Journal of Child and Adolescent Psychopharmacology

The Clinical Global Impressions-Improvement (CGI-I) scale is widely used in clinical research to assess symptoms and functioning in the context of treatment. The correlates of the CGI-I with efficacy scales for adolescent major depressive disorder are poorly understood. This study focused on benchmarking CGI-I scores with changes in the Children's Depression Rating Scale-Revised (CDRS-R) and the Quick Inventory of Depressive Symptomatology-Adolescent (17-item) Self-Report (QIDS-A17-SR).

We examined three datasets with the clinician-rated CDRS-R to ascertain equivalent percent changes in total scores and CGI-I ratings. Exploratory analyses examined corresponding percentage changes in the QIDS-A17-SR and the CGI-I ratings. The CGI-I was the reference scale for nonparametric equipercentile linking with the Equate package in R.

CGI-I scores of 1 mapped to ≥78%–95% change in CDRS-R scores at 4–6 weeks across three datasets. CGI-I scores of 2 mapped to 56%–94% change in CDRS-R scores at 4–6 weeks across three studies. CGI-I scores of 3 mapped to 30%–68% changes in CDRS-R scores at 4–6 weeks across three studies. CGI-I scores of 4 mapped to a range of 29%–44% at 4–6 weeks across three studies. There was no significant difference (p ≥ 0.6) between treatment groups in both the Treatment of Adolescents with Depression and Treatment of Resistant Depression in Adolescents studies, for each CGI-I score ( = 1, or = 2 or = 3, or ≥4), associated mapping of total depression severity score, or associated percent change from baseline for corresponding follow-up visits. There was no significant sex difference (p > 0.2) in CGI-I linkages to CDRS-R total or percentage changes.

These findings establish clear relationships among CGI-I scores and the CDRS-R and the QIDS-A17-SR. These benchmarks have utility for clinical trial study design, inter-rater reliability training, and clinical implementation.

The study was designed to determine (1) the pharmacokinetic (PK) profile of dexmethylphenidate (d-MPH) after oral administration of three dosage strengths of a new treatment containing d-MPH and a novel prodrug, serdexmethylphenidate (SDX); (2) the dose proportionality of the different SDX/d-MPH dosages; and (3) the steady-state PK profile of d-MPH and SDX after multiple dosing of SDX/d-MPH.

Twenty-three healthy volunteers (aged 18–55 years) under fasted conditions received in a crossover design SDX/d-MPH 26.1/5.2 mg (Treatment A), 39.2/7.8 mg (Treatment B), and 52.3/10.4 mg (Treatment C) for a total d-MPH hydrochloride equivalent dose of 20, 30, and 40 mg, respectively. After a 96-hour washout period, all participants received four consecutive daily doses of SDX/d-MPH 52.3/10.4 mg. Blood samples were collected for measurement of plasma d-MPH and SDX and for PK analysis.

Administration of all three doses of SDX/d-MPH resulted in a rapid rise and slow decline in the plasma concentration of d-MPH. For Treatments A, B, and C, mean (± standard deviation) maximum concentrations (C _max) were 7.1 ± 2.1, 9.8 ± 2.8, and 13.8 ± 3.8 ng/mL, and overall exposures (AUC_0−last) were 97.2 ± 28.8, 142.5 ± 41.2, and 199.8 ± 57.2 h*ng/mL, respectively. Dose-normalized C _max, AUC_0–last, and AUC_0–inf for d-MPH were similar when comparing the high and low doses versus the middle dose. Power model regression analysis revealed that C _max and AUC_0–inf proportionally increased with an increase in SDX/d-MPH dose. In the multiple-dose study, d-MPH reached steady state before the third dose, and SDX after the first dose.

The PK profile of SDX/d-MPH is characterized by a rapid rise and a gradual decline in d-MPH concentration, with proportional C _max and AUC_0–inf across doses. The PK attributes of SDX/d-MPH may optimize symptom control from early morning to early evening, while the demonstrated dose proportionality may facilitate initial dose titration and ongoing dose adjustment.

Prescription of second-generation antipsychotics (SGAs) in youth is rapidly increasing globally and in Australia. Lack of timely metabolic monitoring for potential adverse effects puts youth at greater risk for lifelong adverse health impact. Metabolic monitoring is recommended as best practice to prevent and/or manage SGA-induced weight gain/metabolic syndrome. The adherence to clinical guidelines remains suboptimal. It is crucial to gauge insight to challenges and strategies from the perspective of prescribers and to recommend strategies in promoting quality use of SGAs and adherence to pharmacovigilance standards.

Psychiatrists participated through semistructured interviews within the community mental health clinics in the Queensland State of Australia. The interviews focused on barriers to monitoring and strategies to enhance rate of monitoring with key focus on practical strategies for future implications in community setting.

Ten participants completed the interviews. Barriers were specified such as lack of adequate resources to conduct monitoring, carers' disengagement in their youth's treatments, and patients' refusal to undergo blood tests. Strategies to enhance metabolic monitoring heavily relied on organizational support, provision of training, and education opportunities.

Clinical recommendations require mental health providers to facilitate conduction of metabolic monitoring among youth prescribed SGA/s. However, they are not provided with enough support and there are challenges that prevent such care. It is crucial to understand the challenges in managing a complex and vulnerable patient cohort. This research has thrown light on these key aspects of existing gap between best practice standards and clinical practice in youth prescribed SGAs.

Although recent articles have investigated the use of low-dose olanzapine in different psychiatric conditions, only one study so far has assessed this treatment in 13 girls with anorexia nervosa (AN).

Observational naturalistic case–control study aimed at reporting the use and tolerability of low-dose olanzapine in the context of a multidisciplinary hospital intervention for adolescents with AN. Three groups with AN were compared: group 1 was treated with low-dose olanzapine (≤5 mg/day), group 2 with full-dose olanzapine (>5 mg/day), and group 3 (control group) was treated without antipsychotics. Psychopathology was assessed at admission (T0) and discharge (T1) with Eating Disorders Inventory-3 Eating Disorders Risk, Body Uneasiness Test Global Severity Index (BUT-GSI), Beck's Depression Inventory-II (BDI-II), and Self-administered Psychiatric Scales for Children and Adolescents, Depression subtest (SAFA-D). Possible differences among the three groups, concerning clinical and treatment variables, were screened. Then, potential differences of T0–T1 modifications in psychopathological variables among the three treatment groups were assessed with analyses of covariance, corrected for baseline psychopathology and potential confounders, including possible concurrent antidepressants.

A total of 118 patients were enrolled (F = 94.1%; mean age = 15.4 ± 1.7 years), including 52 controls, 37 treated with low-dose olanzapine, and 29 with full-dose olanzapine. Low-dose olanzapine was well tolerated and used for a mean of 132.1 (±98.6) days, starting with a dosage of 3.4 (±1.2) mg/day and increasing to a maximum dose of 4.4 (±1.1) mg/day. The multidisciplinary intervention resulted in an improvement of BUT-GSI (p < 0.001), BDI-II (p < 0.001), and SAFA-D (p < 0.001) for the entire sample. Individuals treated with full-dose olanzapine experienced a significantly lower improvement in depressive measures: BDI-II (F[2,61] = 12.653, p < 0.001, η² = 0.269) and SAFA-D (F[2,57] = 7.413, p = 0.001, η² = 0.170), than the other groups.

This naturalistic controlled study expands the existing evidence on the use and tolerability of low-dose olanzapine in adolescents with AN. These results should be assessed in wider and prospective samples.