer. The primary outcome, actigraphic acceptability, will derive from the narrative synthesis of the main themes identified from included qualitative literature and pooled descriptive statistics relating to acceptability identified from quantitative literature. Subgroup analyses will determine if acceptability changes as a function of the key participant and actigraphic device factors. ETHICS AND DISSEMINATION: Ethical approval is not required for this systematic review as it uses data from previously published literature. The results will be presented in a manuscript and published in a peer review journal and will be considered alongside a separate stream of codesign research to inform the development of a novel child-worn actigraphic device. PROSPERO REGISTRATION NUMBER: CRD42021232466.

Experience of stigmatization in children receiving inpatient and outpatient mental health treatment: a longitudinal study.

Mental health-related stigma is poorly understood, and minimal research has focused on the experience of stigma from children's perspectives. We sought to investigate whether children treated as inpatients and outpatients had different experiences of stigma over time and whether stigma is linked to global functioning cross-sectionally and longitudinally. Children, aged 8-12 years, receiving treatment within a national specialist mental health inpatient unit were matched for age, gender and diagnosis with children receiving outpatient treatment (N = 64). Validated measures of stigma, global functioning and symptom severity were collected at the start of treatment and upon discharge from the ward for inpatients, and a similar timeframe for their individually matched outpatients. Latent change score models and partial correlation coefficients were employed to test our hypotheses. No differences in most aspects of stigma between children treated as inpatients and outpatients were observed, except for personal rejection at baseline and self-stigma at follow-up favouring outpatients. A reduction in stigma was observed in societal devaluation, personal rejection and secrecy for inpatients, and self-stigma and secrecy for outpatients between the two assessments. Societal devaluation declined at a higher rate among inpatients compared to outpatients, albeit reductions in stigma were comparable for all remaining measures. No association was found between the change in stigma and change in global functioning. Future research may offer further insights into the development and maintenance of stigma and identify key targets for anti-stigma interventions to reduce its long-term impact.

The role of stigma in children and adolescents with mental health difficulties.

PURPOSE OF REVIEW: Children and adolescents with mental health difficulties, and people associated with them, can experience stigma as a result of these difficulties. This article aims to provide an update on the literature pertaining to mental health-related stigma in children and adolescents. RECENT FINDINGS: Recent studies have investigated public stigma, self-stigma and affiliate stigma related to child and adolescent mental health difficulties. Research has typically employed a cross-sectional design. Significant variation was identified in both study methodology and study findings. Qualitative studies offer a unique perspective of stigma from the point of view of the stigmatized individual. Significantly, quantitative analysis has found different variables to be associated with stigma in different geographical locations, even when similar measures are used. SUMMARY: Stigma can have a significant detrimental impact on the quality of life for those affected. Careful attention should therefore be paid to stigma in the assessment and treatment of children and adolescents with mental health difficulties. Furthermore, its impact on their caregivers should not be overlooked. Further research is needed to understand the role of social and cultural factors in the development and impact of stigma, and may aid production of antistigma interventions.

A qualitative study of women's views on the acceptability of being asked about mental health problems at antenatal booking appointments.

OBJECTIVE: To explore women's views on the acceptability of being asked about mental health problems at antenatal booking. DESIGN: Qualitative study. SETTING: Brief semi-structured qualitative interviews were conducted with women in a private setting at a hospital, or at women's homes. Interview discussions centered around three key questions: "What was it like for you answering the questions about your mood?", "Were there any questions you found upsetting, distressing or confronting?" and "Did the midwife give you some feedback about your answers?" MEASUREMENTS: Interviews were audio-recorded, transcribed verbatim, and analysed using thematic and framework approaches. PARTICIPANTS: An ethnically diverse sample [32% white British/Irish, 68% non-white, non-British] of 52 women living in the study area. FINDINGS: Most women found mental health enquiry acceptable. A smaller proportion reported difficulties and many of these women had a past or current mental health problem and/or a history of abuse. These women reported difficulty due to the emotional responses triggered by the questions and the way disclosures were handled. In general, women wanted to be asked clear questions about mental health problems, to have sufficient time to discuss issues, and to receive responses from midwives which were normalising and well-informed about mental health. CONCLUSIONS: This study highlights that women want midwives to ask clearly-framed questions about mental health problems [addressing past and current mental health concerns], and value responses from midwives that are normalising, well-informed and allow for discussion. IMPLICATIONS FOR PRACTICE: Training should be provided to midwives on how to appropriately respond to women's distress during mental health enquiry, and on referral to support services.

Antidepressants for preventing postnatal depression.

BACKGROUND: Depression is common in the postnatal period and can lead to adverse effects on the infant and wider family, in addition to the morbidity for the mother. It is not clear whether antidepressants are effective for the prevention of postnatal depression and little is known about possible adverse effects for the mother and infant, particularly during breastfeeding. This is an update of a Cochrane Review last published in 2005. OBJECTIVES: To assess the effectiveness of antidepressant medication for the prevention of postnatal depression, in comparison with any other treatment, placebo or standard care. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR ‒ both Studies and References), CENTRAL (Wiley), MEDLINE (OVID), Embase (OVID), PsycINFO (OVID), on 13 February 2018. We also searched the World Health Organization (WHO) trials portal (ICTRP) and ClinicalTrials.gov on 13 February 2018 to identify any additional unpublished or ongoing studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) of initiation of antidepressants (alone or in combination with another treatment), compared with any other treatment, placebo or standard care for the prevention of postnatal depression among women who were either pregnant or had given birth in the previous six weeks and were not currently depressed at baseline. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We requested missing information from investigators wherever possible and sought data to allow intention-to-treat analyses. MAIN RESULTS: Two trials including a total of 81 participants fulfilled the inclusion criteria for this review. All participants in both studies had a history of postnatal depression and were not taking antidepressant medication at baseline. Both trials were conducted by the same research group. Risk of bias was low or unclear in most domains for both studies. We were unable to perform a meta-analysis due to the small number of studies.One study compared nortriptyline with placebo and did not find any evidence that nortriptyline was effective in preventing postnatal depression. In this study, 23% (6/26) of women who took nortriptyline and 24% (6/25) of women who took placebo experienced postnatal depression (RR 0.96, 95% CI 0.36 to 2.59, very low quality evidence) in the first 17 weeks postpartum. One woman taking nortriptyline developed mania; and one side effect, constipation, was more common among women taking nortriptyline than those taking placebo.The second study compared sertraline with placebo. In this study, 7% (1/14) of women who took sertraline developed postnatal depression in the first 17 weeks postpartum compared with 50% (4/8) of women who took placebo. It is uncertain whether sertraline reduces the risk of postnatal depression (RR 0.14, 95% CI 0.02 to 1.07, very low quality evidence). One woman taking sertraline had a hypomanic episode. Two side effects (dizziness and drowsiness) were more common among women taking sertraline than women taking placebo.Conclusions are limited by the small number of studies, small sample sizes and incomplete outcome data due to study drop-out which may have led to bias in the results. We have assessed the certainty of the evidence as very low, based on the GRADE system. No data were available on secondary outcomes of interest including child development, the mother‒infant relationship, breastfeeding, maternal daily functioning, family relationships or maternal satisfaction. AUTHORS' CONCLUSIONS: Due to the limitations of the current evidence base, such as the low statistical power of the included studies, it is not possible to draw any clear conclusions about the effectiveness of antidepressants for the prevention of postnatal depression. It is striking that no new eligible trials have been completed in the period of over a decade since the last published version of this review. Larger trials are needed which include comparisons of antidepressant drugs with other prophylactic treatments (e.g. psychological interventions), and examine adverse effects for the fetus or infant. Future reviews in this area may benefit from broadening their focus to examine the effectiveness of antidepressants for the prevention of perinatal (i.e. antenatal or postnatal) depression, which could include studies comparing antidepressant discontinuation with continuation for the prevention of relapse of depression during pregnancy and the postnatal period.